Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSP...Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.展开更多
BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultraso...BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.展开更多
Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amy...Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.展开更多
To date,few models are available in the literature to consider the creep behavior of geosynthetics when predicting the lateral deformation(d)of geosynthetics-reinforced soil(GRS)retaining walls.In this study,a general...To date,few models are available in the literature to consider the creep behavior of geosynthetics when predicting the lateral deformation(d)of geosynthetics-reinforced soil(GRS)retaining walls.In this study,a general hyperbolic creep model was first introduced to describe the long-term deformation of geosynthetics,which is a function of elapsed time and two empirical parameters a and b.The conventional creep tests with three different tensile loads(Pr)were conducted on two uniaxial geogrids to determine their creep behavior,as well as the a-Pr and b-Pr relationships.The test results show that increasing Pr accelerates the development of creep deformation for both geogrids.Meanwhile,a and b respectively show exponential and negatively linear relationships with Pr,which were confirmed by abundant experimental data available in other studies.Based on the above creep model and relationships,an accurate and reliable analytical model was then proposed for predicting the time-dependent d of GRS walls with modular block facing,which was further validated using a relevant numerical investigation from the previous literature.Performance evaluation and comparison of the proposed model with six available prediction models were performed.Then a parametric study was carried out to evaluate the effects of wall height,vertical spacing of geogrids,unit weight and internal friction angle of backfills,and factor of safety against pullout on d at the end of construction and 5 years afterwards.The findings show that the creep effect not only promotes d but also raises the elevation of the maximum d along the wall height.Finally,the limitations and application prospects of the proposed model were discussed and analyzed.展开更多
In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The t...In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.展开更多
BACKGROUND Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm.However,managing cases becomes more challenging when a m...BACKGROUND Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm.However,managing cases becomes more challenging when a maxillary sinus pseudocyst is present or when there is insufficient bone width.In this case,we utilized the bone window prepared during the lateral window sinus lift as a shell for horizontal bone augmentation.This allowed for simultaneous horizontal and vertical bone augmentation immediately after the removal of the maxillary sinus pseudocyst.CASE SUMMARY A 28-year-old female presented to our clinic with the chief complaint of missing upper left posterior teeth.Intraoral examination showed a horizontal deficiency of the alveolar ridge contour.The height of the alveolar bone was approximately 3.6 mm on cone beam computed tomography(CBCT).And a typical well-defined'dome-shaped'lesion in maxillary sinus was observed on CBCT imaging.The lateral bony window was prepared using a piezo-ultrasonic device,then the bony window was fixed to the buccal side of the 26 alveolar ridge using a titanium screw with a length of 10 mm and a diameter of 1.5 mm.The space between the bony window and the alveolar ridge was filled with Bio-Oss,covered with a Bio-Gide collagen membrane,and subsequently sutured.Nine months later,the patient’s bone width increased from 4.8 to 10.5 mm,and the bone height increased from 3.6 to 15.6 mm.Subsequently,a Straumann^(■)4.1 mm×10 mm implant was placed.The final all-ceramic crown restoration was completed four months later,and both clinical and radiographic examinations showed that the implant was successful,and the patient was satisfied with the results.CONCLUSION The bone block harvested from the lateral window sinus lift can be used for simultaneous horizontal bone augmentation acting as a shell for good two-dimensional bone augmentation.展开更多
Although the internal stress state of soils can be affected by repetitive loading,there are few studies evaluating the lateral stress(or K 0)of soils under repetitive loading.This study investigates the changes in K 0...Although the internal stress state of soils can be affected by repetitive loading,there are few studies evaluating the lateral stress(or K 0)of soils under repetitive loading.This study investigates the changes in K 0 and directional shear wave velocity(V s)in samples of two granular materials with different particle shapes during repetitive loading.A modified oedometer cell equipped with bender elements and a diaphragm transducer was developed to measure the variations in the lateral stress and the shear wave velocity,under repetitive loading on the loading and unloading paths.The study produced the following results:(1)Repetitive loading on the loading path resulted in an increase in the K 0 of test samples as a function of cyclic loading number(i),and(2)Repetitive loading on the unloading path resulted in a decrease in K 0 according to i.The shear wave velocity ratio(i.e.V s(HH)/V s(VH),where the first and second letters in parentheses corresponds to the directions of wave propagation and particle motion,respectively,and V and H corresponds to the vertical and horizontal directions,respectively)according to i supports the experimental observations of this study.However,when the tested material was in lightly over-consolidated state,there was an increase in K 0 during repetitive loading,indicating that it was the initial K 0,rather than the loading path,which is responsible for the change in K 0.The power model can capture the variation in the K 0 of samples according to i.Notably,the K 0=1 line acts as the boundary between the increase and decrease in K 0 under repetitive loading.展开更多
The surrounding rock of underground space is always affected by external dynamic disturbance from the side position,such as blasting vibration from a stope at the same level or seismic waves from adjacent strata.A ser...The surrounding rock of underground space is always affected by external dynamic disturbance from the side position,such as blasting vibration from a stope at the same level or seismic waves from adjacent strata.A series of laboratory tests,numerical simulations and theoretical analyses were carried out in this study to disclose the sliding mechanism of roof rock blocks under lateral disturbance.Firstly,the experiments on trapezoidal key block under various clamping loads and disturbance were conducted,followed by numerical simulations using the fast Lagrangian analysis of continua(FLAC3D).Then,based on the conventional wave propagation model and the classical shear-slip constitutive model,a theoretical model was proposed to capture the relative displacement between blocks and the sliding displacement of the key block.The results indicate that the sliding displacement of the key block increased linearly with the disturbance energy and decreased exponentially with the clamping load when the key block was disturbed to slide(without instability).Meanwhile,when the key block was disturbed to fall,two types of instability process may appear as immediate type or delayed type.In addition,the propagation of stress waves in the block system exhibited obvious low-velocity and lowfrequency characteristics,resulting in the friction reduction effect appearing at the contact interface,which is the essential reason for the sliding of rock blocks.The results can be applied to practical underground engineering and provide valuable guidance for the early detection and prevention of rockfalling disasters.展开更多
Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly understood.However,inflammation is known to play an important role in the development of...Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly understood.However,inflammation is known to play an important role in the development of this condition.To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis.Therefore,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis.The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response.Furthermore,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis.These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.展开更多
Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to r...Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.展开更多
Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role ...Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.展开更多
Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are sti...A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are still unclear.Here,maize seedlings were grown hydroponically with three N supplied in three different forms (NO_(3)^(–)only,75/25 NO_(3)^(–)/NH_(4)^(+)and NH_(4)^(+)only).Compared with sole NO_(3)^(–)or NH_(4)^(+),the mixed N supply increased the total root length of maize but did not affect the number of axial roots.The main reason was the increased total lateral root length,while the average lateral root (LR) length in each axle was only slightly increased.In addition,the average LR density of 2nd whorl crown root under mixed N was also increased.Compared with sole nitrate,mixed N could improve the N metabolism of roots (such as the N influx rate,nitrate reductase (NR) and glutamine synthase (GS)enzyme activities and total amino content of the roots).Experiments with exogenously added NR and GS inhibitors suggested that the increase in the average LR length under mixed N was related to the process of N assimilation,and whether the NR mediated NO synthesis participates in this process needs further exploration.Meanwhile,an investigation of the changes in root-shoot ratio and carbon (C) concentration showed that C transportation from shoots to roots may not be the key factor in mediating lateral root elongation,and the changes in the sugar concentration in roots further proved this conclusion.Furthermore,the synthesis and transportation of auxin in axial roots may play a key role in lateral root elongation,in which the expression of ZmPIN1B and ZmPIN9 may be involved in this pathway.This study preliminarily clarified the changes in root morphology and explored the possible physiological mechanism under a mixed N supply in maize,which may provide some theoretical basis for the cultivation of crop varieties with high N efficiency.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t...The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).展开更多
Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial ri...Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial risk for developing CAI.This study identifies magnetic resonance imaging(MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients.Methods:All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1,2017 to December 1,2019 were identified.Data were collected using the Cumberland Ankle Instability Tool at final follow-up.Demographic and other related clinical variables,including age,sex,body mass index,and treatment were also recorded.Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS.Results:A total 131 out of 362 patients with a mean follow-up of 3.0± 0.6 years(mean ± SD;2.0—4.1 years) developed CAI after first-episode LAS.According to multivariable regression,development of CAI after first-episode LAS was associated with 5 prognostic factors:age(odds ratio(OR)=0.96,95% confidence interval(95%CI):0.93-1.00,p=0.032);body mass index(OR=1.09,95%CI:1.02-1.17,p=0.009);posterior talofibular ligament injury(OR=2.17,95%CI:1.05-4.48,p=0.035);large bone marrow lesion of the talus(OR=2.69,95%CI:1.30-5.58,p=0.008),and Grade 2 effusion of the tibiotalar joint(OR=2.61,95%CI:1.39-4.89,p=0.003).When patients had at least 1 positive clinical finding in the 10-m walk test,anterior drawer test,or inversion tilt test,they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI.Conclusion:MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the10-m walk test,anterior drawer test,and inversion tilt test.Further prospective and large-scale studies are necessary for validation.展开更多
Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Sin...Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.展开更多
BACKGROUND For the management of lateral lymph node(LLN)metastasis in patients with rectal cancer,selective LLN dissection(LLND)is gradually being accepted by Chinese scholars.Theoretically,fascia-oriented LLND allows...BACKGROUND For the management of lateral lymph node(LLN)metastasis in patients with rectal cancer,selective LLN dissection(LLND)is gradually being accepted by Chinese scholars.Theoretically,fascia-oriented LLND allows radical tumor resection and protects of organ function.However,there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND.Through a preliminary study with a small sample size,we found that fasciaoriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs.In this study,we increased the sample size and refined the postoperative functional outcomes.AIM To compare the effects of fascia-and vessel-oriented LLND regarding short-term outcomes and prognosis.METHODS We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021.The short-term outcomes included perioperative outcomes and postoperative functional outcomes.The prognosis was measured based on overall survival(OS)and progression-free survival(PFS).RESULTS A total of 105 patients were included in the final analysis and were divided into fascia-and vesseloriented groups that included 41 and 64 patients,respectively.Regarding the short-term outcomes,the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group.There were no significant differences in the other short-term outcomes.The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group.In addition,there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups.In terms of prognosis,there was no significant difference in PFS or OS between the two groups.CONCLUSION It is safe and feasible to perform fascia-oriented LLND.Compared with vessel-oriented LLND,fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.展开更多
Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited pa...Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.展开更多
Owing to the good adjustability and the strong near-field enhancement,surface plasmons are widely used in optical force trap,thus the optical force trap can achieve excellent performance.Here,we use the Laguerre–Gaus...Owing to the good adjustability and the strong near-field enhancement,surface plasmons are widely used in optical force trap,thus the optical force trap can achieve excellent performance.Here,we use the Laguerre–Gaussian beam and a plasmonic gold ring to separate enantiomers by the chiral optical force.Along with the radial optical force that traps the particles,there is also a chirality-sign-sensitive lateral force arising from the optical spin angular momentum,which is caused by the interaction between optical orbit angular momentum and gold ring structure.By selecting a specific incident wavelength,the strong angular scattering and non-chiral related azimuthal optical force can be suppressed.Thus the chiral related azimuthal optical force can induce an opposite orbital rotation of the trapped particles with chirality of different sign near the gold ring.This work proposes an effective approach for catchingand separating chiral enantiomers.展开更多
基金supported by the Scientific and Innovative Action Plan of Shanghai(21N31900800)Shanghai Rising-Star Program(23QB1403500)+4 种基金the Shanghai Sailing Program(20YF1443000)Shanghai Science and Technology Commission,the Belt and Road Project(20310750500)Talent Project of SAAS(2023-2025)Runup Plan of SAAS(ZP22211)the SAAS Program for Excellent Research Team(2022(B-16))。
文摘Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.
基金Supported by the National Natural Science Foundation of China,No.82305380The Postdoctoral Research Program,West China Hospital,Sichuan University,No.2020HXBH018.
文摘BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX).
文摘Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
基金This research work was financially supported by the National Natural Science Foundation of China(Grant Nos.52078182 and 41877255)the Tianjin Municipal Natural Science Foundation(Grant No.20JCYBJC00630).Their financial support is gratefully acknowledged.
文摘To date,few models are available in the literature to consider the creep behavior of geosynthetics when predicting the lateral deformation(d)of geosynthetics-reinforced soil(GRS)retaining walls.In this study,a general hyperbolic creep model was first introduced to describe the long-term deformation of geosynthetics,which is a function of elapsed time and two empirical parameters a and b.The conventional creep tests with three different tensile loads(Pr)were conducted on two uniaxial geogrids to determine their creep behavior,as well as the a-Pr and b-Pr relationships.The test results show that increasing Pr accelerates the development of creep deformation for both geogrids.Meanwhile,a and b respectively show exponential and negatively linear relationships with Pr,which were confirmed by abundant experimental data available in other studies.Based on the above creep model and relationships,an accurate and reliable analytical model was then proposed for predicting the time-dependent d of GRS walls with modular block facing,which was further validated using a relevant numerical investigation from the previous literature.Performance evaluation and comparison of the proposed model with six available prediction models were performed.Then a parametric study was carried out to evaluate the effects of wall height,vertical spacing of geogrids,unit weight and internal friction angle of backfills,and factor of safety against pullout on d at the end of construction and 5 years afterwards.The findings show that the creep effect not only promotes d but also raises the elevation of the maximum d along the wall height.Finally,the limitations and application prospects of the proposed model were discussed and analyzed.
文摘In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.
文摘BACKGROUND Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm.However,managing cases becomes more challenging when a maxillary sinus pseudocyst is present or when there is insufficient bone width.In this case,we utilized the bone window prepared during the lateral window sinus lift as a shell for horizontal bone augmentation.This allowed for simultaneous horizontal and vertical bone augmentation immediately after the removal of the maxillary sinus pseudocyst.CASE SUMMARY A 28-year-old female presented to our clinic with the chief complaint of missing upper left posterior teeth.Intraoral examination showed a horizontal deficiency of the alveolar ridge contour.The height of the alveolar bone was approximately 3.6 mm on cone beam computed tomography(CBCT).And a typical well-defined'dome-shaped'lesion in maxillary sinus was observed on CBCT imaging.The lateral bony window was prepared using a piezo-ultrasonic device,then the bony window was fixed to the buccal side of the 26 alveolar ridge using a titanium screw with a length of 10 mm and a diameter of 1.5 mm.The space between the bony window and the alveolar ridge was filled with Bio-Oss,covered with a Bio-Gide collagen membrane,and subsequently sutured.Nine months later,the patient’s bone width increased from 4.8 to 10.5 mm,and the bone height increased from 3.6 to 15.6 mm.Subsequently,a Straumann^(■)4.1 mm×10 mm implant was placed.The final all-ceramic crown restoration was completed four months later,and both clinical and radiographic examinations showed that the implant was successful,and the patient was satisfied with the results.CONCLUSION The bone block harvested from the lateral window sinus lift can be used for simultaneous horizontal bone augmentation acting as a shell for good two-dimensional bone augmentation.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(Grant No.RS-2023-00208844).
文摘Although the internal stress state of soils can be affected by repetitive loading,there are few studies evaluating the lateral stress(or K 0)of soils under repetitive loading.This study investigates the changes in K 0 and directional shear wave velocity(V s)in samples of two granular materials with different particle shapes during repetitive loading.A modified oedometer cell equipped with bender elements and a diaphragm transducer was developed to measure the variations in the lateral stress and the shear wave velocity,under repetitive loading on the loading and unloading paths.The study produced the following results:(1)Repetitive loading on the loading path resulted in an increase in the K 0 of test samples as a function of cyclic loading number(i),and(2)Repetitive loading on the unloading path resulted in a decrease in K 0 according to i.The shear wave velocity ratio(i.e.V s(HH)/V s(VH),where the first and second letters in parentheses corresponds to the directions of wave propagation and particle motion,respectively,and V and H corresponds to the vertical and horizontal directions,respectively)according to i supports the experimental observations of this study.However,when the tested material was in lightly over-consolidated state,there was an increase in K 0 during repetitive loading,indicating that it was the initial K 0,rather than the loading path,which is responsible for the change in K 0.The power model can capture the variation in the K 0 of samples according to i.Notably,the K 0=1 line acts as the boundary between the increase and decrease in K 0 under repetitive loading.
基金This work was financially supported by National Key Research and Development Program of China(Grant No.2022YFC2903903)National Natural Science Foundation of China(Grant No.52304132)Yunnan Major Scientific and Technological Projects(Grant No.202202AG050014).These support is gratefully acknowledged.
文摘The surrounding rock of underground space is always affected by external dynamic disturbance from the side position,such as blasting vibration from a stope at the same level or seismic waves from adjacent strata.A series of laboratory tests,numerical simulations and theoretical analyses were carried out in this study to disclose the sliding mechanism of roof rock blocks under lateral disturbance.Firstly,the experiments on trapezoidal key block under various clamping loads and disturbance were conducted,followed by numerical simulations using the fast Lagrangian analysis of continua(FLAC3D).Then,based on the conventional wave propagation model and the classical shear-slip constitutive model,a theoretical model was proposed to capture the relative displacement between blocks and the sliding displacement of the key block.The results indicate that the sliding displacement of the key block increased linearly with the disturbance energy and decreased exponentially with the clamping load when the key block was disturbed to slide(without instability).Meanwhile,when the key block was disturbed to fall,two types of instability process may appear as immediate type or delayed type.In addition,the propagation of stress waves in the block system exhibited obvious low-velocity and lowfrequency characteristics,resulting in the friction reduction effect appearing at the contact interface,which is the essential reason for the sliding of rock blocks.The results can be applied to practical underground engineering and provide valuable guidance for the early detection and prevention of rockfalling disasters.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,82160255a grant from Department of Education of Jiangxi Province,Nos.GJJ13198,GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,Nos.[2014]-47,20142BBG70062,20171BAB215022,20192BAB205043Science and Technology Plan of Jiangxi Commission of Health,Nos.202210002,202310119(all to RX).
文摘Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly understood.However,inflammation is known to play an important role in the development of this condition.To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis.Therefore,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis.The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response.Furthermore,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis.These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.
基金supported by a grant from the Association Française contre les Myopathies(AFM Téléthongrant 23667,to JCL).
文摘Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.
基金supported by the National Natural Science Foundation of China,No.82171521(to CL)the Special Funds ofTaishan Scholars Project of Shandong Province,No.tsqn202211368(to CL)+2 种基金the Natural Science Foundation of Shandong Province,Nos.ZR2022YQ65(to CL),ZR2021MH073(to CL),ZR2019PH109(to WW)the Projects of Medical and Health Technology Development Program in Shandong Province,China,Nos.202003090720(to DZ),202003070728(to JL),2019 WS329(to DW)the Scientific Research Foundation of Binzhou Medical University,No.BY2018KJ21(to DW)。
文摘Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金supported by the National Natural Science Foundation of China(31421092)the Central Publicinterest Scientific Institution Basal Research Fund,China(1610232023023)。
文摘A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are still unclear.Here,maize seedlings were grown hydroponically with three N supplied in three different forms (NO_(3)^(–)only,75/25 NO_(3)^(–)/NH_(4)^(+)and NH_(4)^(+)only).Compared with sole NO_(3)^(–)or NH_(4)^(+),the mixed N supply increased the total root length of maize but did not affect the number of axial roots.The main reason was the increased total lateral root length,while the average lateral root (LR) length in each axle was only slightly increased.In addition,the average LR density of 2nd whorl crown root under mixed N was also increased.Compared with sole nitrate,mixed N could improve the N metabolism of roots (such as the N influx rate,nitrate reductase (NR) and glutamine synthase (GS)enzyme activities and total amino content of the roots).Experiments with exogenously added NR and GS inhibitors suggested that the increase in the average LR length under mixed N was related to the process of N assimilation,and whether the NR mediated NO synthesis participates in this process needs further exploration.Meanwhile,an investigation of the changes in root-shoot ratio and carbon (C) concentration showed that C transportation from shoots to roots may not be the key factor in mediating lateral root elongation,and the changes in the sugar concentration in roots further proved this conclusion.Furthermore,the synthesis and transportation of auxin in axial roots may play a key role in lateral root elongation,in which the expression of ZmPIN1B and ZmPIN9 may be involved in this pathway.This study preliminarily clarified the changes in root morphology and explored the possible physiological mechanism under a mixed N supply in maize,which may provide some theoretical basis for the cultivation of crop varieties with high N efficiency.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).
基金supported by the Biomedicine Supporting Program of Shanghai "Science and Technology Innovation Plan" (19441902400)the Ningxia Hui Autonomous Region Key R&D program (2020BCH01001)+1 种基金the Shanghai "Science and Technology Innovation Action Plan" Domestic Science and Technology Cooperation Project (20025800200)the Clinical Research Program of Shanghai Municipal Health Commission (201940367)。
文摘Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial risk for developing CAI.This study identifies magnetic resonance imaging(MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients.Methods:All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1,2017 to December 1,2019 were identified.Data were collected using the Cumberland Ankle Instability Tool at final follow-up.Demographic and other related clinical variables,including age,sex,body mass index,and treatment were also recorded.Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS.Results:A total 131 out of 362 patients with a mean follow-up of 3.0± 0.6 years(mean ± SD;2.0—4.1 years) developed CAI after first-episode LAS.According to multivariable regression,development of CAI after first-episode LAS was associated with 5 prognostic factors:age(odds ratio(OR)=0.96,95% confidence interval(95%CI):0.93-1.00,p=0.032);body mass index(OR=1.09,95%CI:1.02-1.17,p=0.009);posterior talofibular ligament injury(OR=2.17,95%CI:1.05-4.48,p=0.035);large bone marrow lesion of the talus(OR=2.69,95%CI:1.30-5.58,p=0.008),and Grade 2 effusion of the tibiotalar joint(OR=2.61,95%CI:1.39-4.89,p=0.003).When patients had at least 1 positive clinical finding in the 10-m walk test,anterior drawer test,or inversion tilt test,they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI.Conclusion:MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the10-m walk test,anterior drawer test,and inversion tilt test.Further prospective and large-scale studies are necessary for validation.
文摘Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.
文摘BACKGROUND For the management of lateral lymph node(LLN)metastasis in patients with rectal cancer,selective LLN dissection(LLND)is gradually being accepted by Chinese scholars.Theoretically,fascia-oriented LLND allows radical tumor resection and protects of organ function.However,there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND.Through a preliminary study with a small sample size,we found that fasciaoriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs.In this study,we increased the sample size and refined the postoperative functional outcomes.AIM To compare the effects of fascia-and vessel-oriented LLND regarding short-term outcomes and prognosis.METHODS We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021.The short-term outcomes included perioperative outcomes and postoperative functional outcomes.The prognosis was measured based on overall survival(OS)and progression-free survival(PFS).RESULTS A total of 105 patients were included in the final analysis and were divided into fascia-and vesseloriented groups that included 41 and 64 patients,respectively.Regarding the short-term outcomes,the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group.There were no significant differences in the other short-term outcomes.The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group.In addition,there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups.In terms of prognosis,there was no significant difference in PFS or OS between the two groups.CONCLUSION It is safe and feasible to perform fascia-oriented LLND.Compared with vessel-oriented LLND,fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.
基金funded by the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-003)National High Level Hospital Clinical Research Funding(2022-PUMCH-B-017)The Strategic Priority Research Program(Pilot study)"Biological Basis of Aging and Therapeutic Strategies"of the Chinese Academy of Sciences(grant XDB39040000).
文摘Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
基金Project supported by the National Natural Science Foundation of China (Grant No.12074054)the Fundamental Research Funds for the Central Universities,China (Grant No.DUT21LK06)。
文摘Owing to the good adjustability and the strong near-field enhancement,surface plasmons are widely used in optical force trap,thus the optical force trap can achieve excellent performance.Here,we use the Laguerre–Gaussian beam and a plasmonic gold ring to separate enantiomers by the chiral optical force.Along with the radial optical force that traps the particles,there is also a chirality-sign-sensitive lateral force arising from the optical spin angular momentum,which is caused by the interaction between optical orbit angular momentum and gold ring structure.By selecting a specific incident wavelength,the strong angular scattering and non-chiral related azimuthal optical force can be suppressed.Thus the chiral related azimuthal optical force can induce an opposite orbital rotation of the trapped particles with chirality of different sign near the gold ring.This work proposes an effective approach for catchingand separating chiral enantiomers.
