This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area(LHA) in obese r...This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area(LHA) in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations(GES) with different parameters were performed and the neuronal activities of gastric-distension responsive(GD-R) neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter(0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off) activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation(GIES) with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations(stomach, duodenum and ileum) on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.展开更多
This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experime...This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experimental tooth movement with a controlled force of 70 g, applied to the superior central incisors of rats. Adult male rats were anesthetized and divided into four groups: Control, no orthodontic appliance (OA);OA activated with 70 g;OA activated with 70 g and pretreated with diclofenac sodium (5 mg/kg, intramuscular);and diclofenac sodium alone. Six hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing the CEA and LH were processed for Fos protein immunohistochemistry. The results show that in the control group, intramuscular injection of a ketamine/xylazine mixture did not induce IR-Fos cells in the CEA or LH. However, in the 70 g group, IR-Fos was the strongest observed展开更多
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
This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between the...This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between theσL and the vertical stressσV during soaking and consolidation,(ii)the influences of initial dry densityρd0 and moisture content w 0 on the vertical and lateral swelling pressures at no swelling strain(i.e.σV0 andσL0),and(iii)evolution of theσL during five long-term wetting-drying cycles.Experimental results demonstrated that the post-soakingσL-σV relationships are piecewise linear and their slopes in the passive state(σL>σV)and active state(σL<σV)are similar to that of the consolidationσL-σV relationships in the normal-and over-consolidated states,respectively.The soakingσL-σV relationships converge to the consolidationσL-σV relationships at a thresholdσV where the interparticle swelling is restrained.TheσL0 andσV0 increase monotonically withρd0;however,they show increasing-then-decreasing trends with the w 0.The extent of compaction-induced swelling anisotropy,which is evaluated byσL0/σV0,reduces with an increase in the compaction energy and molding water content.TheσL reduces over moisture cycles and the stress relaxation in theσL during soaking is observed.An approach was developed to predict the at-rest soakingσL-σV relationships,which requires conventional consolidation and shear strength properties and one measurement of theσL-σV relationships during soaking.The proposed approach was validated using the results of three different expansive soils available in the literature.展开更多
Planar sliding is one of the frequently observed types of failure in rock slopes.Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses.The accuracy of planar slid...Planar sliding is one of the frequently observed types of failure in rock slopes.Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses.The accuracy of planar sliding kinematic analysis is significantly influenced by the value assigned to the lateral limit angleγlim.However,the assignment ofγlim is currently used generally based on an empirical criterion.This study aims to propose an approach for determining the value ofγlim in deterministic and probabilistic kinematic planar sliding analysis.A new perspective is presented to reveal thatγlim essentially influences the probability of forming a potential planar sliding block.The procedure to calculate this probability is introduced using the block theory method.It is found that the probability is correlated with the number of discontinuity sets presented in rock masses.Thus,different values ofγlim for rock masses with different sets of discontinuities are recommended in both probabilistic and deterministic planar sliding kinematic analyses;whereas a fixed value ofγlim is commonly assigned to different types of rock masses in traditional method.Finally,an engineering case was used to compare the proposed and traditional kinematic analysis methods.The error rates of the traditional method vary from 45%to 119%,while that of the proposed method ranges between 1%and 17%.Therefore,it is likely that the proposed method is superior to the traditional one.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
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
Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,t...Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,the failure mode and the earth pressure acting on the rigid retaining wall with EPS geofoam inclusions and granular backfills(henceforth referred to as EPS-wall),under limited surcharge loading are investigated through two-and three-dimensional model tests.The testing results show that different from the sliding of almost all the backfill in the EPS-wall under semi-infinite surcharge loading,only an approximately triangular backfill slides in the wall under limited surcharge loading.The distribution of the lateral earth pressure on the EPS-wall under limited surcharge loading is non-linear,and the distribution changes from the increase of the wall depth to the decrease with the increase of the limited surcharge loading.An approach based on the force equilibrium of a differential element is developed to predict the lateral earth pressure behind the EPS-wall subjected to limited surcharge loading,and its performance was fully validated by the three-dimensional model tests.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
Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regul...Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study,electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1,SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h.Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. These findings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the 丨ate「a丨 hypothalamus, perhaps by exciting giutamatergic input to orexin neurons via the action0 f orexin receptor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
Erythropoietin-producing hepatocellular carcinoma A3(EphA3)is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors.Previous studies have shown that EphA3 is associated with tissue development.R...Erythropoietin-producing hepatocellular carcinoma A3(EphA3)is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors.Previous studies have shown that EphA3 is associated with tissue development.Recently,we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity(DIO).However,the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear.In the current study,we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding.Moreover,the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure.Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells.The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.展开更多
基金financially supported by National Natural Science Foundation of China(No.30870927)
文摘This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area(LHA) in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations(GES) with different parameters were performed and the neuronal activities of gastric-distension responsive(GD-R) neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter(0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off) activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation(GIES) with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations(stomach, duodenum and ileum) on those neurons are similar, and GES is preferential because of its easy clinical performance and safety.
文摘This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experimental tooth movement with a controlled force of 70 g, applied to the superior central incisors of rats. Adult male rats were anesthetized and divided into four groups: Control, no orthodontic appliance (OA);OA activated with 70 g;OA activated with 70 g and pretreated with diclofenac sodium (5 mg/kg, intramuscular);and diclofenac sodium alone. Six hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing the CEA and LH were processed for Fos protein immunohistochemistry. The results show that in the control group, intramuscular injection of a ketamine/xylazine mixture did not induce IR-Fos cells in the CEA or LH. However, in the 70 g group, IR-Fos was the strongest observed
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sponsored by the National Natural Science Foundation of China(Grant Nos.52378365 and 52179109)Jiangsu Province Excellent Postdoctoral Program(Grant No.2023)China Scholarship Council-University of Ottawa Joint Scholarship.
文摘This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between theσL and the vertical stressσV during soaking and consolidation,(ii)the influences of initial dry densityρd0 and moisture content w 0 on the vertical and lateral swelling pressures at no swelling strain(i.e.σV0 andσL0),and(iii)evolution of theσL during five long-term wetting-drying cycles.Experimental results demonstrated that the post-soakingσL-σV relationships are piecewise linear and their slopes in the passive state(σL>σV)and active state(σL<σV)are similar to that of the consolidationσL-σV relationships in the normal-and over-consolidated states,respectively.The soakingσL-σV relationships converge to the consolidationσL-σV relationships at a thresholdσV where the interparticle swelling is restrained.TheσL0 andσV0 increase monotonically withρd0;however,they show increasing-then-decreasing trends with the w 0.The extent of compaction-induced swelling anisotropy,which is evaluated byσL0/σV0,reduces with an increase in the compaction energy and molding water content.TheσL reduces over moisture cycles and the stress relaxation in theσL during soaking is observed.An approach was developed to predict the at-rest soakingσL-σV relationships,which requires conventional consolidation and shear strength properties and one measurement of theσL-σV relationships during soaking.The proposed approach was validated using the results of three different expansive soils available in the literature.
基金funded by National Natural Science Foundation,China(Grant Nos.41972264 and 42207214)Zhejiang Provincial Natural Science Foundation,China(Grant No.LR22E080002).
文摘Planar sliding is one of the frequently observed types of failure in rock slopes.Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses.The accuracy of planar sliding kinematic analysis is significantly influenced by the value assigned to the lateral limit angleγlim.However,the assignment ofγlim is currently used generally based on an empirical criterion.This study aims to propose an approach for determining the value ofγlim in deterministic and probabilistic kinematic planar sliding analysis.A new perspective is presented to reveal thatγlim essentially influences the probability of forming a potential planar sliding block.The procedure to calculate this probability is introduced using the block theory method.It is found that the probability is correlated with the number of discontinuity sets presented in rock masses.Thus,different values ofγlim for rock masses with different sets of discontinuities are recommended in both probabilistic and deterministic planar sliding kinematic analyses;whereas a fixed value ofγlim is commonly assigned to different types of rock masses in traditional method.Finally,an engineering case was used to compare the proposed and traditional kinematic analysis methods.The error rates of the traditional method vary from 45%to 119%,while that of the proposed method ranges between 1%and 17%.Therefore,it is likely that the proposed method is superior to the traditional one.
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.
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funding support from National Natural Science Foundation of China(Grant No.52179109)Jiangsu Provincial Natural Science Foundation(Grant No.BK20230967)Open Research Fund of State Key Laboratory of Mechanical Behavior and System Safety of Traffic Engineering Structures,Shijiazhuang Tiedao University(Grant No.KF2022-02).
文摘Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,the failure mode and the earth pressure acting on the rigid retaining wall with EPS geofoam inclusions and granular backfills(henceforth referred to as EPS-wall),under limited surcharge loading are investigated through two-and three-dimensional model tests.The testing results show that different from the sliding of almost all the backfill in the EPS-wall under semi-infinite surcharge loading,only an approximately triangular backfill slides in the wall under limited surcharge loading.The distribution of the lateral earth pressure on the EPS-wall under limited surcharge loading is non-linear,and the distribution changes from the increase of the wall depth to the decrease with the increase of the limited surcharge loading.An approach based on the force equilibrium of a differential element is developed to predict the lateral earth pressure behind the EPS-wall subjected to limited surcharge loading,and its performance was fully validated by the three-dimensional model tests.
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 National Natural Science Foundation of China(81071074)
文摘Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study,electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1,SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h.Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. These findings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the 丨ate「a丨 hypothalamus, perhaps by exciting giutamatergic input to orexin neurons via the action0 f orexin receptor
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.
基金supported by the National Natural Science Foundation of China (Grants No.82070872,92049118,and 81570774)the Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province (Grant No.JSSCTD2021)+1 种基金the National Key Research and Development Program of China (Grant No.2018YFC1003504)the Junior Thousand Talents Program of China,the NJMU startup fund.
文摘Erythropoietin-producing hepatocellular carcinoma A3(EphA3)is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors.Previous studies have shown that EphA3 is associated with tissue development.Recently,we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity(DIO).However,the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear.In the current study,we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding.Moreover,the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure.Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells.The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.
