Potato cyst nematodes(PCNs)are a significant threat to potato production,having caused substantial damage in many countries.Predicting the future distribution of PCN species is crucial to implementing effective biosec...Potato cyst nematodes(PCNs)are a significant threat to potato production,having caused substantial damage in many countries.Predicting the future distribution of PCN species is crucial to implementing effective biosecurity strategies,especially given the impact of climate change on pest species invasion and distribution.Machine learning(ML),specifically ensemble models,has emerged as a powerful tool in predicting species distributions due to its ability to learn and make predictions based on complex data sets.Thus,this research utilised advanced machine learning techniques to predict the distribution of PCN species under climate change conditions,providing the initial element for invasion risk assessment.We first used Global Climate Models to generate homogeneous climate predictors to mitigate the variation among predictors.Then,five machine learning models were employed to build two groups of ensembles,single-algorithm ensembles(ESA)and multi-algorithm ensembles(EMA),and compared their performances.In this research,the EMA did not always perform better than the ESA,and the ESA of Artificial Neural Network gave the highest performance while being cost-effective.Prediction results indicated that the distribution range of PCNs would shift northward with a decrease in tropical zones and an increase in northern latitudes.However,the total area of suitable regions will not change significantly,occupying 16-20%of the total land surface(18%under current conditions).This research alerts policymakers and practitioners to the risk of PCNs’incursion into new regions.Additionally,this ML process offers the capability to track changes in the distribution of various species and provides scientifically grounded evidence for formulating long-term biosecurity plans for their control.展开更多
The development of highly efficient OER catalysts with superior durability for seawater electrolysis and Zn-air battery is important but challenging.Herein,the vacancy-modified heterostructured bimetallic Fe Mo S_(x)/...The development of highly efficient OER catalysts with superior durability for seawater electrolysis and Zn-air battery is important but challenging.Herein,the vacancy-modified heterostructured bimetallic Fe Mo S_(x)/Co Ni P_(x)OER electrocatalyst is exploited.Benefiting from the electron redistribution and reaction kinetics modulation resulting from vacancy introduction and heterojunction formation,it yields ultralow OER overpotentials of 196,276,303 m V in 1 M KOH and 197,318,348 m V in 1 M KOH+seawater at 10,500,1000 m A cm^(-2),respectively,surviving 600 h at 800 m A cm^(-2)without obvious decay.Further,FeMoS_(x)/CoNiP_(x)-based Zn-air battery not only affords the high peak power density of 214.5 m W cm^(-2)but also exhibits the small voltage gap of 0.698 V and long lifetime of 500 h at 10 m A cm^(-2),overmatching overwhelming majority of reported advanced catalysts.It is revealed experimentally that the OER process on rationally designed Fe Mo S_(x)/Co Ni P_(x)follows the adsorbate evolution mechanism and the ratedetermining step shifts from^(*)OOH formation in individual building blocks to^(*)OOH deprotonation process in FeMoS_(x)/CoNiP_(x),providing the directly proof of how the vacancy introduction and heterojunction formation affect the reaction kinetics.展开更多
Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MM...Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MMDS5 disease in the nervous system to investigate its pathological features and neuronal death.Methods:We generated neuron-specific Isca1 knockout rat(Isca1 flox/flox-NeuN-Cre)using CRISPR-Cas9 technology.The brain structure changes of CKO rats were studied with MRI,and the behavior abnormalities were analyzed through gait analysis and open field tests,Y maze tests and food maze tests.The pathological changes of neurons were analyzed through H&E staining,Nissl staining,and Golgi staining.Mitochondrial damage was assessed by TEM,western blot and ATP assay,and the morphology of neurons was assessed by WGA immunofluorescence to detect the death of neurons.Results:This study established the disease model of MMDS5 in the nervous system for the first time,and found that after Isca1 loss,the rats suffered from developmental retardation,epilepsy,memory impairment,massive neuronal death,reduced number of Nissl bodies and dendritic spines,mitochondrial fragmentation,cristae fracture,reduced content of respiratory chain complex protein,and reduced production of ATP.Isca1 knockout caused neuronal oncosis.Conclusions:This rat model can be used to study the pathogenesis of MMDS.In addition,compared with human MMDS5,the rat model can survive up to 8 weeks of age,effectively extending the window of clinical treatment research,and can be used for the treatment of neurological symptoms in other mitochondrial diseases.展开更多
Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin com...Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin compliance,mechanical properties,environmental adaptation,and biocompatibility to avoid signal attenuation and motion artifacts is challenging,and accurate physiological feature extraction necessitates effective signal-processing algorithms.This review presents the latest advancements in smart electrodes for epidermal electrophysiological monitoring,focusing on materials,structures,and algorithms.First,smart materials incorporating self-adhesion,self-healing,and self-sensing functions offer promising solutions for long-term monitoring.Second,smart meso-structures,together with micro/nanostructures endowed the electrodes with self-adaption and multifunctionality.Third,intelligent algorithms give smart electrodes a“soul,”facilitating faster and more-accurate identification of required information via automatic processing of collected electrical signals.Finally,the existing challenges and future opportunities for developing smart electrodes are discussed.Recognized as a crucial direction for next-generation epidermal electrodes,intelligence holds the potential for extensive,effective,and transformative applications in the future.展开更多
Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therap...Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.展开更多
Background:The survival of pancreatic cancer cells,particularly cancer stem cells which are responsible for tumor relapse,depends on mitochondrial function.Mitochondrial transcription factor A(TFAM)is critical for the...Background:The survival of pancreatic cancer cells,particularly cancer stem cells which are responsible for tumor relapse,depends on mitochondrial function.Mitochondrial transcription factor A(TFAM)is critical for the regulation of mitochondrial DNA and thus mitochondrial function.However,the possible involvement of TFAM in pancreatic cancer is unknown.Methods:Human samples were obtained from pancreatic cancers and their adjacent tissues;human pancreatic cell lines were cultured in RPMI1640 medium.TFAM expressions in pancreatic tissues and cultured cells were determined using immunohistochemistry,ELISA,and reverse transcription polymerase chain reaction(RT-PCR).The effect of TFAM on cell growth,migration,colony formation and apoptosis were evaluated.Mitochondrial biogenesis in pancreatic cancer and normal cells were examined.Results:The majority of pancreatic cancer tissues exhibited higher TFAM expression compared to the adjacent counterparts.Consistently,TFAM mRNA and protein levels were higher in pancreatic cancer cell lines than in immortalized normal pancreatic epithelial cells.There was no difference on TFAM level between gemcitabine-sensitive and resistant pancreatic cancer cells.Functional analysis demonstrated that TFAM overexpression activated pancreatic normal and tumor cells whereas TFAM inhibition effectively inhibited the growth of pancreatic cancer cells.TFAM inhibition enhanced gemcitabine’s cytotoxicity and suppressed growth,anchorage-independent colony formation and survival of gemcitabine-resistant pancreatic cancer cells.Mechanistic studies showed that TFAM inhibition resulted in remarkable mitochondrial dysfunction and energy crisis followed by oxidative stress.The basal mitochondrial biogenesis level correlated well with TFAM level in pancreatic cancer cells.Conclusions:TFAM played essential roles in pancreatic cancer via regulating mitochondrial functions which highlighted the therapeutic value of inhibiting TFAM to overcome gemcitabine resistance.展开更多
BACKGROUND Hysteromyoma is not a rare tumor among pregnant women.During pregnancy,the symptoms caused by hysteromyoma can be improved through conservative treatment in most cases.However,in order to ensure the safety ...BACKGROUND Hysteromyoma is not a rare tumor among pregnant women.During pregnancy,the symptoms caused by hysteromyoma can be improved through conservative treatment in most cases.However,in order to ensure the safety of mothers and children,surgeries are necessary in some special cases.CASE SUMMARY We report a case of pregnancy complicated with hysteromyoma red degeneration.The patient had peritonitis after sudden abdominal pain during the 20th week of pregnancy.Laparoscopic exploration suggested rupture and bleeding of hysteromyoma,which were improved after drainage and an anti-inflammatory treatment.A cesarean section was performed after full term.This case shows the complications of rupture after red degeneration of hysteromyoma during pregnancy.CONCLUSION We should be alert to rupture of hysteromyoma during pregnancy,and active laparoscopic exploration is essential to improve the prognosis of such patients.展开更多
Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb ...Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb of L.radiata.Studies have shown that lycorine hydrochloride has many pharmacological effects(anti-fungal,anti-viral and anti-tumor).In this paper,the related research on pharmacological effects and mechanism of lycorine hydrochloride is systematically summarized in order to provide a theoretical basis for further research and application of lycorine hydrochloride.展开更多
X oilfield is a typical multi-layer sandstone reservoir in offshore China. In the early stage, in order to obtain economic oil production, directional well was used to adopt a set of multi-layer combined production, w...X oilfield is a typical multi-layer sandstone reservoir in offshore China. In the early stage, in order to obtain economic oil production, directional well was used to adopt a set of multi-layer combined production, which resulted in serious interlayer interference, water injection inrush and low reserve utilization. Based on the theory of single-phase unstable seepage flow and the theory of oil-water two-phase non-piston displacement, the author innovatively established a mathematical model of interlayer dynamic interference in multilayer sandstone reservoirs, revealed the influence law of main controlling factors such as permeability, viscosity, starting pressure gradient and reservoir type on interlayer interference, and innovatively formed a quantitative characterization theory of interlayer interference in multilayer combined oil production. The technical demarcation of offshore multi-zone combined oil production reservoir system is formulated and the recombination of oil field development system is guided.展开更多
BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the ...BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.展开更多
AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease(IBD).METHODS Fecal calprotectin(FC), clinical activity index(CDAI or CAI), C-reactive protein...AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease(IBD).METHODS Fecal calprotectin(FC), clinical activity index(CDAI or CAI), C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), and procalcitonin(PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome(IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn's disease(CICD) with the "simple endoscopic score for Crohn's disease"(SES-CD), CDrelated surgery patients with the Rutgeerts score, and ulcerative colitis(UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ~2 test, Spearman's correlation, and multiple linear regression analysis.RESULTS The median FC levels in CD, UC, and IBS patients were 449.6(IQR, 137.9-1344.8), 497.9(IQR, 131.7-118.0), and 9.9(IQR, 0-49.7) μg/g, respectively(P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC(r = 0.802), followed by CDAI(r = 0.734), CRP(r = 0.658), and ESR(r = 0.557). The Mayo score also correlated significantly with FC(r = 0.837), CAI(r = 0.776), ESR(r = 0.644), and CRP(r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity(CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve(AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC(0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.展开更多
BACKGROUND Receptor interacting protein kinase 1(RIPK1)-mediated cell death,including apoptosis and necroptosis,belongs to programmed cell death.It has been reported that RIPK1-mediated necroptosis exists in lesions o...BACKGROUND Receptor interacting protein kinase 1(RIPK1)-mediated cell death,including apoptosis and necroptosis,belongs to programmed cell death.It has been reported that RIPK1-mediated necroptosis exists in lesions of cerebral hemorrhage(CH).Electroacupuncture,a treatment derived from traditional Chinese medicine,could improve neurological impairment in patients with brain injury.AIM To investigate the protective role of cross electro-nape acupuncture(CENA)in CH,and clarify the potential mechanism.METHODS CH rat models were established,and CENA was applied to the experimental rats.Neurological functions and encephaledema were then measured.Necrotic cells in the brain of rats with CH were evaluated by propidium iodide staining.Necroptosis was assessed by immunofluorescence.Activation of the necroptosisrelated pathway was detected by western blot.Extraction of brain tissue,cerebrospinal fluid and serum samples was conducted to measure the expression and secretion of inflammatory cytokines by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS The necroptotic marker p-MLKL was detectable in the brains of rats with CH.Next,we found that CENA could ameliorate neurological functions in rat models of CH.Moreover,the upregulation of RIPK1-mediated necroptosis-related molecules in the brains of rats with CH were inhibited by CENA.Further investigation revealed that CENA partially blocked the interaction between RIPK1 and RIPK3.Finally,in vivo assays showed that CENA decreased the expression of the inflammatory cytokines tumor necrosis factor-α,interleukin-6 and interleukin-8 in CH rat models.CONCLUSION These findings revealed that CENA exerts a protective role in CH models by inhibiting RIPK1-mediated necroptosis.展开更多
Divergence of gene expression and alter native splicing is a crucial driving force in the evolution of species;to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a sui...Divergence of gene expression and alter native splicing is a crucial driving force in the evolution of species;to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expressi on (ASE) and allele-specific alter native splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interferenee of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horsex don key (mule/hi nny) and cattlexyak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, IncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptati on. In con clusi on, our study dem on strated that explorati on of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.展开更多
Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the prima...Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.展开更多
The hepatitis B virus(HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an est...The hepatitis B virus(HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the HBV polymerase(P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene(S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.展开更多
AIM:To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes(MHs)and present the surgical procedure.METHODS:Patients with ...AIM:To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes(MHs)and present the surgical procedure.METHODS:Patients with giant(minimum diameter>800 pm),recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study.After surgery,all patients were informed to maintain a prone position for at least 7d.Preoperative and postoperative best-corrected visual acuities(BCVAs)were compared and MH closure rate was measured as the main outcome.RESULTS:A total of 13 MH patients consisted of 6 giant MHs,4 persistent holes and 3 recurrent holes(5 men and 8 women;average age was 56.40±11.72y)were enrolled in this study.MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed.Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed.No intraoperative complications were observed.BCVA improved from 1.73 IogMAR to 0.74 IogMAR at 6mo postoperation.There was significant difference in BCVA before versus after the surgery(P<0.05).There were no adverse events occurred during the follow-up period.CONCLUSION:With easier surgical procedure,parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.展开更多
基金funded by the National Key R&D Program of China(2021YFD1400200)the Taishan Scholar Constructive Engineering Foundation of Shandong,China(tstp20221135)。
文摘Potato cyst nematodes(PCNs)are a significant threat to potato production,having caused substantial damage in many countries.Predicting the future distribution of PCN species is crucial to implementing effective biosecurity strategies,especially given the impact of climate change on pest species invasion and distribution.Machine learning(ML),specifically ensemble models,has emerged as a powerful tool in predicting species distributions due to its ability to learn and make predictions based on complex data sets.Thus,this research utilised advanced machine learning techniques to predict the distribution of PCN species under climate change conditions,providing the initial element for invasion risk assessment.We first used Global Climate Models to generate homogeneous climate predictors to mitigate the variation among predictors.Then,five machine learning models were employed to build two groups of ensembles,single-algorithm ensembles(ESA)and multi-algorithm ensembles(EMA),and compared their performances.In this research,the EMA did not always perform better than the ESA,and the ESA of Artificial Neural Network gave the highest performance while being cost-effective.Prediction results indicated that the distribution range of PCNs would shift northward with a decrease in tropical zones and an increase in northern latitudes.However,the total area of suitable regions will not change significantly,occupying 16-20%of the total land surface(18%under current conditions).This research alerts policymakers and practitioners to the risk of PCNs’incursion into new regions.Additionally,this ML process offers the capability to track changes in the distribution of various species and provides scientifically grounded evidence for formulating long-term biosecurity plans for their control.
基金supported by the National Natural Science Foundation of China (21975136,22102076)the Fundamental Research Funds for the Central Universities (63185015)+2 种基金the Shenzhen Science,Technology and Innovation Committee (JCYJ20190808151603654,JCYJ20210324121002007)the Open Funds from National Engineering Lab for Mobile Source Emission Control Technology (NELMS2020A12)the Open Fund for Key Laboratory of Civil Aviation Thermal Hazards Prevention and Emergency Response (RZH2021-KF-03)。
文摘The development of highly efficient OER catalysts with superior durability for seawater electrolysis and Zn-air battery is important but challenging.Herein,the vacancy-modified heterostructured bimetallic Fe Mo S_(x)/Co Ni P_(x)OER electrocatalyst is exploited.Benefiting from the electron redistribution and reaction kinetics modulation resulting from vacancy introduction and heterojunction formation,it yields ultralow OER overpotentials of 196,276,303 m V in 1 M KOH and 197,318,348 m V in 1 M KOH+seawater at 10,500,1000 m A cm^(-2),respectively,surviving 600 h at 800 m A cm^(-2)without obvious decay.Further,FeMoS_(x)/CoNiP_(x)-based Zn-air battery not only affords the high peak power density of 214.5 m W cm^(-2)but also exhibits the small voltage gap of 0.698 V and long lifetime of 500 h at 10 m A cm^(-2),overmatching overwhelming majority of reported advanced catalysts.It is revealed experimentally that the OER process on rationally designed Fe Mo S_(x)/Co Ni P_(x)follows the adsorbate evolution mechanism and the ratedetermining step shifts from^(*)OOH formation in individual building blocks to^(*)OOH deprotonation process in FeMoS_(x)/CoNiP_(x),providing the directly proof of how the vacancy introduction and heterojunction formation affect the reaction kinetics.
基金CAMS Innovation Fund for Medical Sciences CIFMSGrant/Award Number:2021-I2M-1-034+3 种基金National Key Research and Development Program of ChinaGrant/Award Number:2022YFF0710702National Natural Science Foundation of ChinaGrant/Award Number:31970508。
文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MMDS5 disease in the nervous system to investigate its pathological features and neuronal death.Methods:We generated neuron-specific Isca1 knockout rat(Isca1 flox/flox-NeuN-Cre)using CRISPR-Cas9 technology.The brain structure changes of CKO rats were studied with MRI,and the behavior abnormalities were analyzed through gait analysis and open field tests,Y maze tests and food maze tests.The pathological changes of neurons were analyzed through H&E staining,Nissl staining,and Golgi staining.Mitochondrial damage was assessed by TEM,western blot and ATP assay,and the morphology of neurons was assessed by WGA immunofluorescence to detect the death of neurons.Results:This study established the disease model of MMDS5 in the nervous system for the first time,and found that after Isca1 loss,the rats suffered from developmental retardation,epilepsy,memory impairment,massive neuronal death,reduced number of Nissl bodies and dendritic spines,mitochondrial fragmentation,cristae fracture,reduced content of respiratory chain complex protein,and reduced production of ATP.Isca1 knockout caused neuronal oncosis.Conclusions:This rat model can be used to study the pathogenesis of MMDS.In addition,compared with human MMDS5,the rat model can survive up to 8 weeks of age,effectively extending the window of clinical treatment research,and can be used for the treatment of neurological symptoms in other mitochondrial diseases.
基金supported by Science and Technology Innovation 2030-Major Project(Grant No.2022ZD0208601)the National Natural Science Foundation of China(Grant Nos.62104056,62106041,and 62204204)+2 种基金the Shanghai Sailing Program(Grant No.21YF1451000)the Key Research and Development Program of Shaanxi(Grant No.2022GY-001)the Fundamental Research Funds for the Central Universities(Grant No.223202100019).
文摘Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin compliance,mechanical properties,environmental adaptation,and biocompatibility to avoid signal attenuation and motion artifacts is challenging,and accurate physiological feature extraction necessitates effective signal-processing algorithms.This review presents the latest advancements in smart electrodes for epidermal electrophysiological monitoring,focusing on materials,structures,and algorithms.First,smart materials incorporating self-adhesion,self-healing,and self-sensing functions offer promising solutions for long-term monitoring.Second,smart meso-structures,together with micro/nanostructures endowed the electrodes with self-adaption and multifunctionality.Third,intelligent algorithms give smart electrodes a“soul,”facilitating faster and more-accurate identification of required information via automatic processing of collected electrical signals.Finally,the existing challenges and future opportunities for developing smart electrodes are discussed.Recognized as a crucial direction for next-generation epidermal electrodes,intelligence holds the potential for extensive,effective,and transformative applications in the future.
基金supported by National Science and Technology Major Special Project-Major New Drug Creation(2019ZX09301-112)Shandong Natural Science Foundation(ZR2020QH351)+1 种基金Shandong Provincial Program of Taishan Industrial Experts(2019TSCYCX-31)the Fundamental Research Funds of Shandong University(2020GN091)
文摘Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.
基金This work was supported by the grant from Science and Technology Project of Hubei Provincial Department of Education(B2020139).
文摘Background:The survival of pancreatic cancer cells,particularly cancer stem cells which are responsible for tumor relapse,depends on mitochondrial function.Mitochondrial transcription factor A(TFAM)is critical for the regulation of mitochondrial DNA and thus mitochondrial function.However,the possible involvement of TFAM in pancreatic cancer is unknown.Methods:Human samples were obtained from pancreatic cancers and their adjacent tissues;human pancreatic cell lines were cultured in RPMI1640 medium.TFAM expressions in pancreatic tissues and cultured cells were determined using immunohistochemistry,ELISA,and reverse transcription polymerase chain reaction(RT-PCR).The effect of TFAM on cell growth,migration,colony formation and apoptosis were evaluated.Mitochondrial biogenesis in pancreatic cancer and normal cells were examined.Results:The majority of pancreatic cancer tissues exhibited higher TFAM expression compared to the adjacent counterparts.Consistently,TFAM mRNA and protein levels were higher in pancreatic cancer cell lines than in immortalized normal pancreatic epithelial cells.There was no difference on TFAM level between gemcitabine-sensitive and resistant pancreatic cancer cells.Functional analysis demonstrated that TFAM overexpression activated pancreatic normal and tumor cells whereas TFAM inhibition effectively inhibited the growth of pancreatic cancer cells.TFAM inhibition enhanced gemcitabine’s cytotoxicity and suppressed growth,anchorage-independent colony formation and survival of gemcitabine-resistant pancreatic cancer cells.Mechanistic studies showed that TFAM inhibition resulted in remarkable mitochondrial dysfunction and energy crisis followed by oxidative stress.The basal mitochondrial biogenesis level correlated well with TFAM level in pancreatic cancer cells.Conclusions:TFAM played essential roles in pancreatic cancer via regulating mitochondrial functions which highlighted the therapeutic value of inhibiting TFAM to overcome gemcitabine resistance.
文摘BACKGROUND Hysteromyoma is not a rare tumor among pregnant women.During pregnancy,the symptoms caused by hysteromyoma can be improved through conservative treatment in most cases.However,in order to ensure the safety of mothers and children,surgeries are necessary in some special cases.CASE SUMMARY We report a case of pregnancy complicated with hysteromyoma red degeneration.The patient had peritonitis after sudden abdominal pain during the 20th week of pregnancy.Laparoscopic exploration suggested rupture and bleeding of hysteromyoma,which were improved after drainage and an anti-inflammatory treatment.A cesarean section was performed after full term.This case shows the complications of rupture after red degeneration of hysteromyoma during pregnancy.CONCLUSION We should be alert to rupture of hysteromyoma during pregnancy,and active laparoscopic exploration is essential to improve the prognosis of such patients.
基金Supported by the Talent Training Program for the Reform and Development of Local Colleges and University of the Central Government(2020GSP16)。
文摘Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb of L.radiata.Studies have shown that lycorine hydrochloride has many pharmacological effects(anti-fungal,anti-viral and anti-tumor).In this paper,the related research on pharmacological effects and mechanism of lycorine hydrochloride is systematically summarized in order to provide a theoretical basis for further research and application of lycorine hydrochloride.
文摘X oilfield is a typical multi-layer sandstone reservoir in offshore China. In the early stage, in order to obtain economic oil production, directional well was used to adopt a set of multi-layer combined production, which resulted in serious interlayer interference, water injection inrush and low reserve utilization. Based on the theory of single-phase unstable seepage flow and the theory of oil-water two-phase non-piston displacement, the author innovatively established a mathematical model of interlayer dynamic interference in multilayer sandstone reservoirs, revealed the influence law of main controlling factors such as permeability, viscosity, starting pressure gradient and reservoir type on interlayer interference, and innovatively formed a quantitative characterization theory of interlayer interference in multilayer combined oil production. The technical demarcation of offshore multi-zone combined oil production reservoir system is formulated and the recombination of oil field development system is guided.
基金Supported by the Foundation of Innovative Talents in Higher Education of Liaoning Province,No.LR2016043
文摘BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.
基金Supported by National Natural Science Foundation of China to Biao Nie,No.81471080
文摘AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease(IBD).METHODS Fecal calprotectin(FC), clinical activity index(CDAI or CAI), C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), and procalcitonin(PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome(IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn's disease(CICD) with the "simple endoscopic score for Crohn's disease"(SES-CD), CDrelated surgery patients with the Rutgeerts score, and ulcerative colitis(UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ~2 test, Spearman's correlation, and multiple linear regression analysis.RESULTS The median FC levels in CD, UC, and IBS patients were 449.6(IQR, 137.9-1344.8), 497.9(IQR, 131.7-118.0), and 9.9(IQR, 0-49.7) μg/g, respectively(P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC(r = 0.802), followed by CDAI(r = 0.734), CRP(r = 0.658), and ESR(r = 0.557). The Mayo score also correlated significantly with FC(r = 0.837), CAI(r = 0.776), ESR(r = 0.644), and CRP(r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity(CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve(AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC(0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.
基金Supported by State Administration of Traditional Chinese Medicine of Heilongjiang Province,No.ZHY16-027Harbin Municipal Science and Technology BureauYouth Reserve Talent Project,No.2017RAQXJ170
文摘BACKGROUND Receptor interacting protein kinase 1(RIPK1)-mediated cell death,including apoptosis and necroptosis,belongs to programmed cell death.It has been reported that RIPK1-mediated necroptosis exists in lesions of cerebral hemorrhage(CH).Electroacupuncture,a treatment derived from traditional Chinese medicine,could improve neurological impairment in patients with brain injury.AIM To investigate the protective role of cross electro-nape acupuncture(CENA)in CH,and clarify the potential mechanism.METHODS CH rat models were established,and CENA was applied to the experimental rats.Neurological functions and encephaledema were then measured.Necrotic cells in the brain of rats with CH were evaluated by propidium iodide staining.Necroptosis was assessed by immunofluorescence.Activation of the necroptosisrelated pathway was detected by western blot.Extraction of brain tissue,cerebrospinal fluid and serum samples was conducted to measure the expression and secretion of inflammatory cytokines by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS The necroptotic marker p-MLKL was detectable in the brains of rats with CH.Next,we found that CENA could ameliorate neurological functions in rat models of CH.Moreover,the upregulation of RIPK1-mediated necroptosis-related molecules in the brains of rats with CH were inhibited by CENA.Further investigation revealed that CENA partially blocked the interaction between RIPK1 and RIPK3.Finally,in vivo assays showed that CENA decreased the expression of the inflammatory cytokines tumor necrosis factor-α,interleukin-6 and interleukin-8 in CH rat models.CONCLUSION These findings revealed that CENA exerts a protective role in CH models by inhibiting RIPK1-mediated necroptosis.
基金supported by grants from the National Natural Science Foundation of China(31572381)National Thousand Youth Talents Plan of the International Science and Technology Cooperation Project of China(2013DFA31420)Science and Technology Innovation Capability Promotion Program of the Science and Technology Department of Qinghai Province(2015-ZJ-712)
文摘Divergence of gene expression and alter native splicing is a crucial driving force in the evolution of species;to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expressi on (ASE) and allele-specific alter native splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interferenee of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horsex don key (mule/hi nny) and cattlexyak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, IncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptati on. In con clusi on, our study dem on strated that explorati on of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.
基金National Natural Science Foundation of China (No.31671020) for financial support
文摘Thermosensitive liposomes(TSLs) have been an important research area in the field of tumor targeted chemotherapy. Since the first TSLs appeared that using 1,2-dipalmitoyl-snglyce-ro-3-phosphocholine(DPPC) as the primary liposomal lipid, many studies have been done using this type of liposome from basic and practical aspects. While TSLs composed of DPPC enhance the cargo release near the phase transition temperature, it has been shown that many factors affect their temperature sensitivity. Thus numerous attempts have been undertaken to develop new TSLs for improving their thermal response performance. The main objective of this review is to introduce the development and recent update of innovative TSLs formulations, including combination of radiofrequency ablation(RFA), highintensity focused ultrasound(HIFU), magnetic resonance imaging(MRI) and alternating magnetic field(AMF). In addition, various factors affecting the design of TSLs, such as lipid composition, surfactant, size and serum components are also discussed.
基金Supported by The National Science and Technology Key Project of China on"Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment",No.2013-ZX10002002-006(Duan ZP)Speaker,advisory board and/or consulting fees from Boehringer ingelheim,Glaxo Smith Kline,Janssen Pharmaceuticals,Bristol Myers Squibb,Roche Pharmaceuticals and Gilead Sciences(Coffin CS)The Canadian Institutes for Health Research(Coffin CS)
文摘The hepatitis B virus(HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the HBV polymerase(P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene(S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.
文摘AIM:To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes(MHs)and present the surgical procedure.METHODS:Patients with giant(minimum diameter>800 pm),recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study.After surgery,all patients were informed to maintain a prone position for at least 7d.Preoperative and postoperative best-corrected visual acuities(BCVAs)were compared and MH closure rate was measured as the main outcome.RESULTS:A total of 13 MH patients consisted of 6 giant MHs,4 persistent holes and 3 recurrent holes(5 men and 8 women;average age was 56.40±11.72y)were enrolled in this study.MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed.Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed.No intraoperative complications were observed.BCVA improved from 1.73 IogMAR to 0.74 IogMAR at 6mo postoperation.There was significant difference in BCVA before versus after the surgery(P<0.05).There were no adverse events occurred during the follow-up period.CONCLUSION:With easier surgical procedure,parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.
