Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous...Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous electrophysiological recording and Ca^(2+) imaging of cultured hippocampal neurons to investigate neuronal excitability and synaptic transmission during ultrasound stimulation.This study revealed,for the first time,three distinct neuronal response patterns induced by SAW ultrasound:an immediate response showing rapid activation,a delayed response exhibiting facilitation after several minutes,and a non-response maintaining baseline activity.Ultrasound stimulation increased action potential firing,enhanced excitatory postsynaptic currents,and elevated intracellular Ca^(2+) levels.These effects were dependent on extracellular Ca^(2+) influx and primarily dominated by L-type Ca^(2+) channels.Our findings suggest that individual neurons exhibit heterogeneous responses to SAW ultrasound stimulation based on their intracellular Ca^(2+) levels and L-type Ca^(2+) channel activity.This integrated approach provides new insights into the cellular mechanisms of ultrasound neuromodulation while highlighting the potential of SAW technology for precise,cell-type-specific neural control.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine...Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.展开更多
Garnet lithium lanthanum zirconium oxide(Li_(7)La_(3)Zr_(2)O_(12),LLZO)is a benchmark solid-state electrolyte(SSE)material receiving considerable attention owing to its high conductivity and chemical stability against...Garnet lithium lanthanum zirconium oxide(Li_(7)La_(3)Zr_(2)O_(12),LLZO)is a benchmark solid-state electrolyte(SSE)material receiving considerable attention owing to its high conductivity and chemical stability against Li metal.Although its electro-chemo-mechanical failure mechanisms have been much investigated,the equivocal roles of grain boundary strength and grain size of LLZO remain under-explored,hindering further performance improvements.Here we decoupled the effects of grain size and grain boundary strength of polycrystalline LLZO via the combination of electrochemical kinetics and the cohesive zone model.We discovered that the disintegration of LLZO is initiated by the accumulation of local displacements,which strongly relates to the changes in both grain size and grain boundary strength.However,variations in grain boundary strength affect the diffusion and propagation pathways of damage,while the failure of LLZO is determined by the grain size.Large LLZO grains facilitate transgranular damage under low grain boundary strength,which can alter local chemo-mechanics within the bulk of LLZO,leading to more extensive damage propagation.The results showcase the structure optimization pathways by preferentially controlling the growth of lithium dendrites at grain boundaries and their penetration in garnet-type SSE.展开更多
Metal ions play crucial roles in various biologi-cal functions,in-cluding maintain-ing homeostasis,regulating mus-cle contraction,and facilitating enzyme catalysis.However,accurately simulating the interaction between...Metal ions play crucial roles in various biologi-cal functions,in-cluding maintain-ing homeostasis,regulating mus-cle contraction,and facilitating enzyme catalysis.However,accurately simulating the interaction between metal ions and amino acid side chain analogs using high-level wave function theories remains challenging due to the significant computational costs involved.In this study,deep potential molecular dynamics(DeePMD)simulation was employed to investigate the solvation structure of the Mg^(2+)-Ac^(−)ion pair in aqueous solution.To address the computational bottleneck associated with expensive quan-tum mechanics(QM)methods,the Deep Kohn-Sham(DeePKS)approach was utilized,which allows us to generate highly accurate self-consistent energy functionals while significantly re-ducing computational costs.The root mean square error and mean absolute error of energies and atomic forces indicate close agreement between DeePKS predictions and QM strongly constrained and appropriately normed(SCAN)calculations.Moreover,the neural network potential(NNP)generated using the SCAN-level dataset predicted by DeePKS exhibits high-er accuracy compared to previous work,which employed a moderate BLYP functional.The potential of mean force for the Mg^(2+)-Ac−system was further examined,revealing a prefer-ence for monodentate coordination of Mg^(2+)with a~5.8 kcal/mol energy barrier between bidentate and monodentate geometries.Overall,this work provides a comprehensive,precise,and reliable methodology for investigating metal ions’properties in aqueous solutions.展开更多
Background:This study explored the value of integrating problem-based learning(PBL)and team-based learning(TBL)methods into plastic and reconstructive surgery clinical practice.By addressing the challenges faced in tr...Background:This study explored the value of integrating problem-based learning(PBL)and team-based learning(TBL)methods into plastic and reconstructive surgery clinical practice.By addressing the challenges faced in traditional teachings,this study aimed to enhance educational outcomes and prepare students for real-world surgical scenarios,thereby improving patient care in this specialized field.Methods:Fifty undergraduate students majoring in clinical medicine at the Shanghai Jiao Tong University School of Medicine were selected as research subjects.They were randomly divided into experimental and control groups.The experimental group received the combined PBL-TBL teaching method,whereas the control group received the traditional teaching.The teaching effect was evaluated based on student satisfaction and academic performance.Results:The student satisfaction in the experimental group was higher than that of the control group(P<0.05).Subjective scoring for academic performance by instructors was higher in the experimental group than in the control group(P<0.05).Conclusion:The PBL and TBL combination had a significant effect when applied in plastic and reconstructive surgery clinical practice.展开更多
In order to improve the traditional teaching model of traditional Chinese medicine identification course for graduate students of pharmacy,this paper described the research on constructing and practicing the blended t...In order to improve the traditional teaching model of traditional Chinese medicine identification course for graduate students of pharmacy,this paper described the research on constructing and practicing the blended teaching model of"online+offline"based on the teaching concept of TfU by taking the course of"Authentic Medicinal Materials and Quality of Traditional Chinese Medicine"as an example.In the preparatory phase,through resource integration and course content decomposition,it identifies"generative topics"to engage students in pre-class online discussions.During the instructional phase,"comprehension-oriented objectives"are established based on learning analytics,followed by the implementation of"understanding-focused activities"for guided inquiry in offline classrooms.The post-class phase employs online extended materials to conduct"sustained assessment"through evaluations and summaries,thereby continuously optimizing subsequent teaching practices.This pedagogical framework not only effectively cultivates investigative research thinking among graduate students but also enhances standardized management and scientific development of the teaching team.The practical research outcomes and experiences derived from this model can provide valuable references for analogous course reforms.展开更多
[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"wer...[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"were predicted using databases(OMIM and GeneCards),and the key targets were obtained after screening the retrieval data.The binding relationship between Schaftoside and key targets was analyzed by molecular docking.[Results]There were 3370 and 4433 targets for"cholestasis"and"steatosis",respectively,and 1767 overlapping genes were obtained.The results of molecular docking showed that Schaftoside had high binding energy with key targets.[Conclusions]Schaftoside can alleviate cholestasis and steatosis by regulating SREBP-1,CYP7,PPAR-gamma and other key targets to protect liver.展开更多
More than 600,000 people are diagnosed with esophageal cancer(EC)every year globally,and the five-year survival rate of EC is less than 20%.Two common histological subtypes of EC,esophageal squamous cell carcinoma(ESC...More than 600,000 people are diagnosed with esophageal cancer(EC)every year globally,and the five-year survival rate of EC is less than 20%.Two common histological subtypes of EC,esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),have great geographical variations in incidence rates.About half of the world’s EC was diagnosed in China and a majority of which belong to ESCC.Globally,the overall incidence rate of EC is decreasing.In some high-risk Asian regions,such as China,the incidence rate of ESCC has generally declined,potentially due to economic growth and improvement of diet habits.In some European high-income countries and the United States,the decline is mainly attributed to the decrease in smoking and drinking.The risk factors of EC are not well understood,and the importance of environmental and genetic factors in the pathogenesis is also unclear.The incidence and mortality of advanced EC can be reduced through early diagnosis and screening.White light endoscopy is still the gold standard in the current screening technology.This article reviews the epidemiology,risk factors,and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.展开更多
This study investigated the effects of H_(2)O_(2)treatment on xanthate interaction and flotation separation of chalcopyrite and pyrite by making use of a series of laboratory flotation experiments and surface analysis...This study investigated the effects of H_(2)O_(2)treatment on xanthate interaction and flotation separation of chalcopyrite and pyrite by making use of a series of laboratory flotation experiments and surface analysis techniques.Flotation test results showed that H2O2 treatment influenced the flotation behaviors of the two minerals;however,flotation of pyrite was depressed more significantly than that of the chalcopyrite.Under well-controlled H_(2)O_(2)concentration,the selective separation of chalcopyrite from pyrite was realized at pH 9.0,at which the recovery of chalcopyrite was over 84%and that of pyrite was less than 24%.Zeta potential,UV-visible and IR spectrum measurements revealed that the collector interacted differently with the two minerals after H_(2)O_(2)treatment,and the surface of chalcopyrite adsorbed much greater amount of xanthate than that of the pyrite.IR and XPS analyses showed that the H_(2)O_(2)treatment significantly changed the surface properties of pyrite to very hydrophilic species that inhibited the adsorption of collector and thus depressed the floatability of pyrite.While,the surface of chalcopyrite remained mildly inert to H_(2)O_(2),as a result,the adsorption of xanthate and its oxidation to dixanthogen were very effective,which enhanced the flotation of chalcopyrite.展开更多
Commercial A356 alloy was refined with a homemade A1-5Ti-0.25C-2RE master alloy, and the microstructure and macrostructure of the refined alloy were investigated. The results show that the grain refining effect of A35...Commercial A356 alloy was refined with a homemade A1-5Ti-0.25C-2RE master alloy, and the microstructure and macrostructure of the refined alloy were investigated. The results show that the grain refining effect of A356 is poor by the addition level of 0.5 wt% master alloy, but when the level reaches 3.0 wt% the grain can get a satisfactory refining effect. Dendrite of A356 can be effectively refined by addition of 0.5 wt% master alloy; however, the refining effect is not significantly improved by further increasing the addition of master alloy. Grain and dendrite refining effects are compared in this article, and the results show that the grain and dendrite exhibit different refining effects with the same addition level of master alloy. Dendrite is easier to reach the optimal refining effect than grain.展开更多
Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the g...Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.展开更多
MIL-88A(Fe)@sponge(MS) was synthesized by a dip-coating method, which displayed efficient photocatalytic Cr(Ⅵ) reduction efficiency under both low power LED UV light and real solar light irradiation. It was observed ...MIL-88A(Fe)@sponge(MS) was synthesized by a dip-coating method, which displayed efficient photocatalytic Cr(Ⅵ) reduction efficiency under both low power LED UV light and real solar light irradiation. It was observed that MS(0.2 g/L) could remove 100% Cr(Ⅵ)(10 mg/L) by adding 0.4 mmol/L tartaric acid(TA) without adjusting pH(pH 5.05) within 6.0 min and 3.0 min under UV light and real solar light irradiation, respectively. Besides, the photo-induced e-and radicals(O_(2)^(·-) and CO_(2)^(·-)) were found to play the momentous roles in the MS/TA/UVL/Cr(Ⅵ) system by the scavenger experiments and electron spin resonance(ESR) tests. MS was also filled into a fixed-bed reactor to test the possibility of long-term Cr(Ⅵ)reduction operation in TA/UVL system. As expected, the results revealed that MS could still maintain 100% activity up to 60 h. These results demonstrated that MIL-88A(Fe) might be the potentially efficient catalyst for large-scale wastewater treatment in the near future.展开更多
Pathological scarring and scleroderma,which are the most common conditions of skin fibrosis,pathologically manifest as fibroblast proliferation and extracellular matrix(ECM)hyperplasia.Fibroblast proliferation and ECM...Pathological scarring and scleroderma,which are the most common conditions of skin fibrosis,pathologically manifest as fibroblast proliferation and extracellular matrix(ECM)hyperplasia.Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling,causing an exaggerated and prolonged wound-healing response.The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects.Currently,a promising and relatively low-cost treatment has emerged-adipose-derived stem cell(ASC)therapy as a branch of stem cell therapy,including ASCs and their derivatives-purified ASC,stromal vascular fraction,ASC-conditioned medium,ASC exosomes,etc.,which are rich in sources and easy to obtain.ASCs have been widely used in therapeutic settings for patients,primarily for the defection of soft tissues,such as breast enhancement and facial contouring.In the field of skin regeneration,ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis.The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review,as well as their new applications in the treatment of skin fibrosis.Although the long-term effect of ASC therapy is still unclear,ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.展开更多
By using a new method, ^60Co γ-ray irradiation, Fe3O4 magnetic nano-particles were successfully synthesized at room temperature under ambient pressure. The structure, morphology and magnetic properties of these nanop...By using a new method, ^60Co γ-ray irradiation, Fe3O4 magnetic nano-particles were successfully synthesized at room temperature under ambient pressure. The structure, morphology and magnetic properties of these nanoparticles were characterized by X-ray diffraction （XRD）, transmission electron microscope （TEM） and vibrating sample magnetometer （VSM）, respectively. The radiation formation mechanism was also discussed. The results show that the absorbed dose can greatly influence the structure, morphology and magnetic properties of the products. XRD and TEM studies show that the product prepared by γ-ray irradiation （10 kGy） is pure FesO4 phase and the mean diameter of these nano-particles is about 21 nm. The Fe3O4 nano-particles synthesized by γ-ray irradiation （10 kGy） are mainly in small cubic shape and the size uniformity of these particles is good.展开更多
Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs)labeled with superparamagnetic iron oxide(SPIO)by using magnetic resonance imaging(MRI)in a swine model of myocardial infarction(...Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs)labeled with superparamagnetic iron oxide(SPIO)by using magnetic resonance imaging(MRI)in a swine model of myocardial infarction(MI).Methods MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent protein(GFP)and labeled in vitro with SPIO.Two weeks after MI,swine were randomized to intracoronary transplantation of dual-labeled MSCs(n=10),MSCs-GFP(n=10)and saline(n=5).MRI examination was performed with a 1.5T clinical scanner at 24 hours,3 weeks and 8 weeks after cells transplantation.Signal intensity(SI)changes,cardiac function and MI size were measured using MRI.Correlation between MR findings and histomorphologic findings was also investigated.Results The labeling efficiency at a combination of 25μg Fe/ml SPIO and 0.8 pi/ml Lipofectamine 2000 reached 100%.SPIO labeling did not affect GFP fluorescence and dual-labeling did not affect cell proliferation(P】0.05).Multipotentiality was not affected especially for cardiomyocyte-like cells differentiation.Cardiac cell marker of a-MHC and actinin were positively expressed by immunofluorescence staining after induction.SI on T2*WI decreased substantial-ly in the interventricular septum 24 hours after injection of MSCs.The intensity of hypo-intense signals appeared to increase throughout the later time points.Changes in SI at 24 hours,3 weeks and 8 weeks were 52.98%±10.74%,21.53%±5.40%and 6.23%±2.01%,respectively(P【0.01).DE-MRI demonstrated both dual-labeled MSCSs and MSCs-GFP could dramatically reduce the size of MI and improve cardiac function.Histological data revealed that prussian blue stain-positive cells were found mainly in the border zone which also showed green fluorescence but negative for macrophage marker(CD68).Gross pathologic examination revealed that engrafted MSCs dramatically reduce the extent of necrotic myocardium and promote the regeneration of new,contractile myocardium along the subendocardial surface of the MI.Conclusions MSCs could be efficiently and safely labeled with SPIO and GFP,and could be detected reproducibly and noninvasively in vivo using cardiac MRI.Intracoronary transplantation of dual-labeled MSCs could increase cardiac function and reduce the size of MI.展开更多
基金supported by the National Key Research&Development Program of China(2022YFC3602700,2022YFC3602702)the Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0201301)+2 种基金the National Natural Science Foundation of China(12034015,62088101,32170688,323B1004)Program of Shanghai Academic Research Leader(21XD1403600)Shanghai Municipal Science and Technology Major Project(2021SHZDZX0100,2018SHZDZX01).
文摘Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous electrophysiological recording and Ca^(2+) imaging of cultured hippocampal neurons to investigate neuronal excitability and synaptic transmission during ultrasound stimulation.This study revealed,for the first time,three distinct neuronal response patterns induced by SAW ultrasound:an immediate response showing rapid activation,a delayed response exhibiting facilitation after several minutes,and a non-response maintaining baseline activity.Ultrasound stimulation increased action potential firing,enhanced excitatory postsynaptic currents,and elevated intracellular Ca^(2+) levels.These effects were dependent on extracellular Ca^(2+) influx and primarily dominated by L-type Ca^(2+) channels.Our findings suggest that individual neurons exhibit heterogeneous responses to SAW ultrasound stimulation based on their intracellular Ca^(2+) levels and L-type Ca^(2+) channel activity.This integrated approach provides new insights into the cellular mechanisms of ultrasound neuromodulation while highlighting the potential of SAW technology for precise,cell-type-specific neural control.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
基金supported by the Budgeted Fund of Shanghai University of Traditional Chinese Medicine(Natural Science)(No.2021LK037)the Open Project of Qinghai Province Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation(No.2021-ZY-03).
文摘Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.
基金the financial support from the National Natural Science Foundation of China(12102328,52104312,22278329)the Qin Chuangyuan Talent Project of Shaanxi Province(2021QCYRC4-43,QCYRCXM-2022-308)the Fundamental Research Funds for the Central Universities,China.
文摘Garnet lithium lanthanum zirconium oxide(Li_(7)La_(3)Zr_(2)O_(12),LLZO)is a benchmark solid-state electrolyte(SSE)material receiving considerable attention owing to its high conductivity and chemical stability against Li metal.Although its electro-chemo-mechanical failure mechanisms have been much investigated,the equivocal roles of grain boundary strength and grain size of LLZO remain under-explored,hindering further performance improvements.Here we decoupled the effects of grain size and grain boundary strength of polycrystalline LLZO via the combination of electrochemical kinetics and the cohesive zone model.We discovered that the disintegration of LLZO is initiated by the accumulation of local displacements,which strongly relates to the changes in both grain size and grain boundary strength.However,variations in grain boundary strength affect the diffusion and propagation pathways of damage,while the failure of LLZO is determined by the grain size.Large LLZO grains facilitate transgranular damage under low grain boundary strength,which can alter local chemo-mechanics within the bulk of LLZO,leading to more extensive damage propagation.The results showcase the structure optimization pathways by preferentially controlling the growth of lithium dendrites at grain boundaries and their penetration in garnet-type SSE.
基金supported by the National Natural Sci-ence Foundation of China(No.22373065,No.62072296,No.22222303,No.22173032,No.21933010)the Nation-al Key R&D Program of China(No.2023YFF1204903)NYU-ECNU Center for Computational Chemistry at NYU Shanghai,the Opening Project of Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA.
文摘Metal ions play crucial roles in various biologi-cal functions,in-cluding maintain-ing homeostasis,regulating mus-cle contraction,and facilitating enzyme catalysis.However,accurately simulating the interaction between metal ions and amino acid side chain analogs using high-level wave function theories remains challenging due to the significant computational costs involved.In this study,deep potential molecular dynamics(DeePMD)simulation was employed to investigate the solvation structure of the Mg^(2+)-Ac^(−)ion pair in aqueous solution.To address the computational bottleneck associated with expensive quan-tum mechanics(QM)methods,the Deep Kohn-Sham(DeePKS)approach was utilized,which allows us to generate highly accurate self-consistent energy functionals while significantly re-ducing computational costs.The root mean square error and mean absolute error of energies and atomic forces indicate close agreement between DeePKS predictions and QM strongly constrained and appropriately normed(SCAN)calculations.Moreover,the neural network potential(NNP)generated using the SCAN-level dataset predicted by DeePKS exhibits high-er accuracy compared to previous work,which employed a moderate BLYP functional.The potential of mean force for the Mg^(2+)-Ac−system was further examined,revealing a prefer-ence for monodentate coordination of Mg^(2+)with a~5.8 kcal/mol energy barrier between bidentate and monodentate geometries.Overall,this work provides a comprehensive,precise,and reliable methodology for investigating metal ions’properties in aqueous solutions.
基金supported by grants from the National Natural Science Foundation of China(grant nos.82472554 and 82202449)the Fund for Excellent Young Scholars of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(grant no.JYYQ006).
文摘Background:This study explored the value of integrating problem-based learning(PBL)and team-based learning(TBL)methods into plastic and reconstructive surgery clinical practice.By addressing the challenges faced in traditional teachings,this study aimed to enhance educational outcomes and prepare students for real-world surgical scenarios,thereby improving patient care in this specialized field.Methods:Fifty undergraduate students majoring in clinical medicine at the Shanghai Jiao Tong University School of Medicine were selected as research subjects.They were randomly divided into experimental and control groups.The experimental group received the combined PBL-TBL teaching method,whereas the control group received the traditional teaching.The teaching effect was evaluated based on student satisfaction and academic performance.Results:The student satisfaction in the experimental group was higher than that of the control group(P<0.05).Subjective scoring for academic performance by instructors was higher in the experimental group than in the control group(P<0.05).Conclusion:The PBL and TBL combination had a significant effect when applied in plastic and reconstructive surgery clinical practice.
基金Supported by Guangxi Degree and Postgraduate Education Reform Project(JGY2023213,JGY2023211).
文摘In order to improve the traditional teaching model of traditional Chinese medicine identification course for graduate students of pharmacy,this paper described the research on constructing and practicing the blended teaching model of"online+offline"based on the teaching concept of TfU by taking the course of"Authentic Medicinal Materials and Quality of Traditional Chinese Medicine"as an example.In the preparatory phase,through resource integration and course content decomposition,it identifies"generative topics"to engage students in pre-class online discussions.During the instructional phase,"comprehension-oriented objectives"are established based on learning analytics,followed by the implementation of"understanding-focused activities"for guided inquiry in offline classrooms.The post-class phase employs online extended materials to conduct"sustained assessment"through evaluations and summaries,thereby continuously optimizing subsequent teaching practices.This pedagogical framework not only effectively cultivates investigative research thinking among graduate students but also enhances standardized management and scientific development of the teaching team.The practical research outcomes and experiences derived from this model can provide valuable references for analogous course reforms.
基金Supported by Qingmiao Talent Funding Research Project of Guangxi ProvinceNational College Student Innovation and Entrepreneurship Training Program(202310601031).
文摘[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"were predicted using databases(OMIM and GeneCards),and the key targets were obtained after screening the retrieval data.The binding relationship between Schaftoside and key targets was analyzed by molecular docking.[Results]There were 3370 and 4433 targets for"cholestasis"and"steatosis",respectively,and 1767 overlapping genes were obtained.The results of molecular docking showed that Schaftoside had high binding energy with key targets.[Conclusions]Schaftoside can alleviate cholestasis and steatosis by regulating SREBP-1,CYP7,PPAR-gamma and other key targets to protect liver.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2020-PT330-001)Beijing Nova Program(No.Z201100006820070)from Beijing Municipal Science/Technology Commission+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2019PT320027)Cooperation Project in Beijing,Tianjin and Hebei of China(No.J200017)。
文摘More than 600,000 people are diagnosed with esophageal cancer(EC)every year globally,and the five-year survival rate of EC is less than 20%.Two common histological subtypes of EC,esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),have great geographical variations in incidence rates.About half of the world’s EC was diagnosed in China and a majority of which belong to ESCC.Globally,the overall incidence rate of EC is decreasing.In some high-risk Asian regions,such as China,the incidence rate of ESCC has generally declined,potentially due to economic growth and improvement of diet habits.In some European high-income countries and the United States,the decline is mainly attributed to the decrease in smoking and drinking.The risk factors of EC are not well understood,and the importance of environmental and genetic factors in the pathogenesis is also unclear.The incidence and mortality of advanced EC can be reduced through early diagnosis and screening.White light endoscopy is still the gold standard in the current screening technology.This article reviews the epidemiology,risk factors,and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.
基金Projects(51704329,51705540)supported by the National Natural Science Foundation of ChinaProject(2015CX005)supported by the Innovation Driven Plan of Central South University,China+1 种基金Project(B14034)supported by the National“111”Project,ChinaProject(2018TP1002)supported by the Collaborative Innovation Center for Clean and Efficient Utilization of Strategic Metal Mineral Resources,China
文摘This study investigated the effects of H_(2)O_(2)treatment on xanthate interaction and flotation separation of chalcopyrite and pyrite by making use of a series of laboratory flotation experiments and surface analysis techniques.Flotation test results showed that H2O2 treatment influenced the flotation behaviors of the two minerals;however,flotation of pyrite was depressed more significantly than that of the chalcopyrite.Under well-controlled H_(2)O_(2)concentration,the selective separation of chalcopyrite from pyrite was realized at pH 9.0,at which the recovery of chalcopyrite was over 84%and that of pyrite was less than 24%.Zeta potential,UV-visible and IR spectrum measurements revealed that the collector interacted differently with the two minerals after H_(2)O_(2)treatment,and the surface of chalcopyrite adsorbed much greater amount of xanthate than that of the pyrite.IR and XPS analyses showed that the H_(2)O_(2)treatment significantly changed the surface properties of pyrite to very hydrophilic species that inhibited the adsorption of collector and thus depressed the floatability of pyrite.While,the surface of chalcopyrite remained mildly inert to H_(2)O_(2),as a result,the adsorption of xanthate and its oxidation to dixanthogen were very effective,which enhanced the flotation of chalcopyrite.
基金financially supported by the National Natural Science Foundation of China (No. 51174177)
文摘Commercial A356 alloy was refined with a homemade A1-5Ti-0.25C-2RE master alloy, and the microstructure and macrostructure of the refined alloy were investigated. The results show that the grain refining effect of A356 is poor by the addition level of 0.5 wt% master alloy, but when the level reaches 3.0 wt% the grain can get a satisfactory refining effect. Dendrite of A356 can be effectively refined by addition of 0.5 wt% master alloy; however, the refining effect is not significantly improved by further increasing the addition of master alloy. Grain and dendrite refining effects are compared in this article, and the results show that the grain and dendrite exhibit different refining effects with the same addition level of master alloy. Dendrite is easier to reach the optimal refining effect than grain.
基金funded by the grants from the National Key R&D Program of China(No.2022YFD1301004)National Natural Science Foundation of China(No.31601962)+1 种基金Fundamental Research Funds for the Central Universities(2662019QD021)Key Laboratory of Molecular Animal Nutrition of Zhejiang University(KLMAN202101 and KLMAN202205)。
文摘Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.
基金supported by National Natural Science Foundation of China (Nos. 22176012, 51878023)Beijing Natural Science Foundation (No. 8202016)+1 种基金Beijing Talent Project (No. 2020A27)BUCEA Doctor Graduate Scientific Research Ability Improvement Project (No. DG2021004)。
文摘MIL-88A(Fe)@sponge(MS) was synthesized by a dip-coating method, which displayed efficient photocatalytic Cr(Ⅵ) reduction efficiency under both low power LED UV light and real solar light irradiation. It was observed that MS(0.2 g/L) could remove 100% Cr(Ⅵ)(10 mg/L) by adding 0.4 mmol/L tartaric acid(TA) without adjusting pH(pH 5.05) within 6.0 min and 3.0 min under UV light and real solar light irradiation, respectively. Besides, the photo-induced e-and radicals(O_(2)^(·-) and CO_(2)^(·-)) were found to play the momentous roles in the MS/TA/UVL/Cr(Ⅵ) system by the scavenger experiments and electron spin resonance(ESR) tests. MS was also filled into a fixed-bed reactor to test the possibility of long-term Cr(Ⅵ)reduction operation in TA/UVL system. As expected, the results revealed that MS could still maintain 100% activity up to 60 h. These results demonstrated that MIL-88A(Fe) might be the potentially efficient catalyst for large-scale wastewater treatment in the near future.
基金Supported by National Natural Science Foundation of China,No.81772103 and No.82172234Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality,China,No.22MC1940300。
文摘Pathological scarring and scleroderma,which are the most common conditions of skin fibrosis,pathologically manifest as fibroblast proliferation and extracellular matrix(ECM)hyperplasia.Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling,causing an exaggerated and prolonged wound-healing response.The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects.Currently,a promising and relatively low-cost treatment has emerged-adipose-derived stem cell(ASC)therapy as a branch of stem cell therapy,including ASCs and their derivatives-purified ASC,stromal vascular fraction,ASC-conditioned medium,ASC exosomes,etc.,which are rich in sources and easy to obtain.ASCs have been widely used in therapeutic settings for patients,primarily for the defection of soft tissues,such as breast enhancement and facial contouring.In the field of skin regeneration,ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis.The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review,as well as their new applications in the treatment of skin fibrosis.Although the long-term effect of ASC therapy is still unclear,ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.
基金This work was supported by the Natural Science Foundation of Henan Province under grant No. 0611023900.
文摘By using a new method, ^60Co γ-ray irradiation, Fe3O4 magnetic nano-particles were successfully synthesized at room temperature under ambient pressure. The structure, morphology and magnetic properties of these nanoparticles were characterized by X-ray diffraction （XRD）, transmission electron microscope （TEM） and vibrating sample magnetometer （VSM）, respectively. The radiation formation mechanism was also discussed. The results show that the absorbed dose can greatly influence the structure, morphology and magnetic properties of the products. XRD and TEM studies show that the product prepared by γ-ray irradiation （10 kGy） is pure FesO4 phase and the mean diameter of these nano-particles is about 21 nm. The Fe3O4 nano-particles synthesized by γ-ray irradiation （10 kGy） are mainly in small cubic shape and the size uniformity of these particles is good.
文摘Objectives To trace and evaluate intracoronary transplanted mesenchymal stem cells(MSCs)labeled with superparamagnetic iron oxide(SPIO)by using magnetic resonance imaging(MRI)in a swine model of myocardial infarction(MI).Methods MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent protein(GFP)and labeled in vitro with SPIO.Two weeks after MI,swine were randomized to intracoronary transplantation of dual-labeled MSCs(n=10),MSCs-GFP(n=10)and saline(n=5).MRI examination was performed with a 1.5T clinical scanner at 24 hours,3 weeks and 8 weeks after cells transplantation.Signal intensity(SI)changes,cardiac function and MI size were measured using MRI.Correlation between MR findings and histomorphologic findings was also investigated.Results The labeling efficiency at a combination of 25μg Fe/ml SPIO and 0.8 pi/ml Lipofectamine 2000 reached 100%.SPIO labeling did not affect GFP fluorescence and dual-labeling did not affect cell proliferation(P】0.05).Multipotentiality was not affected especially for cardiomyocyte-like cells differentiation.Cardiac cell marker of a-MHC and actinin were positively expressed by immunofluorescence staining after induction.SI on T2*WI decreased substantial-ly in the interventricular septum 24 hours after injection of MSCs.The intensity of hypo-intense signals appeared to increase throughout the later time points.Changes in SI at 24 hours,3 weeks and 8 weeks were 52.98%±10.74%,21.53%±5.40%and 6.23%±2.01%,respectively(P【0.01).DE-MRI demonstrated both dual-labeled MSCSs and MSCs-GFP could dramatically reduce the size of MI and improve cardiac function.Histological data revealed that prussian blue stain-positive cells were found mainly in the border zone which also showed green fluorescence but negative for macrophage marker(CD68).Gross pathologic examination revealed that engrafted MSCs dramatically reduce the extent of necrotic myocardium and promote the regeneration of new,contractile myocardium along the subendocardial surface of the MI.Conclusions MSCs could be efficiently and safely labeled with SPIO and GFP,and could be detected reproducibly and noninvasively in vivo using cardiac MRI.Intracoronary transplantation of dual-labeled MSCs could increase cardiac function and reduce the size of MI.
