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
In this paper,we investigate spacelike graphs defined over a domain Ω⊂M^(n) in the Lorentz manifold M^(n)×ℝ with the metric−ds^(2)+σ,where M^(n) is a complete Riemannian n-manifold with the metricσ,Ωhas piece...In this paper,we investigate spacelike graphs defined over a domain Ω⊂M^(n) in the Lorentz manifold M^(n)×ℝ with the metric−ds^(2)+σ,where M^(n) is a complete Riemannian n-manifold with the metricσ,Ωhas piecewise smooth boundary,and ℝ denotes the Euclidean 1-space.We prove an interesting stability result for translating spacelike graphs in M^(n)×ℝ under a conformal transformation.展开更多
Stock volatility constitutes an adverse psychological stressor,but few large-scale studies have focused on its impact on major adverse cardiovascular events(MACEs)and suicide.Here,we conducted an individual-level time...Stock volatility constitutes an adverse psychological stressor,but few large-scale studies have focused on its impact on major adverse cardiovascular events(MACEs)and suicide.Here,we conducted an individual-level time-stratified case-crossover study to explore the association of daily stock volatility(daily returns and intra-daily oscillations for three kinds of stock indices)with MACEs and suicide among more than 12 million individual decedents from all counties in the mainland of China between 2013 and 2019.For daily stock returns,both stock increases and decreases were associated with increased mortal-ity risks of all MACEs and suicide.There were consistent and positive associations between intra-daily stock oscillations and mortality due to MACEs and suicide.The excess mortality risks occurred at the cur-rent day(lag 0 d),persisted for two days,and were greatest for suicide and hemorrhagic stroke.Taking the present-day Shanghai and Shenzhen 300 Index as an example,a 1%decrease in daily returns was associated with 0.74%-1.04%and 1.77%increases in mortality risks of MACEs and suicide,respectively;the corresponding risk increments were 0.57%-0.85%and 0.92%for a 1%increase in daily returns and 0.67%-0.77%and 1.09%for a 1%increase in intra-daily stock oscillations.The excess risks were more pro-nounced among individuals aged 65-74 years,males,and those with lower education levels.Our findings revealed considerable health risks linked to sociopsychological stressors,which are helpful for the gov-ernment and general public to mitigate the immediate cardiovascular and mental health risks associated with stock market volatility.展开更多
Fibrosis is a pathological outcome of a dysregulated repair response to injury,which can occur in any organ and have devastating effects on hundreds of millions of patients worldwide.However,challenges remain in delin...Fibrosis is a pathological outcome of a dysregulated repair response to injury,which can occur in any organ and have devastating effects on hundreds of millions of patients worldwide.However,challenges remain in delineating the complex and dynamic network regulating fibrosis,as well as translating this information into effective anti-fibrotic treatments.A comprehensive understanding of existing methodologies and the development of new research tools are essential for ensuring the transferability of findings from bench to bedside.In this review,we present a framework consisting of a large biospecimen repository that integrates diverse patient cohorts with corresponding clinical data,and a systematic research platform incorporating multiple layers of experimental strategies,primarily focused on skin fibrosis.We summarize current advancements and the applications of various tools for preclinical fibrosis research and examine the limitations of traditional methods used to simulate and investigate biomechanical signals in the fibrotic environment.Importantly,we highlight the strengths of research techniques and translational approaches of varying physiological relevance developed by us over the past decade.Collectively,we emphasize a trend toward more faithfully replicating the functional,structural,and biological complexity of fibrosis while providing high spatio-temporal control over soluble cues and intricate interactions.Our comprehensive overview of methodology paves the way for minimizing batch-to-batch variation and improving the reproducibility of experimental systems.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 H2O2 treatment on xanthate interaction and flotation separation of chalcopyrite and pyrite by making use of a series of laboratory flotation experiments and surface analysis tech...This study investigated the effects of H2O2 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 H2O2 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 H2O2 treatment,and the surface of chalcopyrite adsorbed much greater amount of xanthate than that of the pyrite.IR and XPS analyses showed that the H2O2 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 H2O2,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
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
Due to the unique magnetic, mechanical and thermal properties, magnetic nanoparticles(MNPs) have comprehensive applications as the contrast and therapeutic agents in biomedical imaging and magnetic hyperthermia. The l...Due to the unique magnetic, mechanical and thermal properties, magnetic nanoparticles(MNPs) have comprehensive applications as the contrast and therapeutic agents in biomedical imaging and magnetic hyperthermia. The linear and nonlinear magnetoacoustic responses determined by the magnetic properties of MNPs have attracted more and more attention in biomedical engineering. By considering the relaxation time of MNPs, we derive the formulae of second harmonic magnetoacoustic responses(2H-MARs) for a cylindrical MNP solution model based on the mechanical oscillations of MNPs in magnetoacoustic tomography with magnetic induction(MAT-MI). It is proved that only the second harmonic magnetoacoustic oscillations can be generated by MNPs under an alternating magnetic excitation. The acoustic pressure of the 2H-MAR is proportional to the square of the magnetic field intensity and exhibits a linear increase with the concentration of MNPs. Numerical simulations of the 2H-MAR are confirmed by the experimental measurements for various magnetic field intensities and solution concentrations using a laser vibrometer. The favorable results demonstrate the feasibility of the harmonic measurements without the fundamental interference of the electromagnetic excitation, and suggest a new harmonic imaging strategy of MAT-MI for MNPs with enhanced spatial resolution and improved signal-to-noise ratio in biomedical applications.展开更多
In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potent...In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.展开更多
Based on data observed from 1979 to 2017,the influence of Arctic sea ice in the previous spring on the first mode of interannual variation in summer drought in the middle and high latitudes of Asia(MHA)is analyzed in ...Based on data observed from 1979 to 2017,the influence of Arctic sea ice in the previous spring on the first mode of interannual variation in summer drought in the middle and high latitudes of Asia(MHA)is analyzed in this paper,and the possible associated physical mechanism is discussed.The results show that when there is more sea ice near the Svalbard Islands in spring while the sea ice in the Barents-Kara Sea decreases,the drought distribution in the MHA shows a north-south dipole pattern in late summer,and drought weakens in the northern MHA region and strengthens in the southern MHA region.By analyzing the main physical process affecting these changes,the change in sea ice in spring is found to lead to the Polar-Eurasian teleconnection pattern,resulting in more precipitation,thicker snow depths,higher temperatures,and higher soil moisture in the northern MHA region in spring and less precipitation,smaller snow depths,and lower soil moisture in the southern MHA region.Such soil conditions last until summer,affect summer precipitation and temperature conditions through soil moisture–atmosphere feedbacks,and ultimately modulate changes in summer drought in the MHA.展开更多
[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly di...[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly divided into 2 groups,namely normal group(12 rats)and high-fat feed group(42 rats).After 8 weeks,2 rats were randomly selected from each group.After pathological examination confirmed the success of the NAFLD model,the high-fat feed group was divided into model group,Yinzhihuang(9000 mg/kg),metformin group(200 mg/kg),Yinzhihuang combined with metformin group(4500 mg/kg+100 mg/kg),10 rats in each group.Except the normal group and the model group,the other groups were given treatment drugs at the same time,one time a day,on the fifth weekend of the experiment,at the last time of administration,fasting but giving water for 16 h,then collected blood and liver tissue.Biochemical method was used to detect AST and ALT in serum and SOD,MDA,GSH-px biochemical indicators in liver tissue;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,IL-6 and TGF-βin liver tissue;Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α(PPAR-α)protein in rat liver tissue.[Results]Compared with the model group,the serum levels of ALT,AST and MDA in liver tissue of model group rats were significantly increased;the levels of SOD and GSH-px in liver tissue were significantly increased;TNF-αand IL-6 and TGF-βcontents in liver tissue were significantly increased.[Conclusions]Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats,and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone,the mechanism is possibly associated with the regulation of PPAR-αsignaling pathway.展开更多
This paper introduced the application of the WebGIS and virtual reality technology in the tourism industry and analyzed the existing problems in the tourism information system.Taking Daqing Oil Field Scenic Sport as a...This paper introduced the application of the WebGIS and virtual reality technology in the tourism industry and analyzed the existing problems in the tourism information system.Taking Daqing Oil Field Scenic Sport as an example,it introduced a method of constructing the virtual simulation platform for tourism based on the combination of WebGIS and virtual reality technology.Through the virtual simulation platform of Daqing Tourism Scenic Spot,it verified the design idea,methods,and technical feasibility of the virtual tourism system,and built a specific,feasible,and practical virtual simulation platform for tourism.It showed the bright prospects of virtual tourism development based on WebGIS and virtual reality technology.展开更多
[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mic...[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mice were selected and then randomly divided into normal control,model group and positive group( bifendate 120 mg/kg),high-dose arabinose + mannose group( 800 mg/kg),middle-dose arabinose + mannose group( 400 mg/kg) and low-dose arabinose + mannose group( 200 mg/kg),each group had 10 mice,which were fed adaptively for 1 week. Except normal control group and model group,each treatment group was given medicine by gavage once a day and lasted for7 days according to the dosage of 20 ml/kg. After the last drug,except normal control group,the mice of other groups were injected 10 ml/kg0. 12% CC14 peanut oil through enterocoelia,thereby establishing acute liver injury model. The mice were fasted but not water for 24 h,after that,blood was sampled from mice eyes,then dissected rapidly. The activities of ALT and AST in the serum were determined,the expression levels of TNF-α,IL-1β and IL-6 from the hepatic tissues were detected by enzyme-linked immunosorbent assay( ELISA); then after HE dye,the changes of liver histopathology were observed. [Results]Compared with CCl_4 model,the activities of ALT and AST from the serum of mice from high-dose and middle dose groups decreased significantly( P < 0. 01); the contents of TNF-α,IL-1β and IL-6 from the hepatic tissues of mice decreased significantly( P < 0. 01); the pathological section showed that the liver injury of mice from the combined drug groups showed alleviating trend to varying degrees,in which the liver injury of mice from the high-dose group was the best. [Conclusions] Arabinose + mannose has an obvious protective effect on mice with acute liver injury induced by CCl_4,and its mechanism may relate to anti-inflammatory.展开更多
The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE...The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE and MEDLINE databases were searched from inception to November 2017,with no language restriction.Two reviewers selected inclusion dependently and extracted the basic characteristics.Review Manager 5.3,stata 12.0,and SPSS 21 software were used to conduct analyses.A total of 46 SRs/MAs were included.The results showed that the English databases with high retrieval frequency are PubMed/MEDLINE,EMBASE,and Web of Science.67.31%(31/46)of the articles reported the search strategy in the full text or the appendix.65.22%(30/46)reported the literature screening flow diagram,and only 19.57%(9/46)reported the number of works of literature retrieved in each database.60.87%(28/46)illustrated supplement retrieval.Through 2 subgroup analyses,it was found that there were no significant differences in the quality of reports of PRISMA items.But referring to the methodological quality or reporting of PRESS items,SCI was better than that of non-SCI,while there seemed a source of funding to have no significant impact on the methodological quality or the items of PRESS.The results of PRESS,AMSTAR 2,and PRISMA were correlated,and the correlation between PRISMA and AMSTAR 2 was strong.These results demonstrated that search strategies of animal model SRs/MAs are still not enough comprehensive,report specification and methodological quality still need to be ameliorated.To show users the scientificity and rigor of the study,future research should focus on these various guidelines like PRESS,PRISMA,and AMSTAR 2 checklists that have been issued,it can help to increase the value of research and improve the utilization of medical resources.展开更多
PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEP06 directly targets tumor cel...PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.展开更多
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 in part by the NSFC(11801496,11926352)the Fok Ying-Tung Education Foundation(China)the Hubei Key Laboratory of Applied Mathematics(Hubei University).
文摘In this paper,we investigate spacelike graphs defined over a domain Ω⊂M^(n) in the Lorentz manifold M^(n)×ℝ with the metric−ds^(2)+σ,where M^(n) is a complete Riemannian n-manifold with the metricσ,Ωhas piecewise smooth boundary,and ℝ denotes the Euclidean 1-space.We prove an interesting stability result for translating spacelike graphs in M^(n)×ℝ under a conformal transformation.
基金supported by the National Key Research and Development Program(2022YFC3702701)the Shanghai Municipal Science and Technology Commission(21TQ015)the Shanghai International Science and Technology Partnership Project,China(21230780200).
文摘Stock volatility constitutes an adverse psychological stressor,but few large-scale studies have focused on its impact on major adverse cardiovascular events(MACEs)and suicide.Here,we conducted an individual-level time-stratified case-crossover study to explore the association of daily stock volatility(daily returns and intra-daily oscillations for three kinds of stock indices)with MACEs and suicide among more than 12 million individual decedents from all counties in the mainland of China between 2013 and 2019.For daily stock returns,both stock increases and decreases were associated with increased mortal-ity risks of all MACEs and suicide.There were consistent and positive associations between intra-daily stock oscillations and mortality due to MACEs and suicide.The excess mortality risks occurred at the cur-rent day(lag 0 d),persisted for two days,and were greatest for suicide and hemorrhagic stroke.Taking the present-day Shanghai and Shenzhen 300 Index as an example,a 1%decrease in daily returns was associated with 0.74%-1.04%and 1.77%increases in mortality risks of MACEs and suicide,respectively;the corresponding risk increments were 0.57%-0.85%and 0.92%for a 1%increase in daily returns and 0.67%-0.77%and 1.09%for a 1%increase in intra-daily stock oscillations.The excess risks were more pro-nounced among individuals aged 65-74 years,males,and those with lower education levels.Our findings revealed considerable health risks linked to sociopsychological stressors,which are helpful for the gov-ernment and general public to mitigate the immediate cardiovascular and mental health risks associated with stock market volatility.
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)the Shanghai Clinical Research Center of Plastic and Reconstructive Surgery(grant no.22MC1940300).
文摘Fibrosis is a pathological outcome of a dysregulated repair response to injury,which can occur in any organ and have devastating effects on hundreds of millions of patients worldwide.However,challenges remain in delineating the complex and dynamic network regulating fibrosis,as well as translating this information into effective anti-fibrotic treatments.A comprehensive understanding of existing methodologies and the development of new research tools are essential for ensuring the transferability of findings from bench to bedside.In this review,we present a framework consisting of a large biospecimen repository that integrates diverse patient cohorts with corresponding clinical data,and a systematic research platform incorporating multiple layers of experimental strategies,primarily focused on skin fibrosis.We summarize current advancements and the applications of various tools for preclinical fibrosis research and examine the limitations of traditional methods used to simulate and investigate biomechanical signals in the fibrotic environment.Importantly,we highlight the strengths of research techniques and translational approaches of varying physiological relevance developed by us over the past decade.Collectively,we emphasize a trend toward more faithfully replicating the functional,structural,and biological complexity of fibrosis while providing high spatio-temporal control over soluble cues and intricate interactions.Our comprehensive overview of methodology paves the way for minimizing batch-to-batch variation and improving the reproducibility of experimental systems.
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 H2O2 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 H2O2 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 H2O2 treatment,and the surface of chalcopyrite adsorbed much greater amount of xanthate than that of the pyrite.IR and XPS analyses showed that the H2O2 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 H2O2,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,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.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11934009,11974187,and 11604156)。
文摘Due to the unique magnetic, mechanical and thermal properties, magnetic nanoparticles(MNPs) have comprehensive applications as the contrast and therapeutic agents in biomedical imaging and magnetic hyperthermia. The linear and nonlinear magnetoacoustic responses determined by the magnetic properties of MNPs have attracted more and more attention in biomedical engineering. By considering the relaxation time of MNPs, we derive the formulae of second harmonic magnetoacoustic responses(2H-MARs) for a cylindrical MNP solution model based on the mechanical oscillations of MNPs in magnetoacoustic tomography with magnetic induction(MAT-MI). It is proved that only the second harmonic magnetoacoustic oscillations can be generated by MNPs under an alternating magnetic excitation. The acoustic pressure of the 2H-MAR is proportional to the square of the magnetic field intensity and exhibits a linear increase with the concentration of MNPs. Numerical simulations of the 2H-MAR are confirmed by the experimental measurements for various magnetic field intensities and solution concentrations using a laser vibrometer. The favorable results demonstrate the feasibility of the harmonic measurements without the fundamental interference of the electromagnetic excitation, and suggest a new harmonic imaging strategy of MAT-MI for MNPs with enhanced spatial resolution and improved signal-to-noise ratio in biomedical applications.
基金supported by the National Natural Science Foundation of China,Nos.82071692(to HY),81741096(to HY),81770513(to YG),81270435(to WKP)Shaanxi Youth Science and Technology Project of China,No.2019KJXX-044(to HY)+1 种基金the National Natural Science Foundation of Shaanxi Province of China,No.2020JM-407(to HY)Fund Project of the Second Affiliated Hospital,Xi’an Jiaotong University No.RC(XM)201703(to HY).
文摘In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.
基金jointly supported by the National Key R&D Program of China[grant number 2017YFE0111800]the National Science Foundation of China[grant numbers 41991281 and 41875110].
文摘Based on data observed from 1979 to 2017,the influence of Arctic sea ice in the previous spring on the first mode of interannual variation in summer drought in the middle and high latitudes of Asia(MHA)is analyzed in this paper,and the possible associated physical mechanism is discussed.The results show that when there is more sea ice near the Svalbard Islands in spring while the sea ice in the Barents-Kara Sea decreases,the drought distribution in the MHA shows a north-south dipole pattern in late summer,and drought weakens in the northern MHA region and strengthens in the southern MHA region.By analyzing the main physical process affecting these changes,the change in sea ice in spring is found to lead to the Polar-Eurasian teleconnection pattern,resulting in more precipitation,thicker snow depths,higher temperatures,and higher soil moisture in the northern MHA region in spring and less precipitation,smaller snow depths,and lower soil moisture in the southern MHA region.Such soil conditions last until summer,affect summer precipitation and temperature conditions through soil moisture–atmosphere feedbacks,and ultimately modulate changes in summer drought in the MHA.
基金Student's Platform for Innovation and Entrepreneurship Training Program of Guangxi Zhuang Autonomous Region,China(201810601070)。
文摘[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly divided into 2 groups,namely normal group(12 rats)and high-fat feed group(42 rats).After 8 weeks,2 rats were randomly selected from each group.After pathological examination confirmed the success of the NAFLD model,the high-fat feed group was divided into model group,Yinzhihuang(9000 mg/kg),metformin group(200 mg/kg),Yinzhihuang combined with metformin group(4500 mg/kg+100 mg/kg),10 rats in each group.Except the normal group and the model group,the other groups were given treatment drugs at the same time,one time a day,on the fifth weekend of the experiment,at the last time of administration,fasting but giving water for 16 h,then collected blood and liver tissue.Biochemical method was used to detect AST and ALT in serum and SOD,MDA,GSH-px biochemical indicators in liver tissue;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,IL-6 and TGF-βin liver tissue;Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α(PPAR-α)protein in rat liver tissue.[Results]Compared with the model group,the serum levels of ALT,AST and MDA in liver tissue of model group rats were significantly increased;the levels of SOD and GSH-px in liver tissue were significantly increased;TNF-αand IL-6 and TGF-βcontents in liver tissue were significantly increased.[Conclusions]Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats,and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone,the mechanism is possibly associated with the regulation of PPAR-αsignaling pathway.
基金Supported by Student's Platform for Innovation and Entrepreneurship Training Program "Development of Campus Precise Navigation System Based on Mobile Terminal"(201610223065)Heilongjiang Provincial Level and Postgraduate Education Reform Research Project "Research on the Integration of Production,Study and Practice Training Mode of Agricultural Information Professional Master"(JGXM_HLJ_2014094)Heilongjiang Provincial Level and Postgraduate Education Teaching Reform Project "Training Model of Practical and Innovative Agricultural Information Professional Master"(JGXM_HLJ_2016126)
文摘This paper introduced the application of the WebGIS and virtual reality technology in the tourism industry and analyzed the existing problems in the tourism information system.Taking Daqing Oil Field Scenic Sport as an example,it introduced a method of constructing the virtual simulation platform for tourism based on the combination of WebGIS and virtual reality technology.Through the virtual simulation platform of Daqing Tourism Scenic Spot,it verified the design idea,methods,and technical feasibility of the virtual tourism system,and built a specific,feasible,and practical virtual simulation platform for tourism.It showed the bright prospects of virtual tourism development based on WebGIS and virtual reality technology.
基金Supported by Natural Science Foundation of China(81360685)
文摘[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mice were selected and then randomly divided into normal control,model group and positive group( bifendate 120 mg/kg),high-dose arabinose + mannose group( 800 mg/kg),middle-dose arabinose + mannose group( 400 mg/kg) and low-dose arabinose + mannose group( 200 mg/kg),each group had 10 mice,which were fed adaptively for 1 week. Except normal control group and model group,each treatment group was given medicine by gavage once a day and lasted for7 days according to the dosage of 20 ml/kg. After the last drug,except normal control group,the mice of other groups were injected 10 ml/kg0. 12% CC14 peanut oil through enterocoelia,thereby establishing acute liver injury model. The mice were fasted but not water for 24 h,after that,blood was sampled from mice eyes,then dissected rapidly. The activities of ALT and AST in the serum were determined,the expression levels of TNF-α,IL-1β and IL-6 from the hepatic tissues were detected by enzyme-linked immunosorbent assay( ELISA); then after HE dye,the changes of liver histopathology were observed. [Results]Compared with CCl_4 model,the activities of ALT and AST from the serum of mice from high-dose and middle dose groups decreased significantly( P < 0. 01); the contents of TNF-α,IL-1β and IL-6 from the hepatic tissues of mice decreased significantly( P < 0. 01); the pathological section showed that the liver injury of mice from the combined drug groups showed alleviating trend to varying degrees,in which the liver injury of mice from the high-dose group was the best. [Conclusions] Arabinose + mannose has an obvious protective effect on mice with acute liver injury induced by CCl_4,and its mechanism may relate to anti-inflammatory.
文摘The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE and MEDLINE databases were searched from inception to November 2017,with no language restriction.Two reviewers selected inclusion dependently and extracted the basic characteristics.Review Manager 5.3,stata 12.0,and SPSS 21 software were used to conduct analyses.A total of 46 SRs/MAs were included.The results showed that the English databases with high retrieval frequency are PubMed/MEDLINE,EMBASE,and Web of Science.67.31%(31/46)of the articles reported the search strategy in the full text or the appendix.65.22%(30/46)reported the literature screening flow diagram,and only 19.57%(9/46)reported the number of works of literature retrieved in each database.60.87%(28/46)illustrated supplement retrieval.Through 2 subgroup analyses,it was found that there were no significant differences in the quality of reports of PRISMA items.But referring to the methodological quality or reporting of PRESS items,SCI was better than that of non-SCI,while there seemed a source of funding to have no significant impact on the methodological quality or the items of PRESS.The results of PRESS,AMSTAR 2,and PRISMA were correlated,and the correlation between PRISMA and AMSTAR 2 was strong.These results demonstrated that search strategies of animal model SRs/MAs are still not enough comprehensive,report specification and methodological quality still need to be ameliorated.To show users the scientificity and rigor of the study,future research should focus on these various guidelines like PRESS,PRISMA,and AMSTAR 2 checklists that have been issued,it can help to increase the value of research and improve the utilization of medical resources.
文摘PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.
