Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprot...Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.展开更多
In spite of ill-effects of high heel shoes, they are widely used for women. Hence, it is essential to understand the load transfer biomechanics in order to design better fit and comfortable shoes. In this study, both ...In spite of ill-effects of high heel shoes, they are widely used for women. Hence, it is essential to understand the load transfer biomechanics in order to design better fit and comfortable shoes. In this study, both experimental measurement and finite element analysis were used to evaluate the biomechanical effects of heel height on foot load transfer. A controlled experiment was conducted using custom-designed platforms. Under different weight-bearing conditions, peak plantar pressure, contact area and center of pressure were analyzed. A three-dimensional finite element foot model was used to simulate the high-heel support and to predict the internal stress distributions and deformations for different heel heights. Results from both experiment and model indicated that heel elevations had significant effects on all variables. When heel elevation increased, the center of pressure shifted from the midfoot region to the forefoot region, the contact area was reduced by 26% from 0 to 10.2 cm heel and the internal stress of foot bones increased. Prediction results also showed that the strain and total tension force of plantar fascia was minimum at 5.1 cm heel condition. This study helps to better understand the biomechanical behavior of foot, and to provide better suggestions for design parameters of high heeled shoes.展开更多
Retinoic acid level in the retina/choroid is altered in induced myopia models.All-trans-retinol dehydrogenase(RDH8) is an important enzyme of retinoic acid metabolism.This study aimed to investigate the association of...Retinoic acid level in the retina/choroid is altered in induced myopia models.All-trans-retinol dehydrogenase(RDH8) is an important enzyme of retinoic acid metabolism.This study aimed to investigate the association of the RDH8 gene with high myopia.Three single nucleotide polymorphisms(SNPs) [RDH851(rs2233789) ,RDH8E5a(rs1644731) ,and RDH855b(rs3760753) ]were selected,based on the linkage disequilibrium pattern of RDH8 from a previous study,and genotyped for 160 Han Chinese nuclear families with highly myopic(-10 diopters or worse) offspring as well as in an independent group with 166 highly myopic cases(-10 diopters or worse) and 211 controls. Family-based association analysis was performed using the family-based association test(FBAT) package,and genotype relative risk(GRR) was calculated using the GenAssoc program.Population-based association analysis was performed using Chi-square test.These SNPs were in linkage equilibrium with each other.SNPs RDH851(rs2233789) and RDH8E5a(rs1644731) both did not show association with high myopia.SNP RDH855b(rs3760753) demonstrated significant association(P=0.0269) with a GRR of 0.543(95%confidence interval=0.304-0.968,P=0.038) .The association became statistically insignificant,however,after multiple comparison correction.Haplotype analysis did not show a significant association either.Population-based association analysis also showed no significant association(P>0.05) .Our family-and population-based data both suggest that the RDH8 gene is unlikely to be associated with high myopia in Chinese.展开更多
Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotect...Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.展开更多
Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiven...Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.展开更多
The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens we...The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography （micro-CT） system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions （transverse directions） were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels： stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.展开更多
Background:The prevalence of MRSA(Methicillin-resistant Staphylococcus aureus)colonized wounds in home care residents is expected to grow continuously as a result of the substantial proportion of older people requirin...Background:The prevalence of MRSA(Methicillin-resistant Staphylococcus aureus)colonized wounds in home care residents is expected to grow continuously as a result of the substantial proportion of older people requiring institutionalized care due to chronic disease and declining functional status,which contribute to more frequent skin breakdown and wound formation.Tea tree oil has been claimed to have anti-bacterial,analgesic and anti-inflammatory effects that have been suggested in many in-vitro studies to have good efficacy against MRSA.The aims of this study were to evaluate the effectiveness of 10%topical tea tree preparation to eradicateMRSA and to ascertain its influence on wound healing forMRSA-colonized wounds.Methods:It was a randomized controlled trial,single-blind study.Those with stage II or above MRSA-colonized wounds and who had given their informed consent formed the sample.The determined sample sizewasbasedonthe effect size of our previouspilot study,whichwas 0.46.Five outcome measurements were taken for the MRSA bacterial count and wound healing condition at baseline and at 1-week intervals during the 4-week dressing intervention period.Results:Thirty-two participants were recruited from two non-government nursing homes,16 in the control group and 16 in the tea tree oil group.The control group residents received routine saline gauze dressing,while the tea tree oil group residents received the 10%topical tea tree preparation dressing.In the tea tree oil group,all chronic wounds that had previously been delayed in healing were healed within 28 days without adverse reaction.MRSA was also completely eradicated in 14(87.5%)out of 16 wounds in the group receiving the 10%topical tea tree preparation.展开更多
The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrop...The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.展开更多
Redox-active organic materials are emerging as the new playground for the design of new exciting battery materials for rechargeable batteries because of the merits including structural diversity and tunable electroche...Redox-active organic materials are emerging as the new playground for the design of new exciting battery materials for rechargeable batteries because of the merits including structural diversity and tunable electrochemical properties that are not easily accessible for the inorganic counterparts.More importantly,the sustainability developed by using naturally abundant chemical elements(C,H,N,O and S) makes them as an ideal alternative material for Li-ion batteries(LIBs).However,the identification and screening of proper organic materials is still challenging in the past decades.Assisted by the artificial intelligence,this review will give a summary of the theoretical design aspects of redox-active organic materials from densityfunctional theory(DFT) to machine learning(ML) methods in the past two decades,with a particular emphasis on the calculation method to predict the chemical/electrochemical stability and reversibility.This review will also analyze and discuss the challenges and perspectives for the development of organic battery materials.展开更多
Using the software Anybody Modeling System, a human static-standing musculoskeletal model based on inverse dynamics is presented, which are defined as segments, muscles and joints as dements. Simulation is based on da...Using the software Anybody Modeling System, a human static-standing musculoskeletal model based on inverse dynamics is presented, which are defined as segments, muscles and joints as dements. Simulation is based on data obtained from experiments using motion capture system VICADN and force plate AMTI. In the model AnyBody Modeling System is introduced to help solve the redundancy problem and obtain results of muscle activities, muscle forces and joint forces. From the model, hip and knee joint forces could be analyzed under normal standing posture. Also, activities of the musculus rectus femoris and several other muscles of the lower limbs can be obtained. From the results it could be concluded that stresses at joints are much stronger than theoretical reasoning because of the functions of relevant soft tissues such as muscles, tendons and so on. Results show that joint forces from the simulations are in good conformation with previous experimental researches. And this complicated model would be of use for better understanding human body functions.展开更多
Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of...Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.展开更多
TIM： To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS： Twelve healthy volunteers underwent distension ...TIM： To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS： Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale （VAS）. The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anticholinergic drug butylscopolamine. RESULTS： The stimulus-response （volume-VAS） curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION： The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.展开更多
Metabolic changes together with cardiovascular and hepatic factors are related to the development of diseases like myocardial lipidosis,heart disease,and profound toxicity.The aim of this animal study is to determine ...Metabolic changes together with cardiovascular and hepatic factors are related to the development of diseases like myocardial lipidosis,heart disease,and profound toxicity.The aim of this animal study is to determine the effects of high erucic acid containing rapeseed oil(Brassica napus L.)varieties on liver,kidney and heart muscles in Wistar rats.Male Wistar rats were divided into three groups where each group containing four rats.Group A was considered as control diet group,while Group B rapeseed wild oil group and Group C rapeseed hybrid oil group were considered as experimental diet groups.The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),creatine kinase-MB(CK-MB)and creatinine of two experimental groups were significantly elevated while compared to the control groups(p<0.05–0.001).Nevertheless,an increment in weight retardation(p<0.05)was also observed in rapeseed hybrid oil treated groups.No significant weight retardation found in other two groups(p>0.05).Noticeable tissue injury observed in this study is a sign of the relative toxicity of erucic acid containing rapeseed oil to mammalian species.The use of Brassica napus as a supplementary feed ingredient should be,therefore,thoroughly considered.展开更多
Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the ...Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear.Our previous study indicated the potential of APPL2(adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system.In the present study,we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells(NSCs) and an in vivo animal model-APPL2 transgenic(Tg) mice.In the in vitro study,we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis.In the in vivo study,APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system,including the corpus callosum,OB,and rostral migratory stream.Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice.Furthermore,we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors.In conclusion,APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.展开更多
Bacterial quorum sensing（QS） molecules are involved in the coordination of certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS molecules（autoinducers） and their corresponding recep...Bacterial quorum sensing（QS） molecules are involved in the coordination of certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS molecules（autoinducers） and their corresponding receptors have been recognized as important therapeutic targets for drug-resistant infections and biofilm-associated infections（BAI）. This study assessed the multiple biological effects of homogentisic acid y-lactone（HgAL）, a furanone derivative. The anti-QS and anti-biofilm effects of HgAL against PAO1 strain were evaluated using CLSM, SEM, HPLC and other biochemical methods The results showed that HgAL could effectively inhibit the production of pyocyanin and extracellular matrix, as well as reduce the adherence ability and biofilm formation of Pseudomonas aeruginosa. Inhibition of virulence is attributed to the suppressive effect of HgAL on biosynthesis of 3-oxo-C12-HSLand C4-HSL（two kinds of QS signaling molecules in P. aeruginosa）. Our results support HgAL as a potential agent for prevention of BAI in the healthcare settings.展开更多
Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To invest...Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.展开更多
BACKGROUND There is recently a concern regarding the reinfection and reactivation of previously reCoVered coronavirus disease 2019(CoVID-19)patients.AIM To summarize the recent findings and reports of CoVID-19 reinfec...BACKGROUND There is recently a concern regarding the reinfection and reactivation of previously reCoVered coronavirus disease 2019(CoVID-19)patients.AIM To summarize the recent findings and reports of CoVID-19 reinfection in patients previously reCoVered from the disease.METHODS This study was a systematic review of current evidence conducted in August 2020.The authors studied the probable reinfection risk of novel coronavirus(CoVID-19).We performed a systematic search using the keywords in online databases.The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)checklist to ensure the reliability and validity of this study and results.RESULTS We reviewed 31 studies.Eight studies described reCoVered patients with reinfection.Only one study reported reinfected patients who died.In 26 studies,there was no information about the status of the patients.Several studies indicated that reinfection is not probable and that post-infection immunity is at least temporary and short.CONCLUSION Based on our review,we concluded that a positive polymerase chain reaction retest could be due to several reasons and should not always be considered as reinfection or reactivation of the disease.Most relevant studies in positive retest patients have shown relative and probably temporary immunity after the reCoVery of the disease.展开更多
Myopia and astigmatism, two common refractive errors frequently co-exist, are degrading vision at all working distances in populations worldwide. Eyeballs having high degrees of myopia and astigmatism are known to exh...Myopia and astigmatism, two common refractive errors frequently co-exist, are degrading vision at all working distances in populations worldwide. Eyeballs having high degrees of myopia and astigmatism are known to exhibit abnormal eye shape at the anterior and posterior eye segments, but whether the outer coats of these abnormal eyeballs, cornea anteriorly and sclera posteriorly, are regulated by region-specific molecular mechanism remains unclear. Here we presented the changes in eye shape and mRNA expression levels of three genes (MMP2, TIMP2, and TGFB2), all known to participate in extracellular matrix organization, at five regions of the cornea and sclera in chickens developing high myopia and astigmatism induced by form deprivation. Our results showed that, compared to normal chicks, the highly myopic-astigmatic chicks had significantly astigmatic cornea, deeper anterior chamber, longer axial length, and higher expressions of all three genes in the superior sclera. These results imply that local molecular mechanism may manipulate the eye’s structural remodeling across the globe during refractive eye growth.展开更多
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
基金This work was supported by the National Natural Science Foundation of China(Nos.81403066 and 81473417).
文摘Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.
基金supported by the Research Grant Council of Hong Kong (PolyU5317/05E, PolyU5331/07E, PolyU5352/08E)
文摘In spite of ill-effects of high heel shoes, they are widely used for women. Hence, it is essential to understand the load transfer biomechanics in order to design better fit and comfortable shoes. In this study, both experimental measurement and finite element analysis were used to evaluate the biomechanical effects of heel height on foot load transfer. A controlled experiment was conducted using custom-designed platforms. Under different weight-bearing conditions, peak plantar pressure, contact area and center of pressure were analyzed. A three-dimensional finite element foot model was used to simulate the high-heel support and to predict the internal stress distributions and deformations for different heel heights. Results from both experiment and model indicated that heel elevations had significant effects on all variables. When heel elevation increased, the center of pressure shifted from the midfoot region to the forefoot region, the contact area was reduced by 26% from 0 to 10.2 cm heel and the internal stress of foot bones increased. Prediction results also showed that the strain and total tension force of plantar fascia was minimum at 5.1 cm heel condition. This study helps to better understand the biomechanical behavior of foot, and to provide better suggestions for design parameters of high heeled shoes.
基金Project supported by the National Natural Science Foundation of China(No.30600693)the Qianjiang Talent Project of Zhejiang Province(No.2010R10068)the Hong Kong Polytechnic University(No.J-BB7P),China
文摘Retinoic acid level in the retina/choroid is altered in induced myopia models.All-trans-retinol dehydrogenase(RDH8) is an important enzyme of retinoic acid metabolism.This study aimed to investigate the association of the RDH8 gene with high myopia.Three single nucleotide polymorphisms(SNPs) [RDH851(rs2233789) ,RDH8E5a(rs1644731) ,and RDH855b(rs3760753) ]were selected,based on the linkage disequilibrium pattern of RDH8 from a previous study,and genotyped for 160 Han Chinese nuclear families with highly myopic(-10 diopters or worse) offspring as well as in an independent group with 166 highly myopic cases(-10 diopters or worse) and 211 controls. Family-based association analysis was performed using the family-based association test(FBAT) package,and genotype relative risk(GRR) was calculated using the GenAssoc program.Population-based association analysis was performed using Chi-square test.These SNPs were in linkage equilibrium with each other.SNPs RDH851(rs2233789) and RDH8E5a(rs1644731) both did not show association with high myopia.SNP RDH855b(rs3760753) demonstrated significant association(P=0.0269) with a GRR of 0.543(95%confidence interval=0.304-0.968,P=0.038) .The association became statistically insignificant,however,after multiple comparison correction.Haplotype analysis did not show a significant association either.Population-based association analysis also showed no significant association(P>0.05) .Our family-and population-based data both suggest that the RDH8 gene is unlikely to be associated with high myopia in Chinese.
基金supported by the National Natural Science Foundation of China grant (NSFC81970247)。
文摘Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.
基金support from the National Natural Science Foundation of China(Grants No.82304827,82074098,81841001)the Fundamental Research Funds for the Central public welfare research institutes(ZZ13-ZD-07),the National Key Research and Development Programof China(2020YFA0908000,2022YFC2303600)+7 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No:ZYYCXTD-C-202002)The Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation(B2302051)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grants No.ZZ13-YQ-108)the Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002)Supported by Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034)Supported by Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234)Supported by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(NO.SZGSP001).
文摘Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.
基金The project supported by the Hong Kong Polytechnic University Research Grants(G-U273) the National Natural Science Foundation of China(10502021 and 10529202)
文摘The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography （micro-CT） system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions （transverse directions） were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels： stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.
文摘Background:The prevalence of MRSA(Methicillin-resistant Staphylococcus aureus)colonized wounds in home care residents is expected to grow continuously as a result of the substantial proportion of older people requiring institutionalized care due to chronic disease and declining functional status,which contribute to more frequent skin breakdown and wound formation.Tea tree oil has been claimed to have anti-bacterial,analgesic and anti-inflammatory effects that have been suggested in many in-vitro studies to have good efficacy against MRSA.The aims of this study were to evaluate the effectiveness of 10%topical tea tree preparation to eradicateMRSA and to ascertain its influence on wound healing forMRSA-colonized wounds.Methods:It was a randomized controlled trial,single-blind study.Those with stage II or above MRSA-colonized wounds and who had given their informed consent formed the sample.The determined sample sizewasbasedonthe effect size of our previouspilot study,whichwas 0.46.Five outcome measurements were taken for the MRSA bacterial count and wound healing condition at baseline and at 1-week intervals during the 4-week dressing intervention period.Results:Thirty-two participants were recruited from two non-government nursing homes,16 in the control group and 16 in the tea tree oil group.The control group residents received routine saline gauze dressing,while the tea tree oil group residents received the 10%topical tea tree preparation dressing.In the tea tree oil group,all chronic wounds that had previously been delayed in healing were healed within 28 days without adverse reaction.MRSA was also completely eradicated in 14(87.5%)out of 16 wounds in the group receiving the 10%topical tea tree preparation.
基金supported by grants from the National Natural Science Foundation of China(81800245,81970228,82102306,81900779)the China Postdoctoral Science Foundation(2020M670030ZX)+1 种基金the Shaoguan Science and Technology Program(2019sn078)the Start-up Fund for RAPs under the Strategic Hiring Scheme(P0035913)。
文摘The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
基金financially supported by the National Natural Science Foundation of China (Nos. 22179031 and 22109111)the Natural Science Foundation of Zhejiang Province (Nos. LY22B030008 and LQ22B030006)+3 种基金the Collaborative Innovation Center of Suzhou Nano Science & Technology, the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the 111 Projectthe Open Research Fund of CNMGE Platform & NSCC-TJ (No. CNGME202101006)the support from Hefei advanced computing center。
文摘Redox-active organic materials are emerging as the new playground for the design of new exciting battery materials for rechargeable batteries because of the merits including structural diversity and tunable electrochemical properties that are not easily accessible for the inorganic counterparts.More importantly,the sustainability developed by using naturally abundant chemical elements(C,H,N,O and S) makes them as an ideal alternative material for Li-ion batteries(LIBs).However,the identification and screening of proper organic materials is still challenging in the past decades.Assisted by the artificial intelligence,this review will give a summary of the theoretical design aspects of redox-active organic materials from densityfunctional theory(DFT) to machine learning(ML) methods in the past two decades,with a particular emphasis on the calculation method to predict the chemical/electrochemical stability and reversibility.This review will also analyze and discuss the challenges and perspectives for the development of organic battery materials.
文摘Using the software Anybody Modeling System, a human static-standing musculoskeletal model based on inverse dynamics is presented, which are defined as segments, muscles and joints as dements. Simulation is based on data obtained from experiments using motion capture system VICADN and force plate AMTI. In the model AnyBody Modeling System is introduced to help solve the redundancy problem and obtain results of muscle activities, muscle forces and joint forces. From the model, hip and knee joint forces could be analyzed under normal standing posture. Also, activities of the musculus rectus femoris and several other muscles of the lower limbs can be obtained. From the results it could be concluded that stresses at joints are much stronger than theoretical reasoning because of the functions of relevant soft tissues such as muscles, tendons and so on. Results show that joint forces from the simulations are in good conformation with previous experimental researches. And this complicated model would be of use for better understanding human body functions.
基金supported in part by the National Natural Science Foundation of China(82072019)the Shenzhen Basic Research Program(JCYJ20210324130209023)+5 种基金the Shenzhen-Hong Kong-Macao S&T Program(Category C)(SGDX20201103095002019)the Mainland-Hong Kong Joint Funding Scheme(MHKJFS)(MHP/005/20),the Project of Strategic Importance Fund(P0035421)the Projects of RISA(P0043001)from the Hong Kong Polytechnic University,the Natural Science Foundation of Jiangsu Province(BK20201441)the Provincial and Ministry Co-constructed Project of Henan Province Medical Science and Technology Research(SBGJ202103038,SBGJ202102056)the Henan Province Key R&D and Promotion Project(Science and Technology Research)(222102310015)the Natural Science Foundation of Henan Province(222300420575),and the Henan Province Science and Technology Research(222102310322).
文摘Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.
基金Supported by Del Obelske Familiefond,Spar Nord Fonden,Peter TΦfting og Dagmar TΦftings Fund and North Jutland County Research Fund。
文摘TIM： To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS： Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale （VAS）. The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anticholinergic drug butylscopolamine. RESULTS： The stimulus-response （volume-VAS） curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION： The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.
基金The work was supported by a grant from Ministry of Human Resource Development,Government of India,through the University Grants Commission to University of Mysore,under the Institution of Excellence scheme.
基金This research received funding from Department of Biotechnology and Genetic Engineering,Faculty of Applied Science and Technology,Islamic University,Kushtia,7003,Bangladesh.The authors would like to thank Dr.Jahangir Alam and Professor Dr.Md.Anwarul Haque who helped with sample collection,analysis and critical revision of the manuscript.
文摘Metabolic changes together with cardiovascular and hepatic factors are related to the development of diseases like myocardial lipidosis,heart disease,and profound toxicity.The aim of this animal study is to determine the effects of high erucic acid containing rapeseed oil(Brassica napus L.)varieties on liver,kidney and heart muscles in Wistar rats.Male Wistar rats were divided into three groups where each group containing four rats.Group A was considered as control diet group,while Group B rapeseed wild oil group and Group C rapeseed hybrid oil group were considered as experimental diet groups.The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),creatine kinase-MB(CK-MB)and creatinine of two experimental groups were significantly elevated while compared to the control groups(p<0.05–0.001).Nevertheless,an increment in weight retardation(p<0.05)was also observed in rapeseed hybrid oil treated groups.No significant weight retardation found in other two groups(p>0.05).Noticeable tissue injury observed in this study is a sign of the relative toxicity of erucic acid containing rapeseed oil to mammalian species.The use of Brassica napus as a supplementary feed ingredient should be,therefore,thoroughly considered.
基金supported by Areas of Excellence (AoE/P-705/16)the General Research Fund,Hong Kong SAR (GRF No.777313 M)。
文摘Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions.Newly-generated neurons in the subventricular zone migrate to the olfactory bulb(OB) and determine olfactory discrimination,but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear.Our previous study indicated the potential of APPL2(adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system.In the present study,we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells(NSCs) and an in vivo animal model-APPL2 transgenic(Tg) mice.In the in vitro study,we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis.In the in vivo study,APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system,including the corpus callosum,OB,and rostral migratory stream.Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice.Furthermore,we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors.In conclusion,APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.
基金supported by the National Natural Science Foundation of China (Nos. 81401512, 41606186)the Scientific Research Fund of Hunan Provincial Education Department (No. 14B157)+1 种基金China Postdoctoral Science Foundation (No. 2016M602419)the Hong Kong Scholars Program (No. XJ2015022)
文摘Bacterial quorum sensing（QS） molecules are involved in the coordination of certain behaviors such as biofilm formation, virulence and antibiotic resistance. QS molecules（autoinducers） and their corresponding receptors have been recognized as important therapeutic targets for drug-resistant infections and biofilm-associated infections（BAI）. This study assessed the multiple biological effects of homogentisic acid y-lactone（HgAL）, a furanone derivative. The anti-QS and anti-biofilm effects of HgAL against PAO1 strain were evaluated using CLSM, SEM, HPLC and other biochemical methods The results showed that HgAL could effectively inhibit the production of pyocyanin and extracellular matrix, as well as reduce the adherence ability and biofilm formation of Pseudomonas aeruginosa. Inhibition of virulence is attributed to the suppressive effect of HgAL on biosynthesis of 3-oxo-C12-HSLand C4-HSL（two kinds of QS signaling molecules in P. aeruginosa）. Our results support HgAL as a potential agent for prevention of BAI in the healthcare settings.
基金funded by the National Natural Science Foundation of China(32100880)Guangzhou Municipal Key Discipline in Medicine(2021-2023)Guangzhou High-level Clinical Key Specialty and Guangzhou Research-oriented Hospital.
文摘Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.
文摘BACKGROUND There is recently a concern regarding the reinfection and reactivation of previously reCoVered coronavirus disease 2019(CoVID-19)patients.AIM To summarize the recent findings and reports of CoVID-19 reinfection in patients previously reCoVered from the disease.METHODS This study was a systematic review of current evidence conducted in August 2020.The authors studied the probable reinfection risk of novel coronavirus(CoVID-19).We performed a systematic search using the keywords in online databases.The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)checklist to ensure the reliability and validity of this study and results.RESULTS We reviewed 31 studies.Eight studies described reCoVered patients with reinfection.Only one study reported reinfected patients who died.In 26 studies,there was no information about the status of the patients.Several studies indicated that reinfection is not probable and that post-infection immunity is at least temporary and short.CONCLUSION Based on our review,we concluded that a positive polymerase chain reaction retest could be due to several reasons and should not always be considered as reinfection or reactivation of the disease.Most relevant studies in positive retest patients have shown relative and probably temporary immunity after the reCoVery of the disease.
文摘Myopia and astigmatism, two common refractive errors frequently co-exist, are degrading vision at all working distances in populations worldwide. Eyeballs having high degrees of myopia and astigmatism are known to exhibit abnormal eye shape at the anterior and posterior eye segments, but whether the outer coats of these abnormal eyeballs, cornea anteriorly and sclera posteriorly, are regulated by region-specific molecular mechanism remains unclear. Here we presented the changes in eye shape and mRNA expression levels of three genes (MMP2, TIMP2, and TGFB2), all known to participate in extracellular matrix organization, at five regions of the cornea and sclera in chickens developing high myopia and astigmatism induced by form deprivation. Our results showed that, compared to normal chicks, the highly myopic-astigmatic chicks had significantly astigmatic cornea, deeper anterior chamber, longer axial length, and higher expressions of all three genes in the superior sclera. These results imply that local molecular mechanism may manipulate the eye’s structural remodeling across the globe during refractive eye growth.
