Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electro...Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electrocatalytic oxidations of saturated alcohols(C_(1)-C_(6))to selectively form formate using Ni Co hydroxide(Ni Co-OH)derived Ni Co_(2)O_(4)solid-acid electrocatalysts with balanced Lewis acid(LASs)and Brønsted acid sites(BASs).Thermal treatment transforms BASs-rich(89.6%)Ni Co-OH into Ni Co_(2)O_(4)with nearly equal distribution of LASs(53.1%)and BASs(46.9%)which synergistically promote adsorption and activation of OH-and alcohol molecules for enhanced oxidation activity.In contrast,BASs-enriched Ni Co-OH facilitates formation of higher valence metal sites,beneficial for water oxidation.The combined experimental studies and theoretical calculation imply the oxidation ability of C1-C6alcohols increases as increased number of hydroxyl groups and decreased HOMO-LUMO gaps:methanol(C_(1))<ethylene glycol(C_(2))<glycerol(C3)<meso-erythritol(C4)<xylitol(C5)<sorbitol(C6),while the formate selectivity shows the opposite trend from 100 to 80%.This study unveils synergistic roles of LASs and BASs,as well as hydroxyl group effect in electro-upgrading of alcohols using solid-acid electrocatalysts.展开更多
AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This o...AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This observational clinical study utilized a cross-sectional and prospective design,focusing on chronic alcohol consumers alongside a non-consuming control group.OCT/OCTA imaging parameters including central retinal subfield thickness(CST),subfoveal choroidal thickness(SCT),foveal avascular zone(FAZ)and vessel density(VD)in the superficial and deep capillary plexuses in both the macular and optic disc(OD)regions were recorded.Data were analyzed using SPSS 15.0;descriptive statistics were reported,group comparisons were performed with Chisquare,Kruskal–Wallis,and Bonferroni-corrected Mann–Whitney U tests,and relationships were assessed using Spearman correlation,with statistical significance set at P<0.05.RESULTS:A total of 160 eyes of 160 participants(110 females and 50 males with mean age 38.7±9.9y)who don’t smoke were divided into five groups:never,occasional,monthly,weekly and daily drinkers.The mean CST was 216.6±14.2μm and the mean SCT was 358.9±84.5μm.There was no statistically significantly difference in CST and SCT among the groups(P=0.890,0.799).Foveal superficial capillary plexuses(SCPs)VD was higher in monthly drinkers compared to occasional drinkers(P=0.015).Foveal VD in deep capillary plexus was also higher in monthly drinkers than in never and occasional drinkers(P=0.004,0.006).Nasal SCPs VD at the OD was higher in monthly drinkers compared to never drinkers(P=0.005).There was no significant difference FAZ area among the groups(P=0.071).CONCLUSION:Both superficial and deep microvascular structures in the inferior quadrants of macula are positively correlated with frequency of alcohol use.Also in our study results is that the monthly drinker group has uniquely higher VDs in both macula and OD.This leads us to consider moderate alcohol consumption may also have protective effects on retinal microcirculation.展开更多
This review highlights the performance enhancement of polyvinyl alcohol(PVA)composites through the incorporation of nanofillers,focusing on mechanical,thermal,electrical and piezoelectric improvements.It examines bio-...This review highlights the performance enhancement of polyvinyl alcohol(PVA)composites through the incorporation of nanofillers,focusing on mechanical,thermal,electrical and piezoelectric improvements.It examines bio-based fillers such as nanocellulose cellulose nanofibrils(CNF)and cellulose nanocrystals(CNC),and carbon-based fillers like graphene nanoplatelets(GNP)and carbon nanotubes(CNT).CNF and CNC increase tensile strength by up to 40%and 17.9%,respectively,due to their ability to reinforce polymer networks.CNC also improves thermal stability,raising degradation temperatures to approximately 327℃through enhanced hydrogen bonding.Electrical and piezoelectric properties are significantly improved,with dielectric behaviour enhanced by up to 107%and open-circuit voltage reaching 25.6 V,suitable for energy harvesting.GNP and CNT contribute by forming conductive networks within the PVA matrix,enabling superior electrical conductivity and consistent piezoresistive responses under strain.These characteristics make such composites ideal for applications in flexible electronics,sensors,structural health monitoring and other advanced fields.This synthesis of experimental results and critical insights underscores the broad utility and future potential of nanofillerenhanced PVA composites across aerospace,automotive,healthcare,and defence sectors.展开更多
Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National In...Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.展开更多
Alcohol-associated liver disease(ALD)is a rapidly increasing indication for liver transplantation(LT)globally with a significant rise in transplants for ALD with limited sobriety including patients with alcohol-associ...Alcohol-associated liver disease(ALD)is a rapidly increasing indication for liver transplantation(LT)globally with a significant rise in transplants for ALD with limited sobriety including patients with alcohol-associated hepatitis(AH).This evolution challenges the older paradigm that mandates prolonged periods of alcohol abstinence prior to LT.Due to the limited armamentarium of effective pharmacotherapy to treat severe AH,the mortality rates are significantly higher when LT is not available.In the patients who are transplanted for ALD with limited sobriety including AH,patient and graft survival are equivalent,if not better,compared to patients transplanted for other etiologies.However,due to the risk of alcohol relapse and other psychosocial factors,public opinion regarding early LT may continue to impact how the field moves forward particularly regarding organ stewardship and the need for equitable allocation of organs.Numerous tools for psychosocial evaluations have been developed to assist liver transplant teams to identify appropriate patients in a more uniform manner.In this review,we aim to assess the available evidence to support early LT for alcohol AH and propose directions for the future as the field continues to evolve.展开更多
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic ...Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.展开更多
Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, en...Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.展开更多
BACKGROUND Alcohol can cause alcoholic fatty liver,alcoholic steatohepatitis,alcoholic liver cirrhosis(ALC),and hepatocellular carcinoma.China has become the secondlargest country in the world in terms of alcohol cons...BACKGROUND Alcohol can cause alcoholic fatty liver,alcoholic steatohepatitis,alcoholic liver cirrhosis(ALC),and hepatocellular carcinoma.China has become the secondlargest country in the world in terms of alcohol consumption,lacking national epidemiological data on alcoholic liver disease(ALD).AIM To understand the incidence and characteristics of ALD in Hainan Province of China.METHODS From October 2022 to April 2023,a stratified proportional multi-stage whole population sampling method was adopted to select permanent residents of Haikou,Sanya,Qionghai,Dongfang,and Wuzhishan in Hainan Province to carry out questionnaire surveys,blood tests,and ultrasound examinations of the liver.RESULTS A total of 2704 valid questionnaires were obtained from residents aged 15-93 years old.The rates of drinking,hazardous drinking,and harmful drinking were 31.73%,14.53%,and 5.03%,respectively.The above rates were higher for males than for females,increasing with income,and the rates for ethnic minorities,such as Li,were higher than for Han Chinese(P<0.05).Drinking rates increased with literacy(P<0.05).Drinking rate and hazardous drinking rate decreased with age,were higher for residents of agricultural households than non-agricultural households,and higher for married than unmarried individuals(P<0.05).The total number of patients with ALD was 142,with a detection rate of 5.25%.ALD detection rate was higher for males than females,decreased with age,and higher with income(P<0.05).Patients with ALD included 48(33.8%)cases of mild ALD,64(45.1%)cases of alcoholic fatty liver,18(12.7%)cases of alcoholic steatohepatitis,and 12(8.5%)cases of ALC.The proportion of those who consumed more than 80 g of alcohol per day increased as they progressed from mild ALD to ALC stage.Diabetes mellitus and hyperlipidemia were easily combined in some cases,accounting for 25(17.6%)and 80(56.3%),respectively.The average daily alcohol consumption of ALD patients of Li ethnicity≥80 g was significantly more than that of Han ethnicity(χ2=5.652,P=0.02),and was predominantly among those who drank large amounts of alcohol intermittently(χ2=89.093,P<0.001).CONCLUSION The rates of drinking,hazardous drinking,harmful drinking,and detection of ALD in Hainan Province need to be paid attention to by advocating a healthy lifestyle,such as abstinence and limiting alcohol consumption.展开更多
Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenol...Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.展开更多
BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scor...BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scores,in addition to identifying reliable predictors of complications and mortality such as renal dysfunction and nutritional status.AIM To identify predictors of complications and mortality in AH,particularly focusing on demographics,renal involvement,underlying liver disease,and nutrition.METHODS This is a retrospective analysis of patients admitted to a large urban tertiary care center with AH from 2020 to 2022.Receiver operating characteristics(ROC)curve analysis was conducted to compare established prognostic scores with Lille scores from day 3 to day 7(LM3-7).Logistic regression equations were conducted to identify predictor variables.RESULTS Severe AH(SAH)as defined by Maddrey’s discriminant function≥32 was diagnosed in 150 out of 425 patients with AH.LM3-7 had 28-day mortality rates in the responder group of 7%-11%,while in the non-responder group,mortality rates were approximately 38%-42%.LM3-7 had 90-day mortality rates in the responder group of 12%to 17%,while in the non-responder group,mortality rates were 48%-53%.Furthermore,all LM3-7 scores showed comparable efficacy in predicting mortality using ROC curve analysis;Area under ROC ranged from 0.771 to 0.802 for 28-day mortality and 0.743 to 0.809 for 90-day mortality.Regarding complications and mortality in AH,significant predictors included poor nutritional status,underlying cirrhosis,and acute renal dysfunction.CONCLUSION LM3-6 is as accurate as LM7 in predicting corticosteroid efficacy for 28-day and 90-day mortality in patients with SAH.Holding glucocorticoids early during the disease course can prevent unnecessary complications.展开更多
Chinese Wine Culture influences people’s attitudes toward alcohol.The current study focuses on exploring the main features of a localized digital alcohol consumption intervention mini-program to address the difficult...Chinese Wine Culture influences people’s attitudes toward alcohol.The current study focuses on exploring the main features of a localized digital alcohol consumption intervention mini-program to address the difficulties of abstinence for native drinkers,as a promising way for long-term management of rehabilitation from alcohol use disorder.A mixed-method approach was used in this study.The self-report quantitative questionnaire recruited three groups of participants:89 drinkers,67 drinkers’relatives,and 30 medical staff.The focus group qualitative interview inspected 36 participants’perspectives on the core topics,including 21 drinkers,4 drinkers’relatives,and 11 medical staff.The results of combining the quantitative study and qualitative study indicated that the top difficulties of abstinence for native drinkers are the strong craving from the inside,the environmental influence,and the psychological health status,especially emotional states.Correspondingly,the most desired main features in an alcohol consumption digital intervention tool are the daily track of drinking conditions and craving level,periodic feedback reports that can share with others,and mood improvement training.Moreover,the top factors that influence participants’intention to use/recommend the tool are whether the tool is effective,whether the user experience is good,and whether the tool can replenish the deficiency of the current alcohol treatment.Future work needs to balance what patients want and what others around them expect,so that potential users can benefit best from the digital intervention tool in the context of Chinese culture.展开更多
BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term ...BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term impact of available therapies remains unclear.This systematic review provides a critical evaluation of treatments for SAH,specifically focusing on survival or mortality at 90 days as an essential window that captures short-and mid-term outcomes.The 90-day window is clinically significant,as it reflects the remission of systemic inflam-mation,early liver recovery,and minimizes confounding long-term behaviors such as alcohol relapse.AIM To review the effect of different treatments for SAH on survival and mortality at 90 days.METHODS A systematic search of PubMed and EMBASE(last updated March 2025)was performed without language restrictions,focusing on studies published in the last decade.Study selection and data extraction were performed independently by at least two reviewers.Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools.Due to heterogeneity in study designs and interventions,a meta-analysis was not feasible.A qualitative synthesis was conducted using narrative summaries and evidence tables.RESULTS Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE.Of these 2161 studies,618 were duplicates and therefore removed.A total of eight studies were included in qualitative synthesis.Among the included publications,six were randomized control trials(RCT)and two were retrospective cohort studies.These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids(n=2),pentoxifylline(n=1),anakinra plus zinc(n=2),granulocyte colony-stimulating factor(n=1),amoxicillin-clavulanate(n=1),fecal microbiota transplantation(n=1)or extracorporeal liver assist device(n=1).While most studies were conducted in Western countries,two had a global scope.CONCLUSION Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit.These results highlight the need for multicenter,biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.展开更多
BACKGROUND Patients and providers are often unaware of available treatment options for alcohol use disorder(AUD)and how to pursue them.AIM To improve AUD treatment rates using an educational video module(EVM).METHODS ...BACKGROUND Patients and providers are often unaware of available treatment options for alcohol use disorder(AUD)and how to pursue them.AIM To improve AUD treatment rates using an educational video module(EVM).METHODS Prospective single-center cohort study evaluating the impact of a novel interactive patient EVM in promoting AUD treatment among hospitalized patients with alcohol-associated liver disease.Treatment was defined as receiving medication or participating in psychosocial treatment within 30 days of discharge.Primary outcome was change in treatment rates after viewing the EVM compared to a retrospective control cohort.Secondary outcomes were predictors of receiving treatment,EVM feedback,30-day hospital readmission,outpatient follow-up,return to alcohol use,and mortality.RESULTS Forty-two patients were included.Mean age was 45 years,50%were female,and mean model for end-stage liver disease score 15.5.After viewing the EVM,treatment rates increased for pharmacologic(50%vs 22%,P=0.0008)and psychosocial treatment(73.8%vs 44%,P=0.01).Return to alcohol use was significantly lower(7.9%vs 35.6%,P=0.003).All 100%of patients would recommend the EVM.CONCLUSION EVM allows hospitalized patients to receive standardized education about AUD treatment.This may address patient and provider knowledge gaps and reduce the growing burden of alcohol-associated liver disease.Future studies should evaluate EVM in larger patient populations using a multi-center study design.展开更多
Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by ...Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.展开更多
BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the rol...BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.展开更多
BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increas...BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.展开更多
Engineering nanomaterials at single-atomic sites could enable unprecedented catalytic properties for broad applications,yet it remains challenging to do so on the surface of multimetallic nanocrystals.Herein,we presen...Engineering nanomaterials at single-atomic sites could enable unprecedented catalytic properties for broad applications,yet it remains challenging to do so on the surface of multimetallic nanocrystals.Herein,we present the multifactorial engineering(size,shape,phase,and composition)of the fully ordered PtBi nanoplates at atomic level,achieving a unique catalyst surface where the face-centered cubic(fcc)Pt edges are modified by the isolated Pd atoms and BiO_(x)adatoms.This Pd_(1)/Pt-BiO_(x)electrocatalyst exhibits an ultrahigh mass activity of 16.01 A mg^(-1)Pt+Pd toward ethanol oxidation in alkaline electrolyte and enables a direct ethanol fuel cell of peak power density of 56.7 mW cm^(−2).The surrounding BiO_(x)adatoms are critical for mitigating CO-poisoning on the Pt surface,and the Pd_(1)/Pt single-atom alloy further facilitates the electrooxidation of CH_(3)CH_(2)OH.This work offers new insights into the rational design and construction of sophisticated catalyst surface at single-atomic sites for highly efficient electrocatalysis.展开更多
Objectives:Cold-acclimated organisms accumulate low molecular weight organic solutes such as sugar alcohols and soluble sugars.This study aimed to compare the efficacy of five sugar alcohols and 14 soluble sugars in s...Objectives:Cold-acclimated organisms accumulate low molecular weight organic solutes such as sugar alcohols and soluble sugars.This study aimed to compare the efficacy of five sugar alcohols and 14 soluble sugars in stabilizing proteins under freezing,freeze-drying,and air-drying stresses.Materials and methods:Glucose-6-Phosphate Dehydrogenase(G6PD)was used as the model protein.G6PD solutions with or without sugar alcohols and or sugars were subjected to freezing,freeze-drying,and air-drying stresses.The recovery of G6PD activity was measured to evaluate the protective efficacy of these compounds.Results:Without stabilizers,freezing G6PD at-20℃ or-80℃ reduced enzyme activity by around 24%,while freeze-drying or air-drying reduced activity by 90%-95%.Among the five sugar alcohols tested,pinitol,quebrachitol and sorbitol stabilized G6PD,whereas mannitol and myo-inositol destabilized it.Among 14 soluble sugars,trehalose and raffinose showed slightly lower enzyme recovery after repeated freeze-thaw cycles at-20℃.Most soluble sugars(except arabinose and xylose)protected G6PD during freeze-drying,with di-,tri-,and oligosaccharides generally outperforming monosaccharides.During air-drying,lactose was ineffective,while arabinose,galactose,and xylose were detrimental.Conclusion:The study highlights the diverse mechanisms of sugar alcohols and sugars in protein stabilization under stress,offering insights for formulating stable protein-and cell-based drugs.展开更多
Phase change absorbents based on amine chemical absorption for CO_(2)capture exhibit energy-saving potential,but generally suffer from difficulties in CO_(2)regeneration.Alcohol,characterized as a protic reagent with ...Phase change absorbents based on amine chemical absorption for CO_(2)capture exhibit energy-saving potential,but generally suffer from difficulties in CO_(2)regeneration.Alcohol,characterized as a protic reagent with a low dielectric constant,can provide free protons to the rich phase of the absorbent,thereby facilitating CO_(2)regeneration.In this investigation,N-aminoethylpiperazine(AEP)/sulfolane/H_(2)O was employed as the liquid-liquid phase change absorbent,with alcohol serving as the regulator.First,appropriate ion pair models were constructed to simulate the solvent effect of the CO_(2)products in different alcohol solutions.The results demonstrated that these ion pair products reached the maximum solvation-free energy(△E_(solvation))in the rich phase containing ethanol(EtOH).Desorption experiment results validated that the inclusion of EtOH led to a maximum regeneration rate of 0.00763 mol/min,thus confirming EtOH’s suitability as the preferred regulator.Quantum chemical calculations and^(13)C NMR characterization were performed,revealing that the addition of EtOH resulted in the partial conversion of AEP-carbamate(AEPCOO−)into a new product known as ethyl carbonate(C_(2)H_(5)OCOO−),which enhanced the regeneration reactivity.In addition,the decomposition paths of different CO_(2)products were simulated visually,and every reaction’s activation energy(△E_(act))was calculated.Remarkably,the△E_(act)for the decomposition of C_(2)H_(5)OCOO−(9.465 kJ/mol)was lower than that of the AEPCOO−(26.163 kJ/mol),implying that CO_(2)was more likely to be released.Finally,the regeneration energy consumption of the alcohol-regulated absorbentwas estimated to be only 1.92 GJ/ton CO_(2),which had excellent energy-saving potential.展开更多
Photoredox dual reaction of organic synthesis and H2 evolution opens up a novel pathway for collaboratively generating clean fuels and high-quality chemicals,providing a more effective approach of solar energy convers...Photoredox dual reaction of organic synthesis and H2 evolution opens up a novel pathway for collaboratively generating clean fuels and high-quality chemicals,providing a more effective approach of solar energy conversion.Herein,a surface defect-engineered ZnCoS/ZnCdS heterostructure with zinc blende(ZB)/wurtzite(WZ)phase junctions is synthesized for photocatalytic cooperative coupling of benzaldehyde(BAD)and H_(2) production.This surface defect-engineered ZnCoS/ZnCdS heterostructure elaborately integrates the mixed phase junction advantage of ZnCdS semiconductor and the cocatalytic function of ZnCoS possessing Zn(VZn-ZnCoS/ZnCdS)or S vacancies(VS-ZnCoS/ZnCdS).The optimum VS-ZnCoS/ZnCdS simultaneously exhibits a superior H2 production rate of 14.23 mmol h^(-1) g^(-1) accompanied with BAD formation rate of 12.29 mmol h^(-1) g^(-1) under visible-light irradiation,which is approximately two-fold greater than that of pristine ZnCdS.Under simulated sunlight irradiation(AM 1.5),VS-ZnCoS/ZnCdS achieves H2 evolution(27.43 mmol gcat^(-1) h^(-1))with 0.52%of STH efficiency,accompany with 26.31 mmol gcat^(-1) h^(-1) of BAD formation rate.The underlying solar-driven mechanism is elucidated by a series of in-situ characterization and control experiments,which reveals the synergistic effect of interfacial ZB/WZ phase junctions in ZnCdS and S vacancies of ZnCoS on enhancement of the photoredox dual reaction.The VS-ZnCoS/ZnCdS follows a predominant oxygen-centered radical integrating with carbon-centered radical pathways for BAD formation and a simultaneous electron-driven proton reduction for H_(2) production.Interestingly,the nature of surface vacancies not only facilitates the separation of photoinduced charge carriers but also able to selectively adjust the mechanism pathway for BAD production via tuning the oxygen-centered radical and carbon-centered radical formation.展开更多
基金the financial support from the National Natural Science Foundation of China(52172110,52472231,52311530113)Shanghai"Science and Technology Innovation Action Plan"intergovernmental international science and technology cooperation project(23520710600)+1 种基金Science and Technology Commission of Shanghai Municipality(22DZ1205600)the Central Guidance on Science and Technology Development Fund of Zhejiang Province(2024ZY01011)。
文摘Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electrocatalytic oxidations of saturated alcohols(C_(1)-C_(6))to selectively form formate using Ni Co hydroxide(Ni Co-OH)derived Ni Co_(2)O_(4)solid-acid electrocatalysts with balanced Lewis acid(LASs)and Brønsted acid sites(BASs).Thermal treatment transforms BASs-rich(89.6%)Ni Co-OH into Ni Co_(2)O_(4)with nearly equal distribution of LASs(53.1%)and BASs(46.9%)which synergistically promote adsorption and activation of OH-and alcohol molecules for enhanced oxidation activity.In contrast,BASs-enriched Ni Co-OH facilitates formation of higher valence metal sites,beneficial for water oxidation.The combined experimental studies and theoretical calculation imply the oxidation ability of C1-C6alcohols increases as increased number of hydroxyl groups and decreased HOMO-LUMO gaps:methanol(C_(1))<ethylene glycol(C_(2))<glycerol(C3)<meso-erythritol(C4)<xylitol(C5)<sorbitol(C6),while the formate selectivity shows the opposite trend from 100 to 80%.This study unveils synergistic roles of LASs and BASs,as well as hydroxyl group effect in electro-upgrading of alcohols using solid-acid electrocatalysts.
文摘AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This observational clinical study utilized a cross-sectional and prospective design,focusing on chronic alcohol consumers alongside a non-consuming control group.OCT/OCTA imaging parameters including central retinal subfield thickness(CST),subfoveal choroidal thickness(SCT),foveal avascular zone(FAZ)and vessel density(VD)in the superficial and deep capillary plexuses in both the macular and optic disc(OD)regions were recorded.Data were analyzed using SPSS 15.0;descriptive statistics were reported,group comparisons were performed with Chisquare,Kruskal–Wallis,and Bonferroni-corrected Mann–Whitney U tests,and relationships were assessed using Spearman correlation,with statistical significance set at P<0.05.RESULTS:A total of 160 eyes of 160 participants(110 females and 50 males with mean age 38.7±9.9y)who don’t smoke were divided into five groups:never,occasional,monthly,weekly and daily drinkers.The mean CST was 216.6±14.2μm and the mean SCT was 358.9±84.5μm.There was no statistically significantly difference in CST and SCT among the groups(P=0.890,0.799).Foveal superficial capillary plexuses(SCPs)VD was higher in monthly drinkers compared to occasional drinkers(P=0.015).Foveal VD in deep capillary plexus was also higher in monthly drinkers than in never and occasional drinkers(P=0.004,0.006).Nasal SCPs VD at the OD was higher in monthly drinkers compared to never drinkers(P=0.005).There was no significant difference FAZ area among the groups(P=0.071).CONCLUSION:Both superficial and deep microvascular structures in the inferior quadrants of macula are positively correlated with frequency of alcohol use.Also in our study results is that the monthly drinker group has uniquely higher VDs in both macula and OD.This leads us to consider moderate alcohol consumption may also have protective effects on retinal microcirculation.
基金Ministry of Higher Education Malaysia(MoHE)and Universiti Putra Malaysia under the Fundamental Research Grant Scheme(FRGS)(Grant Nos.FRGS/1/2023/TK09/UPM/01/3 and 5540599。
文摘This review highlights the performance enhancement of polyvinyl alcohol(PVA)composites through the incorporation of nanofillers,focusing on mechanical,thermal,electrical and piezoelectric improvements.It examines bio-based fillers such as nanocellulose cellulose nanofibrils(CNF)and cellulose nanocrystals(CNC),and carbon-based fillers like graphene nanoplatelets(GNP)and carbon nanotubes(CNT).CNF and CNC increase tensile strength by up to 40%and 17.9%,respectively,due to their ability to reinforce polymer networks.CNC also improves thermal stability,raising degradation temperatures to approximately 327℃through enhanced hydrogen bonding.Electrical and piezoelectric properties are significantly improved,with dielectric behaviour enhanced by up to 107%and open-circuit voltage reaching 25.6 V,suitable for energy harvesting.GNP and CNT contribute by forming conductive networks within the PVA matrix,enabling superior electrical conductivity and consistent piezoresistive responses under strain.These characteristics make such composites ideal for applications in flexible electronics,sensors,structural health monitoring and other advanced fields.This synthesis of experimental results and critical insights underscores the broad utility and future potential of nanofillerenhanced PVA composites across aerospace,automotive,healthcare,and defence sectors.
文摘Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
文摘Alcohol-associated liver disease(ALD)is a rapidly increasing indication for liver transplantation(LT)globally with a significant rise in transplants for ALD with limited sobriety including patients with alcohol-associated hepatitis(AH).This evolution challenges the older paradigm that mandates prolonged periods of alcohol abstinence prior to LT.Due to the limited armamentarium of effective pharmacotherapy to treat severe AH,the mortality rates are significantly higher when LT is not available.In the patients who are transplanted for ALD with limited sobriety including AH,patient and graft survival are equivalent,if not better,compared to patients transplanted for other etiologies.However,due to the risk of alcohol relapse and other psychosocial factors,public opinion regarding early LT may continue to impact how the field moves forward particularly regarding organ stewardship and the need for equitable allocation of organs.Numerous tools for psychosocial evaluations have been developed to assist liver transplant teams to identify appropriate patients in a more uniform manner.In this review,we aim to assess the available evidence to support early LT for alcohol AH and propose directions for the future as the field continues to evolve.
文摘Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.
文摘Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.
基金Supported by the Hainan Medical University Academic Enhancement Support Program,No.XSTS2025001National Clinical Key Speciality Capacity Building Project,No.202330+3 种基金Hainan Province Clinical Medical Center,No.2021818Specific Research Fund of The Innovation Platform for Academicians of Hainan Province,No.YSPTZX202313Joint Project on Health Science and Technology Innovation in Hainan Province,No.SQ2023WSJK0301Hainan Province Education Reform Project,No.hnjg2024-67.
文摘BACKGROUND Alcohol can cause alcoholic fatty liver,alcoholic steatohepatitis,alcoholic liver cirrhosis(ALC),and hepatocellular carcinoma.China has become the secondlargest country in the world in terms of alcohol consumption,lacking national epidemiological data on alcoholic liver disease(ALD).AIM To understand the incidence and characteristics of ALD in Hainan Province of China.METHODS From October 2022 to April 2023,a stratified proportional multi-stage whole population sampling method was adopted to select permanent residents of Haikou,Sanya,Qionghai,Dongfang,and Wuzhishan in Hainan Province to carry out questionnaire surveys,blood tests,and ultrasound examinations of the liver.RESULTS A total of 2704 valid questionnaires were obtained from residents aged 15-93 years old.The rates of drinking,hazardous drinking,and harmful drinking were 31.73%,14.53%,and 5.03%,respectively.The above rates were higher for males than for females,increasing with income,and the rates for ethnic minorities,such as Li,were higher than for Han Chinese(P<0.05).Drinking rates increased with literacy(P<0.05).Drinking rate and hazardous drinking rate decreased with age,were higher for residents of agricultural households than non-agricultural households,and higher for married than unmarried individuals(P<0.05).The total number of patients with ALD was 142,with a detection rate of 5.25%.ALD detection rate was higher for males than females,decreased with age,and higher with income(P<0.05).Patients with ALD included 48(33.8%)cases of mild ALD,64(45.1%)cases of alcoholic fatty liver,18(12.7%)cases of alcoholic steatohepatitis,and 12(8.5%)cases of ALC.The proportion of those who consumed more than 80 g of alcohol per day increased as they progressed from mild ALD to ALC stage.Diabetes mellitus and hyperlipidemia were easily combined in some cases,accounting for 25(17.6%)and 80(56.3%),respectively.The average daily alcohol consumption of ALD patients of Li ethnicity≥80 g was significantly more than that of Han ethnicity(χ2=5.652,P=0.02),and was predominantly among those who drank large amounts of alcohol intermittently(χ2=89.093,P<0.001).CONCLUSION The rates of drinking,hazardous drinking,harmful drinking,and detection of ALD in Hainan Province need to be paid attention to by advocating a healthy lifestyle,such as abstinence and limiting alcohol consumption.
基金supported by Key Research and Development Program of Hubei Province(2022BBA0072)Applied Fundamental Frontier Project of Wuhan Science and Technology Bureau(2020020601012271)。
文摘Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.
文摘BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scores,in addition to identifying reliable predictors of complications and mortality such as renal dysfunction and nutritional status.AIM To identify predictors of complications and mortality in AH,particularly focusing on demographics,renal involvement,underlying liver disease,and nutrition.METHODS This is a retrospective analysis of patients admitted to a large urban tertiary care center with AH from 2020 to 2022.Receiver operating characteristics(ROC)curve analysis was conducted to compare established prognostic scores with Lille scores from day 3 to day 7(LM3-7).Logistic regression equations were conducted to identify predictor variables.RESULTS Severe AH(SAH)as defined by Maddrey’s discriminant function≥32 was diagnosed in 150 out of 425 patients with AH.LM3-7 had 28-day mortality rates in the responder group of 7%-11%,while in the non-responder group,mortality rates were approximately 38%-42%.LM3-7 had 90-day mortality rates in the responder group of 12%to 17%,while in the non-responder group,mortality rates were 48%-53%.Furthermore,all LM3-7 scores showed comparable efficacy in predicting mortality using ROC curve analysis;Area under ROC ranged from 0.771 to 0.802 for 28-day mortality and 0.743 to 0.809 for 90-day mortality.Regarding complications and mortality in AH,significant predictors included poor nutritional status,underlying cirrhosis,and acute renal dysfunction.CONCLUSION LM3-6 is as accurate as LM7 in predicting corticosteroid efficacy for 28-day and 90-day mortality in patients with SAH.Holding glucocorticoids early during the disease course can prevent unnecessary complications.
基金the National Natural Science Foundation of China(No.82171484)the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2023ZD25)。
文摘Chinese Wine Culture influences people’s attitudes toward alcohol.The current study focuses on exploring the main features of a localized digital alcohol consumption intervention mini-program to address the difficulties of abstinence for native drinkers,as a promising way for long-term management of rehabilitation from alcohol use disorder.A mixed-method approach was used in this study.The self-report quantitative questionnaire recruited three groups of participants:89 drinkers,67 drinkers’relatives,and 30 medical staff.The focus group qualitative interview inspected 36 participants’perspectives on the core topics,including 21 drinkers,4 drinkers’relatives,and 11 medical staff.The results of combining the quantitative study and qualitative study indicated that the top difficulties of abstinence for native drinkers are the strong craving from the inside,the environmental influence,and the psychological health status,especially emotional states.Correspondingly,the most desired main features in an alcohol consumption digital intervention tool are the daily track of drinking conditions and craving level,periodic feedback reports that can share with others,and mood improvement training.Moreover,the top factors that influence participants’intention to use/recommend the tool are whether the tool is effective,whether the user experience is good,and whether the tool can replenish the deficiency of the current alcohol treatment.Future work needs to balance what patients want and what others around them expect,so that potential users can benefit best from the digital intervention tool in the context of Chinese culture.
基金Supported by Hepatology Training Grant from the Spanish Association for The Study of Liver(AEEH-Asociación Española para el Estudio del Hígado)in 2023,No.G28551570(to Quiñones-Calvo M).
文摘BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term impact of available therapies remains unclear.This systematic review provides a critical evaluation of treatments for SAH,specifically focusing on survival or mortality at 90 days as an essential window that captures short-and mid-term outcomes.The 90-day window is clinically significant,as it reflects the remission of systemic inflam-mation,early liver recovery,and minimizes confounding long-term behaviors such as alcohol relapse.AIM To review the effect of different treatments for SAH on survival and mortality at 90 days.METHODS A systematic search of PubMed and EMBASE(last updated March 2025)was performed without language restrictions,focusing on studies published in the last decade.Study selection and data extraction were performed independently by at least two reviewers.Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools.Due to heterogeneity in study designs and interventions,a meta-analysis was not feasible.A qualitative synthesis was conducted using narrative summaries and evidence tables.RESULTS Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE.Of these 2161 studies,618 were duplicates and therefore removed.A total of eight studies were included in qualitative synthesis.Among the included publications,six were randomized control trials(RCT)and two were retrospective cohort studies.These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids(n=2),pentoxifylline(n=1),anakinra plus zinc(n=2),granulocyte colony-stimulating factor(n=1),amoxicillin-clavulanate(n=1),fecal microbiota transplantation(n=1)or extracorporeal liver assist device(n=1).While most studies were conducted in Western countries,two had a global scope.CONCLUSION Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit.These results highlight the need for multicenter,biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.
文摘BACKGROUND Patients and providers are often unaware of available treatment options for alcohol use disorder(AUD)and how to pursue them.AIM To improve AUD treatment rates using an educational video module(EVM).METHODS Prospective single-center cohort study evaluating the impact of a novel interactive patient EVM in promoting AUD treatment among hospitalized patients with alcohol-associated liver disease.Treatment was defined as receiving medication or participating in psychosocial treatment within 30 days of discharge.Primary outcome was change in treatment rates after viewing the EVM compared to a retrospective control cohort.Secondary outcomes were predictors of receiving treatment,EVM feedback,30-day hospital readmission,outpatient follow-up,return to alcohol use,and mortality.RESULTS Forty-two patients were included.Mean age was 45 years,50%were female,and mean model for end-stage liver disease score 15.5.After viewing the EVM,treatment rates increased for pharmacologic(50%vs 22%,P=0.0008)and psychosocial treatment(73.8%vs 44%,P=0.01).Return to alcohol use was significantly lower(7.9%vs 35.6%,P=0.003).All 100%of patients would recommend the EVM.CONCLUSION EVM allows hospitalized patients to receive standardized education about AUD treatment.This may address patient and provider knowledge gaps and reduce the growing burden of alcohol-associated liver disease.Future studies should evaluate EVM in larger patient populations using a multi-center study design.
文摘Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.
基金Supported by the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2024-00440477the Korea Institute of Science and Technology Institutional Program,No.2E33111-24-042.
文摘BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.
文摘BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant Nos.22475132 and 52101259)the Shenzhen Science and Technology Innovation Committee(Grant No.JCYJ20210324105008022)financially supported by the Shenzhen Science and Technology Innovation Program(Nos.KQTD20190929173914967 and ZDSYS20220527171401003).
文摘Engineering nanomaterials at single-atomic sites could enable unprecedented catalytic properties for broad applications,yet it remains challenging to do so on the surface of multimetallic nanocrystals.Herein,we present the multifactorial engineering(size,shape,phase,and composition)of the fully ordered PtBi nanoplates at atomic level,achieving a unique catalyst surface where the face-centered cubic(fcc)Pt edges are modified by the isolated Pd atoms and BiO_(x)adatoms.This Pd_(1)/Pt-BiO_(x)electrocatalyst exhibits an ultrahigh mass activity of 16.01 A mg^(-1)Pt+Pd toward ethanol oxidation in alkaline electrolyte and enables a direct ethanol fuel cell of peak power density of 56.7 mW cm^(−2).The surrounding BiO_(x)adatoms are critical for mitigating CO-poisoning on the Pt surface,and the Pd_(1)/Pt single-atom alloy further facilitates the electrooxidation of CH_(3)CH_(2)OH.This work offers new insights into the rational design and construction of sophisticated catalyst surface at single-atomic sites for highly efficient electrocatalysis.
基金supported by a research grant from the National University of Singapore to WQS(RP-3960366)a collaborative research grant from Sichuan Zhongke Organ Co.Ltd(Chengdu,China).
文摘Objectives:Cold-acclimated organisms accumulate low molecular weight organic solutes such as sugar alcohols and soluble sugars.This study aimed to compare the efficacy of five sugar alcohols and 14 soluble sugars in stabilizing proteins under freezing,freeze-drying,and air-drying stresses.Materials and methods:Glucose-6-Phosphate Dehydrogenase(G6PD)was used as the model protein.G6PD solutions with or without sugar alcohols and or sugars were subjected to freezing,freeze-drying,and air-drying stresses.The recovery of G6PD activity was measured to evaluate the protective efficacy of these compounds.Results:Without stabilizers,freezing G6PD at-20℃ or-80℃ reduced enzyme activity by around 24%,while freeze-drying or air-drying reduced activity by 90%-95%.Among the five sugar alcohols tested,pinitol,quebrachitol and sorbitol stabilized G6PD,whereas mannitol and myo-inositol destabilized it.Among 14 soluble sugars,trehalose and raffinose showed slightly lower enzyme recovery after repeated freeze-thaw cycles at-20℃.Most soluble sugars(except arabinose and xylose)protected G6PD during freeze-drying,with di-,tri-,and oligosaccharides generally outperforming monosaccharides.During air-drying,lactose was ineffective,while arabinose,galactose,and xylose were detrimental.Conclusion:The study highlights the diverse mechanisms of sugar alcohols and sugars in protein stabilization under stress,offering insights for formulating stable protein-and cell-based drugs.
基金supported by the National Natural Science Foundation of China(Nos.22278168 and 22276064)the MOE Key Laboratory of Resources and Environmental System Optimization(No.KLRE-KF202205)the Science and Technology Project of Fujian province(No.2022Y3007).
文摘Phase change absorbents based on amine chemical absorption for CO_(2)capture exhibit energy-saving potential,but generally suffer from difficulties in CO_(2)regeneration.Alcohol,characterized as a protic reagent with a low dielectric constant,can provide free protons to the rich phase of the absorbent,thereby facilitating CO_(2)regeneration.In this investigation,N-aminoethylpiperazine(AEP)/sulfolane/H_(2)O was employed as the liquid-liquid phase change absorbent,with alcohol serving as the regulator.First,appropriate ion pair models were constructed to simulate the solvent effect of the CO_(2)products in different alcohol solutions.The results demonstrated that these ion pair products reached the maximum solvation-free energy(△E_(solvation))in the rich phase containing ethanol(EtOH).Desorption experiment results validated that the inclusion of EtOH led to a maximum regeneration rate of 0.00763 mol/min,thus confirming EtOH’s suitability as the preferred regulator.Quantum chemical calculations and^(13)C NMR characterization were performed,revealing that the addition of EtOH resulted in the partial conversion of AEP-carbamate(AEPCOO−)into a new product known as ethyl carbonate(C_(2)H_(5)OCOO−),which enhanced the regeneration reactivity.In addition,the decomposition paths of different CO_(2)products were simulated visually,and every reaction’s activation energy(△E_(act))was calculated.Remarkably,the△E_(act)for the decomposition of C_(2)H_(5)OCOO−(9.465 kJ/mol)was lower than that of the AEPCOO−(26.163 kJ/mol),implying that CO_(2)was more likely to be released.Finally,the regeneration energy consumption of the alcohol-regulated absorbentwas estimated to be only 1.92 GJ/ton CO_(2),which had excellent energy-saving potential.
文摘Photoredox dual reaction of organic synthesis and H2 evolution opens up a novel pathway for collaboratively generating clean fuels and high-quality chemicals,providing a more effective approach of solar energy conversion.Herein,a surface defect-engineered ZnCoS/ZnCdS heterostructure with zinc blende(ZB)/wurtzite(WZ)phase junctions is synthesized for photocatalytic cooperative coupling of benzaldehyde(BAD)and H_(2) production.This surface defect-engineered ZnCoS/ZnCdS heterostructure elaborately integrates the mixed phase junction advantage of ZnCdS semiconductor and the cocatalytic function of ZnCoS possessing Zn(VZn-ZnCoS/ZnCdS)or S vacancies(VS-ZnCoS/ZnCdS).The optimum VS-ZnCoS/ZnCdS simultaneously exhibits a superior H2 production rate of 14.23 mmol h^(-1) g^(-1) accompanied with BAD formation rate of 12.29 mmol h^(-1) g^(-1) under visible-light irradiation,which is approximately two-fold greater than that of pristine ZnCdS.Under simulated sunlight irradiation(AM 1.5),VS-ZnCoS/ZnCdS achieves H2 evolution(27.43 mmol gcat^(-1) h^(-1))with 0.52%of STH efficiency,accompany with 26.31 mmol gcat^(-1) h^(-1) of BAD formation rate.The underlying solar-driven mechanism is elucidated by a series of in-situ characterization and control experiments,which reveals the synergistic effect of interfacial ZB/WZ phase junctions in ZnCdS and S vacancies of ZnCoS on enhancement of the photoredox dual reaction.The VS-ZnCoS/ZnCdS follows a predominant oxygen-centered radical integrating with carbon-centered radical pathways for BAD formation and a simultaneous electron-driven proton reduction for H_(2) production.Interestingly,the nature of surface vacancies not only facilitates the separation of photoinduced charge carriers but also able to selectively adjust the mechanism pathway for BAD production via tuning the oxygen-centered radical and carbon-centered radical formation.
