Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Assessment of Some Secondary Metabolites, Minerals and Alcohol Content of Noni Juice Obtained by Fermentation of Morinda citrifolia L. Fruit from Senegal

The fruit of Morinda citrifolia L., commonly known as noni, has an extensive history of use as a food and traditional medicine around the world. Adding value to Morinda citrifolia L. products, particularly the fruit, could be one way of building resilience in vulnerable farming households. The aim of this study was to determine the secondary metabolite and mineral composition of noni juice obtained by fermenting the fruit of Morinda citrifolia L. Fruits were collected in August 2022 from the local field in Thiès region, West of Senegal. Extraction yields were determined and the secondary metabolites were determined using conventional analytical methods. Calcium, magnesium, iron, sodium and potassium were determined by atomic absorption spectrophotometer coupled with a CCD detector. The results show that an average fruit mass (503.2 ± 110.96 g) consists of 171.44 ± 50.01 g pulp and 34.06 ± 10.35 g seeds. The traditional extraction yield of noni juice is 16.46% after three weeks of fermentation. The contents of total polyphenols, flavonoids and tannins obtained in noni are 608.97 ± 4.53 mg EAG/100mL, 7.78 ± 0.01 mg EQ/100mL and 0.191 ± 0.01 mg EC/100mL respectively. The ethanol content of noni varies from 3.57 to 5.23 mL/100mL during extraction. Noni has a high calcium content with a concentration of 383.79 ± 33.23 mg/L. This is followed by a good concentration of magnesium, potassium and sodium, at 278.47 ± 26.30, 187.43 ± 10.7 and 155.95 ± 28.66 mg/L respectively. Noni also has an iron content of 202.15 ± 0.05 mg/L.

Exploring the Impact of Alcohol Consumption and Smoking on Primary Open Angle Glaucoma: A Mendelian Randomization Study

Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle Glaucoma (POAG). Methods: GWAS data for bibulosity, smoking, and POAG were obtained from the Social Science Genetic Association Consortium website and the IEU OpenGWAS Project website, respectively. Using a P-value threshold of −8, a linkage disequilibrium coefficient (r2) of 0.001, and a linkage disequilibrium region width of 10,000 kb, the data were aggregated, resulting in 6 SNPs for bibulosity and 253 SNPs for smoking. Three regression models, MR-Egger, Weighted Median Estimator (WME), and Random-Effects Inverse-Variance Weighted (IVW) were applied to analyze the causal impact of bibulosity and smoking on POAG. Results: The GWAS data for alcohol consumption and smoking were derived from European populations, while the GWAS data for Primary Open-Angle Glaucoma (POAG) were sourced from East Asian populations, with no gender restrictions. Analysis using three different regression models revealed that neither excessive alcohol consumption nor smoking significantly increased the risk of developing POAG. Specifically, the odds ratios with 95% confidence intervals for the alcohol consumption group were 0.854 (0.597 - 1.221) in MR-Egger regression, 0.922 (0.691 - 1.231) in WME regression, and 0.944 (0.711 - 1.252) in IVW regression. For the smoking group, the odds ratios were 1.146 (0.546 - 2.406) in MR-Egger regression, 0.850 (0.653 - 1.111) in WME regression, and 0.939 (0.780 - 1.131) in IVW regression. Given the significant heterogeneity in the SNPs associated with smoking, the focus was primarily on the results from the IVW regression model. Conclusion: Alcohol consumption and smoking are not significant risk factors for the development of POAG.

Alcohol drinking triggered decrease of oxidative balance score is associated with high all-cause and cardiovascular mortality in hypertensive individuals:findings from NHANES 1999–2014

BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.

Effect of Polyvinyl Alcohol in Inner Aqueous Phase on Stability of Millimeter-scale Capsules

The millimeter-scale capsules with controllable morphology,ultra-low permeability and excellent mechanical stability were fabricated by millifluidics.Viscosity of inner phase was adjusted to control the morphology and properties of the capsules.In detail,as the concentration of polyvinyl alcohol(PVA)increased from 0 to 8% in the inner phase of the capsules,the diameter of capsules decreased from 3.33 ± 0.01mm to 2.97 ± 0.01 mm,the shell thickness of capsules decreased from 0.183 ± 0.004 mm to 0.155 ± 0.003 mm.While the capsules had round shape and high sphericity.Notably,the capsules with 2% PVA in the inner phase had remarkably decreased water permeability and good morphological stability.Specifically,the end-time of water losing of the capsules was up to 49 days,while the dehydrated capsules maintained spherical appearance,and crushing force of the capsules was up to 13.73 ± 0.79 N,which ensured stability during processing and transportation.This research provides a new strategy for stable encapsulation of small molecules.

Effects of alcohol on digestion,absorption and metabolism of sea cucumber saponins in healthy mice

Sea cucumber saponins have attracted more attention in recent years due to biological activities.It is a popular practice to soak sea cucumber in Baijiu at home and being applied to industrial manufacturing in China.However,knowledge of the effect of alcohol on the absorption and metabolism of sea cucumber saponins is limited.The effects of alcohol on digestion,absorption and metabolism of sea cucumber saponins in BALB/c mice were investigated after gavage and tail intravenous injection.The results showed that the content of saponins in serum and liver was significantly higher under the influence of alcohol than that in the control group after oral administration.Alcohol promoted the absorption of sea cucumber saponins prototype as well as inhibited the process of saponins being transformed into deglycositic metabolites in the small intestine.Moreover,sea cucumber saponins remained in circulation for a long time and alcohol slowed down the clearance of sea cucumber saponins under the influence of alcohol after intravenous injection.This confirmed the feasibility of marinating sea cucumber in Baijiu to improve the efficacy of saponins and provides an important theoretical basis for the utilization of sea cucumber and the development of sea cucumber liquor.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.

Alcohol solvent effect on the self-assembly behaviors of lignin oligomers

The interactions between lignin oligomers and solvents determine the behaviors of lignin oligomers self-assembling into uniform lignin nanoparticles(LNPs).Herein,several alcohol solvents,which readily interact with the lignin oligomers,were adopted to study their effects during solvent shifting process for LNPs’production.The lignin oligomers with widely distributed molecular weight and abundant guaiacyl units were extracted from wood waste(mainly consists of pine wood),exerting outstanding self-assembly capability.Uniform and spherical LNPs were generated in H_(2)O-n-propanol cosolvent,whereas irregular LNPs were obtained in H_(2)O-methanol cosolvent.The unsatisfactory self-assembly performance of the lignin oligomers in H_(2)O-methanol cosolvent could be attributed to two aspects.On one hand,for the initial dissolution state,the distinguishing Hansen solubility parameter and polarity between methanol solvent and lignin oligomers resulted in the poor dispersion of the lignin oligomers.On the other hand,strong hydrogen bonds between methanol solvent and lignin oligomers during solvent shifting process,hindered the interactions among the lignin oligomers for self-assembly.

Individual alcohol consumption by the population of Russia versus regional living conditions

Background:There are substantial regional differences in drinking alcohol in Russia,both at the population and individual levels.However,the causes of these differences have not been studied yet.Objective:The goal of our study was to examine the effect of regional living conditions on individual alcohol consumption by the population of Russia.Methods:For the analysis,we used data from a cross-sectional epidemiological study conducted in 2013-2014.The final analytical sample included 18,130 people aged 25-64 years.We conducted the interviews face to face,based on which any drinking in the last year,as well as alcohol abuse,were considered as a response.Alcohol abuse was recorded when the respondent consumed 5.75 or more grams of pure ethanol per day(75th percentile of average daily alcohol consumption among alcohol drinkers).The assessment of the regional living conditions was accomplished via integral indexing,which was previously performed based on publicly available data for 2010-2014.Associations were assessed using generalized scoring equations with unchanging standard errors.The associations were expressed by odds ratios(OR)and 95%confidence intervals(C).Results:Deterioration of social conditions and increase in demographic depression in the region of residence increased the odds of any drinking(OR 1.51,95%CI:1.33 to 1.72,P<0.001 and OR 1.22,95%CI:1.05 to 1.41,P=0.oo9,respectively).The odds of alcohol abuse increased with the deterioration of social living conditions and the growth of the industrial development in the region:OR 1.35,95%CI:1.14 to 1.59,P<0.001 and OR 1.16,95%CI:1.05 to 1.28,P=0.002,respectively.Conclusion:Our analysis allowed assessing the impact of the regional living conditions on individual drinking alcohol in the population of Russia.

Increased Mortality Risk in Children with Fetal Alcohol Spectrum Disorders: A Scoping Review

Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around seven years of age. The most severe outcome in cases of FASD is mortality. The purpose of this scoping review is to 1) use a systematic review to provide an estimated mortality proportion for children with FASD, and 2) update a study published in 2014 by reviewing published reports of mortality in individuals diagnosed with FASD. Method: A search of PubMed, CINAHL, and Google Scholar for reports published between 2013 and 2023 on mortality in individuals with FASD. Results: Three population-based studies have reported on all-cause mortality rates, finding a combined mortality rate of 10.9%, a 2.63 fold (95% CI: 2.61 to 2.65) increase in mortality risk over the general population. Since 2016, this review identified only eight new cases meeting the study inclusion criteria. The reported causes of death were five cases of pneumonia, and one case each of failure to thrive and dehydration, intestinal dilatation and asphyxiation caused by overeating due to pica, and acute gastric volvulus. Discussion: While current research suggests a diagnosis of FASD is associated with a 2.6-fold increase in mortality risk, this is likely an underestimation, as most cases of FASD-related mortality go unreported. Globally, about 1 new case is reported every 15 months. However, in the United States alone, between 1752 to 4400 FASD related deaths occur annually. Our review suggests that FASD is rarely identified as a causal or contributing factor in deaths of children and adolescents, resulting in a substantial undercount of FASD-related deaths. Increased attention to the role of FASD in infant and child mortality case reviews, child death review committee reports, and mortality reviews is needed.

Alcohol and illicit drugs:prevalence of alcohol and illicit drug use and their predictors in young people from Argentina,Bulgaria,Chile and Romania

Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns.Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries.Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs.Results:Our data revealed that across the four target countries,49%to 90%of the participants drank alcohol,and 8%to 35%used illicit drugs in the past three months.Between 20%and 91%of them intended to drink,and between 8%and 31%intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P<0.001)amounts of variance in drinking alcohol(between 61%and 72%)and using illicit drugs(between 20.3%and 74.4%).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries.Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.

Is a Mini-Screen for Fetal Alcohol Spectrum Disorder Feasible?

Background: Fetal Alcohol Spectrum Disorders (FASDs) are a global public health concern with lifelong consequences for affected individuals. Recent prevalence studies suggest FASD prevalence rates range from 1-5% among school age children. Most people with FASD are not correctly diagnosed and inadequate screening to identify patients with increased risk may contribute to under-diagnosis. This study developed a 10-item screening tool for FASD and examined its feasibility. Methods: The sample consisted of 355 children who had been evaluated at an FASD clinic. Data from the 33-item Alcohol Related Neurodevelopmental Disorder Behavioral Checklist was used to develop a brief FASD screen by comparing the changes in Cronbach’s alpha for different combinations of items. The validity of the brief scale was then further examined using receiving operating characteristic analyses. Results: The 10-item screen demonstrated acceptable sensitivity, specificity, and accuracy to identify children at high risk for FASD. The percentage correctly classified was 91.3 and the area under the receiving operating characteristic curve was 0.971. Conclusions: This feasibility study demonstrated that a screen for FASD consisting of 10 items with yes or no responses can be completed in 3 - 4 minutes. The tool is brief, with a low administration burden and has acceptable epidemiologic performance characteristics including accuracy. Future research should examine the performance of this tool when used in larger, community-based populations where screening for FASD would be appropriate.

Distinct and Additive Effects of Alcohol and Thiamine Deficiency in the Developing Brain: Relevance to Fetal Alcohol Spectrum Disorder

Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.

Cu-based materials for electrocatalytic CO_(2) to alcohols:Reaction mechanism,catalyst categories,and regulation strategies

Electrocatalytic CO_(2) reduction reaction(CO_(2)RR)technology,which enables carbon capture storage and resource utilization by reducing CO_(2) to valuable chemicals or fuels,has become a global research hotspot in recent decades.Among the many products of CO_(2)RR(carbon monoxide,acids,aldehydes and alcohols,olefins,etc.),alcohols(methanol,ethanol,propanol,etc.)have a higher market value and energy density,but it is also more difficult to produce.Copper is known to be effective in catalyzing CO_(2) to high valueadded alcohols,but with poor selectivity.The progress of Cu-based catalysts for the selective generation of alcohols,including copper oxides,bimetals,single atoms and composites is reviewed.Meanwhile,to improve Cu-based catalyst activity and modulate product selectivity,the modulation strategies are straighten out,including morphological regulation,crystalline surface,oxidation state,as well as elemental doping and defect engineering.Based on the research progress of electrocatalytic CO_(2) reduction for alcohol production on Cu-based materials,the reaction pathways and the key intermediates of the electrocatalytic CO_(2)RR to methanol,ethanol and propanol are summarized.Finally,the problems of traditional electrocatalytic CO_(2)RR are introduced,and the future applications of machine learning and theoretical calculations are prospected.An in-depth discussion and a comprehensive review of the reaction mechanism,catalyst types and regulation strategies were carried out with a view to promoting the development of electrocatalytic CO_(2)RR to alcohols.

Curcumin delivery nanoparticles based on Maillard reaction of Haematococcus pluvialis protein/galactose for alleviating acute alcoholic liver damage

The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.

Modified electronic structure and enhanced hydroxyl adsorption make quaternary Pt-based nanosheets efficient anode electrocatalysts for formic acid-/alcohol-air fuel cells

Surface/interface engineering of a multimetallic nanostructure with diverse electrocatalytic properties for direct liquid fuel cells is desirable yet challenging.Herein,using visible light,a class of quaternary Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)ultrathin nanosheets is fabricated and used as high-performance anode electrocatalysts for formic acid-/alcohol-air fuel cells.The modified electronic structure of Pt,enhanced hydroxyl adsorption,and abundant exterior defects afford Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C high intrinsic anodic electrocatalytic activity to boost the power densities of direct formic acid-/methanol-/ethanol-/ethylene glycol-/glycerol-air fuel cells,and the corresponding peak power density of Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C is respectively 129.7,142.3,105.4,124.3,and 128.0 mW cm^(-2),considerably outperforming Pt/C.Operando in situ Fourier transform infrared reflection spectroscopy reveals that formic acid oxidation on Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C occurs via a CO_(2)-free direct pathway.Density functional theory calculations show that the presence of Ag,Bi,and Te in Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)suppresses CO^(*)formation while optimizing dehydrogenation steps and synergistic effect and modified Pt effectively enhance H_(2)O dissociation to improve electrocatalytic performance.This synthesis strategy can be extended to 43 other types of ultrathin multimetallic nanosheets(from ternary to octonary nanosheets),and efficiently capture precious metals(i.e.,Pd,Pt,Rh,Ru,Au,and Ag)from different water sources.

Increased alcohol consumption during the COVID-19 pandemic:A cross-sectional study

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has significantly impacted health,mental well-being,and societal functioning,particularly for individuals with psychiatric conditions and substance use disorders.Recent evidence highlights a concerning increase in alcohol consumption during the pandemic,with a study spanning 2015-2020 indicating heightened usage,especially among young and middle-aged adults,for relaxation and tension relief.Additionally,addressing challenges exacerbated by the pandemic,another study underscored persistent barriers to healthcare access,resulting in increased alcohol and tobacco use rates and limited healthcare options.These findings shed light on the unique vulnerabilities exposed by the pandemic,emphasizing the need to investigate further its impact on alcohol consumption in diverse non-urban American communities.AIM To investigate the impact of the COVID-19 pandemic on alcohol abuse using socioeconomic and medical parameters in diverse non-urban community in America.METHODS Based on a cross-sectional analysis of 416 participants the United States in 2021,the study utilized The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition criteria to categorize alcohol consumption levels.Participants aged 21 years and above were surveyed through an online platform due to COVID-19 challenges.The survey was conducted from January 14 to January 31,2022,recruiting participants via social media and ensuring anonymity.Informed consent was secured,emphasizing the voluntary nature of participation,and participants could only take the survey once.RESULTS Out of 416 survey respondents,396 met eligibility criteria,with 62.9%reporting increased alcohol consumption during COVID-19.Males(68.8%)and ages 21-29 years(34.6%)predominated.Low alcohol consumption decreased by 2.8%(P=0.237),moderate by 21.4%(P<0.001),and heavy increased by 14.9%(P<0.001).Alcohol abuse rose by 6.5%(P=0.0439),with a 7%increase in self-identified alcohol abusers/alcoholics.Seeking treatment during COVID-19 rose by 6.9%.Easier alcohol access(76.0%)was reported,while 80.7%found it harder to access medical care for alcohol-related issues.These findings highlight the pandemic's impact on alcohol consumption and healthcare access,emphasizing the need for targeted interventions during public health crises.CONCLUSION The COVID-19 pandemic exacerbated alcoholism and abuse,with increased heavy consumption(P<0.001)and abuse(P=0.0439).Access to medical programs for addressing alcohol abuse declined,highlighting the need for targeted intervention.