The present study aimed to evaluate the anti-diabetic property of peanut shell polyphenol extracts （PSPEs）. Diabetic rats were oral-administrated with PSPE at doses of 50, 100, and 200 mg/kg body weight （BW） per d...The present study aimed to evaluate the anti-diabetic property of peanut shell polyphenol extracts （PSPEs）. Diabetic rats were oral-administrated with PSPE at doses of 50, 100, and 200 mg/kg body weight （BW） per day for 28 consecutive days, with metformin （Met） as a positive control. The results showed that, similar to the Met treatment, administration of PSPE caused significant decreases in food intake, water intake, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and methane dicarboxylic aldehyde in serum, and significant increases in BW, insulin level, high-density lipoprotein cholesterol, superoxide dismutase, glutathione, and liver gly- cogen. Further, glucose tolerance was markedly improved in the PSPE-treated diabetic groups. Histopathological results showed that PSPE improved cellular structural and pathological changes in liver, kidney, and pancreatic islets. Collectively, the results indicated that the hypoglycemic effects of PSPE on high-fat diet/streptozotocin （HFD/STZ）induced diabetes are comparable to Met, though their exact mechanism actions are still under investigation. Therefore, the current study suggests that PSPE could be a potential health-care food supplement in the management of diabetes.展开更多
BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate...BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate the association between preoperative serum cholinesterase(ChE)activity—specifically butyrylcholinesterase(BuChE)and acetylcholinesterase(AChE)—and the risk of POD in adult surgical patients in a meta-analysis.METHODS A systematic search was conducted in PubMed,EMBASE,and Web of Science up to March 28,2025 for studies reporting preoperative serum BuChE or AChE activity in relation to subsequent POD incidence.Standardized mean differences(SMDs)and odds ratios(ORs)with 95%confidence intervals(CIs)were pooled using random-effects models.Subgroup and sensitivity analyses were performed based on follow-up duration and analytic models.RESULTS Thirteen studies(n=2730 patients)were included.Patients who developed POD had significantly lower preoperative BuChE activity than those who did not(SMD=-0.28;95%CI:-0.39 to-0.16;I²=18%).Higher BuChE activity was associated with a reduced risk of POD(OR per 100 unit increment=0.97;95%CI:0.95-0.99;I2=0%).In contrast,pooled AChE activity did not differ significantly between POD and non-POD groups(SMD=-0.25;95%CI:-0.53 to 0.03;P=0.08;I2=80%),and the ORs per 1 unit increment in AChE activity were not statistically significant(OR=0.98;95%CI:0.95-1.01).CONCLUSION Lower preoperative serum BuChE activity is associated with an increased risk of POD in adults undergoing surgery.BuChE activity may serve as a potential preoperative biomarker for POD risk stratification.展开更多
Conductive materials(CM)can improve methane production(MP)efficiency in many methanogenic systems.However,several types of CM exist,and there are uncertainties regarding whether they all improve MP efficiency to the s...Conductive materials(CM)can improve methane production(MP)efficiency in many methanogenic systems.However,several types of CM exist,and there are uncertainties regarding whether they all improve MP efficiency to the same extent and modulate microbial communities in a similar way.To investigate that,different microbial enrichments with and without activated carbon(AC),magnetite(Mag),and zeolites(Zeo)(at 0.5 g/L)were developed.MP profiles and microbial composition changes were compared among enrichments.The behavior of all enrichments was different,although the initial inoculum sludge was the same.Lag phase duration was lower in AC enrichment,while the complete conversion of butyrate to methane was faster in Mag enrichment.Syntrophomonas was the most abundant bacterial genus in all enrichments,but changes in the methanogenic community were evident.Acetoclastic methanogens were more diverse in Mag enrichment,with microorganisms assigned to Methanosarcina and Methanothrix gener1,but Methanothrix was the only acetoclastic methanogen in the other enrichments.On the other hand,different species of hydrogenotrophic methanogens prevailed in distinct enrichments.The metatranscriptomics results revealed that the dominant mechanism of interspecies electron transfer in the AC enrichment utilized hydrogen as the electron carrier,and no evidences of direct interspecies electron transfer(DIET)could be found.These results showed how different CM modulate microbial communities and affect MP efficiency through mechanisms that do not necessarily involve DIET or mediation via CM.展开更多
BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly unders...BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.展开更多
Objective:To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of Amaranthus caudatus,Amaranthus spinosus and Amaranthus viridis in normal and streptozotocin(STZ) induced d...Objective:To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of Amaranthus caudatus,Amaranthus spinosus and Amaranthus viridis in normal and streptozotocin(STZ) induced diabetic rats.Methods:In this study,the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of all three plants was evaluated by using normal and STZ induced diabetic rots at a dose of 200 mg/kg and 400 mg/kg p.o.daily for 21 days.Blood glucose levels and body weight were monitored at specific intervals,and different biochemical parameters,serum cholesterol,serum triglyceride,high density lipoprotein, low density lipoprotein and very low density lipoprotein were also assessed in the experimental animals.Histology of pancreas was performed.Results:It was found that all the three plants at 400 mg/kg dose showed significant anti-diabetic and anti-cholesterolemic activity(P<0.01),while at 200 mg/kg dose less significant anti-diabetic activity(P<0.05) was observed.Concluslons: Methanol extracts of Amaranthus caudatus,Amaranlhus spinosus and Amaranthus viridis showed significant anti-diabetic and anti-cholesterolemic activity,which provides the scientific proof for their traditional claims.展开更多
The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence...The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence is still lacking.To validate this framework,here we employ a programmable robotic platform,where a single light-controlled wheeled robot travels in an activity landscape.Our experiments quantitatively demonstrate that the intrinsic pressure difference across the activity interface is balanced by the emerged polarization force.This result unambiguously confirms the theoretical predictions,thus validating the intrinsic pressure framework and laying the experimental foundation for the intrinsic pressure-based mechanical description of dry active matter.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata(U. lobata) through dipeptidyl peptidase IV(DPP-IV) inhibitory activity.Methods: U. lobata leaf was extracted in hot water and ethano...Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata(U. lobata) through dipeptidyl peptidase IV(DPP-IV) inhibitory activity.Methods: U. lobata leaf was extracted in hot water and ethanol. The activity of DPPIV inhibitor was tested by in vitro study using gly-pro-p-nitroanilide as substrat of DPPIV and vildagliptin, as standard reference. A product of the reactions between gly-pro-pnitroanilide and DPP-IV, was observed by microplate readers with λ = 405 nm. All data were expressed as mean ± SD and the IC50 value was determined by non linear regression curve fit. Active substances in leaf extract of U. lobata was analyzed by liquid chromatography-mass spectrometry. DPP-IV inhibitory activity of active compounds was evaluated in silico using docking server. Results: The ethanolic extract of U. lobata showed stronger DPP-IV inhibitor activity than water extract with the IC50 values of 1 654.64 and 6 489.88 μg/mL, respectively. Vildagliptin, based on standard reference for DPP-IV inhibitor activity, has IC50 value of 57.44 μg/mL. Based on in silico analysis, mangiferin, stigmasterol and β-sitosterol in U. lobata extract have a strong inhibitory activity on DPP-IV. Conclusions: The results showed that DPP-IV inhibitory activity of U. lobata is related to its active compounds such as mangiferin, stigmasterol and β-sitosterol.展开更多
To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp...To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.展开更多
Diabetes mellitus(DM)has become one of the most serious and common chronic diseases around the world,leading to various complications and a reduction in life expectancy.Increased sedentary behavior(SB)and decreased ph...Diabetes mellitus(DM)has become one of the most serious and common chronic diseases around the world,leading to various complications and a reduction in life expectancy.Increased sedentary behavior(SB)and decreased physical activity(PA)are important contributors to the rising prevalence of DM.This article reviews the research progress on the pathogenesis of DM,the effects of SB and PA on the risk of DM,aiming to explore the influence of different PA intensities,amounts,frequencies,durations and types on the incidence of DM.Research has shown that blood glucose levels tend to increase with the prolongation of SB.Within a certain range,PA intensity and PA amount are negatively correlated with the risk of DM;Performing PA for more than 3 days per week maintains normal glucose tolerance and lower blood pressure;Engaging in 150–300 min of moderate intensity exercise or 75–150 min of high-intensity exercise per week reduces the risk of DM;PA during leisure time reduces the risk of DM,while PA during work increases the risk of DM;Both aerobic training and resistance training reduce the risk of DM,and the combination of the two training methods produces better benefits;Various types of exercises,such as cycling,soccer,aerobics,yoga,tai chi,all reduce the risk of DM.In summary,prolonged SB increases the risk of DM,while appropriate PA reduces the risk of DM.As the intensity,amount,and frequency of PA increase,the effect of reducing DM risk becomes more significant.Different exercise methods have different effects on reducing DM risk.展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.展开更多
Plants are used traditionally throughout the globe to treat various diseases.Traditionally used medicinal plants are an essential part of the health sector in Bangladesh due to its abundance of a vast source of ethno-...Plants are used traditionally throughout the globe to treat various diseases.Traditionally used medicinal plants are an essential part of the health sector in Bangladesh due to its abundance of a vast source of ethno-medicine.Rural people from developing country like Bangladesh are greatly dependent on traditional source of medicine.The prevalence of diabetes mellitus is increasing from recent years; therefore various researches are going on to discover better medicine to treat this disease.This study has focused on five plants which are Andrographis paniculata, Ageratum conyzoides, Swertia chirata, Terminalia arjuna, and Azadirachta indica to find out their traditional formulation as anti-diabetic medicine and their pharmacological activity has also been explored through literature search.The available information about traditional anti-diabetic uses of these plants and their pharmacological activities were collected from various electronic sources like Pubmed, Sci Finder, Elsevier, Springer, Scopus, Scirus, Science Direct, Google Scholar and Web of Science apart from these locally available books and peer reviewed journal were also used to collect information.This study will help to strengthen the relation between traditional medicine, pharmacology and drug development.A clue may be found from the information provided this review to discover new and better anti-diabetic drugs.展开更多
Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpeno...Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpenoids(euphorwallside H and euphorwallside I,14 and 15),were isolated and characterized from Euphorbia wallichii(E.wallichii).The chemical structures of these compounds were elucidated through nuclear magnetic resonance(NMR),mass spectrometry(MS),and quantum chemical calculations.Compounds 9 and 11 demonstrated protective effects against H2O2-induced BV-2 microglial cell damage.Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR,GSTP1,and SHBG.展开更多
Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial...Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pretraining.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.展开更多
Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid ...Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.展开更多
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.展开更多
BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple...BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple prognostic assessment indicators for ACLF,the overall sensitivity and accuracy are relatively low.AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein(AFP),plasma prothrombin activity(PTA),and serum prealbumin(PA)in ACLF.METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival(n=47)and death(n=40)groups according to their clinical outcomes 3 months posttreatment.All the participants underwent AFP,PTA,and PA level measurements upon admission.Baseline data,as well as AFP,PTA,and PA levels,were comparatively analyzed.Pearson correlation coefficients were utilized to analyze the correlations of AFP,PTA,and PA with different survival outcomes in patients with ACLF.Receiver operating characteristic(ROC)curves and areas under the curves were used to evaluate the predictive value of AFP,PTA,and PA for ACLF prognosis.RESULTS AFP,PTA,and PA levels were markedly decreased in the death group than in the survival group(P<0.05).Pearson analysis indicated a positive association of the AFP,PTA,and PA levels with the survival of patients with ACLF(P<0.05).ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24%and 100.00%,respectively,both of which were notably increased compared to the single-index diagnosis.The ROC of their combined diagnosis was 0.989,significantly surpassing 0.907,0.849,and 0.853 of AFP,PTA,and PA,respectively.No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection(P>0.05).CONCLUSION The combined detection of AFP,PTA,and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF,featuring high sensitivity and specificity.展开更多
Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory sym...Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.展开更多
Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism...Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism(ECD)/optical rotatory dispersion(ORD)methods,and X-ray crystallography.Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system,which is presumably biosynthesized via a[4+2]cycloaddition and an enzymatic cyclization.Chaeglobol A(1)exhibited inhibitory activity against B.dothidea by destroying cell membrane integrity and causing oxidative damage within the cells.展开更多
Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy densi...Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy density.However,the all-solid-state batteries with nickel-rich oxide cathodes suffer from performance degradation due to the reactions between the highly reactive surface oxygen of the cathode and the electrolyte,as well as the instability of the bulk oxygen structure in the cathode.Herein,we propose a synergistic modification design scheme to adjust the oxygen activity from surface to bulk.The LiBO_(2)coating inhibits the reactivity of surface lattice oxygen ions.Meanwhile,Zr doping in the bulk phase forms strong Zr-O covalent bonds that stabilize the bulk lattice oxygen structure.The synergistic effect of these modifications prevents the release of oxygen,thus avoiding the degradation of the cathode/SE interface.Additionally,the regulation of surface-to-bulk oxygen activity establishes a highly stable interface,thereby enhancing the lithium ion diffusion kinetics and mechanical stability of the cathode.Consequently,cathodes modified with this synergistic strategy exhibit outstanding performance in sulfide-based ASSLBs,including an ultra-long cycle life of 100,000 cycles,ultra-high rate capability at 45C,and 85% high active material content in the composite cathode.Additionally,ASSLB exhibits stable cycling under high loading conditions of 82.82 mg cm^(-2),achieving an areal capacity of 17.90 mA h cm^(-2).These encouraging results pave the way for practical applications of ASSLBs in fast charging,long cycle life,and high energy density in the future.展开更多
基金Project supported by the China Scholarship Council(No.201306175110)the Major Scientific and Technological Research Project of Jilin Province(No.20140204048NY),China
文摘The present study aimed to evaluate the anti-diabetic property of peanut shell polyphenol extracts （PSPEs）. Diabetic rats were oral-administrated with PSPE at doses of 50, 100, and 200 mg/kg body weight （BW） per day for 28 consecutive days, with metformin （Met） as a positive control. The results showed that, similar to the Met treatment, administration of PSPE caused significant decreases in food intake, water intake, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and methane dicarboxylic aldehyde in serum, and significant increases in BW, insulin level, high-density lipoprotein cholesterol, superoxide dismutase, glutathione, and liver gly- cogen. Further, glucose tolerance was markedly improved in the PSPE-treated diabetic groups. Histopathological results showed that PSPE improved cellular structural and pathological changes in liver, kidney, and pancreatic islets. Collectively, the results indicated that the hypoglycemic effects of PSPE on high-fat diet/streptozotocin （HFD/STZ）induced diabetes are comparable to Met, though their exact mechanism actions are still under investigation. Therefore, the current study suggests that PSPE could be a potential health-care food supplement in the management of diabetes.
文摘BACKGROUND Postoperative delirium(POD)is a common and serious complication in surgical patients,particularly older adults.Alterations in cholinergic function have been implicated in its pathophysiology.AIM To evaluate the association between preoperative serum cholinesterase(ChE)activity—specifically butyrylcholinesterase(BuChE)and acetylcholinesterase(AChE)—and the risk of POD in adult surgical patients in a meta-analysis.METHODS A systematic search was conducted in PubMed,EMBASE,and Web of Science up to March 28,2025 for studies reporting preoperative serum BuChE or AChE activity in relation to subsequent POD incidence.Standardized mean differences(SMDs)and odds ratios(ORs)with 95%confidence intervals(CIs)were pooled using random-effects models.Subgroup and sensitivity analyses were performed based on follow-up duration and analytic models.RESULTS Thirteen studies(n=2730 patients)were included.Patients who developed POD had significantly lower preoperative BuChE activity than those who did not(SMD=-0.28;95%CI:-0.39 to-0.16;I²=18%).Higher BuChE activity was associated with a reduced risk of POD(OR per 100 unit increment=0.97;95%CI:0.95-0.99;I2=0%).In contrast,pooled AChE activity did not differ significantly between POD and non-POD groups(SMD=-0.25;95%CI:-0.53 to 0.03;P=0.08;I2=80%),and the ORs per 1 unit increment in AChE activity were not statistically significant(OR=0.98;95%CI:0.95-1.01).CONCLUSION Lower preoperative serum BuChE activity is associated with an increased risk of POD in adults undergoing surgery.BuChE activity may serve as a potential preoperative biomarker for POD risk stratification.
基金supported by the Portuguese Foundation for Science and Technology(FCT)under the scope of the strategic funding of UIDB/04469/2020 unit and by the CM4Methane project(Ref:PTDC/BTA-BTA/2249/2021,DOI 10.54499/PTDC/BTABTA/2249/2021)FCT and European Union(EU),through the Portuguese State Budget and the European Social Fund under the scope of Norte2020-Programa Operacional Regional do Norte,also funded the SFRH/BD/132003/2017 and COVID/BD/152431/2022 grants held by Cátia S.N.Braga.,and the SFRH/BD/147271/2019 grant held by João C.Sequeira.M.SaloméDuarte acknowledges FCT for the Junior Research contract obtained under the scope of the Scientific Stimulus Employment 2022(ref:2022.06569.CEECIND/CP1718/CT0004,doi:https://doi.org/10.54499/2022.06569.CEECIND/CP1718/CT0004)PhD M.Fernando R.Pereira and PhD O.SaloméG.Soares from the Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials,Faculty of Engineering(University of Porto),for providing the AC used in this study.
文摘Conductive materials(CM)can improve methane production(MP)efficiency in many methanogenic systems.However,several types of CM exist,and there are uncertainties regarding whether they all improve MP efficiency to the same extent and modulate microbial communities in a similar way.To investigate that,different microbial enrichments with and without activated carbon(AC),magnetite(Mag),and zeolites(Zeo)(at 0.5 g/L)were developed.MP profiles and microbial composition changes were compared among enrichments.The behavior of all enrichments was different,although the initial inoculum sludge was the same.Lag phase duration was lower in AC enrichment,while the complete conversion of butyrate to methane was faster in Mag enrichment.Syntrophomonas was the most abundant bacterial genus in all enrichments,but changes in the methanogenic community were evident.Acetoclastic methanogens were more diverse in Mag enrichment,with microorganisms assigned to Methanosarcina and Methanothrix gener1,but Methanothrix was the only acetoclastic methanogen in the other enrichments.On the other hand,different species of hydrogenotrophic methanogens prevailed in distinct enrichments.The metatranscriptomics results revealed that the dominant mechanism of interspecies electron transfer in the AC enrichment utilized hydrogen as the electron carrier,and no evidences of direct interspecies electron transfer(DIET)could be found.These results showed how different CM modulate microbial communities and affect MP efficiency through mechanisms that do not necessarily involve DIET or mediation via CM.
基金Supported by Provincial Key Research Project of Henan Province,No.232102310081.
文摘BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.
文摘Objective:To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of Amaranthus caudatus,Amaranthus spinosus and Amaranthus viridis in normal and streptozotocin(STZ) induced diabetic rats.Methods:In this study,the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of all three plants was evaluated by using normal and STZ induced diabetic rots at a dose of 200 mg/kg and 400 mg/kg p.o.daily for 21 days.Blood glucose levels and body weight were monitored at specific intervals,and different biochemical parameters,serum cholesterol,serum triglyceride,high density lipoprotein, low density lipoprotein and very low density lipoprotein were also assessed in the experimental animals.Histology of pancreas was performed.Results:It was found that all the three plants at 400 mg/kg dose showed significant anti-diabetic and anti-cholesterolemic activity(P<0.01),while at 200 mg/kg dose less significant anti-diabetic activity(P<0.05) was observed.Concluslons: Methanol extracts of Amaranthus caudatus,Amaranlhus spinosus and Amaranthus viridis showed significant anti-diabetic and anti-cholesterolemic activity,which provides the scientific proof for their traditional claims.
基金supported by the National Natural Science Foundation of China (Grant Nos.T2325027,12274448,T2350007,12404239,12174041,12325405,12090054,and T2221001)the National Key R&D Program of China (Grant No.2022YFF0503504)。
文摘The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence is still lacking.To validate this framework,here we employ a programmable robotic platform,where a single light-controlled wheeled robot travels in an activity landscape.Our experiments quantitatively demonstrate that the intrinsic pressure difference across the activity interface is balanced by the emerged polarization force.This result unambiguously confirms the theoretical predictions,thus validating the intrinsic pressure framework and laying the experimental foundation for the intrinsic pressure-based mechanical description of dry active matter.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Supported by a grant of doctoral dissertation research from Education Ministry of Indonesia
文摘Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata(U. lobata) through dipeptidyl peptidase IV(DPP-IV) inhibitory activity.Methods: U. lobata leaf was extracted in hot water and ethanol. The activity of DPPIV inhibitor was tested by in vitro study using gly-pro-p-nitroanilide as substrat of DPPIV and vildagliptin, as standard reference. A product of the reactions between gly-pro-pnitroanilide and DPP-IV, was observed by microplate readers with λ = 405 nm. All data were expressed as mean ± SD and the IC50 value was determined by non linear regression curve fit. Active substances in leaf extract of U. lobata was analyzed by liquid chromatography-mass spectrometry. DPP-IV inhibitory activity of active compounds was evaluated in silico using docking server. Results: The ethanolic extract of U. lobata showed stronger DPP-IV inhibitor activity than water extract with the IC50 values of 1 654.64 and 6 489.88 μg/mL, respectively. Vildagliptin, based on standard reference for DPP-IV inhibitor activity, has IC50 value of 57.44 μg/mL. Based on in silico analysis, mangiferin, stigmasterol and β-sitosterol in U. lobata extract have a strong inhibitory activity on DPP-IV. Conclusions: The results showed that DPP-IV inhibitory activity of U. lobata is related to its active compounds such as mangiferin, stigmasterol and β-sitosterol.
文摘To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.
基金Key Project of Undergraduate Teaching Reform Research of Shandong Normal University(No.2024ZJ12)sixth batch of"Sports and Health"special topic of Education Research of Chinese Society of Education。
文摘Diabetes mellitus(DM)has become one of the most serious and common chronic diseases around the world,leading to various complications and a reduction in life expectancy.Increased sedentary behavior(SB)and decreased physical activity(PA)are important contributors to the rising prevalence of DM.This article reviews the research progress on the pathogenesis of DM,the effects of SB and PA on the risk of DM,aiming to explore the influence of different PA intensities,amounts,frequencies,durations and types on the incidence of DM.Research has shown that blood glucose levels tend to increase with the prolongation of SB.Within a certain range,PA intensity and PA amount are negatively correlated with the risk of DM;Performing PA for more than 3 days per week maintains normal glucose tolerance and lower blood pressure;Engaging in 150–300 min of moderate intensity exercise or 75–150 min of high-intensity exercise per week reduces the risk of DM;PA during leisure time reduces the risk of DM,while PA during work increases the risk of DM;Both aerobic training and resistance training reduce the risk of DM,and the combination of the two training methods produces better benefits;Various types of exercises,such as cycling,soccer,aerobics,yoga,tai chi,all reduce the risk of DM.In summary,prolonged SB increases the risk of DM,while appropriate PA reduces the risk of DM.As the intensity,amount,and frequency of PA increase,the effect of reducing DM risk becomes more significant.Different exercise methods have different effects on reducing DM risk.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
文摘Plants are used traditionally throughout the globe to treat various diseases.Traditionally used medicinal plants are an essential part of the health sector in Bangladesh due to its abundance of a vast source of ethno-medicine.Rural people from developing country like Bangladesh are greatly dependent on traditional source of medicine.The prevalence of diabetes mellitus is increasing from recent years; therefore various researches are going on to discover better medicine to treat this disease.This study has focused on five plants which are Andrographis paniculata, Ageratum conyzoides, Swertia chirata, Terminalia arjuna, and Azadirachta indica to find out their traditional formulation as anti-diabetic medicine and their pharmacological activity has also been explored through literature search.The available information about traditional anti-diabetic uses of these plants and their pharmacological activities were collected from various electronic sources like Pubmed, Sci Finder, Elsevier, Springer, Scopus, Scirus, Science Direct, Google Scholar and Web of Science apart from these locally available books and peer reviewed journal were also used to collect information.This study will help to strengthen the relation between traditional medicine, pharmacology and drug development.A clue may be found from the information provided this review to discover new and better anti-diabetic drugs.
基金supported by the National Natural Science Foundation of China(Nos.82405016 and 82141216)the Project of Frontier Technology Platform for Research Projects of Liaoning Provincial Department of Education in 2024(No.LJ232410163056)+3 种基金"Select the best candidates to lead key research projects"of Fujian University of Traditional Chinese Medicine(Nos.XJB2022008 and XJB2023001)the Foundation of Fujian University of Traditional Chinese Medicine(Nos.X2023001-Talent and X2024002-Talent)the Young and Middle-aged Teacher Education Research Project in Fujian Province(No.JZ230023)the Central Government Guides Local Science and Technology Development Fund Projects(No.2023L3014).
文摘Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpenoids(euphorwallside H and euphorwallside I,14 and 15),were isolated and characterized from Euphorbia wallichii(E.wallichii).The chemical structures of these compounds were elucidated through nuclear magnetic resonance(NMR),mass spectrometry(MS),and quantum chemical calculations.Compounds 9 and 11 demonstrated protective effects against H2O2-induced BV-2 microglial cell damage.Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR,GSTP1,and SHBG.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U23A20530,82273858,and 82173746)the National Key Research and Development Programof China(Grant No.:2023YFF1204904)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,China).
文摘Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pretraining.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.
基金funded by the National Key Research and Development Program of China(No.2022YFC2804101)the Guangdong Provincial Key R&D Program(No.2023B1111050011)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)the Guangzhou Basic and Applied Basic Research Foundation(No.202201010305)the High-Level Talents Special Program of Zhejiang(No.2022R52036)。
文摘Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.
基金supported by the National Natural Science Foundation of China,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
文摘BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple prognostic assessment indicators for ACLF,the overall sensitivity and accuracy are relatively low.AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein(AFP),plasma prothrombin activity(PTA),and serum prealbumin(PA)in ACLF.METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival(n=47)and death(n=40)groups according to their clinical outcomes 3 months posttreatment.All the participants underwent AFP,PTA,and PA level measurements upon admission.Baseline data,as well as AFP,PTA,and PA levels,were comparatively analyzed.Pearson correlation coefficients were utilized to analyze the correlations of AFP,PTA,and PA with different survival outcomes in patients with ACLF.Receiver operating characteristic(ROC)curves and areas under the curves were used to evaluate the predictive value of AFP,PTA,and PA for ACLF prognosis.RESULTS AFP,PTA,and PA levels were markedly decreased in the death group than in the survival group(P<0.05).Pearson analysis indicated a positive association of the AFP,PTA,and PA levels with the survival of patients with ACLF(P<0.05).ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24%and 100.00%,respectively,both of which were notably increased compared to the single-index diagnosis.The ROC of their combined diagnosis was 0.989,significantly surpassing 0.907,0.849,and 0.853 of AFP,PTA,and PA,respectively.No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection(P>0.05).CONCLUSION The combined detection of AFP,PTA,and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF,featuring high sensitivity and specificity.
基金supported by the National Natural Science Foundation of China(Grant No.:82474195)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:021093002882)+2 种基金the Youth Medical Innovation Research Project of China(Grant No.:P24021887623)Taizhou Science and Technology Support Project,China(Grant No.:TS202420)grants from Nanjing Medical University,China(Grant Nos.:TZKY20230104 and 2024KF0292).
文摘Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
基金funded by the S&T Program of Hebei(No.21323202D)the Natural Science Interdisciplinary Research Program of Hebei University(No.DXK201913)+4 种基金the Natural Sci-ence Foundation of Hebei Province of China(Nos.H2024201028,H2020201029)the Excellent Youth Research Innovation Team of Hebei University(No.QNTD202406)the Hebei University Research and Innovation Team(No.IT2023C1)the Innovation Capacity Improvement Plan of Hebei Province(No.20567605H)the National Training Program of Innovation and Entrepreneurship for Undergraduates(No.DC2024177)。
文摘Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism(ECD)/optical rotatory dispersion(ORD)methods,and X-ray crystallography.Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system,which is presumably biosynthesized via a[4+2]cycloaddition and an enzymatic cyclization.Chaeglobol A(1)exhibited inhibitory activity against B.dothidea by destroying cell membrane integrity and causing oxidative damage within the cells.
基金financially supported by the National Natural Science Foundation of China (52474338,22109084 and 52304338)the Hunan Provincial Key Research and Development Program (2024JK2093,2023GK2016)supported in part by the High Performance Computing Center of Central South University.
文摘Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy density.However,the all-solid-state batteries with nickel-rich oxide cathodes suffer from performance degradation due to the reactions between the highly reactive surface oxygen of the cathode and the electrolyte,as well as the instability of the bulk oxygen structure in the cathode.Herein,we propose a synergistic modification design scheme to adjust the oxygen activity from surface to bulk.The LiBO_(2)coating inhibits the reactivity of surface lattice oxygen ions.Meanwhile,Zr doping in the bulk phase forms strong Zr-O covalent bonds that stabilize the bulk lattice oxygen structure.The synergistic effect of these modifications prevents the release of oxygen,thus avoiding the degradation of the cathode/SE interface.Additionally,the regulation of surface-to-bulk oxygen activity establishes a highly stable interface,thereby enhancing the lithium ion diffusion kinetics and mechanical stability of the cathode.Consequently,cathodes modified with this synergistic strategy exhibit outstanding performance in sulfide-based ASSLBs,including an ultra-long cycle life of 100,000 cycles,ultra-high rate capability at 45C,and 85% high active material content in the composite cathode.Additionally,ASSLB exhibits stable cycling under high loading conditions of 82.82 mg cm^(-2),achieving an areal capacity of 17.90 mA h cm^(-2).These encouraging results pave the way for practical applications of ASSLBs in fast charging,long cycle life,and high energy density in the future.
