Objective:To study the morphology,biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica(C.parasitica)(L.) H.Lev.Methods: Morphological studies on epidermal glands we...Objective:To study the morphology,biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica(C.parasitica)(L.) H.Lev.Methods: Morphological studies on epidermal glands were earned out by using light microscope and scanning electron microscope.To prepare the extract,the shade-dried fronds of glandular morphotype were soaked in acetone.For antibacterial studies paper disc method was followed by using various pathogenic bacteria.Results:Detailed micromorphological,phytochemical and bioactivity studies on a medicinal fern C.parasitica(L.) H.Lev.showed its inlraspecific variation in antibacterial activity.The presence or absence of the epidermal glands was the key factor for antibacterial activity in the morphovariants of this species.The epidermal glands were orange-coloured,stalked and elongated ones of about 84.2μm×45μm,and distributed on the undersurface of cosla,coslules and veins in croziers,young and mature leaves.Frequency of glands varied from 15/cm on costa in mature leaves to 140/cm on costules in croziers.The acetone extract of the glands showed antibacterial activities and also toxic effect against mosquito larvae and tadpoles of frog.Preliminary phytochemical analysis and HPLC studies of the gland extract showed the presence of various kinds of terpenoids,alkaloids,tannins,saponins and flavonoids in it.Conclusions:The present study shows that epidermal glands of the glandular morphotype of C. parasitica(L.) H.Lev.have several bioactive compounds and such rare moiphovariant should be conserved in nature.The next step is to isolate the pure compounds and to screen the bioactivity of individual compounds of the epidermal glands.展开更多
The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcal...The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid(3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid(3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid(4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power–time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs(IC50) were obtained by quantitative analysis. Based on the quantity–activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.展开更多
Objective:To investigate the anti-biofilm and anti-bacterial activity of Junceella juncea(J.juncea)against biofilm forming pathogenic strains.Methods:Gorgonians were extraeted with methanol and analysed with fourier t...Objective:To investigate the anti-biofilm and anti-bacterial activity of Junceella juncea(J.juncea)against biofilm forming pathogenic strains.Methods:Gorgonians were extraeted with methanol and analysed with fourier transform infrared spectroscopy.Biofilm forming pathogens were identified by Congo red agar supplemented with sucrose.A quantitative spectrophotometric method was used to monitor in vitro biofilm reduction by microtitre plate assay.Anti-bacterial activity of methanolic gorgonian extract(MGE)was carried out by disc diffusion method followed by calculating the percentage of increase with crude methanol(CM).Results:The presence of active functional group was exemplified by FT-IR spectroscopy.Dry,black,crystalline colonies confirm the production of extracellular polymeric substances responsible for biofilm formation in Congo red agar.MGE exhibited potential anti-biofilm activity against all tested bacterial strains.The anti-bacterial activity of methanolic extract was comparably higher in Salmonella typhii followed by Escherichia colt,Vibrio cholerae and Shigella flexneri.The overall percentage of increase was higher by 50.2%to CM.Conclusions:To conclude,anti-biofilm and anti-bacterial efficacy of J.juncea is impressive over biofilm producing pathogens and are good source for novel anti-bacterial compounds.展开更多
In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot, three-component reaction of an aldehyde, malononitrile and benzamidine hydrochloride, in the presence of m...In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot, three-component reaction of an aldehyde, malononitrile and benzamidine hydrochloride, in the presence of magnetic nano Fe304 particles as a catalyst under solvent-free conditions. 3-Amino-6-aryl- 2-phenylpyrazolo[3,4-d]pyrimidine derivatives were prepared through an efficient and environmentally friendly reaction between 4-amino-6-aryl-2-phenylpyrimidine-5-carbonitrile derivatives and hydra- zine hvdrate and their antibacterial activity has been evaluated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
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
Hydrogel-based flexible sensors are emerging as ideal candidates for wearable devices and soft robotics.However,most current hydrogels possess limited physicochemical properties,which hinder their practical applicatio...Hydrogel-based flexible sensors are emerging as ideal candidates for wearable devices and soft robotics.However,most current hydrogels possess limited physicochemical properties,which hinder their practical application in long-term and complex scenarios.Herein,inspired by the unique structure of the barnacle,we design multifunctional poly(DMAPA-co-PHEA)hydrogels(CP hydrogels)by employing multiple physical crosslinks in the presence of Ag nanoparticles and NaCl additives.Owing to the synergistic effect of cation-πinteractions,hydrophobic interactions,and ionic bonds,the CP hydrogels exhibit high stretchability(strain up to 1430%),strong adhesion(22.8 kPa),satisfactory antibacterial activity,stable anti-icing ability(<20 kPa after 20 icing-deicing cycles),and high electrical conductivity(18.5 mS/cm).Additionally,the CP hydrogels show fast and sensitive responsiveness and cycling stability and can attach directly to human skin to accurately detect both human motions and tiny physiological signals as a flexible wearable sensor.Collectively,this work significantly contributes a straightforward and efficient design strategy for the development of multifunctional hydrogels,broadening their application scenarios.展开更多
Cranberry,the fruit of Vaccinium macrocarpon Aiton,is becoming popular all over the world,due to its pleasant taste,nutraceutical value and biological activities.For a long time,98%of its yield has been from America.S...Cranberry,the fruit of Vaccinium macrocarpon Aiton,is becoming popular all over the world,due to its pleasant taste,nutraceutical value and biological activities.For a long time,98%of its yield has been from America.Since being introduced to China as an import in recent decades,cranberry has become a rapid success in the food industry even with the high transportation cost.Recently,V.macrocarpon was cultivated in the Northeast of China,and the area of cultivation has increased dramatically.Therefore,it is important to systematically determine the useful compounds and their activity in this“Made-in-China”cranberry.In the present study,the content of total phenolics,anthocyanins,proanthocyanidins,sugars and organic acids was determined.Our results demonstrated that domestic cranberry is a rich source of phenolics,anthocyanins,proanthocyanidins,sugars and organic acids.Analysis of the chemical composition of an acidic ethanol extract by UPLC-QTOF-MS identified 21 compounds as well as the contents determination of catechin and cyanidin-3-O-glucoside using RPHPLC.Furthermore,cranberry extract was tested for its anti-bacterial activity against five clinically important pathogens,as well as its inhibitory effect on the proliferation and migration of cancer cells in vitro.Our results demonstrated that cranberry produced in Chinese cultivation areas is a rich source of bioactive compounds and exhibited in vitro anti-microbial and anti-tumor activities.Our work provides essential information about the quality of domestic cranberry and facilitates the development of related industries.展开更多
Objective:To evaluate in ritro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential.Methods:A total of 58 traditional Chinese medicinal plants were c...Objective:To evaluate in ritro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential.Methods:A total of 58 traditional Chinese medicinal plants were carefully selected based on the literature review and their traditional use.The antimicrobial activities of ethanol extracts of these medicinal plants were tested against fungi(Aspergillus funigaius),yeast(Candida albicans),gram-negative(Acirelobacter haumannii and Pseudornnruis aeruginosa)and gram-positive bacteria(Staphglococcus aureus).The activities were tested at three different concentrations of 1.00,0.10 and 0.01 mg/mL.The data was analysed using Gene data Screener program.Results:The measured antimicrobial activities indicated that out of the 58 plant extracts,15 extracts showed anti-fungal activity and 23 extracts exhibited anti-bacterial activity.Eight plant extracts have exhibited both anti-bacterial and anti-fungal activities.For instance,Eucommia ulmoides,Pohgonum cuspidcrtum,Poria cocas and Uncaria rhineophylla showed activity against both bacterial and fungal strains,indicating their broad spectrum of activity.Conclusions:The results revealed that the ethanol extracts of 30 plants out of the selected 58 possess significant antimicrobial activities.It is interesting to note that the findings from the current study are consistent with the traditional use.A clear correlation has also been found between the antimicrobial activity and the flavonoid content of the plant extracts which is in agreement with the literature.Hence.the results presented here can be used to guide the selection of potential plant species for the isolation and structure elucidation of novel antimicrobial compounds in order to establish the structure-activity relationship.This in turn is expected to lead the way to the discovery of novel antimicrobial agents for therapeutic use.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
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
文摘Objective:To study the morphology,biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica(C.parasitica)(L.) H.Lev.Methods: Morphological studies on epidermal glands were earned out by using light microscope and scanning electron microscope.To prepare the extract,the shade-dried fronds of glandular morphotype were soaked in acetone.For antibacterial studies paper disc method was followed by using various pathogenic bacteria.Results:Detailed micromorphological,phytochemical and bioactivity studies on a medicinal fern C.parasitica(L.) H.Lev.showed its inlraspecific variation in antibacterial activity.The presence or absence of the epidermal glands was the key factor for antibacterial activity in the morphovariants of this species.The epidermal glands were orange-coloured,stalked and elongated ones of about 84.2μm×45μm,and distributed on the undersurface of cosla,coslules and veins in croziers,young and mature leaves.Frequency of glands varied from 15/cm on costa in mature leaves to 140/cm on costules in croziers.The acetone extract of the glands showed antibacterial activities and also toxic effect against mosquito larvae and tadpoles of frog.Preliminary phytochemical analysis and HPLC studies of the gland extract showed the presence of various kinds of terpenoids,alkaloids,tannins,saponins and flavonoids in it.Conclusions:The present study shows that epidermal glands of the glandular morphotype of C. parasitica(L.) H.Lev.have several bioactive compounds and such rare moiphovariant should be conserved in nature.The next step is to isolate the pure compounds and to screen the bioactivity of individual compounds of the epidermal glands.
基金supported the National Natural Science Foundation of China(No.81073069)
文摘The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid(3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid(3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid(4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power–time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs(IC50) were obtained by quantitative analysis. Based on the quantity–activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.
基金Supported by DST-NRDMS,Government of India(grant No.041594/F3/2008/dt.08.12.2010)
文摘Objective:To investigate the anti-biofilm and anti-bacterial activity of Junceella juncea(J.juncea)against biofilm forming pathogenic strains.Methods:Gorgonians were extraeted with methanol and analysed with fourier transform infrared spectroscopy.Biofilm forming pathogens were identified by Congo red agar supplemented with sucrose.A quantitative spectrophotometric method was used to monitor in vitro biofilm reduction by microtitre plate assay.Anti-bacterial activity of methanolic gorgonian extract(MGE)was carried out by disc diffusion method followed by calculating the percentage of increase with crude methanol(CM).Results:The presence of active functional group was exemplified by FT-IR spectroscopy.Dry,black,crystalline colonies confirm the production of extracellular polymeric substances responsible for biofilm formation in Congo red agar.MGE exhibited potential anti-biofilm activity against all tested bacterial strains.The anti-bacterial activity of methanolic extract was comparably higher in Salmonella typhii followed by Escherichia colt,Vibrio cholerae and Shigella flexneri.The overall percentage of increase was higher by 50.2%to CM.Conclusions:To conclude,anti-biofilm and anti-bacterial efficacy of J.juncea is impressive over biofilm producing pathogens and are good source for novel anti-bacterial compounds.
文摘In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot, three-component reaction of an aldehyde, malononitrile and benzamidine hydrochloride, in the presence of magnetic nano Fe304 particles as a catalyst under solvent-free conditions. 3-Amino-6-aryl- 2-phenylpyrazolo[3,4-d]pyrimidine derivatives were prepared through an efficient and environmentally friendly reaction between 4-amino-6-aryl-2-phenylpyrimidine-5-carbonitrile derivatives and hydra- zine hvdrate and their antibacterial activity has been evaluated
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.
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financial support from the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515012218)Macao Science and Technology Development Fund(Nos.FDCT 0009/2020/AMJ,0027/2023/RIB1)+1 种基金National Natural Science Foundation of China(No.32301104)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.23ptpy165).
文摘Hydrogel-based flexible sensors are emerging as ideal candidates for wearable devices and soft robotics.However,most current hydrogels possess limited physicochemical properties,which hinder their practical application in long-term and complex scenarios.Herein,inspired by the unique structure of the barnacle,we design multifunctional poly(DMAPA-co-PHEA)hydrogels(CP hydrogels)by employing multiple physical crosslinks in the presence of Ag nanoparticles and NaCl additives.Owing to the synergistic effect of cation-πinteractions,hydrophobic interactions,and ionic bonds,the CP hydrogels exhibit high stretchability(strain up to 1430%),strong adhesion(22.8 kPa),satisfactory antibacterial activity,stable anti-icing ability(<20 kPa after 20 icing-deicing cycles),and high electrical conductivity(18.5 mS/cm).Additionally,the CP hydrogels show fast and sensitive responsiveness and cycling stability and can attach directly to human skin to accurately detect both human motions and tiny physiological signals as a flexible wearable sensor.Collectively,this work significantly contributes a straightforward and efficient design strategy for the development of multifunctional hydrogels,broadening their application scenarios.
基金This study was financially supported by“Liaoning Provincial Engineering Platform of the Development and Utilization of Endangered and Geo-authentic Medicinal Herbs”and“Propagation of Cranberry and the Establishment of Germplasm Resource Nursery(YZ2018ZR01)”.
文摘Cranberry,the fruit of Vaccinium macrocarpon Aiton,is becoming popular all over the world,due to its pleasant taste,nutraceutical value and biological activities.For a long time,98%of its yield has been from America.Since being introduced to China as an import in recent decades,cranberry has become a rapid success in the food industry even with the high transportation cost.Recently,V.macrocarpon was cultivated in the Northeast of China,and the area of cultivation has increased dramatically.Therefore,it is important to systematically determine the useful compounds and their activity in this“Made-in-China”cranberry.In the present study,the content of total phenolics,anthocyanins,proanthocyanidins,sugars and organic acids was determined.Our results demonstrated that domestic cranberry is a rich source of phenolics,anthocyanins,proanthocyanidins,sugars and organic acids.Analysis of the chemical composition of an acidic ethanol extract by UPLC-QTOF-MS identified 21 compounds as well as the contents determination of catechin and cyanidin-3-O-glucoside using RPHPLC.Furthermore,cranberry extract was tested for its anti-bacterial activity against five clinically important pathogens,as well as its inhibitory effect on the proliferation and migration of cancer cells in vitro.Our results demonstrated that cranberry produced in Chinese cultivation areas is a rich source of bioactive compounds and exhibited in vitro anti-microbial and anti-tumor activities.Our work provides essential information about the quality of domestic cranberry and facilitates the development of related industries.
基金funded by the University of Western Sydney and the Fundacion MEDINAa public-private partnership of Merck Sharp&Dohme de Espana S.A./Universidad de Granada/Junta de Andalucia
文摘Objective:To evaluate in ritro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential.Methods:A total of 58 traditional Chinese medicinal plants were carefully selected based on the literature review and their traditional use.The antimicrobial activities of ethanol extracts of these medicinal plants were tested against fungi(Aspergillus funigaius),yeast(Candida albicans),gram-negative(Acirelobacter haumannii and Pseudornnruis aeruginosa)and gram-positive bacteria(Staphglococcus aureus).The activities were tested at three different concentrations of 1.00,0.10 and 0.01 mg/mL.The data was analysed using Gene data Screener program.Results:The measured antimicrobial activities indicated that out of the 58 plant extracts,15 extracts showed anti-fungal activity and 23 extracts exhibited anti-bacterial activity.Eight plant extracts have exhibited both anti-bacterial and anti-fungal activities.For instance,Eucommia ulmoides,Pohgonum cuspidcrtum,Poria cocas and Uncaria rhineophylla showed activity against both bacterial and fungal strains,indicating their broad spectrum of activity.Conclusions:The results revealed that the ethanol extracts of 30 plants out of the selected 58 possess significant antimicrobial activities.It is interesting to note that the findings from the current study are consistent with the traditional use.A clear correlation has also been found between the antimicrobial activity and the flavonoid content of the plant extracts which is in agreement with the literature.Hence.the results presented here can be used to guide the selection of potential plant species for the isolation and structure elucidation of novel antimicrobial compounds in order to establish the structure-activity relationship.This in turn is expected to lead the way to the discovery of novel antimicrobial agents for therapeutic use.
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.
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.
