Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as ...Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.展开更多
Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identifi...Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identified numerous crystal structures with the Li_(3)MX_(6)composition,although many remain unexplored across various chemical systems.In this research,we developed a comprehensive method to examine all conceivable space groups and structures within theLi-M-X system,where M includes In,Ga,and La,and X includes F,Cl,Br,and 1.Our findings revealed two metastable structures:Li_(3)InF_(6)with P3c1 symmetry and Li_(3)InI_(6)with C2/c symmetry,exhibiting ionic conductivities of 0.55 and 2.18mS/cm at 300K,respectively.Notably,the trigonal symmetry of Li3InF6 demonstrates that high ionic conductivities are not limited to monoclinic structures but can also be achieved with trigonal symmetries.The electrochemical stability windows,mechanical properties,and reaction energies of these materials with known cathodes suggest their potential for use in all-solid-state batteries.Additionally,we predicted the stability of novel materials,including Li_(5)InCl_(8),Li_(5)InBr_(8),Li_(5)InI_(8),LiIn_(2)Cl_(9),LiIn_(2)Br_(9),and LiIn_(2)I_(9).展开更多
For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,end...For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.展开更多
Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study...Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study introduces a novel Fuzzy Nonlinear Additive Regression(FNAR)model to predict monthly GWL in an unconfined aquifer in eastern Iran,using a 19-year(1998–2017)dataset from 11 piezometric wells.Under three distinct scenarios with progressively increasing input complexity,the study utilized readily available climate data,including Precipitation(Prc),Temperature(Tave),Relative Humidity(RH),and Evapotranspiration(ETo).The dataset was split into training(70%)and validation(30%)subsets.Results showed that among three input scenarios,Scenario 3(Sc3,incorporating all four variables)achieved the best predictive performance,with RMSE ranging from 0.305 m to 0.768 m,MAE from 0.203 m to 0.522 m,NSE from 0.661 to 0.980,and PBIAS from 0.771%to 0.981%,indicating low bias and high reliability.However,Sc2(excluding ETo)with RMSE ranging from 0.4226 m to 0.9909 m,MAE from 0.3418 m to 0.8173 m,NSE from 0.2831 to 0.9674,and PBIAS from−0.598%to 0.968%across different months offers practical advantages in data-scarce settings.The FNAR model outperforms conventional Fuzzy Least Squares Regression(FLSR)and holds promise for GWL forecasting in data-scarce regions where physical or numerical models are impractical.Future research should focus on integrating FNAR with deep learning algorithms and real-time data assimilation expanding applications across diverse hydrogeological settings.展开更多
[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]T...[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.展开更多
The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated....The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated.By adjusting the furnace cooling time after solution treatment and the aging temperature,Ti6422 alloy samples were developed with a multi-level lamellar microstructure,in-cluding microscaleαcolonies and α_(p) lamellae,as well as nanoscale α_(s) phases.Extending the furnace cooling time after solution treatment at 920℃ for 1 h from 240 to 540 min,followed by aging at 600℃ for 6 h,increased the α_(p) lamella content,reduced the α_(s) phase content,expanded theαcolonies and α_(p) lamellae size,and improved the impact toughness from 22.7 to 53.8 J/cm^(2).Additionally,under the same solution treatment,raising the aging temperature from 500 to 700℃ resulted in a decrease in the α_(s) phase content and a growth in the thickness of the α_(p) lamella and α_(s) phase.The impact toughness increased significantly with these changes.Samples with high α_(p) lamellae content or large α_(s) phase size exhibited high crack initiation and propagation energies.Impact deformation caused severe kinking of the α_(p) lamellae in crack initiation and propagation areas,leading to a uniform and high-density kernel average misorientation(KAM)distribu-tion,enhancing plastic deformation coordination and uniformity.Moreover,the multidirectional arrangement of coarserαcolonies and α_(p) lamellae continuously deflect the crack propagation direction,inhibiting crack propagation.展开更多
As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lu...As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.展开更多
In the realm of biomedical materials,biomedical magnesium(Mg)alloy materials are progressively emerging as a highly salient research focal point,capitalizing on their distinctive advantages.Mg,as a unique metallic ele...In the realm of biomedical materials,biomedical magnesium(Mg)alloy materials are progressively emerging as a highly salient research focal point,capitalizing on their distinctive advantages.Mg,as a unique metallic element,by virtue of its specific properties,has ushered in novel development opportunities for the biomedical domain[1-3].Firstly,Mg manifests outstanding biodegradability.展开更多
Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the ...Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.展开更多
The Ethical Turn is commonly supposed to have occurred around 1988.In that year,Wayne C.Booth published The Company We Keep,a book considered to be the first attempt to rehabilitate moral judgement in literary critics...The Ethical Turn is commonly supposed to have occurred around 1988.In that year,Wayne C.Booth published The Company We Keep,a book considered to be the first attempt to rehabilitate moral judgement in literary critics and theory.The Ethical Turn can have various consequences for literary theory and criticism.In this paper,I try to describe and examine some,mainly those that concern the possibility of an ethics-based narratology.Are the attempts to define it in the last thirty years satisfactory?What kind of description of narrative structures can they give us?Must an ethics-based narratology be focused on the notion of character?Can it deal with the notion of plot,with the problem of temporality?Should it be necessarily linked with one of the different schools of ethical philosophy?Do different philosophical tendencies lead us to different kinds of narratology?After discussing these questions,I propose some paths for future research in moral narratology.展开更多
In the printing industry,vacuum pumps play a critical role in sheet feeding and gripping processes.In order to improve the efficiency of vacuum pumps,By analyzing the internal flow field of the vane type vacuum pump,t...In the printing industry,vacuum pumps play a critical role in sheet feeding and gripping processes.In order to improve the efficiency of vacuum pumps,By analyzing the internal flow field of the vane type vacuum pump,the CFD method was used to simulate the internal flow field of the air pump,and it was found that a main vortex was formed near the rotor of the trailing blade.Based on this observation,a new rotor shape design was proposed in this study,which design places arc-shaped depressed on the circumference of the rotor where the main vortex forms.The existence of the depression facilitated forward motion of the main airflow and thus effectively restricting reverse flow.Simulation results demonstrated that the proposed design is able to decrease pressure-induced torque load on the pump,and the reduction increases for an increasing operating speed.For all three operating speeds tested,the reduction in pressure-induced torque ranges from 5%to up to 10%comparing to the original pump.展开更多
In recent years,the concept of digital human has attracted widespread attention from all walks of life,and the modelling of high-fidelity human bodies,heads,and hands has been intensively studied.This paper focuses on...In recent years,the concept of digital human has attracted widespread attention from all walks of life,and the modelling of high-fidelity human bodies,heads,and hands has been intensively studied.This paper focuses on head modelling and proposes a generic head parametric model based on neural radiance fields.Specifically,we first use face recognition networks and 3D facial expression database FaceWarehouse to parameterize identity and expression semantics,respectively,and use both as conditional inputs to build a neural radiance field for the human head,thereby improving the head model’s representation ability while ensuring editing capabilities for the identity and expression of the rendered results;then,through a combination of volume rendering and neural rendering,the 3D representation of the head is rapidly rendered into the 2D plane,producing a high-fidelity image of the human head.Thanks to the well-designed loss functions and good implicit representation of the neural radiance field,our model can not only edit the identity and expression independently,but also freely modify the virtual camera position of the rendering results.It has excellent multi-view consistency,and has many applications in novel view synthesis,pose driving and more.展开更多
This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabe...This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment modalities.This editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic retinopathy.It also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
Ethan Wargo,9 years old,sets up a small table on his lawn each morning in Sycamore,Illinois,waiting for people to walk by so that he can offer a compliment to anyone who stops to talk.In mid‑July 2025,Ethan launched w...Ethan Wargo,9 years old,sets up a small table on his lawn each morning in Sycamore,Illinois,waiting for people to walk by so that he can offer a compliment to anyone who stops to talk.In mid‑July 2025,Ethan launched what he calls a“compliments stand”,spending up to five hours a day at his table.The idea was inspired by a scene in a recent graphic(绘画的)novel,where characters run a stand.He parked himself next to his twin sister,Claire,who sells her artwork at her own stand,but Ethan knew charging for compliments didn't feel right.“I didn't want people to pay to be happy,”he said.“Paying for something like that is very silly.”展开更多
这座位于英国巴斯的简·奥斯汀中心让参观者领略到了《傲慢与偏见》作者简·奥斯汀笔下的风情与智慧。Jane Austen,a famous English writer,was born in December,1775.Although she died at just forty-two years of age,she ...这座位于英国巴斯的简·奥斯汀中心让参观者领略到了《傲慢与偏见》作者简·奥斯汀笔下的风情与智慧。Jane Austen,a famous English writer,was born in December,1775.Although she died at just forty-two years of age,she completed six novels in her lifetime,which have been translated into dozens of languages,sold tens of millions of copies and have been adapted for television and film.展开更多
Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestin...Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestinal bacteria are promising potential producers of novel carbohydrate-active enzymes with unique properties.Here,a novel glycoside hydrolase family 128(GH128)laminarinase OUC-BsLam26 from the intestinal bacterium Bacteroides sp.CBA7301 was heterologously expressed and characterized.The recombinant OUC-BsLam26 with a molecular mass of 49.86 kDa exhibits highest activity(6.60 U/mg)at 45℃ and pH 6.0,which shows noticeable temperature and pH stability.The purified OUC-BsLam26 could degrade laminarin via an endo-type mode with the generation of laminaripentaose,laminaritetraose,laminaritriose,and laminaribiose,among them,laminaritetraose is the principal product,which accounts for 45.25% of the total products,which is significantly different from the reported GH128 laminarinases.The minimum recognition substrate of OUC-BsLam26 is laminarihexaose.Furthermore,OUC-BsLam26 also could catalyze the transglycosylation process with the production of some novel glycosides.Altogether,the intestinal bacterium Bacteroides sp.CBA7301 contains laminarinase with unique product composition and OUC-BsLam26 is a hopeful bio-catalyst with the potential to produce laminaritetraose and some novel glycosides.展开更多
This study analyzes Agatha Christie’s mystery novel And Then There Were None from five dimensions—the nursery rhyme,Soldier Island,role of characters,death and psychological interaction—to explore its multi-dimensi...This study analyzes Agatha Christie’s mystery novel And Then There Were None from five dimensions—the nursery rhyme,Soldier Island,role of characters,death and psychological interaction—to explore its multi-dimensional metaphors and their deeper connotations.The key findings reveal that the nursery rhyme serves as a narrative thread,symbolizing both a fate-driven trial and societal rules manipulating individual destinies;Soldier Island’s isolation mirrors moral problem and emotional detachment in modern society;the characters,linked to their crimes and deaths,embody universal human flaws;death acts as both a form of justice and a critique of civilization’s fragility;the psychological struggles among the characters expose the collapse of morality under survival crises.By decoding these interconnected metaphors,the study interprets the work’s thematic framework of Sin and Punishment,offering insights into tensions between societal norms and individual existence today.展开更多
Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and a...Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and animals.The Bocaparvovirus genome.展开更多
文摘Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.
基金supported by the Higher Education and Science Committee of Armenia in the frames of the research projects 20TTSG-2F010, 23AA-2F033 and ANSEF (EN-matsc-2660) grant.
文摘Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identified numerous crystal structures with the Li_(3)MX_(6)composition,although many remain unexplored across various chemical systems.In this research,we developed a comprehensive method to examine all conceivable space groups and structures within theLi-M-X system,where M includes In,Ga,and La,and X includes F,Cl,Br,and 1.Our findings revealed two metastable structures:Li_(3)InF_(6)with P3c1 symmetry and Li_(3)InI_(6)with C2/c symmetry,exhibiting ionic conductivities of 0.55 and 2.18mS/cm at 300K,respectively.Notably,the trigonal symmetry of Li3InF6 demonstrates that high ionic conductivities are not limited to monoclinic structures but can also be achieved with trigonal symmetries.The electrochemical stability windows,mechanical properties,and reaction energies of these materials with known cathodes suggest their potential for use in all-solid-state batteries.Additionally,we predicted the stability of novel materials,including Li_(5)InCl_(8),Li_(5)InBr_(8),Li_(5)InI_(8),LiIn_(2)Cl_(9),LiIn_(2)Br_(9),and LiIn_(2)I_(9).
基金funded by the Science and Technology Research of Henan Province,No.242103810041(to JY)。
文摘For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.
基金supported by the Iran National Science Foundation(INSF)the University of Birjand under grant number 4034771.
文摘Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study introduces a novel Fuzzy Nonlinear Additive Regression(FNAR)model to predict monthly GWL in an unconfined aquifer in eastern Iran,using a 19-year(1998–2017)dataset from 11 piezometric wells.Under three distinct scenarios with progressively increasing input complexity,the study utilized readily available climate data,including Precipitation(Prc),Temperature(Tave),Relative Humidity(RH),and Evapotranspiration(ETo).The dataset was split into training(70%)and validation(30%)subsets.Results showed that among three input scenarios,Scenario 3(Sc3,incorporating all four variables)achieved the best predictive performance,with RMSE ranging from 0.305 m to 0.768 m,MAE from 0.203 m to 0.522 m,NSE from 0.661 to 0.980,and PBIAS from 0.771%to 0.981%,indicating low bias and high reliability.However,Sc2(excluding ETo)with RMSE ranging from 0.4226 m to 0.9909 m,MAE from 0.3418 m to 0.8173 m,NSE from 0.2831 to 0.9674,and PBIAS from−0.598%to 0.968%across different months offers practical advantages in data-scarce settings.The FNAR model outperforms conventional Fuzzy Least Squares Regression(FLSR)and holds promise for GWL forecasting in data-scarce regions where physical or numerical models are impractical.Future research should focus on integrating FNAR with deep learning algorithms and real-time data assimilation expanding applications across diverse hydrogeological settings.
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNS-FAA198255)+2 种基金Open Project of Guangxi Key Laboratory of Brain and Cognitive Neuroscience(GKLBCN-202206-02)Guangxi Undergraduate Innovation and Entrepreneurship Training Program(202410601029,S202410601113)The 4th Thousand Young and Middle-Aged Backbone Teachers Cultivation Program of Guangxi Higher Education Institutions.
文摘[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.
基金supported by the National Natural Science Foundation of China(No.52090041).
文摘The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated.By adjusting the furnace cooling time after solution treatment and the aging temperature,Ti6422 alloy samples were developed with a multi-level lamellar microstructure,in-cluding microscaleαcolonies and α_(p) lamellae,as well as nanoscale α_(s) phases.Extending the furnace cooling time after solution treatment at 920℃ for 1 h from 240 to 540 min,followed by aging at 600℃ for 6 h,increased the α_(p) lamella content,reduced the α_(s) phase content,expanded theαcolonies and α_(p) lamellae size,and improved the impact toughness from 22.7 to 53.8 J/cm^(2).Additionally,under the same solution treatment,raising the aging temperature from 500 to 700℃ resulted in a decrease in the α_(s) phase content and a growth in the thickness of the α_(p) lamella and α_(s) phase.The impact toughness increased significantly with these changes.Samples with high α_(p) lamellae content or large α_(s) phase size exhibited high crack initiation and propagation energies.Impact deformation caused severe kinking of the α_(p) lamellae in crack initiation and propagation areas,leading to a uniform and high-density kernel average misorientation(KAM)distribu-tion,enhancing plastic deformation coordination and uniformity.Moreover,the multidirectional arrangement of coarserαcolonies and α_(p) lamellae continuously deflect the crack propagation direction,inhibiting crack propagation.
基金supported by the National Natural Science Foundation of China(Grant No.82272845)the Natural Science Foundation of Shandong(Grant No.ZR2023LZL001)。
文摘As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.
文摘In the realm of biomedical materials,biomedical magnesium(Mg)alloy materials are progressively emerging as a highly salient research focal point,capitalizing on their distinctive advantages.Mg,as a unique metallic element,by virtue of its specific properties,has ushered in novel development opportunities for the biomedical domain[1-3].Firstly,Mg manifests outstanding biodegradability.
文摘Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.
文摘The Ethical Turn is commonly supposed to have occurred around 1988.In that year,Wayne C.Booth published The Company We Keep,a book considered to be the first attempt to rehabilitate moral judgement in literary critics and theory.The Ethical Turn can have various consequences for literary theory and criticism.In this paper,I try to describe and examine some,mainly those that concern the possibility of an ethics-based narratology.Are the attempts to define it in the last thirty years satisfactory?What kind of description of narrative structures can they give us?Must an ethics-based narratology be focused on the notion of character?Can it deal with the notion of plot,with the problem of temporality?Should it be necessarily linked with one of the different schools of ethical philosophy?Do different philosophical tendencies lead us to different kinds of narratology?After discussing these questions,I propose some paths for future research in moral narratology.
文摘In the printing industry,vacuum pumps play a critical role in sheet feeding and gripping processes.In order to improve the efficiency of vacuum pumps,By analyzing the internal flow field of the vane type vacuum pump,the CFD method was used to simulate the internal flow field of the air pump,and it was found that a main vortex was formed near the rotor of the trailing blade.Based on this observation,a new rotor shape design was proposed in this study,which design places arc-shaped depressed on the circumference of the rotor where the main vortex forms.The existence of the depression facilitated forward motion of the main airflow and thus effectively restricting reverse flow.Simulation results demonstrated that the proposed design is able to decrease pressure-induced torque load on the pump,and the reduction increases for an increasing operating speed.For all three operating speeds tested,the reduction in pressure-induced torque ranges from 5%to up to 10%comparing to the original pump.
文摘In recent years,the concept of digital human has attracted widespread attention from all walks of life,and the modelling of high-fidelity human bodies,heads,and hands has been intensively studied.This paper focuses on head modelling and proposes a generic head parametric model based on neural radiance fields.Specifically,we first use face recognition networks and 3D facial expression database FaceWarehouse to parameterize identity and expression semantics,respectively,and use both as conditional inputs to build a neural radiance field for the human head,thereby improving the head model’s representation ability while ensuring editing capabilities for the identity and expression of the rendered results;then,through a combination of volume rendering and neural rendering,the 3D representation of the head is rapidly rendered into the 2D plane,producing a high-fidelity image of the human head.Thanks to the well-designed loss functions and good implicit representation of the neural radiance field,our model can not only edit the identity and expression independently,but also freely modify the virtual camera position of the rendering results.It has excellent multi-view consistency,and has many applications in novel view synthesis,pose driving and more.
文摘This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment modalities.This editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic retinopathy.It also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
文摘Ethan Wargo,9 years old,sets up a small table on his lawn each morning in Sycamore,Illinois,waiting for people to walk by so that he can offer a compliment to anyone who stops to talk.In mid‑July 2025,Ethan launched what he calls a“compliments stand”,spending up to five hours a day at his table.The idea was inspired by a scene in a recent graphic(绘画的)novel,where characters run a stand.He parked himself next to his twin sister,Claire,who sells her artwork at her own stand,but Ethan knew charging for compliments didn't feel right.“I didn't want people to pay to be happy,”he said.“Paying for something like that is very silly.”
文摘这座位于英国巴斯的简·奥斯汀中心让参观者领略到了《傲慢与偏见》作者简·奥斯汀笔下的风情与智慧。Jane Austen,a famous English writer,was born in December,1775.Although she died at just forty-two years of age,she completed six novels in her lifetime,which have been translated into dozens of languages,sold tens of millions of copies and have been adapted for television and film.
基金supported by the National Natural Science Foundation of China(32072159)Natural Science Foundation of Hainan Province(322QN338)+4 种基金Young Talent of Lifting Engineering for Science and Technology in Shandong,China(SDAST2021qt18)Qingdao Science and Technology Plan Key Research and Development Project(22-3-3-hygg-28-hy)Fundamental Research Funds for the Central Universities(202262003)Taishan Scholar Project of Shandong Province(tsqn202312099)Support Program for Youth Innovation Technology in Colleges and Universities of Shandong Province(2023KJ041)。
文摘Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestinal bacteria are promising potential producers of novel carbohydrate-active enzymes with unique properties.Here,a novel glycoside hydrolase family 128(GH128)laminarinase OUC-BsLam26 from the intestinal bacterium Bacteroides sp.CBA7301 was heterologously expressed and characterized.The recombinant OUC-BsLam26 with a molecular mass of 49.86 kDa exhibits highest activity(6.60 U/mg)at 45℃ and pH 6.0,which shows noticeable temperature and pH stability.The purified OUC-BsLam26 could degrade laminarin via an endo-type mode with the generation of laminaripentaose,laminaritetraose,laminaritriose,and laminaribiose,among them,laminaritetraose is the principal product,which accounts for 45.25% of the total products,which is significantly different from the reported GH128 laminarinases.The minimum recognition substrate of OUC-BsLam26 is laminarihexaose.Furthermore,OUC-BsLam26 also could catalyze the transglycosylation process with the production of some novel glycosides.Altogether,the intestinal bacterium Bacteroides sp.CBA7301 contains laminarinase with unique product composition and OUC-BsLam26 is a hopeful bio-catalyst with the potential to produce laminaritetraose and some novel glycosides.
文摘This study analyzes Agatha Christie’s mystery novel And Then There Were None from five dimensions—the nursery rhyme,Soldier Island,role of characters,death and psychological interaction—to explore its multi-dimensional metaphors and their deeper connotations.The key findings reveal that the nursery rhyme serves as a narrative thread,symbolizing both a fate-driven trial and societal rules manipulating individual destinies;Soldier Island’s isolation mirrors moral problem and emotional detachment in modern society;the characters,linked to their crimes and deaths,embody universal human flaws;death acts as both a form of justice and a critique of civilization’s fragility;the psychological struggles among the characters expose the collapse of morality under survival crises.By decoding these interconnected metaphors,the study interprets the work’s thematic framework of Sin and Punishment,offering insights into tensions between societal norms and individual existence today.
基金supported by the Natural Science Foundation of Sichuan Province,China(2024NSFSC1272)the Innovation Team Development Funds for Sichuan Mutton Goat&Sheep,China(SCCXTD-2024-14)Scientific and Technological Innovation Team for Qinghai-Tibetan Plateau Research in Southwest Minzu University,China(2024CXTD08)。
文摘Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and animals.The Bocaparvovirus genome.
