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
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
Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CA...Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CAR-NK cell therapy has enabled the development of“off-the-shelf”products that bypass the lengthy and expensive cell manufacturing process1.展开更多
Membrane desalination is an economical and energy-efficient method to meet the current worldwide water scarcity.However,state-of-the-art reverse osmosis membranes are gradually being replaced by novel membrane materia...Membrane desalination is an economical and energy-efficient method to meet the current worldwide water scarcity.However,state-of-the-art reverse osmosis membranes are gradually being replaced by novel membrane materials as a result of ongoing technological advancements.These novel materials possess intrinsic pore structures or can be assembled to form lamellar membrane channels for selective transport of water or solutes(e.g.,NaCl).Still,in real applications,the results fall below the theoretical predictions,and a few properties,including large-scale fabrication,mechanical strength,and chemical stability,also have an impact on the overall effectiveness of those materials.In view of this,we develop a new evaluation framework in the form of radar charts with five dimensions(i.e.,water permeance,water/NaCl selectivity,membrane cost,scale of development,and stability)to assess the advantages,disadvantages,and potential of state-of-the-art and newly developed desalination membranes.In this framework,the reported thin film nanocomposite membranes and membranes developed from novel materials were compared with the state-of-the-art thin film composite membranes.This review will demonstrate the current advancements in novel membrane materials and bridge the gap between different desalination membranes.In this review,we also point out the prospects and challenges of next-generation membranes for desalination applications.We believe that this comprehensive framework may be used as a future reference for designing next-generation desalination membranes and will encourage further research and development in the field of membrane technology,leading to new insights and advancements.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
Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great...Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].展开更多
Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligulari...Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligularia jaluensis carlavirus(LJCV),as well as a known iris severe mosaic virus(ISMV),in L.jaluensis plants displaying chlorosis and yellow ring spot symptoms,using RNA-seq analysis.The LJCV genome consists of an 8497 nt positive-sense,single-stranded RNA[excluding the poly(A)tail],and contains six open reading frames(ORFs).Phylogenetic analyses based on the fulllength genome and RNA-dependent RNA polymerase(RdRp)amino acid(aa)sequences revealed that LJCV clusters within an evolutionary branch alongside known viruses in the Carlavirus genus.The RdRp protein encoded by ORF1 of LJCV shared 45.38%–67.41%identity with the corresponding proteins of eight closely related carlaviruses.ORFs 2–4 constitute the triple gene block(TGB),with TGBp1 and TGBp3 localized in the endoplasmic reticulum(ER),while TGBp2 is localized at plasmodesmata(PD)and facilitates viral intercellular movement,as demonstrated by its ability to complement the potato virus X with movement-deficient mutant(PVX-Δp25-GFP).Additionally,ORF6 encodes a cysteine-rich protein(CRP)that is localized in the chloroplast and functions as a viral pathogenicity factor,inducing severe viral symptoms in the heterologous PVX expression system.Furthermore,we successfully constructed an infectious cDNA clone of LJCV,and found that it can infect Nicotiana benthamiana plants through mechanical inoculation or agrobacterium-mediated infiltration of the LJCV infectious clone.These findings enhance our understanding of the characteristics and host range of carlaviruses,as well as the viruses capable of infecting L.jaluensis.展开更多
Cohort studies are important epidemiological methods to investigate associations between environmental factors,individual characteristics,and disease or other health outcomes.As a paradigm of cohort studies,the Framin...Cohort studies are important epidemiological methods to investigate associations between environmental factors,individual characteristics,and disease or other health outcomes.As a paradigm of cohort studies,the Framingham Heart Study(FHS)is the longest-running cardiovascular epidemiological study,starting in 1948.展开更多
Myocardial infarction is a cardiovascular disease(CVD)with high morbidity and mortality,which can trigger a cascade of cardiac pathophysiological changes,including fibrosis,inflammation,ischemia-reperfusion injury(IRI...Myocardial infarction is a cardiovascular disease(CVD)with high morbidity and mortality,which can trigger a cascade of cardiac pathophysiological changes,including fibrosis,inflammation,ischemia-reperfusion injury(IRI),and ventricular remodeling,ultimately leading to heart failure(HF).While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates,both approaches have limitations and adverse effects.Natural products(NPs)are extensively utilized as therapeutics globally,with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies,positioning them as potential alternatives to modern drugs.This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects.These include classical mechanisms such as inhibition of inflammation and oxidative stress,alleviation of cardiomyocyte death,attenuation of cardiac fibrosis,improvement of angiogenesis,and emerging mechanisms such as cardiac metabolic regulation and histone modification.Furthermore,the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms,including other forms of regulated cell death(RCD),endothelial-mesenchymal transition,non-coding ribonucleic acids(ncRNAs)cascade,and endothelial progenitor cell(EPC)function.Additionally,NPs influencing a particular mechanism are categorized based on their chemical structure,and their relevance is discussed.Finally,the current limitations and prospects of NPs therapy are considered,highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.展开更多
Dear editor,As of 2023,the domestic cat population in China reached 65 million,surpassing dogs to become the most numerous companion animal in the country.Feline calicivirus(FCV)infection,one of the three most prevale...Dear editor,As of 2023,the domestic cat population in China reached 65 million,surpassing dogs to become the most numerous companion animal in the country.Feline calicivirus(FCV)infection,one of the three most prevalent infectious diseases in cats,poses a severe threat to feline health.FCV,classified under the Caliciviridae family(genus Vesivirus).展开更多
One of the key components in high-tech products,such as semiconductors,electronic connectors,and lithium batteries,is the lead frame,made from metals like copper and its alloys,as well as aluminum and its alloys,with ...One of the key components in high-tech products,such as semiconductors,electronic connectors,and lithium batteries,is the lead frame,made from metals like copper and its alloys,as well as aluminum and its alloys,with thicknesses ranging from 0.02 mm to 0.8 mm.In manufacturing,butt-joint and overlap-joint welding are crucial for enhancing productivity and minimizing solid waste.However,existing welding technologies face challenges with these types of joints.To overcome this,a novel spot-welding process has been developed using an advanced welding torch with a dual-layer nozzle system,comprising an inner and outer nozzle.This design offers several advantages:it precisely positions the tungsten electrode,extends its lifespan,prevents molten metal from evaporating and re-entering the melt pool,and ensures arc plasma stability.Additionally,the outer nozzle plays a crucial role in controlling the shape of the arc plasma column,melt pool formation,and the size of the welded spot.By integrating both nozzles,this technology enables welding at an extremely short arc length and low current,ensuring minimal heat input while maintaining a high-stability arc plasma,making it ideal for welding ultra-thin metal sheets.展开更多
AIM:To detect and segregate causative mutations in congenital families with optic nerve hypoplasia(ONH).M E T H O D S:Two unrel a ted consanguineous Pakistani families with severe ONH,showing features of micropthalmia...AIM:To detect and segregate causative mutations in congenital families with optic nerve hypoplasia(ONH).M E T H O D S:Two unrel a ted consanguineous Pakistani families with severe ONH,showing features of micropthalmia,nystagmus,corneal opacity,and keratopathy were included.Genetic analysis was carried out by Target Panel Sequencing,and the nucleotide variant was confirmed by Sanger sequencing.In silico analyses were carried out to study the protein order-disorder functions and their effects on messenger ribonucleic acid(mRNA).RESULTS:Target panel sequencing revealed that the afflicted family members carried a novel frameshift mutation(NM_145178.4;c.91del G;p.Gly31Glyfs*55)that ensued in the conservation of an amino acid residue in the bHLH domain of ATOH7 protein.In silico studies predicted that the activity of the ATOH7 gene is probably affected by this mutation,which results in a shortened and nonfunctional protein.Three-dimensional structural analysis shows that DNA binding may be impacted by amino acid changes from non-polar to positively charged and vice versa(Arg42Pro and Pro18Arg),as well as from positively charged(Arg)to a small polar amino acid(Gly).CONCLUSION:A novel ATOH7 mutation is harmful.This study also emphasizes the potential effects of modified ATOH7 configurations on the stability and functionality of proteins.展开更多
The 2024 MRE HP Special Volume selects papers on new theoretical and experimental developments in the use of static largevolume presses(LVPs)1–3 and dynamic compression4,5 for studies under extreme high-pressure and ...The 2024 MRE HP Special Volume selects papers on new theoretical and experimental developments in the use of static largevolume presses(LVPs)1–3 and dynamic compression4,5 for studies under extreme high-pressure and high-temperature(HPHT)conditions.It also continues the previous year’s6 contemporary focus on superhydrides7–11 with extremely high superconducting temperatures Tc and addresses some controversial issues.12–14 In addition,it explores unconventional pressure-induced chemistry,particularly novel chemical stoichiometry and its impact on geochemistry and cosmochemistry in the deep interiors of Earth and other planets.18–21.展开更多
Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widesprea...Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widespread use of fructose-BPA(F-BPA)has been hampered by its limited ability to penetrate the blood-brain barrier(BBB)and potential risks for patients with certain complications such as diabetes,hyperuricemia,and gout,particularly with substantial dosages.Herein,a series of novel BPA derivatives were synthesized.After the primary screening,geniposide-BPA(G-BPA)and salidroside-BPA(S-BPA)exhibited high water solubility,low cytotoxicity and safe profiles for intravenous injection.Furthermore,both G-BPA and S-BPA had demonstrated superior efficacy in vitro against the 4T1 cell line compared with F-BPA.Notably,S-BPA displayed optimal BBB penetration capability,as evidenced by in vitro BBB models and glioblastoma models in vivo,surpassing all other BPA derivative candidates.Meanwhile,GBPA also exhibited enhanced performance relative to the clinical drug F-BPA.In brief,G-BPA and S-BPA,as novel BPA derivatives,demonstrated notable safety profiles and remarkable boron delivery capabilities,thereby offering promising therapeutic options for BNCT in the clinic.展开更多
In robotics and human-robot interaction,a robot’s capacity to express and react correctly to human emotions is essential.A significant aspect of the capability involves controlling the robotic facial skin actuators i...In robotics and human-robot interaction,a robot’s capacity to express and react correctly to human emotions is essential.A significant aspect of the capability involves controlling the robotic facial skin actuators in a way that resonates with human emotions.This research focuses on human anthropometric theories to design and control robotic facial actuators,addressing the limitations of existing approaches in expressing emotions naturally and accurately.The facial landmarks are extracted to determine the anthropometric indicators for designing the robot head and is employed to the displacement of these points to calculate emotional values using Fuzzy C-Mean(FCM).The rotating angles of skin actuators are required to account for the smaller emotions,which enhance the robot’s ability to perform emotions in reality.In addition,this study contributes a novel approach based on facial anthropometric indicators to tailor emotional expressions to diverse human characteristics,ensuring more personalized and intuitive interactions.The results demonstrated howfuzzy logic can be employed to improve a robot’s ability to express emotions,which are digitized into fuzzy values.This is also the contribution of the research,which laid the groundwork for robots that can interact with humans more intuitively and empathetically.The performed experiments demonstrated that the suitability of proposed models to conduct tasks related to human emotions with the accuracy of emotional value determination and motor angles is 0.96 and 0.97,respectively.展开更多
Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology...Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.展开更多
Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common typ...Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common types.The annual incidence of AP ranges from 13 to 49 cases per 100000 individuals[1].AP is character-ized by an abrupt onset and rapid disease progression.Approxi-mately 20%of patients develop moderate to severe AP,which are associated with a high risk of organ failure and mortality due to local and systemic complications[1].The global incidence of CP is approximately 10 cases per 100000 individuals annually.展开更多
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.
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 grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant No.2023ZD0501300)Science Technology Department of Zhejiang Province(Grant No.2021C03117)+2 种基金National Natural Science Foundation of China(Grant No.82350104 and 82170219)Natural Science Foundation of Zhejiang Province,China(Grant No.LY23H080004 and LY24H080001)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(Grant No.2021KY199)。
文摘Chimeric antigen receptor natural killer(CAR-NK)cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease.CAR-NK cell therapy has enabled the development of“off-the-shelf”products that bypass the lengthy and expensive cell manufacturing process1.
基金supported by a grant from the Research Grants Council of the Hong Kong Special Administration Region,China(SRFS2021-7S04)Partial support was also received from the Seed Funding for Strategic Interdisciplinary Research Scheme(102010174)+1 种基金Seed Fund for Basic Research(202111159075)of The University of Hong KongIn addition,part of this work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement INTELWAT(No 958454).
文摘Membrane desalination is an economical and energy-efficient method to meet the current worldwide water scarcity.However,state-of-the-art reverse osmosis membranes are gradually being replaced by novel membrane materials as a result of ongoing technological advancements.These novel materials possess intrinsic pore structures or can be assembled to form lamellar membrane channels for selective transport of water or solutes(e.g.,NaCl).Still,in real applications,the results fall below the theoretical predictions,and a few properties,including large-scale fabrication,mechanical strength,and chemical stability,also have an impact on the overall effectiveness of those materials.In view of this,we develop a new evaluation framework in the form of radar charts with five dimensions(i.e.,water permeance,water/NaCl selectivity,membrane cost,scale of development,and stability)to assess the advantages,disadvantages,and potential of state-of-the-art and newly developed desalination membranes.In this framework,the reported thin film nanocomposite membranes and membranes developed from novel materials were compared with the state-of-the-art thin film composite membranes.This review will demonstrate the current advancements in novel membrane materials and bridge the gap between different desalination membranes.In this review,we also point out the prospects and challenges of next-generation membranes for desalination applications.We believe that this comprehensive framework may be used as a future reference for designing next-generation desalination membranes and will encourage further research and development in the field of membrane technology,leading to new insights and advancements.
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.
基金supported by the Basic Research and Talent Cultivation Program of Zhangjiakou City(No.2511028A).
文摘Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].
基金financially supported by the Hainan Province Science and Technology Special Fund(No.ZDYF2022XDNY240)the National Key Research and Development Program of China(2022YFD1401200).
文摘Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligularia jaluensis carlavirus(LJCV),as well as a known iris severe mosaic virus(ISMV),in L.jaluensis plants displaying chlorosis and yellow ring spot symptoms,using RNA-seq analysis.The LJCV genome consists of an 8497 nt positive-sense,single-stranded RNA[excluding the poly(A)tail],and contains six open reading frames(ORFs).Phylogenetic analyses based on the fulllength genome and RNA-dependent RNA polymerase(RdRp)amino acid(aa)sequences revealed that LJCV clusters within an evolutionary branch alongside known viruses in the Carlavirus genus.The RdRp protein encoded by ORF1 of LJCV shared 45.38%–67.41%identity with the corresponding proteins of eight closely related carlaviruses.ORFs 2–4 constitute the triple gene block(TGB),with TGBp1 and TGBp3 localized in the endoplasmic reticulum(ER),while TGBp2 is localized at plasmodesmata(PD)and facilitates viral intercellular movement,as demonstrated by its ability to complement the potato virus X with movement-deficient mutant(PVX-Δp25-GFP).Additionally,ORF6 encodes a cysteine-rich protein(CRP)that is localized in the chloroplast and functions as a viral pathogenicity factor,inducing severe viral symptoms in the heterologous PVX expression system.Furthermore,we successfully constructed an infectious cDNA clone of LJCV,and found that it can infect Nicotiana benthamiana plants through mechanical inoculation or agrobacterium-mediated infiltration of the LJCV infectious clone.These findings enhance our understanding of the characteristics and host range of carlaviruses,as well as the viruses capable of infecting L.jaluensis.
文摘Cohort studies are important epidemiological methods to investigate associations between environmental factors,individual characteristics,and disease or other health outcomes.As a paradigm of cohort studies,the Framingham Heart Study(FHS)is the longest-running cardiovascular epidemiological study,starting in 1948.
基金supported by No. 82373870 from the National Natural Science Foundation of ChinaNo. 2022D01D50 from Xinjiang Natural Science Foundation
文摘Myocardial infarction is a cardiovascular disease(CVD)with high morbidity and mortality,which can trigger a cascade of cardiac pathophysiological changes,including fibrosis,inflammation,ischemia-reperfusion injury(IRI),and ventricular remodeling,ultimately leading to heart failure(HF).While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates,both approaches have limitations and adverse effects.Natural products(NPs)are extensively utilized as therapeutics globally,with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies,positioning them as potential alternatives to modern drugs.This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects.These include classical mechanisms such as inhibition of inflammation and oxidative stress,alleviation of cardiomyocyte death,attenuation of cardiac fibrosis,improvement of angiogenesis,and emerging mechanisms such as cardiac metabolic regulation and histone modification.Furthermore,the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms,including other forms of regulated cell death(RCD),endothelial-mesenchymal transition,non-coding ribonucleic acids(ncRNAs)cascade,and endothelial progenitor cell(EPC)function.Additionally,NPs influencing a particular mechanism are categorized based on their chemical structure,and their relevance is discussed.Finally,the current limitations and prospects of NPs therapy are considered,highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2022YFD1800100)National Natural Science Foundation of China(Grant No.32272982)Natural Science Foundation of Shanghai(Grant No.23ZR1477100).
文摘Dear editor,As of 2023,the domestic cat population in China reached 65 million,surpassing dogs to become the most numerous companion animal in the country.Feline calicivirus(FCV)infection,one of the three most prevalent infectious diseases in cats,poses a severe threat to feline health.FCV,classified under the Caliciviridae family(genus Vesivirus).
基金supported by the funding from the Hanoi University of Industry(DHCN-No.3).
文摘One of the key components in high-tech products,such as semiconductors,electronic connectors,and lithium batteries,is the lead frame,made from metals like copper and its alloys,as well as aluminum and its alloys,with thicknesses ranging from 0.02 mm to 0.8 mm.In manufacturing,butt-joint and overlap-joint welding are crucial for enhancing productivity and minimizing solid waste.However,existing welding technologies face challenges with these types of joints.To overcome this,a novel spot-welding process has been developed using an advanced welding torch with a dual-layer nozzle system,comprising an inner and outer nozzle.This design offers several advantages:it precisely positions the tungsten electrode,extends its lifespan,prevents molten metal from evaporating and re-entering the melt pool,and ensures arc plasma stability.Additionally,the outer nozzle plays a crucial role in controlling the shape of the arc plasma column,melt pool formation,and the size of the welded spot.By integrating both nozzles,this technology enables welding at an extremely short arc length and low current,ensuring minimal heat input while maintaining a high-stability arc plasma,making it ideal for welding ultra-thin metal sheets.
文摘AIM:To detect and segregate causative mutations in congenital families with optic nerve hypoplasia(ONH).M E T H O D S:Two unrel a ted consanguineous Pakistani families with severe ONH,showing features of micropthalmia,nystagmus,corneal opacity,and keratopathy were included.Genetic analysis was carried out by Target Panel Sequencing,and the nucleotide variant was confirmed by Sanger sequencing.In silico analyses were carried out to study the protein order-disorder functions and their effects on messenger ribonucleic acid(mRNA).RESULTS:Target panel sequencing revealed that the afflicted family members carried a novel frameshift mutation(NM_145178.4;c.91del G;p.Gly31Glyfs*55)that ensued in the conservation of an amino acid residue in the bHLH domain of ATOH7 protein.In silico studies predicted that the activity of the ATOH7 gene is probably affected by this mutation,which results in a shortened and nonfunctional protein.Three-dimensional structural analysis shows that DNA binding may be impacted by amino acid changes from non-polar to positively charged and vice versa(Arg42Pro and Pro18Arg),as well as from positively charged(Arg)to a small polar amino acid(Gly).CONCLUSION:A novel ATOH7 mutation is harmful.This study also emphasizes the potential effects of modified ATOH7 configurations on the stability and functionality of proteins.
基金financial support from the Shanghai Key Laboratory of MFree,China(Grant No.22dz2260800)the Shanghai Science and Technology Committee,China(Grant No.22JC1410300).
文摘The 2024 MRE HP Special Volume selects papers on new theoretical and experimental developments in the use of static largevolume presses(LVPs)1–3 and dynamic compression4,5 for studies under extreme high-pressure and high-temperature(HPHT)conditions.It also continues the previous year’s6 contemporary focus on superhydrides7–11 with extremely high superconducting temperatures Tc and addresses some controversial issues.12–14 In addition,it explores unconventional pressure-induced chemistry,particularly novel chemical stoichiometry and its impact on geochemistry and cosmochemistry in the deep interiors of Earth and other planets.18–21.
基金supported by Guangdong Basic and Applied Basic Research Foundation(No.2021B1515120065)National Natural Science Foundation of China(Nos.82202339,32271420,82202307)+3 种基金China Postdoctoral Science Foundation(Nos.2022M711527,2021M701640)Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(No.B2021201038)National High-End Foreign Expert Recruitment Plan(No.G2022003007L)Natural Science Foundation of Hebei Province(No.B2023201108).
文摘Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widespread use of fructose-BPA(F-BPA)has been hampered by its limited ability to penetrate the blood-brain barrier(BBB)and potential risks for patients with certain complications such as diabetes,hyperuricemia,and gout,particularly with substantial dosages.Herein,a series of novel BPA derivatives were synthesized.After the primary screening,geniposide-BPA(G-BPA)and salidroside-BPA(S-BPA)exhibited high water solubility,low cytotoxicity and safe profiles for intravenous injection.Furthermore,both G-BPA and S-BPA had demonstrated superior efficacy in vitro against the 4T1 cell line compared with F-BPA.Notably,S-BPA displayed optimal BBB penetration capability,as evidenced by in vitro BBB models and glioblastoma models in vivo,surpassing all other BPA derivative candidates.Meanwhile,GBPA also exhibited enhanced performance relative to the clinical drug F-BPA.In brief,G-BPA and S-BPA,as novel BPA derivatives,demonstrated notable safety profiles and remarkable boron delivery capabilities,thereby offering promising therapeutic options for BNCT in the clinic.
基金funded by the University of Economics Ho Chi Minh City-UEH,Vietnam.
文摘In robotics and human-robot interaction,a robot’s capacity to express and react correctly to human emotions is essential.A significant aspect of the capability involves controlling the robotic facial skin actuators in a way that resonates with human emotions.This research focuses on human anthropometric theories to design and control robotic facial actuators,addressing the limitations of existing approaches in expressing emotions naturally and accurately.The facial landmarks are extracted to determine the anthropometric indicators for designing the robot head and is employed to the displacement of these points to calculate emotional values using Fuzzy C-Mean(FCM).The rotating angles of skin actuators are required to account for the smaller emotions,which enhance the robot’s ability to perform emotions in reality.In addition,this study contributes a novel approach based on facial anthropometric indicators to tailor emotional expressions to diverse human characteristics,ensuring more personalized and intuitive interactions.The results demonstrated howfuzzy logic can be employed to improve a robot’s ability to express emotions,which are digitized into fuzzy values.This is also the contribution of the research,which laid the groundwork for robots that can interact with humans more intuitively and empathetically.The performed experiments demonstrated that the suitability of proposed models to conduct tasks related to human emotions with the accuracy of emotional value determination and motor angles is 0.96 and 0.97,respectively.
文摘Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.
文摘Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common types.The annual incidence of AP ranges from 13 to 49 cases per 100000 individuals[1].AP is character-ized by an abrupt onset and rapid disease progression.Approxi-mately 20%of patients develop moderate to severe AP,which are associated with a high risk of organ failure and mortality due to local and systemic complications[1].The global incidence of CP is approximately 10 cases per 100000 individuals annually.
