Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public hea...Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.展开更多
One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o...One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.展开更多
Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl gro...In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.展开更多
On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of t...On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.展开更多
The effects of deformation temperature on the transformation-induced plasticity(TRIP)-aided 304L,twinning-induced plasti-city(TWIP)-assisted 316L,and highly alloyed stable 904L austenitic stainless steels were compare...The effects of deformation temperature on the transformation-induced plasticity(TRIP)-aided 304L,twinning-induced plasti-city(TWIP)-assisted 316L,and highly alloyed stable 904L austenitic stainless steels were compared for the first time to tune the mechan-ical properties,strengthening mechanisms,and strength-ductility synergy.For this purpose,the scanning electron microscopy(SEM),electron backscattered diffraction(EBSD),X-ray diffraction(XRD),tensile testing,work-hardening analysis,and thermodynamics calcu-lations were used.The induced plasticity effects led to a high temperature-dependency of work-hardening behavior in the 304L and 316L stainless steels.As the deformation temperature increased,the metastable 304L stainless steel showed the sequence of TRIP,TWIP,and weakening of the induced plasticity mechanism;while the disappearance of the TWIP effect in the 316L stainless steel was also observed.However,the solid-solution strengthening in the 904L superaustenitic stainless steel maintained the tensile properties over a wide temper-ature range,surpassing the performance of 304L and 316L stainless steels.In this regard,the dependency of the total elongation on the de-formation temperature was less pronounced for the 904L alloy due to the absence of additional plasticity mechanisms.These results re-vealed the importance of solid-solution strengthening and the associated high friction stress for superior mechanical behavior over a wide temperature range.展开更多
The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover t...The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover the mechanisms involved in memory formation and the coordination of movement as well as their alterations occurring in several neurological disorders.展开更多
Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryo...Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.展开更多
Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid compositi...Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).展开更多
Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of hum...Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.展开更多
BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms...BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning.DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources.RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is diflcult to treat,and there is no specific antidote.CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.展开更多
In order to obtain liquefied products with higher yields of aromatic molecules to produce mesophase pitch,a good understanding of the relevant reaction mechanisms is required.Reactive molecular dynamics simulations we...In order to obtain liquefied products with higher yields of aromatic molecules to produce mesophase pitch,a good understanding of the relevant reaction mechanisms is required.Reactive molecular dynamics simulations were used to study the thermal reactions of pyrene,1-methylpyrene,7,8,9,10-tetrahydrobenzopyrene,and mixtures of pyrene with 1-octene,cyclohexene,or styrene.The reactant conversion rates,reaction rates,and product distributions were calculated and compared,and the mechanisms were analyzed and discussed.The results demonstrated that methyl and naphthenic structures in aromatics might improve the conversion rates of reactants in hydrogen transfer processes,but their steric hindrances prohibited the generation of high polymers.The naphthenic structures could generate more free radicals and presented a more obvious inhibition effect on the condensation of polymers compared with the methyl side chains.It was discovered that when different olefins were mixed with pyrene,1-octene primarily underwent pyrolysis reactions,whereas cyclohexene mainly underwent hydrogen transfer reactions with pyrene and styrene,mostly producing superconjugated biradicals through condensation reactions with pyrene.In the mixture systems,the olefins scattered aromatic molecules,hindering the formation of pyrene trimers and higher polymers.According to the reactive molecular dynamics simulations,styrene may enhance the yield of dimer and enable the controlled polycondensation of pyrene.展开更多
Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as bioch...Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.展开更多
Currently,two rotations and one translation(2R1T)three-degree-of-freedom(DOF)parallel mechanisms(PMs)are widely applied in five-DOF hybrid machining robots.However,there is a lack of an effective method to evaluate th...Currently,two rotations and one translation(2R1T)three-degree-of-freedom(DOF)parallel mechanisms(PMs)are widely applied in five-DOF hybrid machining robots.However,there is a lack of an effective method to evaluate the configuration stiffness of mechanisms during the mechanism design stage.It is a challenge to select appropriate 2R1T PMs with excellent stiffness performance during the design stage.Considering the operational status of 2R1T PMs,the bending and torsional stiffness are considered as indices to evaluate PMs'configuration stiffness.Subsequently,a specific method is proposed to calculate these stiffness indices.Initially,the various types of structural and driving stiffness for each branch are assessed and their specific values defined.Subsequently,a rigid-flexible coupled force model for the over-constrained 2R1T PM is established,and the proposed evaluation method is used to analyze the configuration stiffness of the five 2R1T PMs in the entire workspace.Finally,the driving force and constraint force of each branch in the whole working space are calculated to further elucidate the stiffness evaluating results by using the proposed method above.The obtained results demonstrate that the bending and torsional stiffness of the 2RPU/UPR/RPR mechanism along the x and y-directions are larger than the other four mechanisms.展开更多
Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common ...Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.展开更多
Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease...Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.展开更多
Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary pro...Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary process of red clay slopes and their connection to failure mechanisms is still poorly understood.A comprehensive approach integrating field investigation,laboratory tests,and numerical simulations was conducted to study the 168 red clay landslides in Xinshao County,China.The results show that red clay is prone to forming cracks at high moisture content due to its low swelling and high shrinkage properties.The failure mode of red clay slopes can be summarized in three stages:crack generation,slope excavation,and slope failure.Furthermore,the retrospective analysis and numerical simulations of the typical landslide in Guanchong indicated that intense rainfall primarily impacts the shallow layer of soil within approximately 0.5 m on the intact slope.However,cracks change the pattern of rainfall infiltration in the slope.Rainwater infiltrates rapidly through the preferential channels induced by the cracks rather than uniformly and slowly from the slope surface.This results in a significant increase in both the depth of infiltration and the saturated zone area of the cracked slope,reaching 3.8 m and 36.2 m^(2),respectively.Consequently,the factor of safety of the slope decreases by 13.4%compared to the intact slope,ultimately triggering landslides.This study can provide valuable insights into understanding the failure mechanisms of red clay slopes in China and other regions with similar geological settings.展开更多
Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile sa...Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile salts and various enzymes.Fortunately,encapsulation based on various nanomaterials shows tremendous potential to protect probiotics.In this review,we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability,selective adhesion,smart release and colonization,and efficacy exertion of encapsulated probiotics.Furthermore,the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed,with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier,chemical barrier,biological barrier and immune barrier.This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.展开更多
Long-term storage of crop seeds is critical for the conservation of germplasm resources, ensuring food supply, and supporting sustainable production. Rice, as a major food staple, has a substantial stock for consumpti...Long-term storage of crop seeds is critical for the conservation of germplasm resources, ensuring food supply, and supporting sustainable production. Rice, as a major food staple, has a substantial stock for consumption and production worldwide. However, its food value and seed viability tend to decline during storage. Understanding the physiological responses and molecular mechanisms of aging tolerance forms the basis for enhancing seed storability in rice. This review outlines the latest progress in influential factors, evaluation methods, and identification indices of seed storability. It also discusses the physiological consequences, molecular mechanisms, and strategies for breeding aging-tolerant rice in detail. Finally, it highlights challenges in seed storability research that require future attention. This review offers a theoretical foundation and research direction for uncovering the mechanisms behind seed storability and breeding aging-tolerant rice.展开更多
Image description task is the intersection of computer vision and natural language processing,and it has important prospects,including helping computers understand images and obtaining information for the visually imp...Image description task is the intersection of computer vision and natural language processing,and it has important prospects,including helping computers understand images and obtaining information for the visually impaired.This study presents an innovative approach employing deep reinforcement learning to enhance the accuracy of natural language descriptions of images.Our method focuses on refining the reward function in deep reinforcement learning,facilitating the generation of precise descriptions by aligning visual and textual features more closely.Our approach comprises three key architectures.Firstly,it utilizes Residual Network 101(ResNet-101)and Faster Region-based Convolutional Neural Network(Faster R-CNN)to extract average and local image features,respectively,followed by the implementation of a dual attention mechanism for intricate feature fusion.Secondly,the Transformer model is engaged to derive contextual semantic features from textual data.Finally,the generation of descriptive text is executed through a two-layer long short-term memory network(LSTM),directed by the value and reward functions.Compared with the image description method that relies on deep learning,the score of Bilingual Evaluation Understudy(BLEU-1)is 0.762,which is 1.6%higher,and the score of BLEU-4 is 0.299.Consensus-based Image Description Evaluation(CIDEr)scored 0.998,Recall-Oriented Understudy for Gisting Evaluation(ROUGE)scored 0.552,the latter improved by 0.36%.These results not only attest to the viability of our approach but also highlight its superiority in the realm of image description.Future research can explore the integration of our method with other artificial intelligence(AI)domains,such as emotional AI,to create more nuanced and context-aware systems.展开更多
基金supported by the Natural Science Foundation of Beijing,China(7214223,7212027)the Beijing Hospitals Authority Youth Programme(QML20210601)+3 种基金the Chinese Scholarship Council(CSC)scholarship(201706210415)the National Key Research and Development Program of China(2017YFC0908800)the Beijing Municipal Health Commission(PXM2020_026272_000002,PXM2020_026272_000014)the National Natural Science Foundation of China(82070293).
文摘Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
文摘One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
基金The authors gratefully acknowledge the financial support of the Natural Science Foundation of China,China(Grant No.21975082 and 21736003)the Guangdong Basic and Applied Basic Research Foundation(Grant Number:2019A1515011472 and 2022A1515011341)the Science and Technology Program of Guangzhou(Grant Number:202102080479).
文摘In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.
基金the National Natural Science Foundation of China(Project Nos.41804046 and 41974050)the Special Fund of the Key Laboratory of Earthquake Prediction,China Earthquake Administration(No.CEAIEF2022010100).
文摘On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.
基金Saeed Sadeghpour would like to thank Jane,Aatos Erkon säätiö(JAES),and Tiina ja Antti Herlinin säätiö(TAHS)for their financial support on Advanced Steels for Green Planet Project.The authors would also like to greatly thank the members of the“Formability Laboratory”and“Advanced Steels and Thermomechanically Processed Engineering Ma-terials Laboratory”for their help and support。
文摘The effects of deformation temperature on the transformation-induced plasticity(TRIP)-aided 304L,twinning-induced plasti-city(TWIP)-assisted 316L,and highly alloyed stable 904L austenitic stainless steels were compared for the first time to tune the mechan-ical properties,strengthening mechanisms,and strength-ductility synergy.For this purpose,the scanning electron microscopy(SEM),electron backscattered diffraction(EBSD),X-ray diffraction(XRD),tensile testing,work-hardening analysis,and thermodynamics calcu-lations were used.The induced plasticity effects led to a high temperature-dependency of work-hardening behavior in the 304L and 316L stainless steels.As the deformation temperature increased,the metastable 304L stainless steel showed the sequence of TRIP,TWIP,and weakening of the induced plasticity mechanism;while the disappearance of the TWIP effect in the 316L stainless steel was also observed.However,the solid-solution strengthening in the 904L superaustenitic stainless steel maintained the tensile properties over a wide temper-ature range,surpassing the performance of 304L and 316L stainless steels.In this regard,the dependency of the total elongation on the de-formation temperature was less pronounced for the 904L alloy due to the absence of additional plasticity mechanisms.These results re-vealed the importance of solid-solution strengthening and the associated high friction stress for superior mechanical behavior over a wide temperature range.
基金supported by a grant from the Institut Professeur Baulieu (to DT)。
文摘The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover the mechanisms involved in memory formation and the coordination of movement as well as their alterations occurring in several neurological disorders.
基金supported by the National Natural Science Foundation of China (81772017 to[L.F.H.],and 82072106 and 32371371 to[A.R.Q.])The Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China (2023-JC-YB-163 to[L.F.H.])the National Institutes of Health[AR-070135 and AG-056438 to W.C.,and AR075735,DE023813,AR074954,and DE028264 to Y.P.L.]。
文摘Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.
基金supported by PTDC-01778/2022-NeuroDev3D,iNOVA4Health(UIDB/04462/2020 and UIDP/04462/2020)LS4FUTURE(LA/P/0087/2020)。
文摘Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).
文摘Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.
基金supported by the Research Foundation of Ningbo No.2 Hospital (2023HMKY49)Ningbo Key Support Medical Discipline (2022-F16)。
文摘BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning.DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources.RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is diflcult to treat,and there is no specific antidote.CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.
基金financially supported by the National Natural Science Foundation of China(Approval No.42172168).
文摘In order to obtain liquefied products with higher yields of aromatic molecules to produce mesophase pitch,a good understanding of the relevant reaction mechanisms is required.Reactive molecular dynamics simulations were used to study the thermal reactions of pyrene,1-methylpyrene,7,8,9,10-tetrahydrobenzopyrene,and mixtures of pyrene with 1-octene,cyclohexene,or styrene.The reactant conversion rates,reaction rates,and product distributions were calculated and compared,and the mechanisms were analyzed and discussed.The results demonstrated that methyl and naphthenic structures in aromatics might improve the conversion rates of reactants in hydrogen transfer processes,but their steric hindrances prohibited the generation of high polymers.The naphthenic structures could generate more free radicals and presented a more obvious inhibition effect on the condensation of polymers compared with the methyl side chains.It was discovered that when different olefins were mixed with pyrene,1-octene primarily underwent pyrolysis reactions,whereas cyclohexene mainly underwent hydrogen transfer reactions with pyrene and styrene,mostly producing superconjugated biradicals through condensation reactions with pyrene.In the mixture systems,the olefins scattered aromatic molecules,hindering the formation of pyrene trimers and higher polymers.According to the reactive molecular dynamics simulations,styrene may enhance the yield of dimer and enable the controlled polycondensation of pyrene.
文摘Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.
基金Supported by National Natural Science Foundation of China (Grant Nos.51875495,U2037202)Hebei Provincial Science and Technology Project (Grant No.206Z1805G)。
文摘Currently,two rotations and one translation(2R1T)three-degree-of-freedom(DOF)parallel mechanisms(PMs)are widely applied in five-DOF hybrid machining robots.However,there is a lack of an effective method to evaluate the configuration stiffness of mechanisms during the mechanism design stage.It is a challenge to select appropriate 2R1T PMs with excellent stiffness performance during the design stage.Considering the operational status of 2R1T PMs,the bending and torsional stiffness are considered as indices to evaluate PMs'configuration stiffness.Subsequently,a specific method is proposed to calculate these stiffness indices.Initially,the various types of structural and driving stiffness for each branch are assessed and their specific values defined.Subsequently,a rigid-flexible coupled force model for the over-constrained 2R1T PM is established,and the proposed evaluation method is used to analyze the configuration stiffness of the five 2R1T PMs in the entire workspace.Finally,the driving force and constraint force of each branch in the whole working space are calculated to further elucidate the stiffness evaluating results by using the proposed method above.The obtained results demonstrate that the bending and torsional stiffness of the 2RPU/UPR/RPR mechanism along the x and y-directions are larger than the other four mechanisms.
基金funded by the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund(CI2021A00601)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ16-YQ-037 and JJPY2022022)the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021B017-09).
文摘Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.
基金supported by Jiangxi Provincial Natural Science Foundation(20224BAB216091,20224ACB205014)Jiangxi Provincial Department of Education Science and Technology Plan Project(GJJ2200420).
文摘Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.
基金supported by the National Natural Science Foundation of China(Project No.41920104007 and 41772334).
文摘Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary process of red clay slopes and their connection to failure mechanisms is still poorly understood.A comprehensive approach integrating field investigation,laboratory tests,and numerical simulations was conducted to study the 168 red clay landslides in Xinshao County,China.The results show that red clay is prone to forming cracks at high moisture content due to its low swelling and high shrinkage properties.The failure mode of red clay slopes can be summarized in three stages:crack generation,slope excavation,and slope failure.Furthermore,the retrospective analysis and numerical simulations of the typical landslide in Guanchong indicated that intense rainfall primarily impacts the shallow layer of soil within approximately 0.5 m on the intact slope.However,cracks change the pattern of rainfall infiltration in the slope.Rainwater infiltrates rapidly through the preferential channels induced by the cracks rather than uniformly and slowly from the slope surface.This results in a significant increase in both the depth of infiltration and the saturated zone area of the cracked slope,reaching 3.8 m and 36.2 m^(2),respectively.Consequently,the factor of safety of the slope decreases by 13.4%compared to the intact slope,ultimately triggering landslides.This study can provide valuable insights into understanding the failure mechanisms of red clay slopes in China and other regions with similar geological settings.
基金supported by the National Key Research and Development Program(2019YFC1606704)the Key Research and Development Program of Shaanxi Province(2022NY-013)+1 种基金National Natural Science Foundation of China(31801653)the Natural Science Foundation of Shaanxi Province(2019JQ-722).
文摘Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile salts and various enzymes.Fortunately,encapsulation based on various nanomaterials shows tremendous potential to protect probiotics.In this review,we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability,selective adhesion,smart release and colonization,and efficacy exertion of encapsulated probiotics.Furthermore,the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed,with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier,chemical barrier,biological barrier and immune barrier.This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.
基金funded by the Postgraduate Scientific Research Innovative Project of Hunan Province, China (Grant No. QL20220107)the Science and Technology Innovation Program of Hunan Province, China (Grant Nos. 2021RC4066 and 2023NK1010)the Special Funds for the Construction of Innovative Provinces in Hunan Province, China (Grant No. 2021NK1012)。
文摘Long-term storage of crop seeds is critical for the conservation of germplasm resources, ensuring food supply, and supporting sustainable production. Rice, as a major food staple, has a substantial stock for consumption and production worldwide. However, its food value and seed viability tend to decline during storage. Understanding the physiological responses and molecular mechanisms of aging tolerance forms the basis for enhancing seed storability in rice. This review outlines the latest progress in influential factors, evaluation methods, and identification indices of seed storability. It also discusses the physiological consequences, molecular mechanisms, and strategies for breeding aging-tolerant rice in detail. Finally, it highlights challenges in seed storability research that require future attention. This review offers a theoretical foundation and research direction for uncovering the mechanisms behind seed storability and breeding aging-tolerant rice.
基金This research was funded by the Natural Science Foundation of Gansu Province with Approval Numbers 20JR10RA334 and 21JR7RA570Funding is provided for the 2021 Longyuan Youth Innovation and Entrepreneurship Talent Project with Approval Number 2021LQGR20+1 种基金the University Level Innovation Project with Approval NumbersGZF2020XZD18jbzxyb2018-01 of Gansu University of Political Science and Law.
文摘Image description task is the intersection of computer vision and natural language processing,and it has important prospects,including helping computers understand images and obtaining information for the visually impaired.This study presents an innovative approach employing deep reinforcement learning to enhance the accuracy of natural language descriptions of images.Our method focuses on refining the reward function in deep reinforcement learning,facilitating the generation of precise descriptions by aligning visual and textual features more closely.Our approach comprises three key architectures.Firstly,it utilizes Residual Network 101(ResNet-101)and Faster Region-based Convolutional Neural Network(Faster R-CNN)to extract average and local image features,respectively,followed by the implementation of a dual attention mechanism for intricate feature fusion.Secondly,the Transformer model is engaged to derive contextual semantic features from textual data.Finally,the generation of descriptive text is executed through a two-layer long short-term memory network(LSTM),directed by the value and reward functions.Compared with the image description method that relies on deep learning,the score of Bilingual Evaluation Understudy(BLEU-1)is 0.762,which is 1.6%higher,and the score of BLEU-4 is 0.299.Consensus-based Image Description Evaluation(CIDEr)scored 0.998,Recall-Oriented Understudy for Gisting Evaluation(ROUGE)scored 0.552,the latter improved by 0.36%.These results not only attest to the viability of our approach but also highlight its superiority in the realm of image description.Future research can explore the integration of our method with other artificial intelligence(AI)domains,such as emotional AI,to create more nuanced and context-aware systems.
