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
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because o...The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family member...The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family members across various cancer types and their potential molecular mechanisms. This review provides a comprehensive overview of the structural characteristics and functions of the CIRBP family, alongside their expression profiles in tumors and the regulatory molecular mechanisms involved. By synthesizing current knowledge, this review aims to offer new insights and directions for future cancer therapies, emphasizing the importance of CIRBP proteins in oncological research.展开更多
This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers...This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.展开更多
With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and charact...With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.展开更多
Postoperative ileus(POI)remains a prevalent and significant challenge following abdominal surgeries,precipitating patient distress,prolonged hospital stays,and escalated medical expenditures.Conventionally addressed v...Postoperative ileus(POI)remains a prevalent and significant challenge following abdominal surgeries,precipitating patient distress,prolonged hospital stays,and escalated medical expenditures.Conventionally addressed via pharmacological interventions,POI is increasingly being explored through adjunctive therapeutic strategies,with acupuncture gaining recognition as a promising option.Acupuncture has demonstrated encouraging potential in promoting gastrointestinal motility in patients with POI.Moreover,recent research has shed light on the therapeutic mechanisms underlying its efficacy.This article aims to present a comprehensive overview of acupuncture as a treatment for POI,highlighting advancements in clinical research and recent elucidations of its mechanistic underpinnings.It aspires to contribute a pivotal reference point for scholars and enthusiasts keen on garnering a deeper understanding of acupuncture’s role in managing POI.展开更多
Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This...Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.展开更多
Cross roadway collapses are a common occurrence in underground mining operations.While the influence of mining blasts on the stability of surrounding rock is acknowledged,the underlying mechanisms remain inadequately ...Cross roadway collapses are a common occurrence in underground mining operations.While the influence of mining blasts on the stability of surrounding rock is acknowledged,the underlying mechanisms remain inadequately understood.This study investigates the characteristics and mechanisms of collapse in a shallow buried cross roadway subjected to mining blast disturbances,drawing insights from an engineering project in Anshan City,Northeast China.A strain-softening model based on unified strength theory was developed to effectively calculate and analyze the loosened zone thickness and surrounding rock displacement.The PFC3D-FLAC3D coupling method was employed to clarify the concentrated collapse area within the cross roadway,providing insight into the collapse mechanism through a cross-sectional model of the concentrated region.Results demonstrate that 50%of the cross roadway collapsed following the mining blast.Subsidence at the intersection was approximately one-fifth(0.66 m)of cross roadway’s net height,exceeding subsidence in other areas by 1.3.Under the action of repeated mining blasting,the cross section of the connection roadway forms a semi-elliptical high tensile stress zone.After the cumulative damage of the surrounding rock of the connection roadway exceeds the ultimate yield strength,the cumulative stress release causes the tensile failure of the surrounding rock.The plastic zone of the connecting roadway expands to three times of the initial,and continues to develop.The surrounding rock on both sides experienced tensile stress,cumulative stress release,and the vertical propagation of tensile cracks.展开更多
Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affe...Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affecting the growth of fruit trees,and an appropriate ambient temperature is a necessary condition for the normal growth and development of fruit trees.Since the 20th century,due to the intensification of the greenhouse effect and global warming,there has been a significant increase in the occurrence and duration of extreme hot weather in summer has been occurring frequently and for longer durations.Thus,the growth and production of fruit trees are affected by severe hightemperature stress.Therefore,this paper primarily summarized the impacts of high-temperature stress on fruit growth and development,flowering,fruiting,fruit setting and quality.It also discussed the physiological and biochemical responses of fruit trees to high-temperature stress,research progress on the molecular mechanisms and signal transduction pathways underlying fruit tree resistance to heat or high temperature,and research on the investigation of relevant metabolites of fruit trees under stress conditions.The future research directions were discussed,and prospects and potential difficulties were proposed to serve a reference for further investigation on the high-temperature tolerance of fruit trees.展开更多
This paper begins with a discussion of the trust issues that agricultural supply chain finance faces.It then examines the constraints of using blockchain technology to enhance trust in agricultural supply chain financ...This paper begins with a discussion of the trust issues that agricultural supply chain finance faces.It then examines the constraints of using blockchain technology to enhance trust in agricultural supply chain finance in accordance with the technological and institutional logic of combining blockchain with supply chains.This study then proposes the creation of an agricultural“blockchain+supply chain”information service platform and a financing trust mechanism that can effectively ensure the authenticity of the initial information input on the blockchain,consistency between on-chain transaction data and off-chain physical transactions,the controllability of risks in the set up and execution of smart contracts,and the removal of information constraints,resource allocation constraints,and institutional constraints in the agricultural supply chain financing.This aims to improve the efficiency of financing in agricultural supply chains and contribute to the industrial development of rural areas and rural revitalization.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
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
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
Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations ...Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.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
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
Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,a...Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,antipyretic,analgesic,antiosteoporotic,antihypertensive,sedative,and hypnotic effects.To date,research on the effective components of Chrysanthemum extract has mainly focused on flavonoids,whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components.In this review,the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal,aromatherapy,and diet therapy applications.展开更多
Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas an...Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas and economic hubs.This study focuses on the high F^(−)and NO_(3)^(−)concentration groundwater in Tongzhou District,Beijing,North China.A total of 36 groundwater samples were collected to analyze the hydrochemical characteristics,elucidate genetic mechanisms and evaluate the potential human health risks.The results of the analysis indicate:Firstly,most of the groundwater samples are characterized by Mg-HCO_(3) and Na-HCO_(3) with the pH ranging from 7.19 to 8.28 and TDS with a large variation across the range 471-2337 mg/L.The NO_(3)^(−)concentration in 38.89%groundwater samples and the F^(−)concentration in 66.67%groundwater samples exceed the permissible limited value.Secondly,F^(−)in groundwater originates predominantly from water-rock interactions and the fluorite dissolution,which is also regulated by cation exchange,competitive adsorption of HCO_(3)−and an alkaline environment.Thirdly,the effect of sewage disposal and agricultural activities have a significant effect on high NO3-concentration,while the high F^(−)concentration is less influenced by anthropogenic activity.The alkaline environment favors nitrification,thus being conducive to the production of NO_(3)^(−).Finally,the health risk assessment is evaluated for different population groups.The results indicate that high NO_(3)^(−)and F^(−)concentration in groundwater would have the largest threat to children’s health.The findings of this study could contribute to the provision of a scientific basis for groundwater supply policy formulation relating to public health in Tongzhou District.展开更多
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The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
基金supported in part by the National Key Research and Development Program of China under Grant No.2021YFF0901300in part by the National Natural Science Foundation of China under Grant Nos.62173076 and 72271048.
文摘The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent years.The iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution framework.However,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale DPFSPs.As a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the mini-malmakespan.InMLIGA,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous solutions.In addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory mechanism.Meanwhile,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom rules.At last,a discrete adaptive learning rate is employed to enhance the stability of the memory and learningmechanisms.Complete ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large extent.Furthermore,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale DPFSPs.This indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
文摘The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family members across various cancer types and their potential molecular mechanisms. This review provides a comprehensive overview of the structural characteristics and functions of the CIRBP family, alongside their expression profiles in tumors and the regulatory molecular mechanisms involved. By synthesizing current knowledge, this review aims to offer new insights and directions for future cancer therapies, emphasizing the importance of CIRBP proteins in oncological research.
文摘This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.
文摘With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.
基金Supported by Clinical Key Project of Peking University Third Hospital,No.BYSY2023049Funding from State Key Laboratory of Female Fertility Promotion,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,No.BYSYSZKF2023027.
文摘Postoperative ileus(POI)remains a prevalent and significant challenge following abdominal surgeries,precipitating patient distress,prolonged hospital stays,and escalated medical expenditures.Conventionally addressed via pharmacological interventions,POI is increasingly being explored through adjunctive therapeutic strategies,with acupuncture gaining recognition as a promising option.Acupuncture has demonstrated encouraging potential in promoting gastrointestinal motility in patients with POI.Moreover,recent research has shed light on the therapeutic mechanisms underlying its efficacy.This article aims to present a comprehensive overview of acupuncture as a treatment for POI,highlighting advancements in clinical research and recent elucidations of its mechanistic underpinnings.It aspires to contribute a pivotal reference point for scholars and enthusiasts keen on garnering a deeper understanding of acupuncture’s role in managing POI.
基金supported by the Guangdong Provincial Key Laboratory IRADS(2022B1212010006,R0400001-22)。
文摘Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.
基金This research was supported by the National Natural Science Foundation of China(Grant Nos.51974187)Intelligent Mine Blasting and Innovative Technology Platform Construction(LJ232410146045)Liaoning Revitalization Talents Program(XLYC2203173).
文摘Cross roadway collapses are a common occurrence in underground mining operations.While the influence of mining blasts on the stability of surrounding rock is acknowledged,the underlying mechanisms remain inadequately understood.This study investigates the characteristics and mechanisms of collapse in a shallow buried cross roadway subjected to mining blast disturbances,drawing insights from an engineering project in Anshan City,Northeast China.A strain-softening model based on unified strength theory was developed to effectively calculate and analyze the loosened zone thickness and surrounding rock displacement.The PFC3D-FLAC3D coupling method was employed to clarify the concentrated collapse area within the cross roadway,providing insight into the collapse mechanism through a cross-sectional model of the concentrated region.Results demonstrate that 50%of the cross roadway collapsed following the mining blast.Subsidence at the intersection was approximately one-fifth(0.66 m)of cross roadway’s net height,exceeding subsidence in other areas by 1.3.Under the action of repeated mining blasting,the cross section of the connection roadway forms a semi-elliptical high tensile stress zone.After the cumulative damage of the surrounding rock of the connection roadway exceeds the ultimate yield strength,the cumulative stress release causes the tensile failure of the surrounding rock.The plastic zone of the connecting roadway expands to three times of the initial,and continues to develop.The surrounding rock on both sides experienced tensile stress,cumulative stress release,and the vertical propagation of tensile cracks.
基金supported by the“JBGS”Project of Seed Industry Revitalization in Jiangsu Province[Grant No.JBGS(2021)021]the Earmarked Fund for Jiangsu Agricultural Industry Technology System[Grant No.JATS(2022)510]。
文摘Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affecting the growth of fruit trees,and an appropriate ambient temperature is a necessary condition for the normal growth and development of fruit trees.Since the 20th century,due to the intensification of the greenhouse effect and global warming,there has been a significant increase in the occurrence and duration of extreme hot weather in summer has been occurring frequently and for longer durations.Thus,the growth and production of fruit trees are affected by severe hightemperature stress.Therefore,this paper primarily summarized the impacts of high-temperature stress on fruit growth and development,flowering,fruiting,fruit setting and quality.It also discussed the physiological and biochemical responses of fruit trees to high-temperature stress,research progress on the molecular mechanisms and signal transduction pathways underlying fruit tree resistance to heat or high temperature,and research on the investigation of relevant metabolites of fruit trees under stress conditions.The future research directions were discussed,and prospects and potential difficulties were proposed to serve a reference for further investigation on the high-temperature tolerance of fruit trees.
基金an initial outcome of the Research on the Trust Mechanism of Agricultural Supply Chain Financing in the Context of “Blockchain+Supply Chain” Integrated Governance (Project No:20AGL021)a key project under the National Social Science Fund of China (NSSFC)+3 种基金the Research on the Trust Mechanism of Online Bank Lending System Based on Online Social Capital of Long-tail Rural Households (Project No:19BGL155)a project under the NSSFCthe Research on the Cost Formation Mechanism of Data Factor Transactions and the Design of Transaction Mechanism (Project No:23CJY068)a youth project under the NSSFC
文摘This paper begins with a discussion of the trust issues that agricultural supply chain finance faces.It then examines the constraints of using blockchain technology to enhance trust in agricultural supply chain finance in accordance with the technological and institutional logic of combining blockchain with supply chains.This study then proposes the creation of an agricultural“blockchain+supply chain”information service platform and a financing trust mechanism that can effectively ensure the authenticity of the initial information input on the blockchain,consistency between on-chain transaction data and off-chain physical transactions,the controllability of risks in the set up and execution of smart contracts,and the removal of information constraints,resource allocation constraints,and institutional constraints in the agricultural supply chain financing.This aims to improve the efficiency of financing in agricultural supply chains and contribute to the industrial development of rural areas and rural revitalization.
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 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supported by the National Natural Science Foundation of China(Grant No.:82341023)the Interdisciplinary Research Project of School of Stomatology,Wuhan University,China(Grant No.:XNJC202305)+1 种基金the Innovative Research Team of Highlevel Local Universities in Shanghai,China(Grant No.:SHSMUZLCX20212300)Planning Project of Innovation and Entrepreneurship Training of National Undergraduate of Wuhan University,China(Grant No.:202310486122).
文摘Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.
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.
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funded by the National Natural Science Foundation of China(82260695)the Jiangxi Provincial Natural Science Foundation(20232ACB206062,20212ACB206004)+2 种基金Young Jinggang Scholar of Jiangxi Province and New Century Talents Project of Jiangxi Province(2017082,2020028)the Science and Technology Innovation Team of Jiangxi University of Chinese Medicine(CXTD22001,CXTD22006)Project of College Students’Innovation and Entrepreneurship Training Program of Jiangxi University of Chinese Medicine.
文摘Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,antipyretic,analgesic,antiosteoporotic,antihypertensive,sedative,and hypnotic effects.To date,research on the effective components of Chrysanthemum extract has mainly focused on flavonoids,whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components.In this review,the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal,aromatherapy,and diet therapy applications.
基金supported by the project of China Geological Survey(Grant No.DD20221677-2)the fundamental research funds of Chinese Academy of Geological Sciences Basal Research Fund(Grant No.JKYQN202307).
文摘Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas and economic hubs.This study focuses on the high F^(−)and NO_(3)^(−)concentration groundwater in Tongzhou District,Beijing,North China.A total of 36 groundwater samples were collected to analyze the hydrochemical characteristics,elucidate genetic mechanisms and evaluate the potential human health risks.The results of the analysis indicate:Firstly,most of the groundwater samples are characterized by Mg-HCO_(3) and Na-HCO_(3) with the pH ranging from 7.19 to 8.28 and TDS with a large variation across the range 471-2337 mg/L.The NO_(3)^(−)concentration in 38.89%groundwater samples and the F^(−)concentration in 66.67%groundwater samples exceed the permissible limited value.Secondly,F^(−)in groundwater originates predominantly from water-rock interactions and the fluorite dissolution,which is also regulated by cation exchange,competitive adsorption of HCO_(3)−and an alkaline environment.Thirdly,the effect of sewage disposal and agricultural activities have a significant effect on high NO3-concentration,while the high F^(−)concentration is less influenced by anthropogenic activity.The alkaline environment favors nitrification,thus being conducive to the production of NO_(3)^(−).Finally,the health risk assessment is evaluated for different population groups.The results indicate that high NO_(3)^(−)and F^(−)concentration in groundwater would have the largest threat to children’s health.The findings of this study could contribute to the provision of a scientific basis for groundwater supply policy formulation relating to public health in Tongzhou District.
