Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

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.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

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.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

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.

Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

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.

Pathological mechanisms of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

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.

Decoding molecular mechanisms:brain aging and Alzheimer's disease

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.

Activity-dependent mechanisms of neuroprotection:promising avenues against dementia

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.

Adsorption behaviors and mechanisms of gold recovery from thiosulfate solution by ion exchange resin

The adsorption behaviors and mechanisms of gold from thiosulfate solution on strong-base anion exchange resin were systematically investigated.The comparison experiment of adsorption ability and selectivity for gold showed that gel Amberlite IRA-400 resin with Type Ⅰ quaternary ammonium functional group had better adsorption performance.The increases of resin dosage,ammonia concentration and solution pH were favorable to gold adsorption,whereas the rises of cupric and thiosulfate concentrations were disadvantageous to gold loading.Microscopic characterization results indicated that gold was adsorbed in the form of [Au(S_(2)O_(3))_(2)]^(3–) complex anion by exchanging with the counter ion Cl^(–) in the functional group of the resin.Density functional theory calculation result manifested that gold adsorption was mainly depended on the hydrogen bond and van der Waals force generated between O atom in [Au(S_(2)O_(3))_(2)]^(3–) and H atom in the quaternary ammonium functional group of the resin.

Controllable Condensation of Aromatics and Its Mechanisms in Carbonization

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.

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

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).

Obituary:Prof.Yun Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

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.

Magmatic-hydrothermal Evolution and Mineralization Mechanisms of the Wangjiazhuang Cu(-Mo)Deposit in the Zouping Volcanic Basin,Shandong Province,China:Constraints from Fluid Inclusions

The Wangjiazhuang Cu(-Mo)deposit,located within the Zouping volcanic basin in western Shandong Province,China,is unique in this area for having an economic value.In order to expound the metallogenetic characteristics of this porphyry-like hydrothermal deposit,a detailed fluid inclusion study has been conducted,employing the techniques of representative sampling,fluid inclusion petrography,microthermometry,Raman spectroscopy,LA-ICP-MS analysis of single fluid inclusions,as well as cathode fluorescence spectrometer analysis of host mineral quartz.The deposit contains mainly two types of orebodies,i.e.veinlet-dissemination-stockwork orebodies in the K-Si alteration zone and pegmatiticquartz sulfide veins above them.In addition,minor breccia ore occurs locally.Four types of fluid inclusions in the deposit and altered quartz monzonite are identified:L-type one-or two-phase aqueous inclusions,V-type vapor-rich inclusions with V/L ratios greater than 50%-90%,D-type multiphase fluid inclusions containing daughter minerals or solids and S-type silicate-bearing fluid inclusions containing mainly muscovite and biotite.Ore petrography and fluid inclusion study has revealed a three-stage mineralization process,driven by magmatic-hydrothermal fluid activity,as follows.Initially,a hydrothermal fluid,separated from the parent magma,infiltrated into the quartz monzonite,resulting in its extensive K-Si alteration,as indicated by silicate-bearing fluid inclusions trapped in altered quartz monzonite.This is followed by the early mineralization,the formation of quartz veinlets and dissemination-stockwork ores.During the main mineralization stage,due to the participation and mixing of meteoric groundwater with magmatic-sourced hydrothermal fluid,the cooling and phase separation caused deposition of metals from the hydrothermal fluids.As a result,the pegmatitic-quartz sulfide-vein ores formed.In the late mineralization stage,decreasing fluid salinity led to the formation of L-type aqueous inclusions and chalcopyrite-sulfosalt ore.Coexistence of V-type and D-type inclusions and their similar homogenization temperatures with different homogenization modes suggest that phase separation or boiling of the ore-forming fluids took place during the early and the main mineralization stages.The formation P-T conditions of S-type inclusions and the early and the main mineralization stages were estimated as ca.156-182 MPa and 450-650℃,350-450℃,18-35 MPa and 280-380℃,8-15 MPa,respectively,based on the microthermometric data of the fluid inclusions formed at the individual stages.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents

Aflatoxins(AFTs)represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops.Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects,including neuro-,hepato-,nephron-,and immuno-toxicity.In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents.Aflatoxin B1(AFB1)is the most toxic congener among the 21 identified AFTs.Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans.Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes,including anxiety,lethargy disorders,depression-like behavior,cognitive,learning and memory defects,and decreased feeding behavior.Mechanistically,AFB1 exposure has been associated with lipid peroxidation,ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels.AFB1 exposure has also been shown to induce DNA damage,apoptosis,pyroptosis,and mitochondrial dysfunction in the brain tissue.Several signaling pathways,including gasdermin D,toll like receptor 2(TLR2),TLR4,Akt,NF-κB,ERK/MAPK,protein kinase C(PKC),and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death.Targeting these pathways by small molecules(e.g.,quercetin,curcumin,and gallic acid,and dimethyl fumarate),Chinese herbal extracts(e.g.,Artichoke leaf extract,Chelidonium majus ethanolic extract,pumpkin extract,and Crocus sativus L.tea),and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity.To date,the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear.In the present review,the clinical manifestations,molecular mechanisms,and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview.It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins.

Computational and bioinformatics tools for understanding disease mechanisms

Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.

Insights into Formation and Li-Storage Mechanisms of Hierarchical Accordion-Shape Orthorhombic CuNb_(2)O_(6) toward Lithium-Ion Capacitors as an Anode-Active Material

The orthorhombic CuNb_(2)O_(6)(O-CNO)is established as a competitive anode for lithium-ion capacitors(LICs)owing to its attractive compositional/structural merits.However,the high-temperature synthesis(>900℃)and controversial charge-storage mechanism always limit its applications.Herein,we develop a low-temperature strategy to fabricate a nano-blocks-constructed hierarchical accordional O-CNO framework by employing multilayered Nb_(2)CT_(x)as the niobium source.The intrinsic stress-induced formation/transformation mechanism of the monoclinic CuNb_(2)O_(6)to O-CNO is tentatively put forward.Furthermore,the integrated phase conversion and solid solution lithium-storage mechanism is reasonably unveiled with comprehensive in(ex)situ characterizations.Thanks to its unique structural merits and lithium-storage process,the resulted O-CNO anode is endowed with a large capacity of 150.3 mAh g^(-1)at 2.0 A g^(-1),along with long-duration cycling behaviors.Furthermore,the constructed O-CNO-based LICs exhibit a high energy(138.9 Wh kg^(-1))and power(4.0 kW kg^(-1))densities with a modest cycling stability(15.8%capacity degradation after 3000 consecutive cycles).More meaningfully,the in-depth insights into the formation and charge-storage process here can promote the extensive development of binary metal Nb-based oxides for advanced LICs.

Spatiotemporal characteristics and driving mechanisms of land use/land cover(LULC)changes in the Jinghe River Basin,China

Understanding the trajectories and driving mechanisms behind land use/land cover(LULC)changes is essential for effective watershed planning and management.This study quantified the net change,exchange,total change,and transfer rate of LULC in the Jinghe River Basin(JRB),China using LULC data from 2000 to 2020.Through trajectory analysis,knowledge maps,chord diagrams,and standard deviation ellipse method,we examined the spatiotemporal characteristics of LULC changes.We further established an index system encompassing natural factors(digital elevation model(DEM),slope,aspect,and curvature),socio-economic factors(gross domestic product(GDP)and population),and accessibility factors(distance from railways,distance from highways,distance from water,and distance from residents)to investigate the driving mechanisms of LULC changes using factor detector and interaction detector in the geographical detector(Geodetector).The key findings indicate that from 2000 to 2020,the JRB experienced significant LULC changes,particularly for farmland,forest,and grassland.During the study period,LULC change trajectories were categorized into stable,early-stage,late-stage,repeated,and continuous change types.Besides the stable change type,the late-stage change type predominated the LULC change trajectories,comprising 83.31% of the total change area.The period 2010-2020 witnessed more active LULC changes compared to the period 2000-2010.The LULC changes exhibited a discrete spatial expansion trend during 2000-2020,predominantly extending from southeast to northwest of the JRB.Influential driving factors on LULC changes included slope,GDP,and distance from highways.The interaction detection results imply either bilinear or nonlinear enhancement for any two driving factors impacting the LULC changes from 2000 to 2020.This comprehensive understanding of the spatiotemporal characteristics and driving mechanisms of LULC changes offers valuable insights for the planning and sustainable management of LULC in the JRB.

An aqueous BiI_(3)-Zn battery with dual mechanisms of Zn^(2+)(de)intercalation and I^(-)/I_(2)redox

The development of aqueous battery with dual mechanisms is now arousing more and more interest.The dual mechanisms of Zn^(2+)(de)intercalation and I^(-)/I_(2)redox bring unexpected effects.Herein,differing from previous studies using Zn I_(2)additive,this work designs an aqueous Bi I_(3)-Zn battery with selfsupplied I^(-).Ex situ tests reveal the conversion of Bi I_(3)into Bi(discharge)and Bi OI(charge)at the 1st cycle and the dissolved I^(-)in electrolyte.The active I^(-)species enhances the specific capacity and discharge medium voltage of electrode as well as improves the generation of Zn dendrite and by-product.Furthermore,the porous hard carbon is introduced to enhance the electronic/ionic conductivity and adsorb iodine species,proven by experimental and theoretical studies.Accordingly,the well-designed Bi I_(3)-Zn battery delivers a high reversible capacity of 182 m A h g^(-1)at 0.2 A g^(-1),an excellent rate capability with 88 m A h g^(-1)at 10 A g^(-1),and an impressive cyclability with 63%capacity retention over 20 K cycles at 10 A g^(-1).An excellent electrochemical performance is obtained even at a high mass loading of 6 mg cm^(-2).Moreover,a flexible quasi-solid-state Bi I_(3)-Zn battery exhibits satisfactory battery performances.This work provides a new idea for designing high-performance aqueous battery with dual mechanisms.