Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

Enhanced structural damage behavior of liquid-filled tank by reactive material projectile impact

A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.

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.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

软件定义网络Reactive交换模式IP转发效率研究

现代计算机网络技术发展迅速,SDN具有转发与控制分离、应用灵活多变、适应性强等特点,已逐渐被IT厂商和电信运营商所接纳并采用,但SDN作为一种发展中的技术很多方面还有待完善。本文首先将IP层相关协议的通信过程进行了分析,然后针对SDN的Reactive交换机模式将这些协议的通信效率与以太网进行了对比。实验与分析表明,在地址解析、连通性测试和数据传输等基本网络行为中,SDN的Reactive交换模式效率并不占据优势,需要进一步优化。

Formation behaviors of rod-like reactive shaped charge penetrator and their effects on damage capability

Formation behaviors of rod-like reactive shaped charge penetrator(RRSCP)and their effects on damage capability are investigated by experiments and numerical simulations.The pulsed X-ray technology and a spaced aluminum/steel plate with the thicknesses of 5 mm/100 mm are used.Three types of sphericalsegment aluminum-polytetrafluoroethylene-copper(Al-PTFE-Cu)reactive liners with Cu contents of 0%,46.6%,and 66%are fabricated and tested.The experimental results show that the reactive liners can form excellent rod-shaped penetrators with tail skirts under the shaped charge effect,but the tail skirts disappear over time.Moreover,rupturing damage to the aluminum plate and penetration to the steel plate are caused by the RRSCP impact.From simulation analysis,the RRSCP is formed by a mechanically and chemically coupled response with the reactive liner activated by shock in its outer walls and bottom and then backward overturning,forming a leading reactive penetrator and a following chemical energy cluster.The unique formation structure determines the damage modes of the aluminum plate and the steel plate.Further analysis indicates that the formation behaviors and damage capability of Al-PTFE-Cu RRSCP strongly depend on Cu content.With increasing Cu content,the velocity,activation extent,and reaction extent of Al-PTFE-Cu RRSCP decrease,which contribute to elongation and alleviate the negative effects of chemical reactions on elongation,significantly increasing the length-diameter ratio and thus enhancing the capability of steel plate penetration.However,the lower activation extent and energetic density will weaken the RRSCP's capability of causing rupturing damage to the aluminum plate.

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.

Monomeric C-reactive protein:a link between chronic inflammation and neurodegeneration?

Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.

Coupled bio-chemo-hydro-mechanical modeling of microbially induced calcite precipitation process considering biomass encapsulation using a micro-scale relationship

Geomaterials with inferior hydraulic and strength characteristics often need improvement to enhance their engineering behaviors.Traditional ground improvement techniques require enormous mechanical effort or synthetic chemicals.Sustainable stabilization technique such as microbially induced calcite precipitation(MICP)utilizes bacterial metabolic processes to precipitate cementitious calcium carbonate.The reactive transport of biochemical species in the soil mass initiates the precipitation of biocement during the MICP process.The precipitated biocement alters the hydro-mechanical performance of the soil mass.Usually,the flow,deformation,and transport phenomena regulate the biocementation technique via coupled bio-chemo-hydro-mechanical(BCHM)processes.Among all,one crucial phenomenon controlling the precipitation mechanism is the encapsulation of biomass by calcium carbonate.Biomass encapsulation can potentially reduce the biochemical reaction rate and decelerate biocementation.Laboratory examination of the encapsulation process demands a thorough analysis of associated coupled effects.Despite this,a numerical model can assist in capturing the coupled processes influencing encapsulation during the MICP treatment.However,most numerical models did not consider biochemical reaction rate kinetics accounting for the influence of bacterial encapsulation.Given this,the current study developed a coupled BCHM model to evaluate the effect of encapsulation on the precipitated calcite content using a micro-scale semiempirical relationship.Firstly,the developed BCHM model was verified and validated using numerical and experimental observations of soil column tests.Later,the encapsulation phenomenon was investigated in the soil columns of variable maximum calcite crystal sizes.The results depict altered reaction rates due to the encapsulation phenomenon and an observable change in the precipitated calcite content for each maximum crystal size.Furthermore,the permeability and deformation of the soil mass were affected by the simultaneous precipitation of calcium carbonate.Overall,the present study comprehended the influence of the encapsulation of bacteria on cement morphology-induced permeability,biocement-induced stresses and displacements.

Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

Tuning the reactivity of TiO_(2)layer with uniform distribution of Sub-5 nm Fe_(2)O_(3)particles via in situ voltage-assisted oxidation for robust catalytic reduction

The trade-off between efficiency and stability has limited the application of TiO_(2)as a catalyst due to its poor surface reactivity.Here,we present a modification of a TiO_(2)layer with highly stable Sub-5 nm Fe_(2)O_(3)nanoparticles(NP)by modulating its structure-surface reactivity relationship to attain efficiency-stability balance via a voltage-assisted oxidation approach.In situ simultaneous oxidation of the Ti substrate and Fe precursor using high-energy plasma driven by high voltage resulted in uniform distribution of Fe_(2)O_(3)NP embedded within porous TiO_(2)layer.Comprehensive surface characterizations with density functional theory demonstrated an improved electronic transition in TiO_(2)due to the presence of surface defects from reactive oxygen species and possible charge transfer from Ti to Fe;it also unexpectedly increased the active site in the TiO_(2)layer due to uncoordinated electrons in Sub-5 nm Fe_(2)O_(3)NP/TiO_(2)catalyst,thereby enhancing the adsorption of chemical functional groups on the catalyst.This unique embedded structure exhibited remarkable improvement in reducing 4-nitrophenol to 4-aminophenol,achieving approximately 99%efficiency in 20 min without stability decay after 20 consecutive cycles,outperforming previously reported TiO_(2)-based catalysts.This finding proposes a modified-electrochemical strategy enabling facile construction of TiO_(2)with nanoscale oxides extandable to other metal oxide systems.

Spark Plasma Sintering of Boron Carbide Using Ti_(3)SiC_(2) as a Sintering Additive

Boron carbide has unique properties for wide application possibilities;however,poor sinterability limits its applications.One approach to overcome this limitation is the addition of secondary phases into boron carbide.Boron carbide based composite ceramics are produced by the direct addition of secondary phases into the structure or via reactive sintering using a sintering additive.The present study investigated the effect of Ti_(3)SiC_(2) addition to boron carbide by reactive spark plasma sintering in the range of 1700-1900℃.Ti_(3)SiC_(2) phase decomposed at high temperatures and reacted with B4C to form secondary phases of TiB2 and SiC.The results demonstrated that the increase of Ti_(3)SiC_(2) addition(up to 15 vol%)effectively promoted the densification of B4C and yielded higher hardness.However,as the amount of Ti_(3)SiC_(2) increased further,the formation of microstructural inhomogeneity and agglomeration of secondary phases caused a decrease in hardness.

Correction to:Assembly-level analysis on temperature coefficient of reactivity in a graphite-moderated fuel salt reactor fueled with low-enriched uranium

Following publication of the original article,the authors observed that both Fig.5 and Fig.4 depict the same image.Figure 5 was inaccurately referenced and displayed.The correct Fig.5 is copied below:The original article has been updated.

Fabrication and Properties of a New Reactive Diluent for Cationic UV Curing

The reactive diluent prepared by siloxane modified Trimethylene oxide can improve the performance of the UV curing system.Therefore,1,7-bis[(3-ethyl-3-methoxyoxacylobutane)propyl]octadecylosiloxane(BEMOPOMTS)was synthesized from diethyl carbonate,trimethylopropanes,allyl bromide,and 1,1,3,3,5,5,7,7-octadecylosiloxane as the main raw materials.BEMOPOMTS can be used as reactive diluents in the field of cationic UV curing.It has good thermal stability,and the addition of BEMOPOMTS significantly improves the tensile strength and elongation at break of epoxy resin.Compared with the pure epoxy resin,adding 20%BEMOPOMTS increased the elastic modulus by 25%to 677 MPa.

Nonaqueous potassium-ion full-cells:Mapping the progress and identifying missing puzzle pieces

This review addresses the growing interest for potassium-ion full-cells(KIFCs)in view of the transition from potassium-ion half-cells(KIHCs)toward commercial K-ion batteries(KIBs).It focuses on the key parameters of KIFCs such as the electrode/electrolyte interfaces challenge,major barriers,and recent advancements in KIFCs.The strategies for enhancing KIFC performance,including interfaces co ntrol,electrolyte optimization,electrodes capacity ratio,electrode material screening and electrode design,are discussed.The review highlights the need to evaluate KIBs in full-cell configurations as half-cell results are strongly impacted by the K metal reactivity.It also emphasizes the importance of understanding solid electrolyte interphase(SEI)formation in KIFCs and explores promising nonaqueous as well as quasiand all-solid-state electrolytes options.This review thus paves the way for practical,cost-effective,and scalable KIBs as energy storage systems by offering insights and guidance for future research.

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.

Reactive Transport Process of Earthquake-induced Hydrochemical Changes in Guanding Thermal Spring,Western Sichuan,China

Earthquake-related hydrochemical changes in thermal springs have been widely observed;however,quantitative modeling of the reactive transport process is absent.In the present study,we apply reactive transport simulation to capture the hydrochemical responses in a thermal spring following the Wenchuan Ms 8.0 and Lushan Ms 7.0 earthquakes.We first constrain deep reservoir geothermal fluid compositions and temperature by multicomponent geothermometry,and then a reactive geochemical transport model is constructed to reproduce the hydrochemical evolution process.The results show that the recharge from the shallow aquifer increases gradually until it reaches a peak because of the permeability enhancement caused by the Lushan earthquake,which may be the mechanism to explain the earthquake-related hydrochemical responses.In contrast to the postseismic effect of the Wenchuan earthquake,the chemical evolution can be considered as hydrochemical anomalies related to the Lushan earthquake.This study proves that the efficient simulation of reactive transport processes is useful for investigating earthquake-related signals in hydrochemical time series.