Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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.

Regarding the Regulatory Sandbox Route and Mechanism for Governance of Artificial Intelligence

The main challenge in AI governance today is striking a balance between controlling AI dangers and fostering AI innovation.Regulators in a number of nations have progressively extended the regulatory sandbox,which was first implemented in the banking sector,to AI governance in an effort to reduce the conflict between regulation and innovation.The AI regulatory sandbox is a new and feasible route for AI governance in China that not only helps to manage the risks of technology application but also prevents inhibiting AI innovation.It keeps inventors'trial-and-error tolerance space inside the regulatory purview while offering a controlled setting for the development and testing of novel AI that hasn't yet been put on the market.By providing full-cycle governance of AI with the principles of agility and inclusive prudence,the regulatory sandbox offers an alternative to the conventional top-down hard regulation,expost regulation,and tight regulation.However,the current system also has inherent limitations and practical obstacles that need to be overcome by a more rational and effective approach.To achieve its positive impact on AI governance,the AI regulatory sandbox system should build and improve the access and exit mechanism,the coordination mechanism between the sandbox and personal information protection,and the mechanisms of exemption,disclosure,and communication.

Contract Mechanism of Water Environment Regulation for Small and Medium Sized Enterprises Based on Optimal Control Theory

The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.

Cu-based materials for electrocatalytic CO_(2) to alcohols:Reaction mechanism,catalyst categories,and regulation strategies

Electrocatalytic CO_(2) reduction reaction(CO_(2)RR)technology,which enables carbon capture storage and resource utilization by reducing CO_(2) to valuable chemicals or fuels,has become a global research hotspot in recent decades.Among the many products of CO_(2)RR(carbon monoxide,acids,aldehydes and alcohols,olefins,etc.),alcohols(methanol,ethanol,propanol,etc.)have a higher market value and energy density,but it is also more difficult to produce.Copper is known to be effective in catalyzing CO_(2) to high valueadded alcohols,but with poor selectivity.The progress of Cu-based catalysts for the selective generation of alcohols,including copper oxides,bimetals,single atoms and composites is reviewed.Meanwhile,to improve Cu-based catalyst activity and modulate product selectivity,the modulation strategies are straighten out,including morphological regulation,crystalline surface,oxidation state,as well as elemental doping and defect engineering.Based on the research progress of electrocatalytic CO_(2) reduction for alcohol production on Cu-based materials,the reaction pathways and the key intermediates of the electrocatalytic CO_(2)RR to methanol,ethanol and propanol are summarized.Finally,the problems of traditional electrocatalytic CO_(2)RR are introduced,and the future applications of machine learning and theoretical calculations are prospected.An in-depth discussion and a comprehensive review of the reaction mechanism,catalyst types and regulation strategies were carried out with a view to promoting the development of electrocatalytic CO_(2)RR to alcohols.

Mechanism of hypothalamic paraventricular nucleus in regulating asthmatic attack

BACKGROUND:It has been confirmed that c-fos expression increased markedly in hypothalamic paraventricular nucleus(PVN)during asthmatic attack in rats,and PVN has extensive physiological functions,involving in the regulation of respiratory system,etc.OBJECTIVE:To observe the alteration of electroencephalogram(EEG)and power spectra in PVN during the asthmatic attack,and the alteration of lung function and diaphragmatic muscle discharge after bilateral PVN lesion in asthmatic rats.DESIGN:A randomized control study.SETTING:Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University.MATERIALS:Forty-eight male adult SD rats of 260-300 g were used.The rats were randomly divided into 6 groups(n=8):control group,asthma group,electrolytic lesion of PVN group,KA-induced lesion of PVN group,sham electrolytic lesion of PVN group and sham kainic acid(KA)-induced lesion of PVN group.KA,chicken ovalbumin and aluminum hydroxide were purchased from American Sigma Company.Bordetella pertussis vaccine(Institute of Biological Products of Shanghai);stereotaxic apparatus(JiangwanⅡ,China);lesion-producing device(YC-2 programmable stimulato,Chengdu Instrument Company);MD2000 signal processing system(Nanjing Medical School);data acquisition system(RM6240B,Chengdu Instrument Company).METHODs:The experiments were carried out in the Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University from January to August in 2006.①Rats except for control group were sensitized with an intraperitoneal injection of 100 mg chicken ovalbumin and 100 mg aluminum hydroxide and Bordetella pertussis vaccine containing 5×10^(9) heat-killed in 1 mL of sterile saline.From the fifteenth to seventeenth days rats received three times aerosolized ovalbumin challenge.In rats of the control group and asthma group three steel electrodes were placed into the left PVN(AP-1.8 mm,LR 0.4 mm,OH-7.9 mm),parietal cortex and subcutaneous tissue in lower limb.Lung function tests were carried out simultaneously.Small holes were drilled in the skull to introduce a concentric bipolar electrode in the direction of the PVN in order to perform electrolytic lesion.The electrodes were connected to a lesion-producing device and a current of 1.0-1.5 mA was passed over a period of 10-15 s on each side of the PVN.The rats received 0.5μg/0.5μL of KA in phosphate buffer(0.1 mol/L,pH 7.4),and the speed of infusion was 0.1μL per minute in order to perform KA-induced lesion of PVN.②Three days after operation of lesion,lung function tests were carried out.All the electrode and transducer were connected with data acquisition system.This technique yielded airway resistance(Raw),dynamic compliance(Cdyn),the expiratory time(Te)/the inspiratory time(Ti),minute ventilation volume(MVV),EMGdi frequency and EMGdi integral.③The differences of the measurement data were compared using the t test.MAIN OUTCOME MEASURES:①The alteration of EEG and power spectrum of PVN during asthmatic attack in sensitized rats;②The effects of electrolytic lesion or KA-induced lesion of PVN on lung function in asthmatic rats.RESULTS:All the 48 rats were involved in the analysis of results.①Alteration of EEG and power spectrum:Five minutes after injection of ovalbumin into caudal vena,the breathing rate of the rat was obviously speeded up and the total power spectrum was increased[(18476.71±2140.94),(13838.75±2983.26)mV^(2),P<0.01],the percentage of theδpower andθpower decreased significantly(P<0.01),while the percentage ofαpower andβ1 power were enhanced(P<0.05,0.01).Ten minutes after injection,the EEG power spectrum of PVN further shifted rightward,the total power gradually increased(P<0.01)which suggesting that the intensive hypersynchrony activities of PVN neurons.The percentage ofδpower was decreased significantly(P<0.01),but theα,β1 andβ2 were increased(P<0.01).Twenty-five minutes later,the breathing movements became steady,and the EEG power spectrum of PVN returned to the control level step by step.②The alteration of lung function was detected during asthmatic attack after electrolytic lesion or KA-induced lesions of PVN respectively.It was found that EMGdi frequency,Te/Ti and RL were all decreased(P<0.01),EMGdi integral,MVV and Cdyn were all enhanced(P<0.01),while there were no significant changes in the sham surgery group(P>0.05).CONCLUSION:The excitability of PVN is increased during the asthmatic attack.PVN plays a key role in the regulation of asthma.Both electrolytic and KA lesions of PVN can significantly relieve the asthmatic symptoms of rats,and improve their lung function.

MicroRNAs expression dynamics reveal post-transcriptional mechanisms regulating seed development in Phaseolus vulgaris L.

The knowledge on post-transcriptional regulation mechanisms implicated in seed development(SD)is still limited,particularly in one of the most consumed grain legumes,Phaseolus vulgaris L.We explore for the first time the miRNA expression dynamics in P.vulgaris developing seeds.Seventy-two known and 39 new miRNAs were found expressed in P.vulgaris developing seeds.Most of the miRNAs identified were more abundant at 10 and 40 days after anthesis,suggesting that late embryogenesis/early filling and desiccation were SD stages in which miRNA action is more pronounced.Degradome analysis and target prediction identified targets for 77 expressed miRNAs.While several known miRNAs were predicted to target HD-ZIP,ARF,SPL,and NF-Y transcription factors families,most of the predicted targets for new miRNAs encode for functional proteins.MiRNAs-targets expression profiles evidenced that these miRNAs could tune distinct seed developmental stages.MiRNAs more accumulated at early SD stages were implicated in regulating the end of embryogenesis,postponing the seed maturation program,storage compound synthesis and allocation.MiRNAs more accumulated at late SD stages could be implicated in seed quiescence,desiccation tolerance,and longevity with still uncovered roles in germination.The miRNAs herein described represent novel P.vulgaris resources with potential application in future biotechnological approaches to modulate the expression of genes implicated in legume seed traits with impact in horticultural production systems.

Critical protein GAPDH and its regulatory mechanisms in cancer cells

Glyceraldehyde-3-phosphate dehydrogenase （GAPDH）, initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and pnsttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 （HIF-1）, p53, nitric oxide （NO）, and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications （PTMs） occurring in GAPDH in cancer cells result in new activities unrelated to the original glycnlytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described.

Molecular Mechanism of Rice Necrotic Lesion for Optimized Yield and Disease Resistance

How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.

Investigation on mechanical properties regulation of rock-like specimens based on 3D printing and similarity quantification

3D printing is widely adopted to quickly produce rock mass models with complex structures in batches,improving the consistency and repeatability of physical modeling.It is necessary to regulate the mechanical properties of 3D-printed specimens to make them proportionally similar to natural rocks.This study investigates mechanical properties of 3D-printed rock analogues prepared by furan resin-bonded silica sand particles.The mechanical property regulation of 3D-printed specimens is realized through quantifying its similarity to sandstone,so that analogous deformation characteristics and failure mode are acquired.Considering similarity conversion,uniaxial compressive strength,cohesion and stress–strain relationship curve of 3D-printed specimen are similar to those of sandstone.In the study ranges,the strength of 3D-printed specimen is positively correlated with the additive content,negatively correlated with the sand particle size,and first increases then decreases with the increase of curing temperature.The regulation scheme with optimal similarity quantification index,that is the sand type of 70/140,additive content of 2.5‰and curing temperature of 81.6℃,is determined for preparing 3D-printed sandstone analogues and models.The effectiveness of mechanical property regulation is proved through uniaxial compression contrast tests.This study provides a reference for preparing rock-like specimens and engineering models using 3D printing technology.

Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force.However,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive.In this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis,molecular dynamics simulations,and live cell assays.The results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming concentration.Moreover,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane tension.Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin’s ability to induce pore formation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL^(-1)melittin.Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.

Transcriptomic analysis reveals putative osmoregulation mechanisms in the kidney of euryhaline turbot Scophthalmus maximus responded to hypo-saline seawater

Turbot harbor a relatively remarkable ability to adapt to opposing osmotic challenges and are an excellent model species to study the physiological adaptations of flounder associated with osmoregulatory plasticity.The kidney transcriptome of turbot treated 24 h in water of hypo-salinity(salinity 5)and seawater(salinity 30)was sequenced and characterized.In silico analysis indicated that all unigenes had significant hits in seven databases.The functional annotation analysis of the transcriptome showed that the immune system and biological processes associated with digestion,absorption,and metabolism played an important role in the osmoregulation of turbot in response to hypo-salinity.Analysis of biological processes associated with inorganic channels and transporters indicated that mineral absorption and bile secretion contributed to iono-osmoregulation resulting in cell volume regulation and cell phenotypic plasticity.Moreover,we analyzed and predicted the mechanisms of canonical signaling transduction.Biological processes involved in renin secretion,ECM-receptor interaction,adherens junction,and focal adhesion played an important role in the plasticity phenotype in hypo-stress,while the signal transduction network composed of the MAPK signaling pathway and PI3K-Akt signaling pathway with GABAergic synapse,worked in hypoosmoregulation signal transduction in the turbot.In addition,analysis of the tissue specificity of targeted gene expression using qPCR during salinity stress was carried out.The results showed that the kidney,gill,and spleen were vital regulating organs of osmotic pressure,and the osmoregulation pattern of euryhaline fish dif fered among species.

Incentive Mechanism Design for Public Goods Provision:Price Cap Regulation and Optimal Regulation

This paper studies the mechanism design that induces firms to provide public goods under two regulatory means： price cap regulation and optimal regulation, respectively. We first outline two models of monopoly regulation with unobservable marginal costs and effort, which can be regard as an optimal problem with dual restrictions. By solving this problem, we get the two optimal regulatory mechanisms to induce the provision of public goods. Further, by comparative statics, the conclusion is drawn that the welfare loss as sociated with price cap regulation, with respective to optimal regulation, increases more with increase of the expense of public goods.

The Storability and Its Regulatory Mechanism of HuanghuaPear(Pyrus pyrifolia Nakai.)Fruit as Influencedby Postharvest Treatments

Different temperatures and PEF packing treatments were carried out on postharvest Huanghua pear fruit to investigate their effects on fruit storability and the regulatory mechanism. LOX activity, O2- content, AOS activity, ACC synthase activity, ACC content, ACC oxidase activity and ethylene production changed with peaks in the ripening fruit at 20℃ and were inhibited by cold storage, incidence of fruit woolness and fruit decay were lightened as well. Low temperature combined with PEF packing (PEF1 and PEF2) treatments could further improve the fruit storability, maintain preferable quality. There was no significant difference between PEF1 and PEF2 both during cold storage at 1℃ and shelf life at 20℃. The recommended storage period of Huanghua fruit was two months at It and could be extended one month longer with PEF packing treatments.

Relevant Enzymes, Genes and Regulation Mechanisms in Biosynthesis Pathway of Stilbenes

Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the progresses of study on relevant enzymes, genes, and regulation mechanism in biosynthesis pathway of stilbenes are described. Here we introduce a holistic and systematic method of researching relevant enzymes, genes and other regulatory factors in biosynthesis pathway of stilbenes—Systems biology. The application of knowledge of relative enzymes, genes and regulation mechanisms in stilbenes biosynthesis in metabolic engineering which is used as a tool of improving the disease resistance of plants and health caring quality of crops is also discussed.

Molecular regulation mechanism of oocyte maturation in beef cattle

Bovine oocytes are one of the indispensable cells in cattle reproduction and have become a research hot spot in cattle reproduction in recent years.The maturation process of oocytes is mainly regulated by enzymes,hormones,cytokines,and other molecules.The factors affecting cattle oocyte maturation have been previously studied to clarify the molecular mechanisms of cattle oocyte maturation.In this review article,phospholipid protein-3-kinase/protein kinase B,mitogen-activated protein kinase/extracellular signal-regulated kinase,Janus kinase/signal transducer and activator of transcription,epidermal growth factor receptor/extracellular signal-regulated kinase,and other signaling pathways related to oocyte maturation are discussed.In addition,the molecular mechanisms of some coding genes(JY-1,FGF-10,CDC20,etc.)and non-coding genes(miRNA,lncRNA,and circRNA)regulating oocyte maturation have been reviewed to provide new ideas for high reproductive performance molecular breeding of high-quality cattle.

Acetylation as a mechanism that regulates axonal regeneration

The capacity for adult axons to regenerate after injury is diminished compared with developing axons.In the case of central nervous system（CNS）axons,injury causes a total failure to regenerate.This failure is due to both the intrinsic developmental decrease in growth capacity and the extrinsic inhibitory environment formed because of the injury.

Study on the Whole Process Simulation and Regulation Mechanism of Urban Green Ecological Rainwater Drainage System

In view of the frequent waterlogging caused by rapid urbanization and the public’s dissatisfaction with the drainage system,the article based on the concept of the green ecological drainage system,constructed the urban green ecological drainage comprehensive simulation research system,and quickly evaluated pipe network operation and surface water of an industrial park under typical rainfall conditions.The results showed that the drainage capacity of the designed green ecological rainwater drainage system reached 100%,and there was no ponding phenomenon,which indicated that the green ecological rainwater drainage system could effectively solve the practical problems of urban drainage.The green ecological rainwater comprehensive simulation research system had good adaptability.The research results provided the scientific theoretical basis and reference significance for planning,designing,constructing,operating,and managing urban rainwater system scientifically and systematically.

Copper-based bimetallic electrocatalysts for CO_(2) reduction:From mechanism understandings to product regulations

Electrocatalytic carbon dioxide reduction reaction(CO_(2) RR)is a promising method to solve current environment and energy issues.Copper-based catalysts have been widely studied for converting CO_(2) into value-added hy-drocarbon products.Cu monometallic catalyst has been proved to have some shortcomings,including relatively high energy barriers and diverse reaction pathways,leading to low reaction activities and poor product selec-tivity,respectively.Recently copper-based bimetallic tandem catalysts have attracted extensive attentions due to their special catalyst structure,which can be easily regulated to achieve high CO_(2) RR reactivity and product selectivity.With the development of quantum chemistry calculations and spectroscopic characterization methods,deep understandings of CO_(2) RR from the mechanism perspective provide a broad horizon for the design of effi-cient catalysts.This review offers a good summary of reaction mechanisms and product regulation strategies over copper-based bimetallic catalysts,along with a brief discussion on future directions towards their practical applications.

Study on the Operation Mechanism and Effect of the Yellow River Water and Sediment Regulation System

In order to scientifically deal with the problems of less water and more sediment in the Yellow River and the uncoordinated relationship between water and sediment,it is necessary to establish a perfect water and sediment regulation system.Through the calculation of the sediment transport capacity of the Yellow River and the application of the water and sediment regulation system,it is found that the sediment transport efficiency of the Yellow River will increase with the increase of water flow,and there will be an obvious inflection point near the flat discharge.The joint regulation of the backbone reservoir group can discharge the large discharge close to the minimum flat discharge of the downstream river,which improves the sediment transport capacity of the river and alleviates the problem of sediment deposition.In this paper,through the introduction of the Yellow River water and sediment regulation project system,regulation indicators and mechanisms,the author discusses in detail the Yellow River water and sediment regulation scheme and its operation effect,hoping to provide help promote the improvement of the Yellow River governance effect.

Research Progress of Anti-tumor Effects of Curcuma zedoaria and its Active Ingredients Through Immune Regulation Mechanism

The continuous increase in the incidence rate of various fatal malignant tumors in the recent years warrants an imperative search for medications or drugs with obvious anti-tumor eflects and reliable curative effects.Previous studies have found that Curcuma zedoaria and its active ingredients,such as turmeric oil,curcumol,and P-elemene,have obvious antitumor effects,and they do not have the adverse reactions and side effects seen in the anti-tumor drugs of Western medicine.Based on the review and inductive analysis of related literature,we summarize in the present article the results of some researchers who investigated the anti-tumor effects of Curcuma zedoaria and its active ingredients through the immune regulation mechanism.