Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.

Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

J-TEXT achievements in turbulence and transport in support of future device/reactor

Following the reconstruction of the TEXT tokamak at Huazhong University of Science and Technology in China, renamed as J-TEXT, a plethora of experimental and theoretical investigations has been conducted to elucidate the intricacies of turbulent transport within the tokamak configuration. These endeavors encompass not only the J-TEXT device's experimental advancements but also delve into critical issues pertinent to the optimization of future fusion devices and reactors. The research includes topics on the suppression of turbulence, flow drive and damping, density limit, non-local transport, intrinsic toroidal flow, turbulence and flow with magnetic islands, turbulent transport in the stochastic layer, and turbulence and zonal flow with energetic particles or helium ash. Several important achievements have been made in the last few years, which will be further elaborated upon in this comprehensive review.

Application of three-dimensional MHD equilibrium calculation coupled with plasma response to island divertor experiments on J-TEXT

Three-dimensional(3D) equilibrium calculations, including the plasma rotation shielding effect to resonant magnetic perturbations(RMPs) produced by the island divertor(ID) coils, were carried out using the HINT and MARS-F codes on J-TEXT. Validation of 3D equilibrium calculations with experimental observations demonstrates that the shielding effect will prevent the penetration of the edge m/n = 3/1 mode component when the ID coil current is 4 k A, while change the size of magnetic islands once the current exceeds the penetration threshold. This indicates that equilibrium calculations including the plasma rotation shielding effect to RMPs can lead to better agreements with experimental observations compared to the vacuum approximation method. Additionally, the magnetic topology at the boundary undergoes changes,impacting the interaction between the plasma and the target plate. These results may be important in understanding RMP effects on edge transport and magnetohydrodynamic(MHD)instability control, as well as divertor heat and particle flux distribution control.

Characteristics of the SOL ion-to-electron temperature ratio on the J-TEXT tokamak with different plasma configurations

Accurate measurement of the average plasma parameters in the edge region,including the temperature and density of electrons and ions,is critical for understanding the characteristics of the scrape-off layer(SOL) and divertor plasma transport in magnetically confined fusion research.On the J-TEXT tokamak,a multi-channel retarding field analyzer(RFA) probe has been developed to study average plasma parameters in the edge region under various poloidal divertor and island divertor configurations.The edge radial profile of the ion-to-electron temperature ratio,τ_(i/e),has been determined,which gradually decreases as the SOL ion self-collisionality,v_(SOL)*,increases.This is broadly consistent with what has been observed previously from various tokamak experiments.However,the comparison of experimental results under different configurations shows that in the poloidal divertor configuration,even under the same v_(SOL)*,τ_(i/e) in the SOL region becomes smaller as the distance from the X-point to the target plate increases.In the island divertor configuration,τ_(i/e) near the O-point is higher than that near the X-point at the same v_(SOL)*,and both are higher than those in the limiter configuration.These results suggest that the magnetic configuration plays a critical role in the energy distributions between electrons and ions at the plasma boundary.

Effect of the relative phase between pre-existing 2/1 and 3/1 magnetic islands on the suppression of runaway electrons on J-TEXT

In the experiments of actively triggering plasma disruption by massive gas injection, the externally applied resonant magnetic perturbation has been used to mitigate the hazard of runaway electron(RE). Motivated by the experiment of multimode coupling to suppress REs on J-TEXT, some typical simulation cases with non-ideal MHD with rotation-open discussion(NIMROD) code are carried out to explore the influential mechanism of different relative phases between m/n =2/1 and m/n = 3/1 magnetic islands on the confinement of REs. Results show that the RE confinement is drastically affected by the relative phase between 2/1 and 3/1 magnetic islands. When the O point phase of 2/1 and 3/1 magnetic islands is toroidal 330°, REs can be effectively lost. The fitting curve of the remaining ratio of REs vs. the relative toroidal phase is predicted to approximate a sine-like function dependence. Further studies indicate that the phase difference between coexisting 2/1 and 3/1 islands can affect the radial transport of impurities. The loss of runaway electrons is closely related to the deposition effect of impurity. The impurity is easier to spread into the core region with smaller poloidal phase difference between the radial velocity of impurity and the impurity quantity of Ar.

Mitochondrial dysfunction as a target in spinal cord injury:intimate correlation between pathological processes and therapeutic approaches

Traumatic spinal cord injuries interrupt the connection of all axonal projections with their neuronal targets below and above the lesion site. This interruption results in either temporary or permanent alterations in the locomotor, sensory, and autonomic functions. Damage in the spinal tissue prevents the re-growth of severed axons across the lesion and their reconnection with neuronal targets. Therefore, the absence of spontaneous repair leads to sustained impairment in voluntary control of movement below the injury. For decades, axonal regeneration and reconnection have been considered the opitome of spinal cord injury repair with the goal being the repair of the damaged long motor and sensory tracts in a complex process that involves:(1) resealing injured axons;(2) reconstructing the cytoskeletal structure inside axons;(3) re-establishing healthy growth cones;and(4) assembling axonal cargos. These biological processes require an efficient production of adenosine triphosphate, which is affected by mitochondrial dysfunction after spinal cord injury. From a pathological standpoint, during the secondary stage of spinal cord injury, mitochondrial homeostasis is disrupted, mainly in the distal segments of severed axons. This result in a reduction of adenosine triphosphate levels and subsequent inactivation of adenosine triphosphate-dependent ion pumps required for the regulation of ion concentrations and reuptake of neurotransmitters, such as glutamate. The consequences are calcium overload, reactive oxygen species formation, and excitotoxicity. These events are intimately related to the activation of necrotic and apoptotic cell death programs, and further exacerbate the secondary stage of the injury, being a hallmark of spinal cord injury. This is why restoring mitochondrial function during the early stage of secondary injury could represent a potentially effective therapeutic intervention to overcome the motor and sensory failure produced by spinal cord injury. This review discusses the most recent evidence linking mitochondrial dysfunction with axonal regeneration failure in the context of spinal cord injury. It also covers the future of mitochondria-targeted therapeutical approaches, such as antioxidant molecules, removing mitochondrial anchor proteins, and increasing energetic metabolism through creatine treatment. These approaches are intended to enhance functional recovery by promoting axonal regenerationreconnection after spinal cord injury.

Evolutionary Trajectory Planning for an Industrial Robot

This paper presents a novel general method for computing optimal motions of an industrial robot manipulator （AdeptOne XL robot） in the presence of fixed and oscillating obstacles. The optimization model considers the nonlinear manipulator dynamics, actuator constraints, joint limits, and obstacle avoidance. The problem has 6 objective functions, 88 variables, and 21 constraints. Two evolutionary algorithms, namely, elitist non-dominated sorting genetic algorithm （NSGA-II） and multi-objective differential evolution （MODE）, have been used for the optimization. Two methods （normalized weighting objective functions and average fitness factor） are used to select the best solution tradeoffs. Two multi-objective performance measures, namely solution spread measure and ratio of non-dominated individuals, are used to evaluate the Pareto optimal fronts. Two multi-objective performance measures, namely, optimizer overhead and algorithm effort, are used to find the computational effort of the optimization algorithm. The trajectories are defined by B-spline functions. The results obtained from NSGA-II and MODE are compared and analyzed.

Atrial fibrillation and dementia: not just a coincidence

Atrial fibrillation(AF)is the most common form of cardiac arrhythmia,affecting 3 to 6 million people in the US,with an increased incidence in women and elderly,with its prevalence estimated to increase from 5.1 million in 2000 to 15.9 million in 2050 in the US population.[1]Age,hypertension,heart failure,myocardial infarction(MI),genetic factors,and associated systemic inflammatory states are well-established risk factors for the development of AF.[2–6]Lifestyle factors including alcohol consumption,smoking,obesity,sedentary lifestyle,and vigorous physical activity have also been implicated to contribute to the development of AF.[2,7–9]Studies suggest that AF drives up medical expenditure.[10]The European Society of Cardiology,based on the duration,responsiveness to treatment,and therapeutic attitude of the patient and physician,classifies AF into 4 types;when AF occurs and terminates by itself or by intervention within 7 days of onset,it is called paroxysmal AF;if sustained for more than a week,with or without intervention.

Design of new resonant magnetic perturbation coils on the J-TEXT tokamak

The resonant magnetic perturbation(RMP)system is a powerful auxiliary system on tokamaks.On the J-TEXT tokamak,a set of new in-vessel coils is designed to enhance the amplitude of the RMP.The new coils are designed to be two-turn saddle coils.These two-turn saddle coils have been optimized in terms of their structure,support,and protection components to overcome the limitations of the narrow in-vessel space,resulting in a compact coil module that can be accommodated in the vessel.To verify the feasibility of this design,an electromagnetic simulation is performed to investigate the electrical parameters and the generated field of the coils.A multi-field coupled simulation is performed to investigate the capacity of heat dissipation.As a result of these efforts,the new RMP coils have been successfully installed on the J-TEXT tokamak.It has significantly enhanced the RMP amplitude and been widely applied in experiments.

Multi-objective optimization of process parameters for ultra-narrow gap welding based on Universal Kriging and NSGA Ⅱ

The successful confinement of the arc by the flux band depends on the welding process parameters for achieving single-pass,multi-layer, and ultra-narrow gap welding. The sidewall fusion depth, the width of the heat-affected zone, and the line energy are utilized as comprehensive indications of the quality of the welded joint. In order to achieve well fusion and reduce the heat input to the base metal.Three welding process characteristics were chosen as the primary determinants, including welding voltage, welding speed, and wire feeding speed. The metamodel of the welding quality index was built by the orthogonal experiments. The metamodel and NSGA-Ⅱ(Non-dominated sorting genetic algorithm Ⅱ) were combined to develop a multi-objective optimization model of ultra-narrow gap welding process parameters. The results showed that the optimized welding process parameters can increase the sidewall fusion depth, reduce the width of the heataffected zone and the line energy, and to some extent improve the overall quality of the ultra-narrow gap welding process.

Engineering Fe‑N_(4)Electronic Structure with Adjacent Co‑N_(2)C_(2)and Co Nanoclusters on Carbon Nanotubes for Efficient Oxygen Electrocatalysis

Regulating the local configuration of atomically dispersed transition-metal atom catalysts is the key to oxygen electrocatalysis performance enhancement.Unlike the previously reported singleatom or dual-atom configurations,we designed a new type of binary-atom catalyst,through engineering Fe-N_(4)electronic structure with adjacent Co-N_(2)C_(2)and nitrogen-coordinated Co nanoclusters,as oxygen electrocatalysts.The resultant optimized electronic structure of the Fe-N_(4)active center favors the binding capability of intermediates and enhances oxygen reduction reaction(ORR)activity in both alkaline and acid conditions.In addition,anchoring M-N-C atomic sites on highly graphitized carbon supports guarantees of efficient charge-and mass-transports,and escorts the high bifunctional catalytic activity of the entire catalyst.Further,through the combination of electrochemical studies and in-situ X-ray absorption spectroscopy analyses,the ORR degradation mechanisms under highly oxidative conditions during oxygen evolution reaction processes were revealed.This work developed a new binary-atom catalyst and systematically investigates the effect of highly oxidative environments on ORR electrochemical behavior.It demonstrates the strategy for facilitating oxygen electrocatalytic activity and stability of the atomically dispersed M-N-C catalysts.

Where Are the Bromeliads? A Study on Different Trails in the Ecological Reserve of Guapiaçu, RJ

Bromeliaceae are important in ecological restoration, showing easy adaptation to different environments, and constantly interacting with each other through ecological relationships, whose effects may or may not benefit the species involved. The hypothesis tested whether the population density of Hohenbergia augusta is higher in areas at a more advanced successional stage (brown trail), since the species is typical of more structured forest environments, occurring especially in the lower strata of the forest. Six plots of 10 meters (6 × 10 m) were installed, parallel to the brown and yellow trails, and with a distance of 5 m from the edge. Plots were allocated alternately between the two sides of the trail, 10 meters apart from each other when on the same side. In each plot, all H. augusta (Vell.) E. Morren bromeliads were sampled, without a minimum inclusion criterion, provided they were epiphytic phorophytes. The logarithm of the value was used for data normalization and later, the data were tested in a student’s t-test. The study pointed out that the highest population density of H. augusta occurred in the brown trail because the area is in a more advanced successional stage.

The Shishugou Fauna of the Middle-Late Jurassic Transition Period in the Junggar Basin of Western China

The Middle-Late Jurassic transition period is a critical period for the evolution of terrestrial vertebrates,but the global fossil record from this time is relatively poor.The Shishugou Fauna of this period has recently produced significant fossil remains of dinosaurs and other vertebrate groups,some representing the earliest known members of several dinosaurian groups and other vertebrate groups and some representing the best-known specimens of their group.These discoveries are significant for our understanding of the origin and evolution of several vertebrate lineages.Radiometric dating indicates that the fauna is aged approximately 159-164 Ma.Comparisons with other similarly-aged terrestrial faunas such as Shaximiao and Yanliao show both taxonomic similarities and differences between these faunas and indicate that the Junggar deposits might have preserved the most complete vertebrate fossil record for a Middle-Late Jurassic Laurasian terrestrial fauna.

重返单纯——Java回归之路

随着计算机时代的发展，应用软件，应用工具日渐复杂。人们似乎已经逐渐淡忘那个首经单纯的时光，只要掌握在DOS下编程的年代已经一去不复返．各种各样复杂的应用、复杂的工具、复杂的概念、复杂的数据库让计算机软件不堪重盘。软件已经渗透到社会工作的各行各业，结合了工作流，业务流的应用软件似乎可以完成任何你能想象到的工作，代价却是不断复杂和庞大的系统。难道我们真的不需要简单吗?答案是否定的．简单是一切工作的先决条件．否则你无法有效完成任何工作；轻量级的框架是解决问题的方法之一，它将复杂的设计过程变得更加简单。通过本文，将会让你对Java的开发有新的理解。

Production of neutron-rich exotic nuclei in projectile fragmentation at Fermi energies

Isotopic fragment yields of projectile fragmentation in peripheral collisions of^(86)Kr on^(124;112)Sn and the mean neutron-to-proton ratios of the fragments are calculated, theoretically, within the ensemble approach of statistical multifragmentation model. Obtained data are compared to the experimental cross-section measurements for the projectile-like fragmentation in the reaction of 25 Me V/nucleon^(86)Kr+^(124;112)Sn at Texas A&M University.We show the enhancement in the production of neutronrich isotopes close to the projectile as observed in the experiments. We also demonstrate the universality of the limitation of the excitation energy induced in the projectile residues.

Distribution and characterizing sources of polycyclic aromatic hydrocarbons of surface water from Jialing River

Sixteen priority polycyclic aromatic hydrocarbons(PAHs) in surface water samples were analyzed by gas chromatograph-mass spectrometer(GC-MS) to study their distribution and characterizing sources.The water samples were collected from five sites(J1-J5) in the Jialing River of Chongqing downtown area from September 2009 to August 2010.The results demonstrate that the concentration of total PAHs in three samples upstream are relatively higher than those in other two sites downstream,with average concentration of total PAHs for each site ranging from 811.5 ng/L to 1585.8 ng/L.The 2,3 and 4-ring PAHs for sampling stations account for 13.0%,56.6% and 28.6%,respectively,in total PAHs.There are obvious tendencies of seasonal change for PAHs concentration in surface water.The PAHs concentration in April of wet season is 1 301.6 ng/L,which is 1.3 times the lowest amount of total PAHs in August of flood season.Ratios of specific PAH compounds were used to characterize the possible pollution sources.Experimental results indicate that the PAHs in surface water samples are primarily from pyrolytic PAHs because of factories along these sites,while the direct leakage of petroleum products may be significant for two sites,Jiahua Bridge(J4) and Huanghuayuan Bridge(J5),because of the wharf boat nearby.

Essential oil of Curcuma wenyujin induces apoptosis in human hepatoma cells

AIM: To investigate the effects of the essential oil of Curcuma wenyujin (CWO) on growth inhibition and on the induction of apoptosis in human HepG2 cancer cells. METHODS: The cytotoxic effect of drugs on HepG2 cells was measured by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide (MTT) assay. DNA fragmentation was visualized by agarose gel electrophoresis. Cell cycle and mitochondrial transmembrane potential (△Ψm) were determined by flow cytometry (FCM). Cytochrome C immunostaining was evaluated by fluorescence microscopy. Caspase-3 enzymatic activity was assayed by the cleavage of Ac-DEVD-R110. Cleaved PARP and active caspase-3 protein levels were measured by FCM using BD? CBA Human Apoptosis Kit. RESULTS: Treatment with CWO inhibited the growth of HepG2 cells in a dose-dependent manner, and the IC50 of CWO was approximately 70 μg/mL. CWO was found to inhibit the growth of HepG2 cells by inducing a cell cycle arrest at S/G2. DNA fragmentation was evidentlyobserved at 70 μg/mL after 72 h of treatment. During the process, cytosolic HepG2 cytochrome C staining showed a markedly stronger green fluorescence than in control cells in a dose-dependent fashion, and CWO also caused mitochondrial transmembrane depolarization. Furthermore, the results clearly demonstrated that both, activity of caspase-3 enzyme and protein levels of cleaved PARP, significantly increased in a dose- dependent manner after treatment with CWO. CONCLUSION: CWO exhibits an antiproliferative effect in HepG2 cells by inducing apoptosis. This growth inhibition is associated with cell cycle arrest, cytochrome C translocation, caspase 3 activation, Poly- ADP-ribose polymerase (PARP) degradation, and loss of mitochondrial membrane potential. This process involves a mitochondria-caspase dependent apoptosis pathway. As apoptosis is an important anti-cancer therapeutic target, these results suggest a potential of CWO as a chemotherapeutic agent.

东太平洋Juan de Fuca板块的磁变研究

作为EMSLAB电磁感应国际合作计划的一部分,通过对海底观测的三分量变化地磁场的分析,构制了横跨Juan de Fuca洋脊、Juan de Fuca板块到板块俯冲带的三条地磁转换函数剖面,计算了各个测点的地磁场感应矢量。结果表明,Juan de Fuca板块的东、西两部分的浅部电性结构是有差异的,近海岸线的东区更导电;而深部电性结构是相对均匀的。这一结果与由大地电磁资料计算得到的二维模型剖面是一致的。

Absence of high amplitude propagating contractions in subjects with chronic spinal cord injury

AIM: To investigate the presence or absence of high amplitude propagating contractions (HAPC), as well as the other measures of colonic motility, in persons with spinal cord injury (SCI). METHODS: Prolonged colonic ambulatory manometric studies were performed on 14 male volunteers: 8 with SCI (mean age, 59 ± 13 years; mean duration of injury, 13 ± 4 years) and 6 healthy able-bodied controls (mean age, 57 ± 10 years). A solid-state manometry catheter was endoscopically clipped to the splenic flexure. Recording was performed for > 24 h after manometric catheter placement. RESULTS: HAPC were absent in individuals with SCI during pre-sleep, sleep, and post-sleep phases. HAPC were significantly increased after awakening in non-SCI controls (0.8 ± 0.2 HAPC/h vs 10.5 ± 2.0 HAPC/h, P < 0.005). The motility index was lower in those with SCI than in controls preand post-sleep (SCI vs non-SCI: Pre-sleep, 2.4 ± 0.4 vs 8.8 ± 1.9, P < 0.01; Post-sleep, 4.3 ± 0.8 vs 16.5 ± 4.5, P < 0.05). However, a sleepinduced depression of colonic motility was observed in both the SCI and non-SCI groups (Pre-sleep vs Sleep, non-SCI: 8.8 ± 1.9 vs 2.1 ± 0.9, P < 0.002; SCI: 2.4 ± 0.4 vs 0.2 ± 0.03, P < 0.001), with the motility index of those with SCI during sleep not significantly different than that of the controls. CONCLUSION: HAPC were not observed in individuals with SCI preor post-sleep. A sleep-induced depression in general colonic motility was evident in SCI and control subjects.