18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.

Probabilistic Life Calculation Method of NdFeB Based on Brittle Fatigue Damage Model

This paper proposes a probabilistic life calculation method of NdFeB based on brittle fatigue damage model.Firstly,Zhu-Wang-Tang(ZWT)constitutive model considering strain rate is established,and based on this,a numerical co-simulation model for NdFeB life calculation is constructed.The life distribution diagram of NdFeB under different stress levels is obtained after simulation.Secondly,a new model of brittle fatigue damage based on brittle damage mechanism is proposed.Then the parameters in the model are identified according to the life distribution diagram of NdFeB and the parameter distribution of the damage evolution model when applied to NdFeB is obtained.Finally,the probability density evolution equation of NdFeB life calculation is established and solved using the probability density evolution method.Probability density function(PDF)of NdFeB life under different stress levels is obtained and provides theoretical basis for the reliability of NdFeB in engineering applications.

Carbon Emission Factors Prediction of Power Grid by Using Graph Attention Network

Advanced carbon emission factors of a power grid can provide users with effective carbon reduction advice,which is of immense importance in mobilizing the entire society to reduce carbon emissions.The method of calculating node carbon emission factors based on the carbon emissions flow theory requires real-time parameters of a power grid.Therefore,it cannot provide carbon factor information beforehand.To address this issue,a prediction model based on the graph attention network is proposed.The model uses a graph structure that is suitable for the topology of the power grid and designs a supervised network using the loads of the grid nodes and the corresponding carbon factor data.The network extracts features and transmits information more suitable for the power system and can flexibly adjust the equivalent topology,thereby increasing the diversity of the structure.Its input and output data are simple,without the power grid parameters.We demonstrated its effect by testing IEEE-39 bus and IEEE-118 bus systems with average error rates of 2.46%and 2.51%.

Integrated transcriptomics and metabolomics analyses provide insights into cold stress response in wheat

Cold tolerance of crop plants influences survival and productivity under low-temperature conditions. Elucidation of molecular mechanisms underlying low temperature tolerance could be helpful in breeding. In this study, we used integrated transcriptomics and metabolomics analyses to investigate changes in gene/metabolite activity in a winter-hardy wheat cultivar of(cv. Jing 411) when subjected to sold stress. The 223 metabolites mainly enriched during cold acclimation included carbohydrates, flavonoids, and amino acids.Eight common metabolites had altered abundance following freezing treatment;six increased and two decreased. Transcriptome analysis revealed that 29,066 genes were differentially expressed in wheat crowns after cold acclimation compared to the nonacclimated control. Among them, 745 genes were up-regulated following freezing treatment, suggesting substantial change in expression of a large quantity of genes upon cold acclimation and freezing treatment, which impacts on the modified metabolites.Integrated analysis of gene expression and metabolite profiles revealed that the abscisic acid(ABA)/jasmonic acid(JA) phytohormone signaling and proline biosynthesis pathways were significantly modulated under cold acclimation and freezing treatments. Our results indicated that low-temperature stress induced substantial changes in both transcriptomes and metabolomes. Critical pathways associated with ABA/JA signaling and proline biosynthesis played important roles in regulating cold tolerance in wheat.

Characteristic and Thermal Analysis of Permanent Magnet Eddy Current Brake

In this paper,the subdomain analysis model of the eddy current brake(ECB)is established.By comparing with the finite element method,the accuracies of the subdomain model and the finite element model are verified.Furthermore,the resistance characteristics of radial,axial,andHalbach arrays under impact load are calculated and compared.The axial array has a large braking force coefficient but low critical velocity.The radial array has a low braking force coefficient but high critical velocity.The Halbach array has the advantages of the first two arrays.Not only the braking force coefficient is large,but also the critical speed is high.The parameter analysis of the Halbach array is further carried out.The inner tube thickness and air gap length are the sensitive factors of resistance characteristics.The demagnetization effect is significantly enhanced by the increase of the inner tube thickness.In order to ensure that the ECB does not overheat,the electromagnetic-thermal coupling model is established based on the heat transfer theory.The temperature rise of the inner tube is obvious while that of the permanentmagnet is small.The temperature rise of the inner tube is more than 20 K each time,and that of the permanent magnet is less than 1 K each time.

Ultra-high photoresponsive photodetector based on ReS_(2)/SnS_(2)heterostructure

Photodetectors based on two-dimensional materials have attracted much attention because of their unique structure and outstanding performance.The response speed of single ReS_(2)photodetector is slow exceptionally,the heterostructure could improves the response speed of ReS_(2)-based photodetector,but the photodetectors responsivity is reduced greatly,which restricts the development of ReS_(2).In this paper,a vertically structured ReS_(2)/SnS_(2)van der Waals heterostructure photodetectors is prepared,using ReS_(2)as the transport layer and SnS_(2)as the light absorbing layer to regulate the channel current.The device has an ultra-high photoconductive gain of 10^(10),which exhibits an ultra-high responsivity of4706 A/W under 365-nm illumination and response speed in seconds,and has an ultra-high external quantum efficiency of1.602×10^(6)%and a high detectivity of 5.29×10^(12)jones.The study for ReS_(2)-based photodetector displays great potential for developing future optoelectronic devices.

An Incremental Model for Defect Production upon Cascade Overlapping

An analytic incremental model is proposed to predict the defect production upon cascade overlapping.By resolving the coupled annealing events during cascade overlapping,this model handles cascade overlapping with multiple pre-existing defects of different sizes and number densities.The model is first parameterized and then applied to bcc-Fe.The proposed model satisfyingly reproduces the defect production obtained by molecular dynamics simulations with various radiation damage levels and defect cluster size distributions.The present model provides an essential description of the primary source of radiation damage,especially for high dose irradiation,and could be used in conjunction with reactive diffusion models for better understanding of radiation damage.

Mineralogical Characteristics of Garnet in Garnet Mica Schist and Its Tectonic Significance in the Tongbai Section of the Shangdan Fault Zone

Studies on the metamorphism and deformation conditions of rocks in the suture zone are good ways to discuss the orogenic process and mechanism. The microstructure and ultramicrostructure features of minerals are true embodiment of formation environment of the orogenic belt. Based on the study of microstructure, ultramicrostructure deformation characteristic and compositional zonation of garnets in garnets-mica schists in the Tongbai mountain, east section of the Shangdan fault zone, the results show that the three types of garnets have suffered various states of plastic deformation. The dynamic recrystallization of garnets is due to the subgrain growth and boundary migration. The dislocations are mainly free dislocation and dislocation walls. The free dislocation density ρ = 6.14 × 108/cm2, and dislocation movement are mainly slips;slip planes are 1/2 {110} and {001}. Garnet microprobe analysis shows that it belongs to almandine, and reflects it has undergone epidote-amphibolite to amphibolite facies metamorphism. Compositional zonation of garnet shows that the rocks had experienced progressive metamorphism. First metamorphic environment was continuous temperature-pressure and in mid-term there were two non-synchronous transient cooling and decompression processes, and it finally underwent decompression and warming process of the thermal relaxation environment. The formation condition of garnet-mica schist is estimated: T = 562°C - 617°C, and P = 0.77 - 1.02 GPa. The differential stress is 0.511 GPa and strain rate is 4.97536 × 10-10 m/s. After systemic analysis, a conclusion is drawn that the plastic deformation mode, deformation mechanism and formation environment of garnets are closely related to the formation and development of the Shangdan fault zone. It truly reflects that the Shangdan fault zone, as the suture zone of Yangtze and north China plate, has been subjected to early medium-grade metamorphism. With the continuous compression after the collision, the left-lateral shearing happened and caused the formation of high density dislocations and subgrains of the garnets;finally the plastic deformation happened and the bulging recrystallization formed in the period of heat relaxation had a relative low stress.

The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity:Disruption of microbial composition and short-chain fatty acid metabolism

Methamphetamine(METH)abuse is associated with significant neurotoxicity,high addiction potential,and behavioral abnormalities.Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders.However,the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored.In this study,we employed fecal microbiota transplantation(FMT)and antibiotic(Abx)intervention to manipulate the gut microbiota in mice administered METH.Furthermore,we supplemented METH-treated mice with short-chain fatty acids(SCFAs)and pioglitazone(Pio)to determine the protective effects on gut microbiota metabolism.Finally,we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice.Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity,behavioral disorders,gut microbiota disturbances,and intestinal barrier impairment.Furthermore,our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH,which involves supplementation with SCFAs or Pio.

High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation

Human monoamine oxidase B(hMAO-B)has emerged as a pivotal therapeutic target for Parkinson's disease.Due to adverse effects and shortage of commercial drugs,there is a need for novel,highly selective,and reversible hMAO-B inhibitors with good blood-brain barrier permeability.In this study,a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma,which resulted in the discovery of 75 active compounds,including phenolic acids,volatile oils,and phthalides,two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent,selective,reversible and had good blood‒brain permeability.Molecular docking and molecular dynamics simulations elucidated the inhibition mechanism.Sedanolide(IC_(50)=103 nmol/L;SI=645)and neocnidilide(IC_(50)=131 nmol/L;SI=207)demonstrated their excellent potential as hMAO-B inhibitors.They offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as rasagiline.In SH-SY5Y cell assays,sedanolide(EC_(50)=0.962μmol/L)and neocnidilide(EC_(50)=1.161μmol/L)exhibited significant neuroprotective effects,comparable to the positive drugs rasagiline(EC_(50)=0.896μmol/L)and safinamide(EC_(50)=1.079μmol/L).These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing

Using gas-liquid segmented micromixers to prepare nanoparticles that have a homogeneous particle size, controllable shape, and monodispersity advantages. Although nanoparticle aggregation within a microfluid has been shown to be affected by the shear effect, the shear effect triggering conditions in gasliquid two-phase flow is unclear and the aggregation behavior of nanoparticles under the shear effect is difficult to predict, resulting in uncontrollable physical and chemical properties of nanoparticle aggregates. In this study, a numerical simulation of nanoparticle aggregation in gas-liquid two-phase flow under the shear effect is performed using the CFD-DEM method. Then, the effects of total flow rate,gas-liquid two-phase flow ratio, and particle volume fraction on particle aggregation were analyzed to achieve control of particle aggregation shape and size. Meanwhile, the triggering mechanism of the shear effect and the mechanism of the shear effect on the aggregation of nanoparticles were clarified. The results show that increasing the total flow rate or decreasing the gas-liquid two-phase flow rate ratio can induce the shear effect, which reduces the particle aggregation size and makes the morphology tend to be spherical. Moreover, increasing the particle volume fraction, and total flow rate or decreasing the gas-liquid two-phase flow rate ratio also increases the number of particle collisions and induce interparticle adhesion. Hence, particle adhesion and the shear effect compete with each other and together affect particle aggregation.

Buckling failure analysis and numerical manifold method simulation for high and steep slope: A case study

Buckling failure of layered rock slopes due to self-weight is common in mountain areas, especially for high andsteep slope, and it frequently results in serious disasters. Previous research has focused on qualitatively evaluatingslope buckling stability and rarely studied the whole process from bending deformation to forming landslide. Inthis work, considering the tensile and compressive characteristics of rock, the simulation of high and steep slopebucking failure evolved in Bawang Mountain, was conducted by numerical manifold method. The bucklingdeformation mechanism and progressive failure process of Bawang Mountain high steep slope were studied. Thereliability of the numerical method was verified by the comparison of theoretical calculation and field measurement data. The results show that numerical manifold method can accurately simulate high and steep slopebuckling failure process by preforming interlayer and cross joints. The process of slope buckling deformation andinstability failure can be divided into minor sliding-creep deformation, interlayer dislocation-slight bending,traction by slope toe-sharp uplift, accelerated sliding-landslide formation. Under the long-term action of selfweight, the evolution of slope buckling from formation to landslide is a progressive failure process, whichmainly contains three stages: slight bending deformation, intense uplift deformation and landslide formation.

A superior strength-ductility synergy of Al_(0.1)CrFeCoNi high-entropy alloy with fully recrystallized ultrafine grains and annealing twins

Grain refinement usually makes the materials stronger,while ductility has a dramatic loss.Here,a superior tensile strength–ductility synergy in a fully recrystallized ultrafine-grained(UFG)Al_(0.1)CrFeCoNi with abundant annealing twins was achieved by cold rolling at room temperature and short-time annealing.The microstructure characterization using electron backscattered scattering diffraction demonstrates that abundant geometrically necessary dislocations(GNDs)gather around the grain boundaries and twin boundaries after tensile deformation.Although coarse-grained(CG)samples undergo a larger plastic deformation than UFG samples,the GND density decreases with grain size ranging from UFG to CG.Transmission electron microscopy results reveal that the annealing twin boundary,which effectively hinders the dislocation slip and stores dislocation in grain interior,and the activation of multiple deformation twins are responsible for the superior strength–ductility synergy and work hardening ability.In addition,the yield strength of fully recrystallized Al_(0.1)CrFeCoNi follows a Hall–Petch relationship(σ_y=24+676d^(–1/2)),where d takes into account both grain boundaries and annealing twin boundaries.The strengthening effects of grain boundaries and annealing twin boundaries were also evaluated separately.

Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression-and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.

A hydrogel spinal dural patch with potential anti-inflammatory,pain relieving and antibacterial effects

CSFL caused by spinal dural defect is a common complication of spinal surgery,which need repair such as suture or sealants.However,low intracranial pressure symptoms,wound infection and prolonged hospital associated with pin-hole leakage or loose seal effect were often occurred after surgical suture or sealants repair.Stable,pressure resistance and high viscosity spinal dural repair patch in wet environment without suture or sealants was highly needed.Herein,a bioactive patch composed of alginate and polyacrylamide hydrogel matrix cross-linked by calcium ions,and chitosan adhesive was proposed.This fabricated patch exhibits the capabilities of promoting defect closure and good tight seal ability with the bursting pressure is more than 790 mm H2O in wet environment.In addition,the chitosan adhesive layer of the patch could inhibit the growth of bacterial in vitro,which is meaningful for the postoperative infection.Furthermore,the patch also significantly reduced the expression of GFAP,IBA-1,MBP,TNF-α,and COX-2 in early postoperative period in vivo study,exerting the effects of anti-inflammatory,analgesic and adhesion prevention.Thus,the bioactive patch expected to be applied in spinal dural repair with the good properties of withstanding high pressure,promoting defect closure and inhibiting postoperative infection.

Inverse design of 1D color splitter for high-efficiency color imaging

We introduce a simple one-dimensional(1D)structure in the design of 1D color splitters(1D-CSs)with RGB unit cells for color imaging and propose a single-to-double-layer design in 1D-CSs.Based on inverse design metasurfaces,we demonstrate numerically a single-layer 1D-CS with a full-color efficiency of 46.2%and a double-layer 1D-CS with a full-color efficiency of48.2%;both of them are significantly higher than that of traditional color filters.Moreover,we demonstrate a 1D-CS that has application value by evaluating the double-layer 1D-CS’s performances in terms of incident angle sensitivity,polarization angle sensitivity,and assembly tolerance.

Satellite-to-aircraft quantum key distribution performance estimation with boundary layer effects

Remarkable progress has been made in satellite-based quantum key distribution [QKD],which can effectively provide QKD service even at the intercontinental scale and construct an ultralong-distance global quantum network.But there are still some places where terrestrial fiber and ground stations cannot be constructed,like harsh mountainous areas and air space above the sea.So the airborne platform is expected to replace the ground station and provide flexible and relay links for the large-scale integrated communication network.However,the photon transmission rate would be randomly reduced,owing to the randomly distributed boundary layer that surrounds the surface of the aircraft when the flight speed is larger than0.3 Ma.Previous research of airborne QKD with boundary layer effects is mainly under the air-to-ground scenario in which the aircraft is a transmitter,while the satellite-to-aircraft scenario is rarely reported.In this article,we propose a performance evaluation scheme of satellite-to-aircraft QKD with boundary layer effects in which the aircraft is the receiver.With common experimental settings,the boundary layer would introduce a ~31 dB loss to the transmitted photons,decrease ~47% of the quantum communication time,and decrease ~51% of the secure key rate,which shows that the aero-optical effects caused by the boundary layer cannot be ignored.Our study can be performed in future airborne quantum communication designs.

Comprehensive Approach to Assessment of Liver Viability During Normothermic Machine Perfusion

Liver transplantation is the most effective treatment of advanced liver disease,and the use of extended criteria donor organs has broadened the source of available livers.Although normothermic machine perfusion(NMP)has become a useful tool in liver transplantation,there are no consistent criteria that can be used to evaluate the viability of livers during NMP.This review summarizes the criteria,indicators,and methods used to evaluate liver viability during NMP.The shape,appearance,and hemodynamics of the liver can be analyzed at a macroscopic level,while markers of liver injury,indicators of liver and bile duct function,and other relevant indicators can be evaluated by biochemical analysis.The liver can also be assessed by tissue biopsy at the microscopic level.Novel methods for assessment of liver viability are introduced.The limitations of evaluating liver viability during NMP are discussed and suggestions for future clinical practice are provided.

Evolution of the rare earth trade network:A perspective of dependency and competition

As a global strategic reserve resource,rare earth has been widely used in important industries,such as military equipment and biomedicine.However,existing analyses based solely on the total volume of rare earth trade fail to uncover the underlying competition and dependency dynamics.To address this gap,this paper employs the principles of trade preference and import similarity to construct dependency and competition networks.Complex network analysis is then employed to study the evolution of the global rare earth trade network from 2002 to 2018.The main conclusions are as follows.The global rare earth trade follows the Pareto principle,and the trade network shows a scale-free distribution.China has emerged as the world’s largest importer and exporter of rare earth since 2017.In the dependency network,China has become the most dependent country since 2006.The result of community division shows that China has separated from the American community and formed new communities with the Association of Southeast Asian Nations(ASEAN)countries.The United States of America has formed a super-strong community with European and Asian countries.In the competition network,the distribution of competition intensity follows a scale-free distribution.Most countries face low-intensity competition,but there are numerous competing countries.The competition related to China has increased significantly.Lastly,the competition source for the United States of America has shifted from Mexico to China,resulting in China,the USA,and Japan becoming the core participants in the competition network.

Continuously released Zn^(2+)in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.