Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Lite...Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.展开更多
4-Nitrophenol(4-NP),a toxic and persistent pollutant in chemical wastewater,presents significant challenges in degradation and mineralization.Conventional ozone oxidation catalysts are hindered by low efficiency,mass ...4-Nitrophenol(4-NP),a toxic and persistent pollutant in chemical wastewater,presents significant challenges in degradation and mineralization.Conventional ozone oxidation catalysts are hindered by low efficiency,mass transfer constraints and metal leaching,necessitating the development of stable and efficient catalysts.Herein,BCn-H/MS,the derivative of Bi(Ce)-MOF,was prepared by in situ incorporation,thermal decomposition and acid etching.The resulting materials were characterized and employed in catalytic ozonation for the reduction of 4-NP.Under the specific experimental conditions of the O_(3)+BC0.3-H/MS system,the total organic carbon(TOC)and chemical oxygen demand(COD)removal rates of 4-NP were observed to reach 94.6%and 91.8%within 30 min,respectively.These two parameters were improved by raising the initial pH,reducing the pollutant concentration and increasing the catalyst dosage.The abundant oxygen vacancies(OVs)were regarded as the pivotal catalytic site of BC0.3-H/MS,which was conducive to the adsorption of O_(3) and the acceleration of the formation of reactive oxygen species(ROS).The regular hollow square structure effectively boosted the specific surface area,increased OVs exposure and accelerated the adsorption and mass transfer process.The electron paramagnetic resonance(EPR)results demonstrated that the primary ROS engaged in the degradation reaction were⋅OH and⋅O_(2)−.BC0.3-H/MS demonstrated excellent stability and reusability in cyclic experiments.Toxicity analysis revealed that the O_(3)+BC0.3-H/MS system exhibited an effective detoxification effect.Ultimately,the primary degradation pathway of 4-NP was proposed through liquid chromatography-mass spectroscopy(LC-MS)and in-situ diffuse reflectance infrared fourier-transform spectroscopy(DRIFTS)analyses at varying reaction times.展开更多
Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory syste...Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NFκB neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.展开更多
Microplastic accumulation after film mulching affects nutrients cycling in the soil–crop system.Bulk soil(BS)and rhizosphere soil(RS)have two different community compositions which lead to their different microbial n...Microplastic accumulation after film mulching affects nutrients cycling in the soil–crop system.Bulk soil(BS)and rhizosphere soil(RS)have two different community compositions which lead to their different microbial nutrient acquisition abilities.Microplastics influence the rhizosphere effect.However,the mechanism by which microplastic accumulation affects the net photosynthetic rate(NPR)through rhizospheric microbial communities remains unknown.This study aimed to identify the mechanisms underlying the effects of polyethylene(PE)and polyvinyl chloride(PVC)microplastics at 0,1,and 5%(w/w)on the NPR in the wheat–soil ecosystem using a pot experiment.Superoxide dismutase(SOD)activity was reduced by 15.35–36.7%,and that of peroxidase(POD)was increased by 32.47–61.93%,causing reductions in NPR(17.94–23.81%)in the PE5%and PVC(1 and 5%)(w/w)treatments compared with the control.The Chao1,Shannon,and Simpson indices of the bacterial and fungal diversities were lower in BS than in RS at PE1%and PVC5%(w/w),respectively.The bacterial and fungal network complexities were reduced and increased,respectively,owing to alterations in the bacterial and fungal community compositions and structures for wheat growth.The Mantel test showed that the bacterial and fungal diversity indices in BS had positive correlations with Olsen-P and phosphatase;however,those in RS were positively correlated with NO_(3)^(–) and β-1,4-glucosidase.The structural equation model indicated that wheat enzymatic and soil hydrolytic activities negatively affected NPR.Wheat has a profound antioxidant defense strategy for PE and PVC microplastic stress,which produces a synergistic effect of POD by protecting organelles and reducing tissue damage to preserve the NPR.展开更多
Two new species of the Aglaostigma laticinctum subgroup belonging to A.tertium group,are described and illustrated in this study:A.leucogaster Liu,Li&Wei sp.nov.and A.rufitegula Liu,Li&Wei sp.nov.The Aglaostig...Two new species of the Aglaostigma laticinctum subgroup belonging to A.tertium group,are described and illustrated in this study:A.leucogaster Liu,Li&Wei sp.nov.and A.rufitegula Liu,Li&Wei sp.nov.The Aglaostigma laticinctum subgroup is proposed here for the first time,with a brief discussion of its diagnostic features.Additionally,a key to all known species of the A.laticinctum subgroup from China is provided.展开更多
A new species of the Macrophya malaisei group in the genus Macrophya Dahlbom,1835 from Zhejiang in China is described:M.alboclypea Li,Liu&Wei sp.nov.A revised key to the Chinese and Japanese species of the M.malai...A new species of the Macrophya malaisei group in the genus Macrophya Dahlbom,1835 from Zhejiang in China is described:M.alboclypea Li,Liu&Wei sp.nov.A revised key to the Chinese and Japanese species of the M.malaisei group is provided.展开更多
Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic...Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.展开更多
Glaucoma filtration surgery(GFS)stands as the most effective intervention for reducing intraocular pressure,a critical component in glaucoma management.Despite its pivotal role,the scarring of the filtration bleb rema...Glaucoma filtration surgery(GFS)stands as the most effective intervention for reducing intraocular pressure,a critical component in glaucoma management.Despite its pivotal role,the scarring of the filtration bleb remains the primary impediment to successful GFS outcomes.Perioperative utilization of antimitotics,while frontline in combating fibrosis and modulating the wound healing process,carries the risk of vision-threatening complications.Given the complexity of the wound healing cascade and the potential insufficiency of targeting a single molecule,there is an imperative to expand therapeutic modalities through combination therapies.This review offers a comprehensive elucidation of the fibrogenesis post-GFS,a synthesis unprecedented in the available literature,and aims to inform the broadening of therapeutic strategies for GFS.展开更多
To improve the traffic scheduling capability in operator data center networks,an analysis prediction and online scheduling mechanism(APOS)is designed,considering both the network structure and the network traffic in t...To improve the traffic scheduling capability in operator data center networks,an analysis prediction and online scheduling mechanism(APOS)is designed,considering both the network structure and the network traffic in the operator data center.Fibonacci tree optimization algorithm(FTO)is embedded into the analysis prediction and the online scheduling stages,the FTO traffic scheduling strategy is proposed.By taking the global optimal and the multi-modal optimization advantage of FTO,the traffic scheduling optimal solution and many suboptimal solutions can be obtained.The experiment results show that the FTO traffic scheduling strategy can schedule traffic in data center networks reasonably,and improve the load balancing in the operator data center network effectively.展开更多
A hybrid fiber-reinforced polymer(HFRP)continuous sucker rod,comprising a carbon fiber-reinforced polymer(CFRP)core layer,a glass fiber-reinforced polymer(GFRP)winding layer,and a GFRP coating layer(CFRP:GFRP=2:3),has...A hybrid fiber-reinforced polymer(HFRP)continuous sucker rod,comprising a carbon fiber-reinforced polymer(CFRP)core layer,a glass fiber-reinforced polymer(GFRP)winding layer,and a GFRP coating layer(CFRP:GFRP=2:3),has been developed and widely used in oilfield extraction due to its lower specific gravity,enhanced corrosion resistance,and superior strength.However,HFRP rod joints and their adjacent sections are prone to multi-mode failures,including fracture,debonding,and cracking.Due to the complexity of joint structure and the coupling of tension,bending,and torsion,the failure mechanism is unclear.To address this issue,a dual-scale failure assessment methodology for HFRP rods was proposed,utilizing both macro and meso finite element models(FEM).This methodology was validated through tensile and bending experiments,which yielded critical loads for theφ22 mm HFRP rod:a tensile load of 340.2 kN,a torque of 132.3 N m,and a bending moment of 1192.4 N m.Additionally,a comprehensive FEM of the joint was established,which identified potential failure points at the necking of the rotary joint,resin adhesive and the HFRP rod cross-section at the first groove tip.These failure modes closely matched the experimental observations.Furthermore,the simulation results show that stress concentration at the joint reduced the tensile,bending,and torsional strengths of the HFRP rod to 61%,12%,and 82%of their original values,respectively.The effects of bending moments and torque on the tensile strength of HFRP rods were subsequently explored,leading to the development of an equivalent fatigue assessment method for HFRP rod joints.This method,based on the fatigue characteristics of HFRP rods and joint components,reveals that the primary cause of joint failure is the susceptibility of both the joint and the HFRP rod to bending moments and torque induced by dynamic buckling of the sucker rod string(SRS).Using this method,the fatigue ultimate axial force of theφ22 mm HFRP joint was determined to be 91.5 kN,with corresponding fatigue ultimate torque and bending moment under an axial force of 62.4 kN being 89.3 N m and 71.5 N m,respectively.Finally,a design method incorporating a concentrated weighting strategy for HFRP-steel mixed rods was proposed to enhance their service life,and its effectiveness was demonstrated through on-site testing.展开更多
Vegetation change is the most intuitive and sensitive bioindicator reflecting seasonal and interannual variations in the external environment,and it can directly reflect the rapid response of terrestrial ecosystems to...Vegetation change is the most intuitive and sensitive bioindicator reflecting seasonal and interannual variations in the external environment,and it can directly reflect the rapid response of terrestrial ecosystems to climate change.Using remote sensing and meteorological data,this study revealed the spatiotemporal characteristics of leaf area index(LAI)in the north of China during 1982–2022,clarified the response of LAI change to different meteorological factors,quantified the impacts of climate change and human activities on LAI change,and predicted the future trends in LAI change.From 1982 to 2022,the vegetation in the north of China generally showed a greening trend with a change rate of 0.0071 m2/(m2•a).Temperature was strongly positively correlated with LAI and was the main climate factor driving LAI change.Residual analysis revealed that vegetation improvement occurred in across 74.53%of the study area,and vegetation improvement in about 96.83%of the improved zone was attributed to a combination of climate change and human activities.The regions where anthropogenic contribution exceeded 60.00%covered 36.83%of human-affected areas,while the regions where climatic contribution exceeded 60.00%covered 19.77%of climate-affected areas,demonstrating that human activities influenced the intensity of LAI change more deeply despite the broad spatial impact of climate change.Human activities such as afforestation and the Three-North Protective Forest Program played the dominant role in vegetation greening compared to climate change.Hurst index analysis indicated that 80.30%of vegetation in the north of China is expected to experience a non-sustained improvement in the future.These findings will provide a scientific basis for optimizing the protection strategies of the national ecological barrier areas and evaluating the effectiveness of major ecological projects.展开更多
BACKGROUND In recent years,the number of pediatric patients with unexplained liver disease has been increasing.Whole-exome sequencing(WES)technology has played a significant role in the diagnosis;however,related studi...BACKGROUND In recent years,the number of pediatric patients with unexplained liver disease has been increasing.Whole-exome sequencing(WES)technology has played a significant role in the diagnosis;however,related studies remain limited.AIM To investigate the clinical characteristics and genetic causes of unexplained pediatric liver disease to improve the diagnosis and treatment of this disease.METHODS Eighty children with unexplained liver disease were divided into two groups:The liver enzyme elevation group(Group A)and the cholestasis group(Group B).Children with both elevated liver enzymes and cholestasis were assigned to Group B.The clinical characteristics of the patients were retrospectively summarized,and WES was performed in the patients and their parents.RESULTS Genetic results were obtained in 46 patients(46/80,57.5%),including 38 in Group A(38/65,58.5%)and 8 in Group B(8/15,53.3%).A total of 53 pathogenic or likely pathogenic variants were identified in 42 patients(42/80,52.5%),including 40 previously reported variants and 13 novel variants.Seven variants of uncertain significance were identified in 7 patients(7/80,8.8%),of which 4 were novel variants.A total of 19 gene mutations were identified:2 cases of AGL,15 cases of ATP7B,1 case of CAPN3,4 cases of DMD,1 case of FLG,1 case of G6PC,5 cases of JAG1,2 cases of PHKA2,2 cases of PYGL,1 case of SMARCAL1,1 case of SMPD1,1 case of TNFAIP3,1 case of GLB1,and 1 case of MAT1A in Group A;and 1 case of SLC25A13,3 cases of JAG1,1 case of ATP8B1,1 case of ABCC2,1 case of ABCD3,and 1 case of 45X in Group B.CONCLUSION WES significantly improved the etiological diagnosis of unexplained pediatric liver disease,helping guide individualized treatment and improve prognosis.展开更多
Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlatio...Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlations give rise to a diverse array of exotic physical phenomena,including correlated insulating states,superconductivity,magnetism,topological phases,and the quantum anomalous Hall(QAH)effect.Notably,the QAH effect demonstrates substantial promise for applications in electronic and quantum computing devices with low power consumption.This article focuses on the latest developments surrounding the QAH effect in magic-angle TBG.It provides a comprehensive analysis of magnetism and topology—two crucial factors in engineering the QAH effect within magic-angle TBG.Additionally,it offers a detailed overview of the experimental realization of the QAH effect in moir´e superlattices.Furthermore,this review highlights the underlying mechanisms driving these exotic phases in moir´e materials,contributing to a deeper understanding of strongly interacting quantum systems and facilitating the manipulation of new material properties to achieve novel quantum states.展开更多
BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression...BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.展开更多
Full waveform inversion is a precise method for parameter inversion,harnessing the complete wavefield information of seismic waves.It holds the potential to intricately characterize the detailed features of the model ...Full waveform inversion is a precise method for parameter inversion,harnessing the complete wavefield information of seismic waves.It holds the potential to intricately characterize the detailed features of the model with high accuracy.However,due to inaccurate initial models,the absence of low-frequency data,and incomplete observational data,full waveform inversion(FWI)exhibits pronounced nonlinear characteristics.When the strata are buried deep,the inversion capability of this method is constrained.To enhance the accuracy and precision of FWI,this paper introduces a novel approach to address the aforementioned challenges—namely,a fractional-order anisotropic total p-variation regularization for full waveform inversion(FATpV-FWI).This method incorporates fractional-order total variation(TV)regularization to construct the inversion objective function,building upon TV regularization,and subsequently employs the alternating direction multiplier method for solving.This approach mitigates the step effect stemming from total variation in seismic inversion,thereby facilitating the reconstruction of sharp interfaces of geophysical parameters while smoothing background variations.Simultaneously,replacing integer-order differences with fractional-order differences bolsters the correlation among seismic data and diminishes the scattering effect caused by integer-order differences in seismic inversion.The outcomes of model tests validate the efficacy of this method,highlighting its ability to enhance the overall accuracy of the inversion process.展开更多
Two new species in the genus Aglaostigma Kirby(Hymenoptera:Tenthredinidae)are described and illustrated from Mts.Nanling,China:A.luoyoulaii Li,Liu&Wei sp.nov.and A.mengmeng Li&Wei sp.nov.
Hydrated ions play essential roles in diverse chemical and biological processes,yet accurately characterizing their hydration structures remains challenging due to the delicate interplay of ion–water and water–water...Hydrated ions play essential roles in diverse chemical and biological processes,yet accurately characterizing their hydration structures remains challenging due to the delicate interplay of ion–water and water–water interactions.Here,we use ab initio molecular dynamics(AIMD)simulations based on the strongly constrained and appropriately normed(SCAN)exchange–correlation functional to systematically investigate the hydration structures of eight representative ions(Mg^(2+),Ca^(2+),Li^(+),Na^(+),K^(+),F^(-),Cl^(-),Br^(-))in aqueous solution.Compared to the widely used Perdew–Burke–Ernzerhof(PBE)functional,SCAN substantially improves the description of solvent water by weakening the hydrogen-bond network and enhancing structural disorder,yielding results in closer agreement with experiments.SCAN modifies ionic hydration shells in an ion-specific manner,governed by ionic size and charge,and reproduces experimental hydration geometries especially well for intermediate-size monovalent ions(Na^(+),Cl^(-)).Moreover,SCAN consistently reduces the overpolarization of water molecules near ions.These improvements lead to more accurate and physically consistent hydration structures,highlighting SCAN's utility for modeling complex aqueous systems and offering guidance for future studies of ionic solvation.展开更多
This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channel...This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 channels with a particularly low half maximal inhibitory concentration(IC50)for Na_(V)1.9 by promoting sodium channel inactivation,and also effectively increased K_(V)7.2/7.3,K_(V)7.2,and K_(V)7.5 channels,excluding K_(V)7.1 by promoting potassium channel activation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.展开更多
AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/a...AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,展开更多
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
基金financial support from the Postdoctoral Fund of Hebei Medical University(30705010038)the Chunyu Project Initial Funding of Hebei Medical University(CYQD2023012)+3 种基金the Science Research Project of Hebei Education Department(QN2025145)the Hebei Yanzhao Golden Platform Talent Gathering Plan Backbone Talent Project(B2024003013)the Natural Science Foundation of Hebei Province(H2024206375,C2022206018,H2023206068)the Traditional Chinese Medicine Administration Project of Hebei Province(2025427).
文摘Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.
基金supported by the National Natural Science Foundation of China(Regional Fund)(No.51868054)the Natural Science Foundation of Inner Mongolia of China(General Program)(No.2022MS05052).
文摘4-Nitrophenol(4-NP),a toxic and persistent pollutant in chemical wastewater,presents significant challenges in degradation and mineralization.Conventional ozone oxidation catalysts are hindered by low efficiency,mass transfer constraints and metal leaching,necessitating the development of stable and efficient catalysts.Herein,BCn-H/MS,the derivative of Bi(Ce)-MOF,was prepared by in situ incorporation,thermal decomposition and acid etching.The resulting materials were characterized and employed in catalytic ozonation for the reduction of 4-NP.Under the specific experimental conditions of the O_(3)+BC0.3-H/MS system,the total organic carbon(TOC)and chemical oxygen demand(COD)removal rates of 4-NP were observed to reach 94.6%and 91.8%within 30 min,respectively.These two parameters were improved by raising the initial pH,reducing the pollutant concentration and increasing the catalyst dosage.The abundant oxygen vacancies(OVs)were regarded as the pivotal catalytic site of BC0.3-H/MS,which was conducive to the adsorption of O_(3) and the acceleration of the formation of reactive oxygen species(ROS).The regular hollow square structure effectively boosted the specific surface area,increased OVs exposure and accelerated the adsorption and mass transfer process.The electron paramagnetic resonance(EPR)results demonstrated that the primary ROS engaged in the degradation reaction were⋅OH and⋅O_(2)−.BC0.3-H/MS demonstrated excellent stability and reusability in cyclic experiments.Toxicity analysis revealed that the O_(3)+BC0.3-H/MS system exhibited an effective detoxification effect.Ultimately,the primary degradation pathway of 4-NP was proposed through liquid chromatography-mass spectroscopy(LC-MS)and in-situ diffuse reflectance infrared fourier-transform spectroscopy(DRIFTS)analyses at varying reaction times.
基金supported by the National Natural Science Foundation of China(Nos.22236006,22076146 and 22036001).
文摘Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NFκB neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.
基金supported by the National Natural Science Foundation of China(42407458 and 42307420)the Global Challenges Research Fund of the UK Natural Environment Research Council(NE/V005871/1)the Shandong Province First-class Discipline Construction“811”Project,China。
文摘Microplastic accumulation after film mulching affects nutrients cycling in the soil–crop system.Bulk soil(BS)and rhizosphere soil(RS)have two different community compositions which lead to their different microbial nutrient acquisition abilities.Microplastics influence the rhizosphere effect.However,the mechanism by which microplastic accumulation affects the net photosynthetic rate(NPR)through rhizospheric microbial communities remains unknown.This study aimed to identify the mechanisms underlying the effects of polyethylene(PE)and polyvinyl chloride(PVC)microplastics at 0,1,and 5%(w/w)on the NPR in the wheat–soil ecosystem using a pot experiment.Superoxide dismutase(SOD)activity was reduced by 15.35–36.7%,and that of peroxidase(POD)was increased by 32.47–61.93%,causing reductions in NPR(17.94–23.81%)in the PE5%and PVC(1 and 5%)(w/w)treatments compared with the control.The Chao1,Shannon,and Simpson indices of the bacterial and fungal diversities were lower in BS than in RS at PE1%and PVC5%(w/w),respectively.The bacterial and fungal network complexities were reduced and increased,respectively,owing to alterations in the bacterial and fungal community compositions and structures for wheat growth.The Mantel test showed that the bacterial and fungal diversity indices in BS had positive correlations with Olsen-P and phosphatase;however,those in RS were positively correlated with NO_(3)^(–) and β-1,4-glucosidase.The structural equation model indicated that wheat enzymatic and soil hydrolytic activities negatively affected NPR.Wheat has a profound antioxidant defense strategy for PE and PVC microplastic stress,which produces a synergistic effect of POD by protecting organelles and reducing tissue damage to preserve the NPR.
基金supported by the National Natural Science Foundation of China(31970447)starting fund for doctoral research of Lishui University(6004LMM01Z)the Special Funds for Scientific Research of Postdoctoral Work Station Assessment in Zhejiang Province,China(2023).
文摘Two new species of the Aglaostigma laticinctum subgroup belonging to A.tertium group,are described and illustrated in this study:A.leucogaster Liu,Li&Wei sp.nov.and A.rufitegula Liu,Li&Wei sp.nov.The Aglaostigma laticinctum subgroup is proposed here for the first time,with a brief discussion of its diagnostic features.Additionally,a key to all known species of the A.laticinctum subgroup from China is provided.
基金supported by the Scientific Research Project of Baishanzu National Park(2023JBGS07)the National Natural Science Foundation of China(31970447,32370500)the Special Funds for Scientific Research of Postdoctoral Work Station Assessment in Zhejiang Province,China(2023).
文摘A new species of the Macrophya malaisei group in the genus Macrophya Dahlbom,1835 from Zhejiang in China is described:M.alboclypea Li,Liu&Wei sp.nov.A revised key to the Chinese and Japanese species of the M.malaisei group is provided.
基金supported by the National Natural Science Foundation of China(32401919)the Department of Science and Technology of Henan Province(242102111126).
文摘Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.
基金Supported by Hospital Level Project of the Eye Hospital of China Academy of Chinese Medical Sciences(No.GSP5-40)Internal Project of the Eye Hospital of China Academy of Chinese Medical Sciences(No.1011632).
文摘Glaucoma filtration surgery(GFS)stands as the most effective intervention for reducing intraocular pressure,a critical component in glaucoma management.Despite its pivotal role,the scarring of the filtration bleb remains the primary impediment to successful GFS outcomes.Perioperative utilization of antimitotics,while frontline in combating fibrosis and modulating the wound healing process,carries the risk of vision-threatening complications.Given the complexity of the wound healing cascade and the potential insufficiency of targeting a single molecule,there is an imperative to expand therapeutic modalities through combination therapies.This review offers a comprehensive elucidation of the fibrogenesis post-GFS,a synthesis unprecedented in the available literature,and aims to inform the broadening of therapeutic strategies for GFS.
基金supported by National Natural Science Foundation of China(No.62163036).
文摘To improve the traffic scheduling capability in operator data center networks,an analysis prediction and online scheduling mechanism(APOS)is designed,considering both the network structure and the network traffic in the operator data center.Fibonacci tree optimization algorithm(FTO)is embedded into the analysis prediction and the online scheduling stages,the FTO traffic scheduling strategy is proposed.By taking the global optimal and the multi-modal optimization advantage of FTO,the traffic scheduling optimal solution and many suboptimal solutions can be obtained.The experiment results show that the FTO traffic scheduling strategy can schedule traffic in data center networks reasonably,and improve the load balancing in the operator data center network effectively.
基金the Fundamental Research Funds for the Central Universities under Grant no.24CX02019Athe Opening Fund of National Engineering Research Center of Marine Geophysical Prospecting and Exploration and Development Equipment under Grant no.24CX02019A。
文摘A hybrid fiber-reinforced polymer(HFRP)continuous sucker rod,comprising a carbon fiber-reinforced polymer(CFRP)core layer,a glass fiber-reinforced polymer(GFRP)winding layer,and a GFRP coating layer(CFRP:GFRP=2:3),has been developed and widely used in oilfield extraction due to its lower specific gravity,enhanced corrosion resistance,and superior strength.However,HFRP rod joints and their adjacent sections are prone to multi-mode failures,including fracture,debonding,and cracking.Due to the complexity of joint structure and the coupling of tension,bending,and torsion,the failure mechanism is unclear.To address this issue,a dual-scale failure assessment methodology for HFRP rods was proposed,utilizing both macro and meso finite element models(FEM).This methodology was validated through tensile and bending experiments,which yielded critical loads for theφ22 mm HFRP rod:a tensile load of 340.2 kN,a torque of 132.3 N m,and a bending moment of 1192.4 N m.Additionally,a comprehensive FEM of the joint was established,which identified potential failure points at the necking of the rotary joint,resin adhesive and the HFRP rod cross-section at the first groove tip.These failure modes closely matched the experimental observations.Furthermore,the simulation results show that stress concentration at the joint reduced the tensile,bending,and torsional strengths of the HFRP rod to 61%,12%,and 82%of their original values,respectively.The effects of bending moments and torque on the tensile strength of HFRP rods were subsequently explored,leading to the development of an equivalent fatigue assessment method for HFRP rod joints.This method,based on the fatigue characteristics of HFRP rods and joint components,reveals that the primary cause of joint failure is the susceptibility of both the joint and the HFRP rod to bending moments and torque induced by dynamic buckling of the sucker rod string(SRS).Using this method,the fatigue ultimate axial force of theφ22 mm HFRP joint was determined to be 91.5 kN,with corresponding fatigue ultimate torque and bending moment under an axial force of 62.4 kN being 89.3 N m and 71.5 N m,respectively.Finally,a design method incorporating a concentrated weighting strategy for HFRP-steel mixed rods was proposed to enhance their service life,and its effectiveness was demonstrated through on-site testing.
基金supported by the National Natural Science Foundation of China(42301127)the Natural Science Foundation of Xinjiang Uygur Autonomous Region(2023D01C185).
文摘Vegetation change is the most intuitive and sensitive bioindicator reflecting seasonal and interannual variations in the external environment,and it can directly reflect the rapid response of terrestrial ecosystems to climate change.Using remote sensing and meteorological data,this study revealed the spatiotemporal characteristics of leaf area index(LAI)in the north of China during 1982–2022,clarified the response of LAI change to different meteorological factors,quantified the impacts of climate change and human activities on LAI change,and predicted the future trends in LAI change.From 1982 to 2022,the vegetation in the north of China generally showed a greening trend with a change rate of 0.0071 m2/(m2•a).Temperature was strongly positively correlated with LAI and was the main climate factor driving LAI change.Residual analysis revealed that vegetation improvement occurred in across 74.53%of the study area,and vegetation improvement in about 96.83%of the improved zone was attributed to a combination of climate change and human activities.The regions where anthropogenic contribution exceeded 60.00%covered 36.83%of human-affected areas,while the regions where climatic contribution exceeded 60.00%covered 19.77%of climate-affected areas,demonstrating that human activities influenced the intensity of LAI change more deeply despite the broad spatial impact of climate change.Human activities such as afforestation and the Three-North Protective Forest Program played the dominant role in vegetation greening compared to climate change.Hurst index analysis indicated that 80.30%of vegetation in the north of China is expected to experience a non-sustained improvement in the future.These findings will provide a scientific basis for optimizing the protection strategies of the national ecological barrier areas and evaluating the effectiveness of major ecological projects.
基金Supported by National Natural Science Foundation of China,No.82400641Natural Science Foundation of Shandong Province,No.ZR2022QH076 and ZR2021MH381。
文摘BACKGROUND In recent years,the number of pediatric patients with unexplained liver disease has been increasing.Whole-exome sequencing(WES)technology has played a significant role in the diagnosis;however,related studies remain limited.AIM To investigate the clinical characteristics and genetic causes of unexplained pediatric liver disease to improve the diagnosis and treatment of this disease.METHODS Eighty children with unexplained liver disease were divided into two groups:The liver enzyme elevation group(Group A)and the cholestasis group(Group B).Children with both elevated liver enzymes and cholestasis were assigned to Group B.The clinical characteristics of the patients were retrospectively summarized,and WES was performed in the patients and their parents.RESULTS Genetic results were obtained in 46 patients(46/80,57.5%),including 38 in Group A(38/65,58.5%)and 8 in Group B(8/15,53.3%).A total of 53 pathogenic or likely pathogenic variants were identified in 42 patients(42/80,52.5%),including 40 previously reported variants and 13 novel variants.Seven variants of uncertain significance were identified in 7 patients(7/80,8.8%),of which 4 were novel variants.A total of 19 gene mutations were identified:2 cases of AGL,15 cases of ATP7B,1 case of CAPN3,4 cases of DMD,1 case of FLG,1 case of G6PC,5 cases of JAG1,2 cases of PHKA2,2 cases of PYGL,1 case of SMARCAL1,1 case of SMPD1,1 case of TNFAIP3,1 case of GLB1,and 1 case of MAT1A in Group A;and 1 case of SLC25A13,3 cases of JAG1,1 case of ATP8B1,1 case of ABCC2,1 case of ABCD3,and 1 case of 45X in Group B.CONCLUSION WES significantly improved the etiological diagnosis of unexplained pediatric liver disease,helping guide individualized treatment and improve prognosis.
基金supported by the Science Research Project of Hebei Education Department(Grant No.BJK2024168)the National Natural Science Foundation of China(Grant No.11904076)+1 种基金the Natural Science Foundation of Hebei(Grant No.A2019205313)Science Foundation of Hebei Normal University(Grant No.L2024J02).
文摘Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlations give rise to a diverse array of exotic physical phenomena,including correlated insulating states,superconductivity,magnetism,topological phases,and the quantum anomalous Hall(QAH)effect.Notably,the QAH effect demonstrates substantial promise for applications in electronic and quantum computing devices with low power consumption.This article focuses on the latest developments surrounding the QAH effect in magic-angle TBG.It provides a comprehensive analysis of magnetism and topology—two crucial factors in engineering the QAH effect within magic-angle TBG.Additionally,it offers a detailed overview of the experimental realization of the QAH effect in moir´e superlattices.Furthermore,this review highlights the underlying mechanisms driving these exotic phases in moir´e materials,contributing to a deeper understanding of strongly interacting quantum systems and facilitating the manipulation of new material properties to achieve novel quantum states.
文摘BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.
基金supported by the China Postdoctoral Science Foundation(Grant No.2024MF750281)the Postdoctoral Fellowship Program of CPSF(Grant No.GZC20230326)+1 种基金the Natural Science Foundation Project of Sichuan Province(Grant No.2025ZNSFSC1170)Sichuan Science and Technology Program(Grant No.2023ZYD0158).
文摘Full waveform inversion is a precise method for parameter inversion,harnessing the complete wavefield information of seismic waves.It holds the potential to intricately characterize the detailed features of the model with high accuracy.However,due to inaccurate initial models,the absence of low-frequency data,and incomplete observational data,full waveform inversion(FWI)exhibits pronounced nonlinear characteristics.When the strata are buried deep,the inversion capability of this method is constrained.To enhance the accuracy and precision of FWI,this paper introduces a novel approach to address the aforementioned challenges—namely,a fractional-order anisotropic total p-variation regularization for full waveform inversion(FATpV-FWI).This method incorporates fractional-order total variation(TV)regularization to construct the inversion objective function,building upon TV regularization,and subsequently employs the alternating direction multiplier method for solving.This approach mitigates the step effect stemming from total variation in seismic inversion,thereby facilitating the reconstruction of sharp interfaces of geophysical parameters while smoothing background variations.Simultaneously,replacing integer-order differences with fractional-order differences bolsters the correlation among seismic data and diminishes the scattering effect caused by integer-order differences in seismic inversion.The outcomes of model tests validate the efficacy of this method,highlighting its ability to enhance the overall accuracy of the inversion process.
基金supported by the scientific research project of Baishanzu National Park(2023JBGS07)the National Natural Science Foundation of China(31970447,32370500)the Special Funds for Scientific Research of Postdoctoral Work Station Assessment in Zhejiang Province,China(2023).
文摘Two new species in the genus Aglaostigma Kirby(Hymenoptera:Tenthredinidae)are described and illustrated from Mts.Nanling,China:A.luoyoulaii Li,Liu&Wei sp.nov.and A.mengmeng Li&Wei sp.nov.
基金supported by the National Natural Science Foundation of China(Grant Nos.12535001,11935002,and 11525520)the National Key Research and Development Program of China(Grant No.2021YFA1400500)。
文摘Hydrated ions play essential roles in diverse chemical and biological processes,yet accurately characterizing their hydration structures remains challenging due to the delicate interplay of ion–water and water–water interactions.Here,we use ab initio molecular dynamics(AIMD)simulations based on the strongly constrained and appropriately normed(SCAN)exchange–correlation functional to systematically investigate the hydration structures of eight representative ions(Mg^(2+),Ca^(2+),Li^(+),Na^(+),K^(+),F^(-),Cl^(-),Br^(-))in aqueous solution.Compared to the widely used Perdew–Burke–Ernzerhof(PBE)functional,SCAN substantially improves the description of solvent water by weakening the hydrogen-bond network and enhancing structural disorder,yielding results in closer agreement with experiments.SCAN modifies ionic hydration shells in an ion-specific manner,governed by ionic size and charge,and reproduces experimental hydration geometries especially well for intermediate-size monovalent ions(Na^(+),Cl^(-)).Moreover,SCAN consistently reduces the overpolarization of water molecules near ions.These improvements lead to more accurate and physically consistent hydration structures,highlighting SCAN's utility for modeling complex aqueous systems and offering guidance for future studies of ionic solvation.
基金funded by the Key Project from the Hebei Provincial Department of Science and Technology,China(Grant No.:21372601D)the Foundation Postdoctoral Mobile Station of Basic Medical Sciences,Hebei Medical University,China(Grant No.:20123120019)+4 种基金the Natural Science Foundation of Hebei Province,China(Grant No.:H2021206352)the Science and Technology Research Project of Colleges and Universities in Hebei Province,China(Grant No.:QN2023197)Hebei Medical University,Science and Technology,China(Grant No.:CYQD2023014)Hebei Provincial Department of Human Resources and Social Security,China(Grant No.:B2023003034)the Consultative Foundation from Hebei Province,China(Grant No.:2020TXZH01).
文摘This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 and K_(V)7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Na_(V)1.7,Na_(V)1.8,and Na_(V)1.9 channels with a particularly low half maximal inhibitory concentration(IC50)for Na_(V)1.9 by promoting sodium channel inactivation,and also effectively increased K_(V)7.2/7.3,K_(V)7.2,and K_(V)7.5 channels,excluding K_(V)7.1 by promoting potassium channel activation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.
基金Supported by Innovation Fund of Fujian Province,No.2007-CXB-7Key Science and Technology Project of Xiamen,No.3502Z20077045
文摘AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,
