Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attributed to eBAG or additional components in these plants remain unknown.Herein,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells.EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells.The eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux inhibitor.We demonstrated that eBAG induced an autophagy-mediated cell death.Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of mTOR.Co-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by eBAG.We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice.As a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.

Development and optimization of object detection technology in pavement engineering: A literature review

Due to the rapid advancement of the transportation industry and the continual increase in pavement infrastructure,it is difficult to keep up with the huge road maintenance task by relying only on the traditional manual detection method.Intelligent pavement detection technology with deep learning techniques is available for the research and industry areas by the gradual development of computer vision technology.Due to the different characteristics of pavement distress and the uncertainty of the external environment,this kind of object detection technology for distress classification and location still faces great challenges.This paper discusses the development of object detection technology and analyzes classical convolutional neural network(CNN)architecture.In addition to the one-stage and two-stage object detection frameworks,object detection without anchor frames is introduced,which is divided according to whether the anchor box is used or not.This paper also introduces attention mechanisms based on convolutional neural networks and emphasizes the performance of these mechanisms to further enhance the accuracy of object recognition.Lightweight network architecture is introduced for mobile and industrial deployment.Since stereo cameras and sensors are rapidly developed,a detailed summary of three-dimensional object detection algorithms is also provided.While reviewing the history of the development of object detection,the scope of this review is not only limited to the area of pavement crack detection but also guidance for researchers in related fields is shared.

One developed finite element model used in nano-layered flaky Ti_(2)AlC MAX ceramic particles reinforced magnesium composite

As one novel reinforcement used in magnesium composite,nano-layered flaky ternary MAX particle exhibits interesting anisotropic ceramic and metal properties.In order to accurately simulate the mechanical properties and damage behavior of MAX particle reinforced magnesium composite,we developed one finite element(FE)model based on 2D and 3D microstructural observations of 10 vol.%Ti2AlC-AZ91D composite.To improve the accuracy,matrix ductile damage,particle internal delamination deformation behaviors,and particle-matrix interfacial behaviors were respectively introduced into this model.The visual deformation processes of crack generation and propagation were carefully presented and discussed.The effects of interfacial strength and particle orientation on material properties were systematically investigated.

尿液miRNA标志物检测在肿瘤中的研究进展

MicroRNA(miRNA)作为标志物在肿瘤的诊断、监测和预后判断中发挥重要作用。由于尿液标本具有采集过程无创、方便等优点,尿液miRNA作为肿瘤标志物,近年来在肿瘤诊断方面的研究受到越来越多的关注。尿液中多种miRNA标志物被证明与肿瘤的诊断相关。本文将对miRNA的特点和检测方法,以及尿液miRNA在泌尿系统肿瘤和非泌尿系统肿瘤中的标志物价值进行综述,为肿瘤的临床诊断、监测和预后判断提供新思路。

Study on β-TCP Coated Porous Mg as a Bone Tissue Engineering Scaffold Material

Three-dimensional honeycomb-structured magnesium （Mg） scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate （β-TCP） coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells （UMR106） were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.

Improved genetic algorithm for nonlinear programming problems

An improved genetic algorithm（IGA） based on a novel selection strategy to handle nonlinear programming problems is proposed.Each individual in selection process is represented as a three-dimensional feature vector which is composed of objective function value,the degree of constraints violations and the number of constraints violations.It is easy to distinguish excellent individuals from general individuals by using an individuals＇ feature vector.Additionally,a local search（LS） process is incorporated into selection operation so as to find feasible solutions located in the neighboring areas of some infeasible solutions.The combination of IGA and LS should offer the advantage of both the quality of solutions and diversity of solutions.Experimental results over a set of benchmark problems demonstrate that IGA has better performance than other algorithms.

The bHLH transcription factor GhPAS1 mediates BR signaling to regulate plant development and architecture in cotton

Cotton (Gossypium spp.) is the most important natural textile fiber crop in the world.The ideal plant architecture of cotton is suitable for mechanical harvesting and productivity in modern agricultural production.However,cotton genes regulating plant development and architecture have not been fully identified.We identified a basic helix-loop-helix (b HLH) transcription factor,GhPAS1 (PAGODA1 SUPPRESSOR1) in G.hirsutum (Upland cotton).GhPAS1 was located in the nucleus and showed a strong transcription activation effect.Tissue-specific expression patterns showed that GhPAS1 was highly expressed in floral organs,followed by high expression in early stages of ovule development and rapid fiber elongation.GhPAS1 overexpression in Arabidopsis and BRZ (brassinazole,BR biosynthesis inhibitor) treatment indicated that GhPAS1 positively regulates and responds to the BR (brassinosteroid) signaling pathway and promotes cell elongation.GhPAS1 overexpression in Arabidopsis mediated plant development in addition to increasing plant biomass.Virus-induced gene silencing of GhPAS1 indicated that down-regulation of GhPAS1 inhibited cotton growth and development,as plant height,fruit branch length,and boll size of silenced plants were lower than in control plants.Fiber length and seed yield were also lower in silenced plants.We conclude that GhPAS1,a b HLH transcription factor,regulates plant development and architecture in cotton.These findings may help breeders and researchers develop cotton cultivars with desirable agronomic characteristics.

Construction of composite indicator system based on simulation data mining

The indicator system is the foundation and emphasis in the effectiveness evaluation of system of systems(SoS). In the past, indicator systems were founded based on qualitative methods, and every indicator was mainly determined by the expert with experience. This paper proposed a brand-new method to construct indicator systems based on the repeated simulation of the scenario space, and calculated by quantitative data. Firstly, the selection of key indicators using the Gini indicator importance measure(IIM)is calculated by random forests(RFs). Then, principal component analysis(PCA) is applied when we use the selected indicators to construct the composite indicator system of SoS. Furthermore,a set of rulesare is developed to verify the practicability of the indicator system such as correlation, robustness, accuracy and convergence. Experiment shows that the algorithm achieves good results for the construction of composite indicators of So S.

Melatonin improves the first cleavage of parthenogenetic embryos from vitrified-warmed mouse oocytes potentially by promoting cell cycle progression

Background:This study investigated the effect of melatonin(MT)on cell cycle(G1/S/G2/M)of parthenogenetic zygotes developed from vitrified-warmed mouse metaphase II(MII)oocytes and elucidated the potential mechanism of MT action in the first cleavage of embryos.Results:After vitrification and warming,oocytes were parthenogenetically activated(PA)and in vitro cultured(IVC).Then the spindle morphology and chromosome segregation in oocytes,the maternal mRNA levels of genes including Miss,Doc1r,Setd2 and Ythdf2 in activated oocytes,pronuclear formation,the S phase duration in zygotes,mitochondrial function at G1 phase,reactive oxygen species(ROS)level at S phase,DNA damage at G2 phase,early apoptosis in 2-cell embryos,cleavage and blastocyst formation rates were evaluated.The results indicated that the vitrification/warming procedures led to following perturbations 1)spindle abnormalities and chromosome misalignment,alteration of maternal mRNAs and delay in pronucleus formation,2)decreased mitochondrial membrane potential(MMP)and lower adenosine triphosphate(ATP)levels,increased ROS production and DNA damage,G1/S and S/G2 phase transition delay,and delayed first cleavage,and 3)increased early apoptosis and lower levels of cleavage and blastocyst formation.Our results further revealed that such negative impacts of oocyte cryopreservation could be alleviated by supplementation of warming,recovery,PA and IVC media with 10^(−9) mol/L MT before the embryos moved into the 2-cell stage of development.Conclusions:MT might promote cell cycle progression via regulation of MMP,ATP,ROS and maternal mRNA levels,potentially increasing the first cleavage of parthenogenetic zygotes developed from vitrified-warmed mouse oocytes and their subsequent development.

g-C_(3)N_(4) Derived Materials for Photocatalytic Hydrogen Production: A Mini Review on Design Strategies

Hydrogen production through solar energy is one of the most important pathways to meet the growing demand of renewable energy,and photocatalyst participation in solar hydrolytic hydrogen production has received great attention in recent years in terms of low cost,high efficiency,and flexible design.Particularly,g-C_(3)N_(4)(Graphitic-like carbon nitride material),as a unique material,can catalyze the hydrogen production process by completing the separation and transmission of charge.The easily adjustable pore structure/surface area,dimension,band-gap modulation and defect have shown great potential for hydrogen production from water cracking.In this review,the most recent advance of g-C_(3)N_(4) including the doping of metal and non-metal elements,and the formation of semiconductor heterojunction is highlighted.The main modification strategies and approaches for the design of g-C_(3)N_(4) for hydrogen production,as well as the influence of various materials on hydrogen evolution regarding the photocatalysis mechanism and advantages brought by theoretical calculations are specially and briefly illu-strated.Potential design pathways and strategies of g-C_(3)N_(4) are discussed.In addition,current challenges of hydrogen production from g-C_(3)N_(4) water splitting are summarized and can be expected.

A self-adaptive linear evolutionary algorithm for solving constrained optimization problems

In many real-world applications of evolutionary algorithms,the fitness of an individual requires a quantitative measure.This paper proposes a self-adaptive linear evolutionary algorithm （ALEA） in which we introduce a novel strategy for evaluating individual＇s relative strengths and weaknesses.Based on this strategy,searching space of constrained optimization problems with high dimensions for design variables is compressed into two-dimensional performance space in which it is possible to quickly identify ＇good＇ individuals of the performance for a multiobjective optimization application,regardless of original space complexity.This is considered as our main contribution.In addition,the proposed new evolutionary algorithm combines two basic operators with modification in reproduction phase,namely,crossover and mutation.Simulation results over a comprehensive set of benchmark functions show that the proposed strategy is feasible and effective,and provides good performance in terms of uniformity and diversity of solutions.

Recent Advance on Torrefaction Valorization and Application of Biochar from Agricultural Waste for Soil Remediation

With the increase of global proportion of soil pollution and the number of areas at risk,researchers have sought to develop various pathways to repair or relieve the pollutants in soil.Among them,biochar represents one multi-dimensional soil amendment which has got great deal of attention on its physicochemical properties towards the removal or mitigation of contaminants in soil.A variety of agricultural wastes like straw and manure prepared from different torrefaction process have been employed as feedstock for the production of biochar,which can be applied to the contaminated soil to facilitate the growing environment for crops,and to improve soil fertility and microbial environment.In addition,the utilization of biochar for soil remediation is also considered as a pro-cess of carbon sequestration.The purpose of this review is to summarize the latest research progress in torrefac-tion processes and mechanism of agricultural waste,the effects of different torrefaction methods on the formation and properties of biochar were explained,coupled with the effects of process parameters.Especially,the conver-sion and mechanisms of biochar prepared from agricultural wastes composed mainly with lignocellulosic material were discussed,and the characteristics of biochar prepared for improving soil physical and chemical character-istics,microbial community characteristics,nutrients,and the stability and relief of soil pollutants,especially heavy metals,are compared.Finally,this work discussed the application and future technical challenges of soil remediation based on agricultural waste derived biochar.

Determination of Work Function for p-and n-Type 4H-SiC Single Crystals via Scanning Kelvin Probe Force Microscopy

Silicon carbide(SiC) is a promising platform for fabricating high-voltage, high-frequency and high-temperature electronic devices such as metal oxide semiconductor field effect transistors in which many junctions or interfaces are involved. The work function(WF) plays an essential role in these devices. However, studies of the effect of conductive type and polar surfaces on the WF of SiC are limited. Here, we report the measurement of WFs of Si-and C-terminated polar surfaces for both p-type and n-type conductive 4H-SiC single crystals by scanning Kelvin probe microscopy(SKPFM). The results show that p-type SiC exhibits a higher WF than n-type SiC.The WF of a C-terminated polar surface is higher than that of a Si-terminated polar surface, which is further confirmed by first-principles calculations. By revealing this long-standing knowledge gap, our work facilitates the fabrication and development of SiC-based electronic devices, which have tremendous potential applications in electric vehicles, photovoltaics, and so on. This work also shows that SKPFM is a good method for identifying polar surfaces of SiC and other polar materials nondestructively, quickly and conveniently.

The protective effects of Gastrodia elata Bl.decoction and Gastrodin on Acrylamide-induced DNA damage in mice

Acrylamide(AA)is ubiquitous in packaging materials,paints,cosmetics,food and drinking water.However,AA has obvious neurotoxicity,reproductive toxicity and carcinogenicity,which seriously endangers human health.As one of precious traditional Chinese medicines,Gastrodia elata Bl.has been mainly used to lower blood pressure and resist myocardial ischemia.However,the antioxidant activity of Gastrodia elata Bl.on AA-induced DNA damage has not been reported.We found that AA(25,30 and 50 mg/kg)could cause DNA damage and the damage was time/dose dependent.After AA administration,Tail moment,micronuclei formation rate,8-OHdG and MDA level were significantly increased and SOD activity was decreased.Gastrodia elata Bl.decoction,gastrodin and vitamin C could reduce AA-induced DNA damage by decreasing AA-induced increment of tail moment and micronuclei formation rate.What’s more,Gastrodia elata Bl.decoction,gastrodin and vitamin C could lower 8-OHdG and MDA level and improve SOD activity.In conclusion,our research showed that Gastrodia elata Bl.decoction and gastrodin had protective effects on AA-induced DNA damage,and the potential protective mechanism might be related to anti-oxidative stress.

A review:anticancer activity of grape seed proanthocyanidins

For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.

Aberrant Hippocampal Development in Early‑onset Mental Disorders and Promising Interventions:Evidence from a Translational Study

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.

DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer

DNMT3A encodes a DNA methyltransferase involved in development,cell differentiation,and gene transcription,which is mutated and aberrant-expressed in cancers.Here,we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer.Based on the epigenetic inhibitor library synthetic lethal screening,we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells.Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells.However,sensitive cells became resistant when DNMT3A was rescued.Furthermore,the selectivity to HDAC6 inhibition was recapitulated in mice,where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells.Mechanistically,DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding.Notably,our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition.Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6.Interestingly,HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells.These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers.Together,our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

MSLFuzzer:black-box fuzzing of SOHO router devices via message segment list inference

The popularity of small office and home office routers has brought convenience,but it also caused many security issues due to vulnerabilities.Black-box fuzzing through network protocols to discover vulnerabilities becomes a viable option.The main drawbacks of state-of-the-art black-box fuzzers can be summarized as follows.First,the feedback process neglects to discover the mising felds in the raw message.Secondly,the guidance of the raw message content in the mutation process is aimless.Finally,the randomized validity of the test case structure can cause most fuzzing tests to end up with an invalid response of the tested device.To address these challenges,we propose a novel black-box fuzzing framework called MSL Fuzzer.MSL Fuzzer infers the raw message structure according to the response from a tested device and generates a message segment list.Furthermore,MSL Fuzzer performs semantic,sequence,and stability analyses on each message segment to enhance the complementation of missing fields in the raw message and guide the mutation process.We construct a dataset of 35 real-world vulnerabilities and evaluate MSL Fuzzer.The evaluation results show that MSL Fuzzer can find more vulnerabilities and elicit more types of responses from fuzzing targets.Additionally,MSL Fuzzer successfully discovered 10 previously unknown vulnerabilities.

Mechanism of Ginkgo biloba L.leaf in the treatment of ischemic stroke based on network pharmacology,bioinformatics and molecular docking

Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.Here,network pharmacology and bioinformatics were used to predict the active components,important targets,and potential mechanisms of GBL in the treatment of IS.Active compounds of GBL were screened based on drug-like index and oral bioavailability,key target genes were screened based on network pharmacology and gene chip,downstream pathways for the regulation of key target genes were predicted based on gene set enrichment analysis,and the interaction between key targets and active compounds was verified based on molecular docking.The results showed that GBL played a protective role in cerebral ischemia with mainly 14 active compounds,such as isoquercitrin,luteolin-4’-glucoside,beta-sitosterol,campesterol,diosmetin,ginkgolide B,ginkgolide C,ginkgolide J,ginkgolide M,isogoycyrol,laricitrin,luteolin,sesamin,and stigmasterol.Further studies revealed that GBL played important role in immunomodulation and inflammation inhibition after cerebral ischemia by acting on its peripheral targets ARG1 and MMP9 to regulate Toll-like receptor,Chemokine and Notch signaling pathway.Meanwhile,GBL played important role in reducing neuroinflammation and blood-brain barrier damage after cerebral ischemia by acting on its central targets,CCL2,PTGS2,IL6,IL1B and MMP9 to regulate the Cytokine-cytokine receptor interaction,Jak-STAT,and Toll-like receptor signaling pathway.Additionally,molecular docking verified that the active compounds mentioned above could bind to ARG1,MMP9,CCL2,PTGS2,IL6,and IL1B.The present study shows the multicomponent,multitarget and multichannel pharmacological effects of GBL on cerebral ischemia and provides a new strategy for the treatment of IS.