Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Solar energetic particles intensity variations associated with a tilted-dipole 3D corotating interaction region

The effect of a tilted-dipole three-dimensional corotating interaction region(CIR)on the transport and acceleration of solar energetic particles(SEPs)is studied.In this work,we discussed how the particle intensity longitudinal and radial dependence might be influenced by the background structures.Moreover,we investigate how the spectral index distribution is modulated by the CIR structure We use the focused transport equation(FTE)to describe the propagation and acceleration of SEPs in a tilt-dipole 3D CIR,generated by the high-resolution 3D magnetohydrodynamic(MHD)model.The forward stochastic differential method is used to solve the FTE.The protons with theE~(-4.4)spectrum from 0.5 to 15 MeV are injected uniformly at the heliographic equator of 0.15 AU.Physical quantities are extracted along each interplanetary magnetic field(IMF)line to show the results.In the tilted-dipole CIR background,if injected from the solar equator at the inner boundary,particles in the slow flow are transported to higher latitudes due to the extension of the IMF lines to higher latitudes.The longitudinal patterns of the particles are dominated by the density of IMF lines.The focusing effect modulates the longitudinal variation of the particle intensity and gives rise to new longitudinal intensity peaks.The adiabatic effect largely increases the intensity fluctuation along the longitude.The structure of the solar wind can also lead to the difference of the indexαin the empirical functionI_(max)=kR~(-α),describing the radial variation of peak intensity according to our simulation.Under the influence of the CIR structure,the indexαvaries from 1.9 to 3.4 at 0.3-1.0 AU.The variation of the solar wind speed should be considered when estimating the radial dependence of the SEP peak intensity.The spectra indices rise near the CIR boundaries and drop near the stream interface(SI).The adiabatic effect makes the spatial variability of the spectral index larger.The spectral index could be similar at different radial distances in the CIR structure.

Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma

Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still unclear.Methods:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro.The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib.Results:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells.Mechanistically,nobiletin decreased SKP2 protein expression by reducing its transcriptional level.The downregulated SKP2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model.Conclusions:Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM: To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH).METHODS: In this prospective observational trial, 127 patients presenting with typical reflux symptoms for > 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated.RESULTS: Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively.CONCLUSION: Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.

Cyr61 Alleviates Cholangitis by Inhibiting Cytotoxic Effects of CD8^(+) T Cells on Biliary Epithelial Cells

Objective:Primary biliary cholangitis(PBC)is a chronic progressive cholestatic liver disease.In recent years,researchers have found that cysteine-rich angiogenic inducer 61(Cyr61,also known as CCN1)has a potential role in reducing portal inflammation in patients with PBC.This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC.Methods:After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus,hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage.Real-time PCR was used to detect changes in inflammation-related cytokines in the liver.To further study the mechanism,we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects.Results:Serum and hepatic Cyr61 levels were increased in the murine model of PBC.Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo.Cyr61 inhibited the cytotoxic effects of CD8^(+)T cells by acting on biliary epithelial cells(BECs)in vitro.Conclusion:Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC.Consequently,therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.

Extraction and analysis of risk factors from Chinese chemical accident reports

Accidents in chemical production usually result in fatal injury,economic loss and negative social impact.Chemical accident reports which record past accident information,contain a large amount of expert knowledge.However,manually finding out the key factors causing accidents needs reading and analyzing of numerous accident reports,which is time-consuming and labor intensive.Herein,in this paper,a semiautomatic method based on natural language process(NLP)technology is developed to construct a knowledge graph of chemical accidents.Firstly,we build a named entity recognition(NER)model using SoftLexicon(simplify the usage of lexicon)+BERT-Transformer-CRF(conditional random field)to automatically extract the accident information and risk factors.The risk factors leading to accident in chemical accident reports are divided into five categories:human,machine,material,management,and environment.Through analysis of the extraction results of different chemical industries and different accident types,corresponding accident prevention suggestions are given.Secondly,based on the definition of classes and hierarchies of information in chemical accident reports,the seven-step method developed at Stanford University is used to construct the ontology-based chemical accident knowledge description model.Finally,the ontology knowledge description model is imported into the graph database Neo4j,and the knowledge graph is constructed to realize the structu red storage of chemical accident knowledge.In the case of information extraction from 290 Chinese chemical accident reports,SoftLexicon+BERT-Transformer-CRF shows the best extraction performance among nine experimental models.Demonstrating that the method developed in the current work can be a promising tool in obtaining the factors causing accidents,which contributes to intelligent accident analysis and auxiliary accident prevention.

New and interesting diatoms from the Shimen Wetwalls,Yunnan Province,China.Ⅱ.The diatom genus Nupela Vyverman&Compère(Bacillariophyceae)

We detailed the valve morphology of five new species of diatom genus Nupela from wetwall communities in Yunnan Province,China,with light and scanning electron microscope.The five new species demonstrate great variability within the genus,as three of them are biraphid and two are monoraphid.In addition,variation was noted in the structure of internal proximal raphe ends,with some species having anchor-shaped ends and other species have hooked ends.The genus Nupela has grown considerably in 30years since it was first proposed,going from a monotypic genus to over 85 taxa.Diagnosis of the genus is based on the presence of an external covering over the areolae.We discussed the systematic placement of Nupela within the naviculoid diatoms.Yunnan Province appears to harbor many endemic diatom taxa,and many regions of the province have yet to be studied.

Crystal facet engineering coexposed CuIn(200)and In(101)in CuIn alloy nanocatalysts enabling selective and stable CO_(2)electroreduction

The electrocatalytic carbon dioxide reduction reaction(eCO_(2)RR)into high-value-added chemicals and fuels is a promising strategy to mitigate global warming.However,it remains a significant stumbling block to the rationally tuning lattice plane of the catalyst with high activity to produce the target product in the eCO_(2)RR process.To attempt to solve this problem,the Culn bimetallic alloy nanocatalyst with specifically exposed lattice planes is modulated and electrodeposited on the nitrogen-doped porous carbon cloth by a simple two-step electrodeposition method,which induces high Faraday efficiency of 80%towards HCOO-(FEHCOO-)with a partial current density of 13.84 mA cm-2at-1.05 V(vs.RHE).Systematic characterizations and theoretical modeling reveal that the specific coexposed Culn(200)and In(101)lattice facets selectively adsorbed the key intermediate of OCHO*,reducing the overpotential of HCOOH and boosting the FEHCOO-in a wide potential window(-0.65--1.25 V).Moreover,a homogeneous distribution of Culn nanoparticles with an average diameter of merely~3.19 nm affords exposure to abundant active sites,meanwhile prohibiting detachment and agglomeration of nanoparticles during eCO_(2)RR for enhanced stability attributing to the self-assembly electrode strategy.This study highlights the synergistic effect between catalytic activity and facet effect,which opens a new route in surface engineering to tune their electrocatalytic performance.

机构投资者与投资效率——来自深沪A股定向增发公司的经验证据

本文基于深沪A股2006~2015年定向增发公司的数据,以定向增发新股公司引入具有股份锁定期的机构投资者为场景,检验了机构投资者参与公司治理对投资效率的影响;进一步,将定向增发新股公司引入的机构投资者划分为"战略投资者"和"财务投资者",分别检验它们对公司投资效率的影响。研究发现,定向增发新股公司引入机构投资者有助于促进公司投资效率的提高,且该效应主要体现在战略投资者层面;进一步地,相对于非国有控股定向增发新股公司,战略投资者对国有控股定向增发公司投资效率的正面作用更加明显。本研究提供了机构投资者对公司投资效率正面效应的经验证据,为我国定向增发公司选择发行对象和大力发展股票市场的机构投资者提供了理论支撑和政策参考。

角膜滞后量在青光眼中的作用

青光眼是全球首位不可逆致盲性眼病,其具体发病机制尚不清楚,但颇受重视的是眼压和房水流出通道等方面。近年,研究人员开始越来越多地关注非压力依赖因素如角膜滞后量(CH)在青光眼中的作用。CH是角膜的生物力学参数,它反映了角膜的黏性阻力,即吸收和分散能量的能力。CH在临床上很容易获得,可作为眼后部组织生物力学特性的替代标志物,如筛板和乳头周围巩膜,这些组织可能与青光眼损伤的易感性有关。有研究提供了CH与青光眼临床相关结果之间的联系的证据。本文综述了CH在青光眼中的作用的最新发现,从CH的测量方法、CH与中央角膜厚度、青光眼性视野进展、视盘损害、视网膜神经纤维层缺失等方面进行了归纳和总结。

Mucosal-associated invariant T cells in hepatitis B virus-related liver failure

BACKGROUND Liver failure has high mortality and poor prognosis,and establishing new reliable markers for predicting its prognosis is necessary.Mucosal-associated invariant T(MAIT)cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease,and their potential role in liver failure remains unclear.AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus(HBV)-related liver failure.METHODS We recruited 55 patients with HBV-related liver failure,48 patients with chronic hepatitis B and 40 healthy controls(HCs)from Nantong Third People’s Hospital Affiliated to Nantong University.Peripheral blood mononuclear cells were isolated,and the percentage and number of circulating MAIT cells were detected by flow cytometry.Plasma levels of interleukin(IL)-7,IL-12p70,IL-18 and interferon-αwere measured by Luminex assay.RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients(percentage:2.00±1.22 vs 5.19±1.27%,P<0.0001;number:5.47±4.93 vs 84.43±19.59,P<0.0001)compared with HCs.More importantly,there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure.Circulating MAIT cells partially recovered after disease improvement,both in percentage(4.01±1.21 vs 2.04±0.95%,P<0.0001)and in cell count(17.24±8.56 vs 7.41±4.99,P<0.0001).The proportion(2.29±1.01 vs 1.58±1.38%,P<0.05)and number(7.30±5.70 vs 2.94±1.47,P<0.001)of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group,and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells(both percentage and cell count)predicted poor overall survival(P<0.01).Also,the levels of IL-12(20.26±5.42 pg/mL vs 17.76±2.79 pg/mL,P=0.01)and IL-18(1470.05±1525.38 pg/mL vs 362.99±109.64 pg/mL,P<0.0001)were dramatically increased in HBV-related liver failure patients compared with HCs.CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

All roads lead to Rome-a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease

Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.

Does the digital economy contribute to carbon emissions reduction?A city-level spatial analysis in China

The rapid development of the digital economy provides an unprecedented opportunity for China to achieve carbon neutrality by 2060.While previous studies have explored the relationship between the digital economy,digital technologies,and energy,the impact of the digital economy on carbon emissions has not received sufficient attention in the literature.Meanwhile,although cities are the basic units for carbon emission reduction policies,few studies have explored carbon emissions at the city level in China.This study investigates the spatial correlation and spillover effects of the digital economy development on carbon emission reduction in 248 prefecture-level cities in China from 2011 to 2019.The proposed approach relies on Moran’s I test and the spatial Durbin model(SDM).First,the study’s results show that carbon emissions are more severe in industry-intensive cities in northeast and central China than in the eastern coast during the sample period.Second,the development of the digital economy is conducive to reducing carbon emissions.Third,Moran’s I and SDM tests find that the digital economy has a significant spatial effect on carbon emissions,with a close spatial connection between cities.Based on the above findings,this study offers relevant policy recommendations and suggestions for realizing China's carbon neutrality goal.

Deformation and failure behavior of heterogeneous Mg/SiC nanocomposite under compression

The heterogeneous magnesium(Mg) matrix nanocomposite with dispersed soft phase exhibits high strength and toughness. Herein, the deformation behavior and failure process were investigated to reveal the unique mechanical behavior of the heterogeneous microstructure under compression. The extensive plastic deformation is accompanied by the flattening and tilting of the soft phase, inhibiting strain localization and leading to strain hardening. Moreover, a stable crack multiplication process is activated, which endows high damage tolerance to the heterogeneous Mg matrix nanocomposites. The final failure of the composite is caused by crack coalescence in the shear plane along a tortuous path. The presence of dispersed soft phases within the hard matrix induces a noticeable change in mechanical response. Especially,the malleability of the heterogeneous Mg matrix nanocomposite is two and ten times higher than that of pure Mg and the homogeneous Mg matrix nanocomposite, respectively. The current study provides a novel strategy to break the trade-off between strength and toughness in metal matrix nanocomposites.

Coronaviruses and gastrointestinal diseases

The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting.Available data have shown that human coronaviruses,including the newly emerged SARS-CoV-2,mainly infect the respiratory system and cause symptoms such as cough and fever,while they may generate gastrointestinal symptoms.However,there is little about the relation between coronavirus and digestive system.This review specifically addresses the effects of mammalian and human coronaviruses,including SARS-CoV-2,on the digestive tract,helping to cope with the new virus infection-induced disease,COVID-19.

A new species of Athermantus Kirby(Hymenoptera: Argidae) from China

A new species of Argidae is described from Zhejiang, China: Athermantus melanoptera Wei sp. nov. This new species is similar to A. leucopilosus Wen & Wei, 2002, but differs from it by the body hairs black;the upper of hind orbit clearly broader than eye in lateral view;pterostigma entirely black;vein R of fore wing clearly shorter than vein R+M;valviceps of penis valve narrow and hardly oblique, about 3.5 times as long as broad. A key to species of Athermantus Kirby, 1882 is also provided.

Dependence Study of Optoelectronics Performance on Carefully Differed LiF Thickness in Alq₃Based OLEDs

The effect of LiF thickness on the electrical and luminescent characteristics in OLEDs has been studied by carefully varying thickness value range from 0 nm to 1.2 nm. It’s interesting to find that the device with 0.2 nm LiF layer performs the largest current and comparative lower luminescent efficiency, while the one with 0.6 nm LiF performs another current peak (lower than that of device with 0.2 nm LiF layer) but the highest luminescent efficiency in all devices. Here the much enhanced electron injection and destructive efficiency for 0.2 nm LiF device are understood by the chemical interaction model at cathode interface, while the fairly increased electron injection and much improved efficiency for 0.6 nm LiF device would be interpreted by other mechanisms, and LiF plays a protective part in preventing the deposition-induce photoluminescence from quenching by Al cathode.

Efficient production of hydrogen peroxide in microbial reverse-electrodialysis cells coupled with thermolytic solutions

H_(2)O_(2) was produced at an appreciable rate in microbial reverse-electrodialysis cells(MRCs)coupled with thermolytic solutions,which can simultaneously capture waste heat as electrical energy.To determine the optimal cathode and membrane stack configurations for H_(2)O_(2) production,different catalysts,catalyst loadings and numbers of membrane cell pairs were tested.Carbon black(CB)outperformed activated carbon(AC)for H_(2)O_(2) production,although AC showed higher catalytic activity for oxygen reduction.The optimum CB loading was 10 mg/cm^(2) in terms of both the H_(2)O_(2) production rate and power production.The optimum number of cell pairs was determined to be three based on a tradeoff between H_(2)O_(2) production and capital costs.A H_(2)O_(2) production rate as high as 0.99±0.10 mmol/(L·h)was achieved with 10 mg/cm^(2) CB loading and 3 cell pairs,where the H_(2)O_(2) recovery efficiency was 52±2%and the maximum power density was 780±37 mW/m^(2).Increasing the number of cell pairs to five resulted in an increase in maximum power density(980±21 mW/m^(2))but showed limited effects on H_(2)O_(2) production.These results indicated that MRCs can be an efficient method for sustainable H_(2)O_(2) production.

Correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer

Objective: To investigate the correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer. Methods:Superficial gastritis group (n=247), gastric ulcer group (n=159) and gastric cancer group (n=97) who were pathologically diagnosed by gastroscopy in Chongqing wanzhou district people's hospital of 5 between August 2016 and August 2017 were selected, and the differences in serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content as well as proliferation and apoptosis gene expression in lesion tissue were compared among the three groups. Pearson test was used to evaluate the correlation of pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation activity of cancer cells in patients with gastric cancer. Results: Serum pepsinogenⅠ/Ⅱ ratio and gastrin-17 content in gastric cancer group were lower than those in gastric ulcer group and superficial gastritis group. Proliferation genes EIF5A2, MACF1 and PIK3CD mRNA expression levels in gastric cancer group were higher than those in gastric ulcer group and superficial gastritis group whereas SIRT1 mRNA expression level was lower than that in gastric ulcer group and superficial gastritis group;apoptosis gene Livin mRNA expression level was higher than that in gastric ulcer group and superficial gastritis group whereas Bad and Noxa mRNA expression levels were lower than those in gastric ulcer group and superficial gastritis group;serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content in gastric cancer group were negatively correlated with EIF5A2, MACF1, PIK3CD and Livin mRNA expression levels, and positively correlated with SIRT1, Bad and Noxa mRNA expression levels. Conclusion: The serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content abnormally reduce in patients with gastric cancer, and the specific levels are directly correlated with gastric cancer cell proliferation and apoptosis activity.

微塑料和纳米塑料威胁青藏高原环境

Plastic pollution is a planetary level threat which affects Earth’s environment and ecosystems.From the poles to deep ocean basins,the growth of plastic waste has already exceeded its limits.The projected increase of plastic production and waste generation over the coming years makes the situation even more daunting.Even after stagnation in 2020 due to the COVID-19 pandemic,the global plastic production has also increased from 335 to 391 million metric tons(Mt)between 2016 and 2021(Fig.S1 online);yet currently post-consumer recycled and bio-based/attributed plastics only accounts~9%of the world’s plastic production[1].Statistically.