Alu antisense RNA ameliorates methylglyoxal-induced human lens epithelial cell apoptosis by enhancing antioxidant defense

AIM:To determine whether an antisense RNA corresponding to the human Alu transposable element(Aluas RNA)can protect human lens epithelial cells(HLECs)from methylglyoxal-induced apoptosis.METHODS:Cell counting kit-8(CCK-8)and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays were used to assess HLEC viability.HLEC viability/death was detected using a Calcein-AM/PI double staining kit;the annexin V-FITC method was used to detect HLEC apoptosis.The cytosolic reactive oxygen species(ROS)levels in HLECs were determined using a reactive species assay kit.The levels of malondialdehyde(MDA)and the antioxidant activities of total-superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)were assessed in HLECs using their respective kits.RT-q PCR and Western blotting were used to measure m RNA and protein expression levels of the genes.RESULTS:Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxalinduced decrease in Bcl-2 m RNA and the methylglyoxalinduced increase in Bax m RNA.In addition,Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression.Aluas RNA inhibited the production of ROS induced by methylglyoxal,restored T-SOD and GSHPx activity,and moderated the increase in MDA content after treatment with methylglyoxal.Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes,including glutathione peroxidase,heme oxygenase 1,γ-glutamylcysteine synthetase and quinone oxidoreductase 1.Aluas RNA ameliorated methylglyoxal-induced increases of the m RNA and protein expression of Keap1 that is the negative regulator of Nrf2.CONCLUSION:Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.

Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15

Objective:To investigate whether human short interspersed nuclear element antisense RNA(Alu antisense RNA;Alu asRNA)could delay human fibroblast senescence and explore the underlying mechanisms.Methods:We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8(CCK-8),reactive oxygen species(ROS),and senescence-associated beta-galactosidase(SA-β-gal)staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts.We also used an RNA-sequencing(RNA-seq)method to investigate the Alu asRNA-specific mechanisms of anti-aging.We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA.We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts.Results:The CCK-8,ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging.RNA-seq showed 183 differentially expressed genes(DEGs)in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection(CPT)reagent.The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent.Notably,Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway.Conclusion:Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.

CO_2-1,3-PDO-PTT三元体系相平衡的研究

溶质-超临界流体-聚合物三元体系相平衡的研究为超临界流体辅助聚合物脱挥技术提供了热力学基础数据,利用自行研制的一套超临界CO_2高压装置,采用静态法,研究了温度为313.15—353.15 K、压力为7—19 MPa条件下,二氧化碳(CO_2)/1,3-丙二醇(1,3-PDO)/聚对苯二甲酸丙二醇酯(PTT)三元体系相平衡时超临界流体相中的组成。实验测得PTT模拟样品中1,3-PDO在SCCO_2中的溶解度,并计算得到了1,3-PDO在SCCO_2相与PTT相间的分配系数,同时分析了温度和压力对溶解度、分配系数的影响。在上述条件下,1,3-PDO的溶解度为0.262—3.597g/L,分配系数为0.020 5—0.076 2。研究结果显示:当温度一定时,溶解度随压力的增大呈现增大的趋势;溶解度随温度的变化会存在一转变压力(约18 MPa),在转变压两侧,溶解度会呈现相反的变化趋势;分配系数等温线随压力的增大呈现倒U型,即先增大后减小。

Honokiol:a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） cells is unknown. We investigated the antitumor activities of HNK on OSCC ceils in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-（4,5-dimethyl thiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and propidium iodide （PI） assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling （TUNEL）, and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg.mL-1 or 20 μg.mL-1 of HNK were more stronger compared with those of 20 μg-mL-1 5-fluorouracil （5-Fu, the control） applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.

Triptolide protects astrocytes from hypoxia/reoxygenation injury

Astrocytes in an in vitro murine astrocyte model of oxygen and glucose deprivation/hypoxia and reoxygenation were treated with different concentrations of triptolide （250, 500, 1 000 ng/mL） in a broader attempt to elucidate the protection and mechanism underlying triptolide treatment on astrocytes exposed to hypoxia/reoxygenation injury. The results showed that the matrix metalloproteinase-9, interleukin-1β, tumor necrosis factor α and interleukin-6 expressions were significantly decreased after triptolide treatment in the astrocytes exposed to hypoxia/ reoxygenation injury, while interleukin-10 expression was upregulated. In addition, the vitality of the injured astrocytes was enhanced, the triptolide＇s effect was apparent at 500 ng/mL. These experimental findings indicate that triptolide treatment could protect astrocytes against hypoxia/ reoxygenation injury through the inhibition of inflammatory response and the reduction of matrix metalloproteinase-9 expression.

PSO-LSSVM-based Online SOC Estimation for Simulation Substation Battery

As the emergency power supply for a simulation substation,lead-acid batteries have a work pattern featuring noncontinuous operation,which leads to capacity regeneration.However,the accurate estimation of battery state of charge(SOC),a measurement of the amount of energy available in a battery,remains a hard nut to crack because of the non-stationarity and randomness of battery capacity change.This paper has proposed a comprehensive method for lead-acid battery SOC estimation,which may aid in maintaining a reasonable charging schedule in a simulation substation and improving battery’s durability.Based on the battery work pattern,an improved Ampere-hour method is used to calculate the SOC during constant current and constant voltage(CC/CV)charging and discharging.In addition,the combined Particle Swarm Optimization(PSO)and Least Squares Support Vector Machine(LSSVM)model is used to estimate the SOC during non-CC discharging.Experimental results show that this method is workable in online SOC estimation of working batteries in a simulation substaion,with the maximum relative error standing at only 2.1%during the non-training period,indicating a high precision and wide applicability.

Research on the Traveling Characteristics and Comparison of Bike Sharing in College Campus-A Case Study in Hangzhou

Bike sharing emerging from college campus in China's Mainland has become a major part in the daily traveling of Chinese urban residents.It changes the traveling behavior of urban residents,and simultaneously,raises higher requirements on urban transportation facility construction and management.However,the return of bike sharing to college campus causes more troubles to schools.The fundamental cause is the closed peculiarity of campus traveling comparing with city traveling,and also the discrepancy between college campuses of different types.This paper investigates the traveling characteristics of bike sharing in college campus in three different locations in Hangzhou City,Zhejiang Province of China in the questionnaire,and compares the discrepancy with urban bike sharing traveling characteristics and the discrepancy in bike sharing use between college campuses of different types.From the perspective of parking,maintenance and operation,and hardware design,the paper eventually raises suggestions to optimize independent college campus bike sharing service facility and management consistent with urban system.The research may also offer beneficial reference to the release of bike sharing facilities consistent with urban system in all sorts of independent parks,especially college campus.

RNA-seq analysis of a zebrafish caudal fin cell line in response to infection with spring viraemia of carp virus

A cell line,termed ZFIN,was established from the caudal fin of zebrafish and was shown to be susceptible to spring viremia of carp virus(SVCV).The ZFIN cells are epithelial like cells and have a moderate plasmid transfection efficiency of 13.9%.Using an RNA-seq approach,differentially expressed genes(DEGs)regulated by SVCV were identified.Infection of SVCV gave rise to 3931 DEGs and up-regulated DEGs were mostly enriched into the biological regulation and cellular processes,among which pathways for the type I interferon signaling and the response to exogenous dsRNA were the top two GO terms.Several KEGG signaling pathways including TLR signaling pathway,RLR receptor signaling pathway,cytosolic DNA-sensing pathway,NLR signaling pathway,cytokine-cytokine receptor interaction and ferroptosis were significantly enriched.Antiviral genes including ifnφ1,isg15 and mx were significantly up-regulated.In addition,key DEGs involved in autophagy were identified.The results indicate that the ZFIN cell line provides a useful in vitro tool for study on the gene functions and cellular responses to viral infection in fish.

Executive Function Training for Children with Attention Deficit Hyperactivity Disorder

Background： Accumulating evidence indicates that attention deficit hyperactivity disorder （ADHD） is associated with core deficits in executive function （EF） which predicts poorer academic and occupational functioning. This makes early intervention targeting EF impairments important to prevent long-term negative outcomes. Cognitive training is a potential ADHD treatment target. The present study aimed to explore the efficacy, feasibility, and acceptability of a cognitive training program （targeting child＇s multiple EF components and involving parent support in daily life）, as a nonpharmacological intervention for children with ADHD. Methods： Forty-four school-age children with ADHD and their parents participated in 12 sessions of EF training （last for 12 weeks） and 88 health controls （HC） were also recruited. Training effects were explored using both neuropsychological tests （Stroop color-word test, Rey-Osterrieth complex figure test, trail making test, tower of Hanoi, and false-belief task） and reports of daily life （ADHD rating scale-IV, Conners＇ parent rating scale, and behavior rating inventory of executive function [BRIEF]） by analysis of paired sample t-test and Wilcoxon signed-rank test. The differences on EF performances between children with ADHD after training and HC were explored using multivariate analysis. Results： The results （before vs. after EF training） showed that after intervention, the children with ADHD presented better performances of EF both in neuropsychological tests （word interference of Stroop： 36.1 ± 14.6 vs. 27.1 ± 11.1, t = 4.731, P 〈 0.001 ; shift time of TMT： 194.9 ± 115.4 vs. 124.8 ± 72.4, Z = -4.639, P 〈 0.001 ; false-belief task： χ^2 = 6.932, P = 0.008） and reports of daily life （global executive composite of BRIEF： 148.9 ± 17.5 vs. 127.8 ± 17.5, t =6.433, P 〈 0.001）. The performances on EF tasks for children with ADHD after EF training could match with the level of HC children. The ADHD symptoms （ADHD rating scale total score： 32.4 ± 8.9 vs. 22.9 ± 8.2, t = 6.331, P 〈 0.001） and behavioral problems of the children as reported by parents also reduced significantly after the intervention. Participants reported that the EF training program was feasible to administer and acceptable. Conclusions： The EF training program was feasible and acceptable to children with ADH D and parents. Although replication with a larger sample and an active control group are needed, EF training program with multiple EF focus and parent involving in real-life activities could be a potentially promising intervention associated with significant EF （near transfer） and ADHD symptoms improvement （far transfer）.

1990年和2019年中国分省精神障碍伤残负担分析

目的分析1990年和2019年中国人群精神障碍患病及伤残负担变化情况, 为降低精神障碍健康危害提供参考。方法利用2019年全球疾病负担(Global Burden of Disease Study 2019, GBD2019)中国研究结果, 分析2019年中国人群不同年龄、不同性别、不同省份精神障碍患病及伤残负担, 比较1990年与2019年中国精神障碍的患病和伤残损失寿命年(years of life lived with disability, YLDs)指标变化情况。结果 2019年中国精神障碍50~69岁年龄组患病率最高(13.2%, 患病人数为4 853.0万), 0~14岁年龄组患病率最低(7.3%, 患病人数为1 645.6万);女性总体YLDs数量高于男性(1 091.0万人年/938.2万人年);2019年抑郁障碍、焦虑症、精神分裂症的标化患病率分别为2.7%、3.2%、0.3%, 患病人数分别为5 005.6万、4 784.2万、549.9万;与1990年比较, 抑郁障碍和焦虑症的标化患病率下降幅度分别为9.1%和9.8%, 精神分裂症的标化患病率上升幅度为3.1%;2019年中国精神障碍标化患病率前3位的省份分别是湖南省(12.2%)、甘肃省(12.1%)和宁夏回族自治区(11.8%), 3个省份的精神障碍患病人数分别为890.1万、336.4万、87.3万。标化YLDs率位于前3位的省份分别为山东省(1 470.0/10万)、甘肃省(1 415.6/10万)和湖南省(1 399.3/10万)。结论精神障碍是威胁中国人群身心健康的重要疾病, 2019年中国精神障碍伤残负担仍处于较高水平;女性精神障碍伤残负担更加严重;应提早采取干预措施, 减少精神障碍伤残负担。

Chemo-Biocascade Reactions Enabled by Metal-Organic Framework Micro-Nanoreactor

The one-pot combination of biocatalytic and chemocatalytic reactions represents an economically and ecologically attractive concept in the emerging cascade processes for manufacturing.The mutual incompatibility of biocatalysis and chemocatalysis,however,usually causes the deactivation of catalysts,the mismatching of reaction dynamic,and further challenges their integration into concurrent chemo-biocascades.Herein,we have developed a convenient strategy to construct versatile functional metal-organic framework micro-nanoreactors(MOF-MNRs),which can realize not only the encapsulation and protection of biocatalysts but also the controllable transmission of substances and the mutual communication of the incompatible chemo-biosystems.Importantly,the MOFs serving as the shell of MNRs have the capability of enriching the chemocatalysts on the surface and improving the activity of the chemocatalysts to sufficiently match the optimum aqueous reaction system of biocatalysts,which greatly increase the efficiency in the combined concurrent chemo-biocatalysis.Such strategy of constructing MOF-MNRs provides a unique platform for connecting the“two worlds”of chemocatalysis and biocatalysis.

Evaluating Behavioral Risk Factor Interventions for Hypertensive and Diabetic Patient Management in the National Basic Public Health Service Programs from 2009

BACKGROUND In recent decades,China has faced a double burden of infectious diseases and noncommunicable diseases(NCDs).The number of deaths due to NCDs accounts for 88.5%of total deaths in China in 2019.To address these public health issues and improve the accessibility and affordability of primary health care,a National Basic Public Health Service Program(NBPHSP)was introduced as part of China’s healthcare reform initiated in 2009.Subsided by national and local government budgets,NBPHSP is mainly implemented by community and township health service centers,as well as health stations in urban areas and village clinics in rural areas(1).Health management of patients with hypertension and diabetes is an integral and pivotal part of the NBPHSP.

Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor

Background:Overexpression of ATP-binding cassette(ABC)transporter is a major contributor to multidrug resistance(MDR),in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic drugs.In this work,we evaluated the sensitizing effect of sitravatinib,a broad-spectrum tyrosine kinase inhibitor(TKI),on ATP-binding cassette subfamily B member 1(ABCB1)-and ATP-binding cassette subfamily C member 10(ABCC10)-mediated MDR.Methods:MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non-toxic concentrations.Tritium-labeled paclitaxel transportation,Western blotting,immunofluorescence analysis,and ATPase assay were carried out to elucidate the mechanism of sitravatinib-induced chemosensitization.The in vitro findings were translated into preclinical evaluation with the establishment of xenograft models.Results:Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10-mediated MDR.Our in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human-mouse chimeric model.Furthermore,sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ABCB1.Thus,sitravatinib could considerably enhance the intracellular concentration of anticancer drugs.Interestingly,no significant alterations of both expression level and localization of ABCB1 were observed.More importantly,sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1-mediated xenograft model without observable toxic effect.Conclusions:The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.

Optical soliton in a one-dimensional array of a metal nanoparticle-microcavity complex

Quantum coherence can be enhanced by placing metal nanoparticles(MNPs)in optical microcavities.Combining localized-surface plasmon resonances(LSPRs),nonlinear interaction between the LSPR and microcavity arrays of a MNP-microcavity complex offer a unique playground to observe novel optical phenomena and develop novel concepts for quantum manipulation.Here we theoretically demonstrate that optical solitons are achievable with a one-dimensional array which consists of a chain of periodically spaced identical MNP-microcavity complex systems.These differ from the solitons which stem from the MNPs with nonlinear Kerr-like response;the optical soliton here originates from LSPR-microcavity interaction.Using experimentally achievable parameters,we identify the conditions under which the nonlinearity induced by LSPR-microcavity interaction allows us to compensate for the dispersion caused by photon hopping of adjacent microcavities.More interestingly,the dynamics of solitons can be modulated by varying the radius of the MNP.The presented results illustrate the potential to utilize the MNP-microcavity complex for light manipulation,as well as to guide the design of photon switch and on-chip photon architecture.

Time to Take Actions to Reduce the Harmful Use of Alcohol in China

Harmful use of alcohol negatively impacts and harms the drinkers,the people around them,and society at large.Harmful use of alcohol ranks among the top 5 risk factors for disease,disability,and death worldwide,and alcohol consumption is related to approximately 230 health conditions including infectious disease,noncommunicable diseases,and injuries(1–2).

Artificial synthesis of polyesters at ambient condition via consecutive CO_(2)electrolysis and fermentation

Electrochemically converting CO_(2)into value-added chemicals is a promising approach to mitigate anthropogenic carbon emissions,yet largely limited to short-chained C_(1)–C_(3)products.Herein,we demonstrate a tandem artificial synthesis of biodegradable polyhydroxybutyrate(PHB)plastic from CO_(2)building blocks.Batch synthesis of defects-enriched Bi catalyst is firstly demonstrated by plasma bombardment and following in situ electrochemical reduction,which delivers a HCOOH Faradaic efficiency above 80%at tunable concentration from 2 to 250 mM,an energy efficiency up to 41%,and a single-pass carbon conversion efficiency up to 60%.Annular dark field and second electron microscopic analysis,density functional theory(DFT)calcualtions,coupled with H-type and solid-state electrolyzer assessments,point out the vital role of defective and/or stepped Bi surface sites in promoting CO_(2)-to-HCOOH conversion.Thereafter,as-synthesized high-purity HCOOH is used as the sole carbon source for C-chain growth within microbial fermentation reactor with Ralstonia eutropha,where activated formate dehydrogenase and increased metabolites related to Calvin–Benson–Bassham cycle are found to be responsible for the enhanced polyester accumulation.