Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

教育领域人工智能伦理研究进展:基于活动理论的分析框架

随着人工智能在教育领域应用的不断深化,教育伦理风险问题随之产生,引起了学术界的高度关注。采用活动理论分析框架,对2012—2022年间有关教育领域人工智能应用伦理风险的150篇文献进行系统性回顾,发现教育领域人工智能伦理研究经历了萌芽探索、成长发生、快速发展三个阶段;研究议题以安全隐私为主,但研究主体尚不明晰,对引起教育领域伦理问题的人工智能技术缺乏明确指向性;研究方法以定性为主,引发伦理问题的应用场景相对局限,且较少针对特定教育群体;研究对伦理困境关注较多,但风险管理视角欠缺;研究成果多为单一视角的理论与现状分析,缺少多理论视域的综合研究;伦理风险的跨领域交叉研究和多视域理论分析,对当下教育伦理及风险治理具有重要意义。基于主要结果及局限性,提出未来研究建议:需要重新审视人工智能与教育之间的交互作用,重塑人工智能教育应用中的伦理规约与评价指标;研究方法不局限于理论研究,应在人工智能技术实践教学中客观收集教学案例、资料等数据,科学性和创新性地提出教育领域人工智能伦理治理策略;深入探讨不同教育层级和教育领域的具体问题,进而针对性地制定相关政策和法规,加强监管与管理,并且提高相关人员的伦理意识和责任意识;不仅要关注教育人工智能应用表层所涉及的伦理问题,对于更深层次的风险发生机制问题也要多加关注;加大对教育人工智能应用伦理原则与政策的研究力度,系统性地思考人工智能的治理维度,通过制定伦理准则,加强政府及相关管理部门对教育人工智能的监管。

A Study on the Impact of A spherical video-based virtual reality on Teaching English Writing Guided by Experiential Learning Circle Theory

English as an international language,English writing is a very important skill as an important form of language output,which is not only an important means of expressing emotions and awareness,but also reflects the ability to use language in an integrated way.In language teaching,the development of English writing skills is an important and challenging teaching task.English writing language is expressed not only at the basic level of vocabulary,grammar,and sentence structure,but also at the higher-order level of text organization,logical reasoning,and argumentation.However,in traditional English writing teaching,students usually do not have the opportunity to have an in-depth experience of the context of the topic,which leads to a lack of motivation and poor writing results.Therefore,this study developed an SVVR learning system based on spherical video-based virtual reality(SVVR)technology and conducted a quasi-experiment in a university English major classroom.The results of the study showed that the SVVR-supported approach to English writing could improve students'writing performance,enrich writing content,and increase learning motivation.

A practical exploration of primary school Chinese Writing Teaching based on experiential teaching approach--"Underwater World" as an example

In language teaching,the development of writing skills is an important and challenging teaching task.Writing performance is not only related to the vocabulary and syntax that students usually accumulate,but also involves richness in terms of content,which is related to students'experience and perception of context.Descriptive essays are one of the writing genres that include specific understanding and perception of space,time,and context.However,in traditional writing instruction,students usually do not have the opportunity to have a deeper sense of the context of the topic.As a result,students usually have limited expression in the writing process.Therefore,this study explores the application of experiential teaching method in teaching writing in elementary schools by taking the"underwater world"as an example.Based on this,an SVVR learning system was developed and a quasi-experiment was conducted in an elementary school writing classroom to compare the learning effects of this method with those of traditional teaching methods.The results of the study showed that the SVVR-supported experiential teaching method could improve students'writing performance as well as their sense of self-efficacy and self-efficacy.

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

AIM To investigate the value of the gamma-glutamyltraspeptidase(GGT)-to-platelet(PLT) ratio(GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B(CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase(AST)-to-PLT ratio index(APRI), and fibrosis-4(FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin(TBil), alanine aminotransferase(ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic(ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated withCHB patients' age, gender, or disease duration(P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count(P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis(P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI(F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.

Assessment of recoverable oil and gas resources by in-situ conversion of shale——Case study of extracting the Chang 7_(3) shale in the Ordos Basin

The purpose of this study is to investigate the entire evolution process of shales with various total organic contents(TOC)in order to build models for quantitative evaluation of oil and gas yields and establish methods for assessing recoverable oil and gas resources from in-situ conversion of organic matters in shale.Thermal simulation experiments under in-situ conversion conditions were conducted on Chang 7_(3) shales from the Ordos Basin in a semi-open system with large capacity.The results showed that TOC and R_(o) were the key factors affecting the in-situ transformation potential of shale.The remaining oil and gas yields increased linearly with TOC but inconsistently with R_(o).R_(o) ranged 0.75%—1.25%and 1.05%—2.3%,respectively,corresponding to the main oil generation stage and gas generation stage of shale in-situ transformation.Thus a model to evaluate the remaining oil/gas yield with TOC and R_(o) was obtained.The TOC of shale suitable for in-situ conversion should be greater than 6%,whereas its R_(o) should be less than 1.0%.Shales with 0.75%(R_(o))could obtain the best economic benefit.The results provided a theoretical basis and evaluation methodology for predicting the hydrocarbon resources from in-situ conversion of shale and for the identification of the optimum“sweet spots”.The assessment of the Chang 7_(3) shale in the Ordos Basin indicated that the recoverable oil and gas resources from in-situ conversion of organic matters in shale are substantial,with oil and gas resources reaching approximately 450×10^(8) t and 30×10^(12)m^(3),respectively,from an area of 4.27×10^(4) km^(2).

Organic matter occurrence and pore-forming mechanisms in lacustrine shales in China

The evolution of pore structure in shales is affected by both the thermal evolution of organic matter(OM)and by inorganic diagenesis,resulting in a wide variety of pore structures.This paper examines the OM distribution in lacustrine shales and its influence on pore structure,and describes the process of porosity development.The principal findings are:(i)Three distribution patterns of OM in lacustrine shales are distinguished;laminated continuous distribution,clumped distribution,and stellate scattered distribution.The differences in total organic carbon(TOC)content,free hydrocarbon content(S_(1)),and OM porosity among these distribution patterns are discussed.(ii)Porosity is negatively correlated with TOC and plagioclase content and positively correlated with quartz,dolomite,and clay mineral content.(iii)Pore evolution in lacustrine shales is characterized by a sequence of decreasing-increasing-decreasing porosity,followed by continuously increasing porosity until a relatively stable condition is reached.(iv)A new model for evaluating porosity in lacustrine shales is proposed.Using this model,the organic and inorganic porosity of shales in the Permian Lucaogou Formation are calculated to be 2.5%-5%and 1%-6.3%,respectively,which correlate closely with measured data.These findings may provide a scientific basis and technical support for the sweet spotting in lacustrine shales in China.

Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the temporal profiles of specific antibodies,as well as the associations between the antibodies,proinflammatory cytokines,and survival of patients with coronavirus disease 2019(COVID-19).A total of 1830 laboratory-confirmed COVID-19 cases were recruited.The temporal profiles of the virus,antibodies,and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method.The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis.Of the 1830 patients,1435 were detectable for SARS-CoV-2,while 395 were positive in specific antibodies only.Of the 1435 patients,2.4%presented seroconversion for neither immunoglobulin G(IgG)nor immunoglobulin M(IgM)during hospitalization.The seropositive rates of IgG and IgM were 29.6%and 48.1%,respectively,in the first week,and plateaued within five weeks.For the patients discharged from the hospital,the IgM decreased slowly,while high levels of IgG were maintained at around 188 AUmL^(-1) for the 12 weeks since illness onset.In contrast,in the patients who subsequently died,IgM declined rapidly and IgG dropped to 87 AUmL^(-1) at the twelfth week.Elevated interleukin-6,interleukin-8,interleukin-10,interleukin-1b,interleukin-2R,and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients,and 12.5%of the association between IgG level and mortality risk was mediated by these cytokines.Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival,which may help to guide prognosis estimation.

miR-541-3p靶向SENP1调控皮肤黑色素瘤细胞增殖、迁移、侵袭机制的研究

目的:探讨微小RNA-541-3p(miR-541-3p)对皮肤黑色素瘤细胞增殖、迁移、侵袭的影响及其分子机制。方法:采用实时荧光定量聚合酶链反应(qRT-PCR)与蛋白免疫印迹法(Western blotting)分别检测皮肤黑色素瘤组织中miR-541-3p、SENP1的表达水平;以人皮肤黑色素瘤细胞A375为研究对象,分别将miR-NC、miR-541-3p mimics、si-NC、si-SENP1、miR-541-3p mimics与pcDNA、miR-541-3p mimics与pcDNA-SENP1转染至A375细胞;甲基噻唑基四唑(MTT)检测细胞增殖;Transwell小室实验检测细胞迁移及侵袭能力;双荧光素酶报告实验验证miR-541-3p过表达对野生型和突变型SENP1荧光素酶活性的影响;Western blotting检测细胞周期蛋白1(CyclinD1)、p21、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)蛋白表达量。结果:与正常皮肤组织比较,皮肤黑色素瘤组织中miR-541-3p的表达量显著降低(P<0.05),SENP1 mRNA及蛋白表达水平显著升高(P<0.05);与miR-NC组比较,miR-541-3p组A375细胞活力显著降低(P<0.05),迁移细胞数与侵袭细胞数显著减少(P<0.05),CyclinD1、MMP-2、MMP-9蛋白水平显著降低(P<0.05),p21蛋白水平显著升高(P<0.05);与si-NC组比较,siSENP1组A375细胞活力显著降低(P<0.05),迁移细胞数与侵袭细胞数显著减少(P<0.05),CyclinD1、MMP-2、MMP-9蛋白水平显著降低(P<0.05),p21蛋白水平显著升高(P<0.05);双荧光素酶报告实验证实miR-541-3p能够抑制SENP1的3′-UTR区荧光素酶活性;与miR-541-3p+pcDNA组比较,miR-541-3p+pcDNA-SENP1组细胞活力显著升高(P<0.05),迁移细胞数与侵袭细胞数显著增多(P<0.05),CyclinD1、MMP-2、MMP-9蛋白水平显著升高(P<0.05),p21蛋白水平显著降低(P<0.05)。结论:miR-541-3p过表达可靶向抑制SENP1表达从而减弱皮肤黑色素瘤细胞增殖、迁移及侵袭能力。

Cellular metabolism: A key player in cancer ferroptosis

Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal.It produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular functions.Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell death.Ferroptosis is a recently discovered form of iron-dependent programmed cell death.The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression.However,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well understood.Here,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process.Additionally,we provided a detailed overview of agents used to induce cancer ferroptosis.We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell killing.The combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Antioxidant and immunomodulatory activities of a polysaccharide from Flammulina velutipes

OBJECTIVE: To evaluate the antioxidant and immunomodulatory activities of a unique polysaccharide from the medicinal fungus Flammulina velutipes in vitro.METHODS: Using water extraction and alcohol precipitation, crude polysaccharides were obtained. After purification by DEAE-cellulose 52 ion exchange chromatography and Sephacryl S-300 HR gel filtration chromatography, High performance liquid chromatography equipped with evaporative light-scattering detector, Infrared radiation and Nuclear magnetic resonance were used to evaluate the structure of the polysaccharide. Its immunomodulatory activity was measured by examining the production of nitric oxide(NO) and cytokine secretion, and via lymphocyte proliferation experiments. Its effects on the scavenging activities of hydroxyl radical, superoxide anion and reducing power were also measured.RESULTS: A water-soluble polysaccharide, Flammulina velutipes polysaccharide I-A(FVP I-A), was obtained with a molecular mass of 8.14×104Da determined by high performance gel permeation chromatography. An in vitro antioxidant assay indicated that FVP I-A could scavenge hydroxyl radical, superoxide anion and possessed reducing power and could largely promote NO production and augment the interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion by RAW264.7 macrophages(P<0.05). Moreover, FVP I-A could promote lymphocyte proliferation(P<0.05), and synergistically enhance the augmentation of the proliferation of mouse lymphocytes by concanavalin A and lipopolysaccharides(P<0.01, P<0.05).CONCLUSION: The FVP I-A obtained from Flammulina velutipes possessed antioxidant activity and could enhance non-specific and specific immune responses in vitro.

A Meta-analysis of the Value of vWF in the Diagnosis of Liver Cirrhosis with Portal Hypertension

Background and Aims:Studies have indicated that serum von Willebrand factor(vWF)has a positive correlation with hepatic venous pressure gradient.However,information on the value of vWF in the diagnosis of liver cirrhosis with portal hypertension has been lacking.The purpose of this meta-analysis was to assess the value of vWF in the diagnosis of liver cirrhosis with portal hypertension.Methods:Studies that analyzed the sensitivity,specificity,diagnostic odds ratio combined with likelihood ratios and test for heterogeneity of vWF in the diagnosis of liver cirrhosis with portal hypertension were found in the Cochrane Library,Ovid,VOS-SCI,CNKI,PubMed,Medline,EMBASE,CMB and Wanfang databases.In the end,the data was used to draw the summary receiver operating characteristic curve and to calculate the area under the curve.Results:Four studies involving 662 patients were analyzed.The results showed that serum vWF in liver cirrhosis with portal hypertension were significantly higher than in those without portal hypertension.Sensitivity combined was 0.823(95%CI:0.788,0.855).Specificity combined was 0.782(95%CI:0.708,0.845).+LR combined was 3.777(95%CI:2.794,5.107).-LR combined was 0.221(95%CI:0.180,0.272).Diagnostic odds ratio combined was 18.347(95%CI:11.725,28.708).The area under the curve was 0.8896.Conclusions:Serum vWF can be used as an effective and feasible method for noninvasive diagnosis of liver cirrhosis with portal hypertension.However,further studies are still needed to evaluate the severity of liver cirrhosis with portal hypertension.

Post-treatment Process of Semi-solid Powder Rolling

Semi-solid powder rolling is a strip manufacturing process, which combines powder rolling with semi-solid rolling in one step to prepare high-performance metallic strips. A total of 7050 aluminum alloy strips were prepared by semi-solid powder rolling and then used to study the post-treatment process and evaluate qualities of post-treated strips.Three post-treatment processes involving sintering, pre-sintering-cold deformation-sintering, and hot rolling were used to process the semi-solid powder rolled strips. The results show that both swelling of pores and densification occur during solid-state sintering while microhardness increases. The decrease in density is due to that the swelling of pores has a larger effect on the density change than that of densification. The relative density reaches 92.6% with the maximum microhardness of 300 HV after ＇＇pre-sintering-cold deformation-sintering＇＇ process. High microhardness is due to the ultrafine secondary particles uniformly distributed within the grains. The microhardness and relative density of a hot rolled strip are 176 HV and 99%, respectively, and the secondary particles disappear. Occurrence of recrystallization in these three post-treatment processes makes the grains finer.

Multi-Factor Intensity Estimation for Tropical Cyclones in the Western North Pacific Based on the Deviation Angle Variance Technique

In this paper, the infrared cloud images from Fengyun series geostationary satellites and the best track data from the China Meteorological Administration(CMA-BST) in 2015–2017 are used to investigate the effects of two multifactor models, generalized linear model(GLM) and long short-term memory(LSTM) model, for tropical cyclone(TC) intensity estimation based on the deviation angle variance(DAV) technique. For comparison, the typical singlefactor Sigmoid function model(SFM) with the map minimum value of DAV is also used to produce TC intensity estimation. Sensitivity experiments regarding the DAV calculation radius and different training data groups are conducted, and the estimation precision and optimum calculation radius for DAV in the western North Pacific(WNP) are analyzed. The results show that the root-mean-square-error(RMSE) of the single-factor SFM is 8.79–13.91 m s^-1 by using the individual years as test sets and the remaining two years as training sets with the optimum calculation radius of 550 km. However, after selecting and using the high-correlation multiple factors from the same test and training data, the RMSEs of GLM and LSTM models decrease to 5.93–8.68 and 4.99–7.00 m s^-1 respectively, with their own optimum calculation radii of 350 and 400 km. All the sensitivity experiments indicate that the SFM results are significantly influenced by the DAV calculation radius and characteristics of the training set data, while the results of multi-factor models appear more stable. Furthermore, the multi-factor models reduce the optimum radius within the process of DAV calculation and improve the precision of TC intensity estimation in the WNP, which can be chosen as an effective approach for TC intensity estimation in marine areas.