First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.

Comparison of genetic impact on growth and wood traits between seedlings and clones from the same plus trees of Pinus koraiensis

To evaluate the relationships among clones and open pollinated families from the same plus trees and to select elite breeding materials,growth,and wood characteristics of 33-year-old Pinus korainsis clones and families were measured and analyzed.The results show that growth and wood characters varied significantly.The variation due to clonal effects was higher than that of family effects.The ratio of genetic to phenotypic coefficient of variation of clones in growth and wood traits was above 90%,and the repeatability of these characteristics was more than 0.8,whereas the ratio of genetic to phenotypic coefficient of variation of families was above 90%.The broad-sense heritability of all characteristics exceeded 0.4,and the narrow-sense family heritability of growth traits was less than 0.3.Growth characteristics were positively correlated with each other,but most wood properties were weakly correlated in both clones and families.Fiber length and width were positively correlated between clones and families.Using the membership function method,eleven clones and four families were selected as superior material for improved diameter growth and wood production,and two families from clonal and open-pollinated trees showed consistently better performance.Generally,selection of the best clones is an effective alternative to deployment of families as the repeatability estimates from clonal trees were higher than narrow-sense heritability estimates from open pollinated families.The results provide valuable insight for improving P.koraiensis breeding programs and subsequent genetic improvement.

Efficacy of Ulinastatin Combined with Continuous Renal Replacement Therapy in the Treatment of Sepsis Acute Kidney Injury and Its Effects on Systemic Inflammation, Immune Function and miRAN Expression

Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

A preliminary site selection system for underground hydrogen storage in salt caverns and its application in Pingdingshan,China

Large‐scale underground hydrogen storage(UHS)provides a promising method for increasing the role of hydrogen in the process of carbon neutrality and energy transition.Of all the existing storage deposits,salt caverns are recognized as ideal sites for pure hydrogen storage.Evaluation and optimization of site selection for hydrogen storage facilities in salt caverns have become significant issues.In this article,the software CiteSpace is used to analyze and filter hot topics in published research.Based on a detailed classification and analysis,a“four‐factor”model for the site selection of salt cavern hydrogen storage is proposed,encompassing the dynamic demands of hydrogen energy,geological,hydrological,and ground factors of salt mines.Subsequently,20 basic indicators for comprehensive suitability grading of the target site were screened using the analytic hierarchy process and expert survey methods were adopted,which provided a preliminary site selection system for salt cavern hydrogen storage.Ultimately,the developed system was applied for the evaluation of salt cavern hydrogen storage sites in the salt mines of Pingdingshan City,Henan Province,thereby confirming its rationality and effectiveness.This research provides a feasible method and theoretical basis for the site selection of UHS in salt caverns in China.

南方某市公租房室内挥发性有机化合物的污染特征及健康风险研究

为了解新装修公租房室内空气中的污染特征及评估其环境健康风险,本研究对南方某市公租房室内挥发性有机化合物(VOCs)的多组分化学物质(33项指标)进行了分析,在此基础上筛选出检出频繁、毒性较高、含量较高的典型VOCs,并讨论了其在不同功能区域、不同楼层、不同装修时间的污染特征,最后,对典型VOCs的致癌和非致癌风险进行评估。结果表明,筛选得到5种典型有毒有害化学物质,分别是苯、乙苯、间,对-二甲苯、1,1,2,2-四氯乙烷、甲醛;公租房装修程度越低、楼层升高、装修时间延长,污染物浓度越来越低;不同年龄人群的致癌风险评估可知,1,1,2,2-四氯乙烷、甲醛的致癌风险均超过1×10^(-6),该风险值不可忽略,且年龄越小、致癌风险越大;非致癌风险评估可知,苯、乙苯、间,对-二甲苯、甲醛的非致癌风险分别为3.3×10^(-3)、9.8×10^(-4)、4.7×10^(-4)、1.99,即甲醛存在非致癌健康风险。

Investigating the Transport Mechanism of PM2.5 Pollution during January 2014 in Wuhan, Central China

Severe haze pollution that occurred in January 2014 in Wuhan was investigated. The factors leading to Wuhan’s PM2.5 pollution and the characteristics and formation mechanism were found to be significantly different from other megacities, like Beijing. Both the growth rates and decline rates of PM2.5 concentrations in Wuhan were lower than those in Beijing, but the monthly PM2.5 value was approximately twice that in Beijing. Furthermore, the sharp increases of PM2.5 concentrations were often accompanied by strong winds. A high-precision modeling system with an online source-tagged method was established to explore the formation mechanism of five haze episodes. The long-range transport of the polluted air masses from the North China Plain (NCP) was the main factor leading to the sharp increases of PM2.5 concentrations in Wuhan, which contributed 53.4% of the monthly PM2.5 concentrations and 38.5% of polluted days. Furthermore, the change in meteorological conditions such as weakened winds and stable weather conditions led to the accumulation of air pollutants in Wuhan after the long-range transport. The contribution from Wuhan and surrounding cities to the PM2.5 concentrations was determined to be 67.4% during this period. Under the complex regional transport of pollutants from surrounding cities, the NCP, East China, and South China, the five episodes resulted in 30 haze days in Wuhan. The findings reveal important roles played by transregional and intercity transport in haze formation in Wuhan.

结直肠癌术后患者异时性进展期腺瘤风险筛查模型的构建及验证

目的 筛选结直肠癌术后患者发生异时性进展期腺瘤的危险因素,构建个体化风险筛查模型并验证模型的筛查效果。方法 将2007年4月至2017年10月行结直肠癌根治术的734例患者分为建模组和验证组,术后3年结肠镜随访。建模组采用单因素及多因素Logistic回归分析,建立风险筛查模型。利用验证组验证模型的筛查效果。结果 734例患者包括建模组485例,验证组249例。平均年龄为(64.6±11.5)岁,男性440例,女性294例。总的异时性进展期腺瘤发生率为11.9%(建模组12.0%,验证组11.6%)。多因素Logistic回归分析显示,男性、糖尿病病史、右半结肠癌、中低分化腺癌、腺癌合并腺瘤,腺癌合并进展期腺瘤为异时性进展期腺瘤的独立预测因素。根据Logistic多因素分析结果,建立筛查结直肠癌术后出现异时性进展期腺瘤的模型,并建立风险筛查列线图。受试者工作特征(receiver operating characteristic,ROC)曲线分析结果显示,该模型的受试者工作特征曲线下面积(area under the curve,AUC)=0.957(95%CI:0.935~0.973),模型筛查临界值为0.938 7。验证结果显示,构建的筛查模型的灵敏度=93.1%,特异度=89.1%,并且筛查结果与实际结果的一致性较高(Kappa=0.62)。结论 以男性、糖尿病病史、右半结肠癌、中低分化腺癌、腺癌合并腺瘤、腺癌合并进展期腺瘤七个因素,构建的结直肠癌术后出现异时性进展期腺瘤筛查模型,具有较高的真实性和与实际结果的一致性,有临床应用价值。

A General Algorithm of Rotating/tilting Positioner Inverse Kinematics for Robotic Arc Welding Off-line Programming

Off-line programming provides an essential link between CAD and CAM, whose development should result in greater use of robotic arc welding. An arc welding system with a robot and a rotating/tilting positioner is a major application area, where manual programming is a very tedious job. Off-line programming is a constructive way to solve the problem. The inverse kinematics algorithm of robot and positioner is the foundation of the off-line programming system. Although previously there were some researchers who studied the positioner inverse kinematics algorithm, they only focused on a special solution of the positioner inverse kinematics, which is the solution at down-hand welding position. However, in welding production, welding position other than down-hand position is also needed. A method for representing welding position was introduced. Then a general algorithm of rotating/tilting positioner inverse kinematics is presented.

Prospective Clinical Application of Thioredoxin Reductase as a Novel Diagnostic Tumor Marker

Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.

Study on the Formation Mechanism of Oxygen-containing Groups on the Surfaces of Hypercrosslinked Polystyrenes

The synthetic parameters were changed to explore the formation mechanism of the oxygen-containing groups on the surfaces of the hypercrosslinked polymers. The FT-IR spectra and the Boehm titration were used to characterize the surface chemistry of the synthesized polymers. The GC-MS was applied to analyze nitrobenzene which was the solvent in the reaction. The functionalities such as carbonyls and phenols were formed through the oxidation of residual chloromethyl groups by nitrobenzene and the carboxylic groups were formed through further oxidation by oxygen. The nitrobenzene was deoxidized to nitrosobenzene and further to aniline.

Coupling virio-and bacterioplankton populations with environmental variable changes in the Bohai Sea

Uncovering the role of environmental factors and finding critical factors which harbor significant fractions in governing microbial communities remain key questions in coastal marine systems.To detect the interactions between environmental factors and distributions of virio-and bacterioplankton in trophic coastal areas,we used flow cytometry to investigate the abundance of virio-and bacterioplankton covering 31 stations in the Bohai Sea of China.Our results suggested that the average abundance of total virus(TV)in winter(~2.29×108 particles/mL)was slightly lower than in summer(~3.83×108 particles/mL).The mean total bacterial abundance(TB)was much lower in winter(~2.54×107 particles/mL)than in summer(~5.43×107 particles/mL).Correlation analysis via redundancy analysis(RDA)and network analysis among virioplankton,bacterioplankton and environmental factors revealed that the abundances of viral and bacterial subpopulations depend on environmental factors.In winter,only temperature significantly influenced the abundances of virio-and bacterioplankton.In summer,in addition to temperature,both salinity and nutrient(SiO2)had a remarkable impact on the distribution of virioand bacterioplankton.Our results showed a clear seasonal and trophic pattern throughout the whole water system,which revealed that temperature and eutrophication may play crucial roles in microbial distribution pattern.

Neural Network Modeling and System Simulating for the Dynamic Process of Varied Gap Pulsed GTAW with Wire Filler

As the base of the research work on the weld shape control during pulsed gas tungsten arc welding (GTAW) with wire filler, this paper addressed the modeling of the dynamic welding process. Topside length Lt, maximum width Wt and half-length ratio Rh1 were selected to depict topside weld pool shape, and were measured on-line by vision sensing. A dynamic neural network model was constructed to predict the usually unmeasured backside width and topside height of the weld through topside shape parameters and welding parameters. The inputs of the model were the welding parameters (peak current, pulse duty ratio, welding speed, filler rate), the joint gap, the topside pool shape parameters (Lt, Wt, and Rhl), and their history values at two former pulse, a total of 24 numbers. The validating experiment results proved that the artificial neural network (ANN) model had high precision and could be used in process control. At last, with the developed dynamic model, steady and dynamic behavior was analyzed by simulation experiments, which discovered the variation rules of weld pool shape parameters under different welding parameters, and further knew well the characteristic of the welding process.

Various models of atrial fibrillation induced by acetylcholine and its application in the field of traditional Chinese medicine

房颤是一种严重危害社会公共健康的疾病,增加了发病率和死亡率,带来了巨大的经济负担.发病率包括增加了心血管结局事件比如心力衰竭和中风,严重影响了病人的生活质量、功能状态和认知.我们期待建立一种接近临床病理状态下的房颤模型来探索房颤的发病机制.乙酰胆碱作为迷走神经的递质,已建立起众多房颤模型,我们通过探讨目前已建立的乙酰胆碱房颤模型,寻求一种更接近生理状态的模型,并对其潜在机制进行讨论以观察药物对此机制的影响.

Feature-based Design of Welded Structure for Robotic Arc Welding Off-line Programming

Feature modeler of welded structure provides both 3D-geographical and non-geographical features for the off-line programming of arc welded robot. Welded structure is regarded as an assembly, the design of welded structure consists of three aspects f plane, joint, and groove design. Each aspect corresponds to a category of features. The plane features are defined by interactive feature definition. A method analogous to the "mating feature" is introduced to represent the joint features. Based on AutoCAD 2000, a B-rep solid modeler, a prototype system is implemented.

Gleaning insights from German energy transition and large-scale underground energy storage for China’s carbon neutrality

The global energy transition is a widespread phenomenon that requires international exchange of experiences and mutual learning.Germany’s success in its first phase of energy transition can be attributed to its adoption of smart energy technology and implementation of electricity futures and spot marketization,which enabled the achievement of multiple energy spatial–temporal complementarities and overall grid balance through energy conversion and reconversion technologies.While China can draw from Germany’s experience to inform its own energy transition efforts,its 11-fold higher annual electricity consumption requires a distinct approach.We recommend a clean energy system based on smart sector coupling(ENSYSCO)as a suitable pathway for achieving sustainable energy in China,given that renewable energy is expected to guarantee 85%of China’s energy production by 2060,requiring significant future electricity storage capacity.Nonetheless,renewable energy storage remains a significant challenge.We propose four large-scale underground energy storage methods based on ENSYSCO to address this challenge,while considering China’s national conditions.These proposals have culminated in pilot projects for large-scale underground energy storage in China,which we believe is a necessary choice for achieving carbon neutrality in China and enabling efficient and safe grid integration of renewable energy within the framework of ENSYSCO.

自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效

目的:探讨通过深度学习的方法来全自动定量评估术前活检标本的肿瘤-间质比(tumor-stroma ratio,TSR)是否可以预测胃癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效。方法:选取2013年3月至2020年3月在云南省肿瘤医院接受NAC治疗的胃癌患者的术前活检切片148张和手术切除切片43张。构建肿瘤区域分割模型和上皮-间质分割模型,使用手术切除切片训练和评估模型,在活检切片上预测,取二者预测结果的交集,根据TSR的定义得到TSR值。根据术后病理学肿瘤退缩分级(tumor regression grade,TRG)将所有患者分为反应良好者(TRG 0~1)和反应不良者(TRG 2~3)。采用单因素和多因素回归分析TSR与胃癌新辅助化疗疗效的相关性。结果:肿瘤组织分割模型的IOU(intersection over union)为0.94,上皮-间质分割模型的IOU为0.88。以44.93%和70.22%作为TSR的临界值,将患者分为低、中、高间质比组,三组之间反应良好者比例具有显著性差异(P<0.05)。多因素分析显示,TSR是治疗前对胃癌NAC反应的独立预测因子(OR=0.10,95%CI:0.03~0.32)。使用常规临床信息预测治疗响应的基础上,加入TSR三分类等级作为治疗响应的预测变量时,曲线下面积(area under curve,AUC)可从0.71提升至0.85。结论:该模型能够在病理切片上自动分割肿瘤区域、上皮区域和间质区域,并能够自动、准确的计算出TSR,同时发现基于此方法自动计算的TSR可以预测NAC疗效。

International experience of carbon neutrality and prospects of key technologies:Lessons for China

Carbon neutrality(or climate neutrality)has been a global consensus,and international experience exchange is essential.Given the differences in the degree of social development,resource endowment and technological level,each country should build a carbon-neutral plan based on its national conditions.Compared with other major developed countries(e.g.,Germany,the United States and Japan),China's carbon neutrality has much bigger challenges,including a heavy and time-pressured carbon reduction task and the current energy structure that is over-dependent on fossil fuels.Here we provide a comprehensive review of the status and prospects of the key technologies for low-carbon,near-zero carbon,and negative carbon emissions.Technological innovations associated with coal,oil-gas and hydrogen industries and their future potential in reducing carbon emissions are particularly explained and assessed.Based on integrated analysis of international experience from the world's major developed countries,in-depth knowledge of the current and future technologies,and China's energy and ecological resources potential,five lessons for the implementation of China's carbon neutrality are proposed:(1)transformation of energy production pattern from a coal-dominated pattern to a diversified renewable energy pattern;(2)renewable power-to-X and large-scale underground energy storage;(3)integration of green hydrogen production,storage,transport and utilization;(4)construction of clean energy systems based on smart sector coupling(ENSYSCO);(5)improvement of ecosystem carbon sinks both in nationwide forest land and potential desert in Northwest China.This paper provides an international perspective for a better understanding of the challenges and opportunities of carbon neutrality in China,and can serve as a theoretical foundation for medium-long term carbon neutral policy formulation.

Paneth cells in farm animals:current status and future direction

A healthy intestine plays an important role in the growth and development of farm animals.In small intestine,Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells(ISCs).Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders,little is known about Paneth cells in farm animals.Most farm animals possess Paneth cells in their small intestine,as identified by various staining methods,and Paneth cells of various livestock species exhibit noticeable differences in cell shape,granule number,and intestinal distribution.Paneth cells in farm animals and their antimicrobial peptides(AMPs)are susceptible to multiple factors such as dietary nutrients and intestinal infection.Thus,the comprehensive understanding of Paneth cells in different livestock species will contribute to the improvement of intestinal health.This review first summarizes the current status of Paneth cells in pig,cattle,sheep,horse,chicken and rabbit,and points out future directions for the investigation of Paneth cells in the reviewed animals.

Numerical simulations of supercritical carbon dioxide fracturing:A review

As an emerging waterless fracturing technology,supercritical carbon dioxide(SC-CO_(2))fracturing can reduce reservoir damage and dependence on water resources,and can also promote the reservoir stimulation and geological storage of carbon dioxide(CO_(2)).It is vital to figure out the laws in SC-CO_(2)fracturing for the large-scale field implementation of this technology.This paper reviews the numerical simulations of wellbore flow and heat transfer,fracture initiation and propagation,and proppant transport in SC-CO_(2)fracturing,including the numerical approaches and the obtained findings.It shows that the variations of wellbore temperature and pressure are complex and strongly transient.The wellhead pressure can be reduced by tubing and annulus co-injection or adding drag reducers into the fracturing fluid.Increasing the temperature of CO_(2)with wellhead heating can promote CO_(2)to reach the well bottom in the supercritical state.Compared with hydraulic fracturing,SC-CO_(2)fracturing has a lower fracture initiation pressure and can form a more complex fracture network,but the fracture width is narrower.The technology of SC-CO_(2)fracturing followed by thickened SC-CO_(2)fracturing,which combines with high injection rates and ultra-light proppants,can improve the placement effect of proppants while improving the complexity and width of fractures.The follow-up research is required to get a deeper insight into the SC-CO_(2)fracturing mechanisms and develop cost-effective drag reducers,thickeners,and ultra-light proppants.This paper can guide further research and promote the field application of SC-CO_(2)fracturing technology.