ABSTRACT:Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo . Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture model was used to detect neutrophil migration, neutrophil extracellular traps level, and organ damage. Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of neutrophil extracellular traps, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.

Sepsis currently remains a major contributor to mortality in the intensive care unit (ICU), with 48.9 million cases reported globally and a mortality rate of 22.5% in 2017, accounting for almost 20% of all-cause mortality worldwide. This highlights the urgent need to improve the understanding and treatment of this condition. Sepsis is now recognized as a dysregulation of the host immune response to infection, characterized by an excessive inflammatory response and immune paralysis. This dysregulation leads to secondary infections, multiple organ dysfunction syndrome (MODS), and ultimately death. PD-L1, a co-inhibitory molecule expressed in immune cells, has emerged as a critical factor in sepsis. Numerous studies have found a significant association between the expression of PD-1/PD-L1 and sepsis, with a particular focus on PD-L1 expressed on neutrophils recently. This review explores the role of PD-1/PD-L1 in immunostimulatory and anti-inflammatory pathways, illustrates the intricate link between PD-1/PD-L1 and sepsis, and summarizes current therapeutic approaches against PD-1/PD-L1 in the treatment and prognosis of sepsis in preclinical and clinical studies.

A comprehensive evaluation indicator system is the basis of car sharing systems (CSS) evaluation. The purpose of this study is to introduce the principles and methods of indicator selection for CSS, and to identify indicators for evaluating car sharing systems due to the reason that the importance of indicators can never be overestimated in CSS evaluation. A framework to identify indicators for evaluating CSS is proposed with four steps. First of all, the structure for indicator selection is established with application of AHP method. Secondly, adequacy check and redundancy check are carried out to ensure the structure is adequate and redundant. Thirdly, underlying individual indicators are proposed according to questionnaires. Fourthly, to ensure the necessity, identification, and feasibility of indicators, we conduct N-I-F check. We carry out a case study of CSS evaluation indicators to validate the proposed framework from four dimensions: economic, environmental, systematic, and social. The proposed framework is quantitative and it is helpful in CSS evaluation to identify proper indicators and find out the best CSS option.

The effect of a hydroxyl radical generating system (HRGS), which contained FeCl3, sodium ascorbate, and different concentrations of H2O2, on the physiochemical properties of myofibrillar protein (MP) from squid mantles, has been investigated. The effect of different exposure times to HRGS was also considered. Compared to non-oxidized MP, a significant (p < 0.05) increase in carbonyl content (more than 50% of its original content) and protein solubility, as well as in surface hydrophobicity, was observed in the oxidative MP. With different treatment times, a sharp decrease (p < 0.05) in sulfhydryl content was detected. In addition, hydroxyl radical treatment significantly reduced the MP gel's texture properties, whiteness and water holding capacity, especially at higher concentrations of H2O2. This observation could be attributed to extensive disorderly and less compact structure of MP gels. The results demonstrate the negative effect of HRGS on the structural and functional properties of MP from squid mantles.

We sequenced the complete mitochondrial (mt) genome of the kisslip cuttlefish, Sepia lycidas, made the comparison with the mt genomes of other cuttlefishes, and constructed phylogenetic trees estimating their relationships. The genome was 16,228 bp and contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 long-noncoding regions [both in the control regions (CR)]. The composition and order of genes in S. lycidas were similar to those of most other invertebrates. The overall base composition of S. lycidas is 35.8% T, 14.8% C, 41.3% A, and 8.1% G, with extremely high A+T content (77.1%). Both control regions contain termination-associated sequences and conserved sequence blocks. Maximum likelihood and Bayesian methods were used to build phylogenetic trees based on protein coding mtDNA genes of 37 cuttlefish species. S. lycidas have a close relationship with S. pharaonis, S. aculeata, and S. esculenta. This result confirmed the relationships of S. lycidas as being similar to the traditional taxonomy. This study plays an important role in the investigation of phylogenetic relationships, taxonomic resolution, and phylogeography for Sepiidae species.

心理档案建设是高校心理健康教育工作的重点之一,也是近年来研究的热点.国内学者对这一课题的研究涉及多个方面,但缺乏整合.从心理档案的概念、内容、建档意义、方法、原则、问题和解决方面梳理已有研究,总结出有效结论,可进一步促进这方面工作开展.

2015年，我国发布了“十二五”规划，其中对中国休闲农业的发展做出了重要部署，各级地方政府也纷纷出台政策扶持休闲农业的发展，特别是在资金、税收等方面出台相当的优惠政策。但是在这样的大好环境下，我国的休闲农业的发展还存在些许的问题。基于此，将对这些问题进行探讨，并提出有助于我国休闲农业发展的对策。

音乐鉴赏课程旨在提高高职院校学生的审美能力,对学生进行审美教育,是素质教育中必不可少的一个重要部分.同时,也是提高高职院校学生综合素质,促进学生健康、和谐、全面发展的有效途径.

Objective To study the association between COMT polymorphism and the hyperprolactinemia of Risperidone in female schizophrenia patients. Methods A total of 62 Chinese Han schizophrenic patients that examined by trained psychiatrists using the Chinese Classification of Mental Disorders (CCMD-3) criteria were recruited in this retrospective study. A microparticle enzyme immunoassay was used for measuring the serum prolactin levels at the beginning of the study and the time of receiving risperidone treatment on the 8th week. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for COMT genotypes determined. Results There was no significant association between the COMT Val158Met polymorphism and demographic characteristics of the patients in this study. The prolactin level increases significantly after risperidone treatment (P<0.001). However, the Val/Val genotype of the patients showed the lowest prolactin level in all subjects (P=0.003). Conclusion The COMT Val158/108Met polymorphism may be a potential biomarker with predictive value in Risperidone-induced hyperprolactinemia in female schizophrenia patients.

环境政策是使企业环境成本内部化从而迫使企业降低污染物排放的重要手段。本文运用动态博弈理论，研究单独的排污税政策和排污税与减排补贴的组合政策对企业污染控制行为的影响机理，并从污染治理效果和社会福利水平两方面对两种政策的减排效应进行比较分析，研究表明：排污税率和减排补贴率均与企业治污量正相关，与社会福利水平的关系均与税率和补贴率的大小有关；政府实施组合政策时企业的治污量和社会福利水平均大于只实行排污税政策时的治污量和社会福利水平，组合政策能激励企业加大治污力度，同时也能带来社会福利的增加。

以单轨吊工字钢为研究对象,利用Workbench软件进行数值模拟和有限元分析,并通过其专业优化模块Design Exploration对单轨吊工字钢横截面参数进行优化设计,仿真分析横截面参数与最大应力和最大变形之间的关系,并依据应力和变形求出工字钢轻量化最优解.优化结果表明:在保证工字钢强度以及刚度的前提下,工字钢的质量最大可降低4.45 kg,约占优化前工字钢质量的13.3％,节约了工字钢的制造成本,提高了材料利用率,为单轨吊工字钢的设计及轻量化提供了理论依据.

Objective To investigate the clinical features of en-bloc kidney transplantation of infant donors into pediatric recipients.Method A retrospective analysis of 4 infant en-bloc kidney transplants in pediatric recipients was performed.Results During the follow-up period of 2 to 14 months,the survival rate of recipients was 100％.Complications included delayed graft function in 1 patient (managed by peritoneal dialysis),urine leak in 1 case (treated by reoperation),and vascular thrombosis in 1.Due to thrombosis,one graft was lost.Of the remaining 3 recipients,all had excellent long-term function.At last follow-up,their serum creatinine levels were 70,102 and 83 μmol/L respectively.Conclusion Favorable outcomes can be obtained from en-bloc transplantation from infant donors.The use of this donor population for pediatric recipients should be encouraged.

Innovation is the basis for survival and sustainable development of enterprises,and financing support has always been considered as an important factor to promote enterprises’innovation. Using FCM clustering method,this paper divided the strategic groups on equipment manufacturing enterprises of China,then compared the difference of financing constrains and profitability between innovation groups and other strategic groups. The results show that only 0.08% of Chinese equipment manufacturing enterprises choose innovation-differentiation strategy,0.43% choose marketing-differentiation strategy,14.17% choose the low cost strategy,while 85.32% enterprises have no obvious strategic orientation;Innovative enterprises have the highest external financing support but the poor profitability. With high R&D investment and high external financing support,but innovative enterprises get low profit,and this should be the important reason for the lack of innovation power of our country’s enterprises.

The former site of Jiangsu Provincial Art Museum was built in 1920s which didn't consider seismic design then and had been used for more than 80 years,so there're seismic risk and inadequacies which don't meet the normal serviceability requirements.Now due to the alteration and protection needs of cultural relics building,a series of methods including reliability inspection,safety assessment and overall seismic calculation and analysis are done to give the proper seismic appraisal and safety evaluation,and then some reasonable reinforcement suggestions and seismic measures are given.

This research is focused on the break vavle, the fluent software is used to analyses and calculate the pressure distribution, velocity distribution, and the pathline distribution, which changes with the smoothness of the elbow for inlet and outlet. The capability of the break valve is determined by the figures above. The research provides theoretics for optimizing the flow field inside break vavle.

Objective: To discuss efficacy of clomipramine combined with quetiapine in treatment of patients with refractory obsessive- compulsive disorder(OCD). Methods: 60 patients with refractory OCD,who had been treated with clomipramine for 12weeks but still not cured,were selected and randomly divided into clomipramine combined with placebo group and clomipramine combined with quetiapine group,and they were treated for 8 weeks. The efficacy was assessed with Yale- Brown obsessive- compulsive scale(Y- BOCS),Hamilton Anxiety Scale(HAMA) and Hamilton Depression Scale(HAMD). Results: 8 weeks after the treatment,the obvious effective rate of clomipramine combined with quetiapine group was higher; and 4 and 8 weeks after the treatment,the scores of Y- BOCS,HAMA and HAMD all significantly decreased compared with those before the treatment(p<0. 05). However,there were no obvious changes in these scores for clomipramine combined with placebo group. Conclusions: It is suggested that clomipramine combined with quetiapine could improve the efficacy in the treatment of refractory OCD.

The Fluent analytic software for fluid is simply introduced, and the simulation of the internal flow field for simple liquid shunt. The pressure, velocity and pathlines are technologically analyzed too,and by changing the shut structure on multiple factors analysis and comparison, then got the best working status of the flow field.

Shortcut BNR scheme(SBNR)can save up to 25% of the oxygen demand for nitrification and 40% of organic donor demand for denitrification.Achieving sustainable partial nitrification to nitrite has been proven difficult in treating low strength nitrogenous wastewater.Above 95% nitrite accumulation ratio was succeed for Aeration duration control operation through 30 day.Process control enhanced the successful accumulation of ammonia oxidizing bacteria(AOB) and washout of nitrite oxidizing bacteria(NOB).Scanning electron microscope observations indicated that the microbial morphology showed small rod-shaped clusters(1μm).

Buildings designed and built during Republican period have complex and diversified structural systems and material properties are different from contemporary ones.The following defects are often detected in these buildings: over-limit service period and afterward random rebuilding cause serious potential safety hazards;buildings don't have aseismic structure and aseismic property is weak due to absence of aseismic consciousness in old design and construction concepts.Bases are provided for reasonable reinforcement of these buildings after careful analysis.

Objective: We combine the reviews about methods of making obsessive-compulsive disorder animal models in recent years, with practical needs of basic researches together, to effect evaluation as to these kind of models, and eventually, to improve basic researches. Method: Literature searches are applied to obtain our Objective. Result: At present the animal models of obsessive-compulsive disorder can be mainly divided into four categories: pharmacological models, behavioral models, surgical models and genetic models. Conclusion: Different methods of modeling lead to different features of the models. Models should be made according to research need.