托珠单抗治疗COVID-19导致继发感染风险的Meta分析

目的通过Meta分析评估托珠单抗(tocilizumab,TCZ)治疗新型冠状病毒感染(corona virus disease2019,COVID-19)导致的继发感染风险,为托珠单抗在COVID-19患者中应用的安全性提供循证依据。方法在The Cochrane Library、PubMed、Web of Science、中国知网、中国生物医学文献数据库以及万方数据库中检索了2019年12月19日至2022年12月30日期间使用托珠单抗治疗COVID-19患者的相关研究,筛选并提取文献中发生继发感染的数据,利用RevMan 5.4.1进行Meta分析。结果共筛选了1691篇参考文献,纳入18项研究,涉及3933名患者。托珠单抗+标准治疗组继发感染发生率为19.14%(331/1729),标准治疗组继发感染发生率为12.11%(267/2204)。Meta分析结果显示,托珠单抗+标准治疗组继发感染发生率高于标准治疗组[RR=1.35,95%CI(1.05,1.74),P=0.02]。亚组分析显示,使用不同剂量的托珠单抗发生继发感染的风险不同。托珠单抗给药剂量为400~800 mg/d的亚组继发感染发生率明显高于标准治疗组,差异具有统计学意义[RR=1.48,95%CI(1.19,1.84),P=0.0004];≤400 mg/d继发感染发生率也显著高于标准治疗组,差异具有统计学意义[RR=1.87,95%CI(1.28,2.72),P=0.001];托珠单抗给药剂量为6~8 mg/kg亚组与标准治疗组比较差异无统计学意义。结论与标准治疗相比,托珠单抗可能增加COVID-19患者发生继发感染的风险,临床给药前应仔细评估使用托珠单抗治疗的利益和风险。但是,目前仍需要更多大样本、高质量的研究来进一步评估。

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer

Long non-coding RNAs(lncRNAs)play a significant role in maintaining tissue morphology and functions,and their precise regulatory effectiveness is closely related to expression patterns.However,the spatial expression patterns of lncRNAs in humans are poorly characterized.Here,we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states.The lncRNA transcriptomes exhibited high consistency within the same tissues across resources,and even higher complexity in specialized tissues.Tissue-elevated(TE)lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis.We detected 1 to 4684 robust TE lncRNAs across tissues;the highest number was in testis tissue,followed by brain tissue.Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways.Moreover,we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues;TE lncRNAs also tended to be associated with cancer,and exhibited differential expression or were correlated with patient survival.In summary,spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.

Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis

Thiostrepton(TST)is a natural antibiotic with pleiotropic properties.This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets.The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium(DSS)-induced colitis model and a T-cell transfer colitis model.The therapeutic targets of TST were investigated by cytokine profiling,immunophenotyping and biochemical approaches.The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation(FMT).Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing.Here,we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models.Specifically,TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A byγδT cells,type 3 innate lymphoid cells(ILC3s)and Th17 cells in mice with DSS-induced colitis.Similarly,TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4^(+)T cells into Th17 cells in vitro.Mechanistically,TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt.Moreover,TST also reversed dysbiosis to control colonic inflammation.Taken together,these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis,suggesting that TST is a promising candidate drug for the treatment of IBD.

Effects of Potassium-Solubilizing Bacteria on Growth, Antioxidant Activity and Expression of Related Genes in Fritillaria taipaiensis P. Y. Li

This study aimed to examine the effects of inoculating Fritillaria taipaiensis P.Y.Li leaves with different strains ofpotassium-solubilizing bacteria (KSB), or combinations thereof, focusing on aspects of photosynthesis and physiologicaland biochemical characteristics. At present, some studies have only studied the rhizosphere microbialcommunity characteristics of F. taipaiensis and have not discussed the effects of different microbial species on thegrowth promotion of F. taipaiensis. This paper will start from the perspective of potassium-solubilizing bacteria toconduct an in-depth study. Seed cultivation commenced at the base with three different KSBs in early October2022. The growth of F. taipaiensis leaves was observed after different treatments. Both single-plant and compoundinoculations were executed. A total of eight treatment groups were established, with aseptic fertilizer and sterilizedsoil functioning as the control group. The results reveal that intercellular CO_(2) concentration (Ci), stomatal conductance(Gs), and transpiration rate (Tr) were at their apex in the S7 group. Most treatment groups exhibited anincrease in leaf area, photosynthetic pigment content, soluble sugar, soluble protein, Superoxide Dismutase(SOD), Peroxidase (POD), Catalase (CAT) activities, and proline content. The expression levels of POD, SOD,and CAT genes were evaluated, following inoculation with different KSB. The highest was the S7 group. Theinoculation with various KSB, or combinations thereof, appears to bolster the growth and development of F. taipaiensis.The composite inoculation group S7, comprising Bacillus cereus, Burkholderia cepacia, and Bacillus subtilis,manifested the most favorable impact on the diverse indices of F. taipaiensis, thereby furnishing valuableinsights for the selection of bacterial fertilizer in the artificial cultivation of F. taipaiensis.

Pneumoconiosis: current status and future prospects

Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust,usually as the result of certain occupations.The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis,which can eventually lead to death caused by respiratory and/or heart failure.Pneumoconiosis is widespread globally,seriously threatening global public health.Its high incidence and mortality lie in improper occupational protection,and in the lack of early diagnostic methods and effective treatments.This article reviews the epidemiology,safeguard procedures,diagnosis,and treatment of pneumoconiosis,and summarizes recent research advances and future research prospects.

Distributed reinforcement learning to coordinate current sharing and voltage restoration for islanded DC microgrid

A novel distributed reinforcement learning(DRL)strategy is proposed in this study to coordinate current sharing and voltage restoration in an islanded DC microgrid.Firstly, a reward function considering both equal proportional current sharing and cooperative voltage restoration is defined for each local agent. The global reward of the whole DC microgrid which is the sum of the local rewards is regarged as the optimization objective for DRL. Secondly,by using the distributed consensus method, the predefined pinning consensus value that will maximize the global reward is obtained. An adaptive updating method is proposed to ensure stability of the above pinning consensus method under uncertain communication. Finally, the proposed DRL is implemented along with the synchronization seeking process of the pinning reward, to maximize the global reward and achieve an optimal solution for a DC microgrid. Simulation studies with a typical DC microgrid demonstrate that the proposed DRL is computationally efficient and able toprovide an optimal solution even when the communication topology changes.

边界理论在组织行为学研究中的应用

技术的发展正在模糊工作和非工作领域之间的界限,人们日常生活中的角色转换变得愈发频繁。边界理论对于探讨个体的微观角色转换具有重要意义。通过文献梳理,本文回顾并归纳了边界理论相关的核心概念和命题,总结了边界理论在组织行为学研究中的主要应用领域:即工作-家庭转换、工作-“第三地”转换和工作领域内转换,并讨论了其在实际应用中的两个重要启示:角色过度分割和角色过度整合这两种边界管理策略各自存在的潜在危害。最后提出未来可以深入开展工作-家庭微边界研究、线上边界管理研究、工作-社交转换研究、中国情境下的边界理论研究以及长期-短期导向文化价值观下的个体角色边界管理研究,来拓展边界理论在组织行为学中的应用。

Vegetation dynamics and its response to driving factors in typical karst regions,Guizhou Province,China

Analyzing the vegetation dynamics and its response to driving factors provides a vital reference for understanding regional ecological processes and ecosystem services.However,this issue has been poorly understood in karst areas.Taking Guizhou Province as a case study,based on the Normalized-Difference Vegetation Index of the Global Inventory Modeling and Mapping Studies and on meteorological data sets during 1982-2015,we evaluated vegetation dynamics and its response to climatic factors and human activities.We used several methods:the Mann-Kendall test,rescaled range analysis,partial correlation analysis,and residual analysis.The results are as follows:1)the mean annual Normalized-Difference Vegetation Index was 0.46 and exhibited a significant increasing trend with a variation rate of 0.01/10a during 1982-2015 in Guizhou Province.The vegetation cover showed was spatially heterogeneous:High vegetation cover was distributed mainly in the center and western margin of the study area,while the other parts of the study area mainly distributed with low vegetation cover,although the vegetation cover was higher in the nonkarst areas than in the karst areas;2)in general,the climate was getting warmer and drier in Guizhou Province during 1982-2015.Vegetation cover was positively correlated with temperature and negatively correlated with precipitation.Compared to precipitation,temperature was the dominant climatic factor impacting vegetation dynamics;3)'large-scale ecological restoration projects have obviously increased vegetation cover in Guizhou Province in recent years.The contribution of human activities to vegetation changes was 76%,while the contribution of climatic factors was 24%.In summary,compared to natural forces such as climatic factors and geographic parameters,human activities were the main factor driving the vegetation dynamics in Guizhou Province.

Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis

The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer.However,cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues.Here,we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples,including blood,normal tissue,para-cancer,polyp,and colorectal cancer.

Comparative metabolomics provides novel insights into the basis of petiole color differences in celery(Apium graveolens L.)

Plant metabolites are important for plant development and human health.Plants of celery(Apium graveolens L.)with different-colored petioles have been formed in the course of long-term evolution.However,the composition,content distribution,and mechanisms of accumulation of metabolites in different-colored petioles remain elusive.Using ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS),1159 metabolites,including 100 lipids,72 organic acids and derivatives,83 phenylpropanoids and polyketides,and several alkaloids and terpenoids,were quantified in four celery cultivars,each with a different petiole color.There were significant differences in the types and contents of metabolites in celery with different-colored petioles,with the most striking difference between green celery and purple celery,followed by white celery and green celery.Annotated analysis of metabolic pathways showed that the metabolites of the different-colored petioles were significantly enriched in biosynthetic pathways such as anthocyanin,flavonoid,and chlorophyll pathways,suggesting that these metabolic pathways may play a key role in determining petiole color in celery.The content of chlorophyll in green celery was significantly higher than that in other celery cultivars,yellow celery was rich in carotenoids,and the content of anthocyanin in purple celery was significantly higher than that in the other celery cultivars.The color of the celery petioles was significantly correlated with the content of related metabolites.Among the four celery cultivars,the metabolites of the anthocyanin biosynthesis pathway were enriched in purple celery.The results of quantitative real-time polymerase chain reaction(q RT-PCR)suggested that the differential expression of the chalcone synthase(CHS)gene in the anthocyanin biosynthesis pathway might affect the biosynthesis of anthocyanin in celery.In addition,HPLC analysis revealed that cyanidin is the main pigment in purple celery.This study explored the differences in the types and contents of metabolites in celery cultivars with different-colored petioles and identified key substances for color formation.The results provide a theoretical basis and technical support for genetic improvement of celery petiole color.