Real time monitoring of generation and decomposition of degradation products in lithium oxygen batteries during discharge/charge cycles by an online cold trap pre-concentrator-gas chromatography/mass spectroscopy system

Degradation products of lithium oxygen batteries with a tetraethylene glycol dimethyl ether (TEGDME) electrolyte solution during discharge/charge cycles were monitored by an online cold trap pre-concentrator-gas chromatography/mass spectroscopy system in real time. A total of 37 peaks were detected and 27 of them were assigned to specific molecules. Degradation compounds were generated and decomposed in very complex manners during discharge/charge cycles. Most molecules were generated during charge as a result of the degradation of TEGDME by active oxygen species and/or electrochemical oxidation. These molecules generated during charge were decomposed during discharge by active oxygen species.

Most degradation compounds of TEGDME in lithium oxygen batteries were generated during charge and molecules generated during charge were decomposed during discharge.     

Chitosan-vancomycin hydrogel incorporated bone repair scaffold based on staggered orthogonal structure: a viable dually controlled drug delivery system

In clinical practice, challenges remain in the treatment of large infected bone defects. Bone tissue engineering scaffolds with good mechanical properties and antibiotic-controlled release are powerful strategies for infection treatment. In this study, we prepared polylactic acid (PLA)/nano-hydroxyapatite (nHA) scaffolds with vertical orthogonal and staggered orthogonal structures by applying 3D printing technology. In addition, vancomycin (Van)-based chitosan (CS) hydrogel (Gel@Van) was loaded on the scaffold (PLA/nHA/CS-Van) to form a local antibiotic release system. The microstructure of the composite scaffold had high porosity with interconnected three-dimensional networks. The mechanical properties of the PLA/nHA/CS-Van composite scaffold were enhanced by the addition of CS-Van. The results of the water contact angle analysis showed that the hydrophilicity of the drug-loaded scaffold improved. In addition, the composite scaffold could produce sustained release in vitro for more than 8 weeks without adverse effects on the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1), which confirmed its good biocompatibility. During the in vitro antimicrobial study, the composite scaffold effectively inhibited the growth of Staphylococcus aureus (S. aureus). Therefore, our results suggest that the PLA/nHA/CS-Van composite scaffold is a promising strategy for treating infected bone defects.

The schematic diagram of preparing the composite scaffolds.     

大鼠减体积肝移植术后移植肝脏应激蛋白的差异表达研究

目的  探讨大鼠减体积肝移植术后肝脏应激蛋白的差异表达情况。 方法  分别将改良大鼠减体积肝移植模型术后1、3、7 d的肝脏组织标本的双向电泳图谱与供体和受体原肝脏组织的双向电泳图谱进行比较, 以变化倍数大于10倍或小于1/10为标准选择差异蛋白点, 再利用质谱技术及数据库对差异表达的蛋白质点进行分析和鉴定。 结果  共发现了72个差异表达的蛋白质点, 通过质谱分析和一系列的鉴定, 最终发现有32种功能明确的蛋白, 其中热休克蛋白-8与肥厚激动剂反应蛋白在减体积移植术后肝脏表达差异较大, 占所有差异蛋白质点的7%(5/72)。 结论  在大鼠减体积肝移植术后移植肝脏中发现参与肝脏应激反应的蛋白质, 为下一步研究这些蛋白与肝移植术后肝脏缺血-再灌注损伤的关系提供了前期研究数据。     

宁夏枸杞对代谢综合征患者TNF-α、NF-κB和iNOS水平的影响

目的探讨枸杞干预对代谢综合征（metabolic syndrome,MS）患者血清肿瘤坏死因子α（tumor necrosis factor,TNF-α）、核因子-κB（nuclear factor-κB,NF-κB）和诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）水平的影响。方法在横断面研究的基础上,采用病例-对照的方法,选取MS组及健康对照组各119人,比较两组间各测定指标的差异;采用随机对照的研究方法将MS组119人分为对照组和干预组,随后对干预组实施枸杞干预,运用酶联免疫吸附法（enzyme-linked immunosorbent assay,ELISA）测定两组干预0 d、干预30 d、干预45 d和干预75 d 4个时间段人群血清TNF-α、NF-κB和iNOS含量,观察枸杞的干预效果。结果代谢综合征患者血清中TNF-α、NF-κB和iNOS含量明显高于正常人（均有P<0.05）;干预前后两组人群的TNF-α、NF-κB和iNOS变化有统计学差异（均有P<0.05）。结论枸杞可以抑制代谢综合征患者TNF-α、NF...     

河北省部分农村地区居民糖尿病筛查知识、态度、行为现状及其影响因素

目的了解农村居民糖尿病筛查知识、态度、行为现状及其影响因素,为制订干预措施提供依据。方法采用多阶段整群随机抽样方法,抽取河北省18岁以上农村常住居民共1 041人进行问卷调查。结果 1 027例完成调查,其中男性401人,女性626人。农村居民对糖尿病慢性并发症的知晓率不足45%,对糖尿病筛查高危人群的知晓率为36.3%~76.4%。40岁以上居民3年内实际检测血糖比例为36.1%;46.2%的40岁以上居民从未检测血糖。51.7%的居民能够接受医生建议检测血糖,非常愿意了解糖尿病筛查相关知识的占58.1%,最好的途径是广播电视和医护人员宣讲。结论农村居民对糖尿病危害及糖尿病筛查高危人群的正确认知水平低,40岁以上居民主动检测血糖比例低,需要公众媒体、医护人员加强糖尿病筛查的教育;医护人员应充分利用患者就医机会,对糖尿病高危人群进行糖尿病筛查。     

影响人胰岛存活的关键基因及靶向保护方法探讨

目的  探讨影响人胰岛存活的关键基因及靶向保护方法。方法  采用生物信息学方法,在基因表达综合（GEO）数据库中经过筛选比对,选择基因表达谱（GSE53454）。使用GEO2R工具筛选出24、48、72 h 3个时间段暴露于白细胞介素（IL）-1β和干扰素（IFN）-γ的人胰岛处理组（暴露组）和非暴露组之间的差异表达基因（DEG）。使用DAVID进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。通过STRING和Cytoscape应用构建蛋白质-蛋白质相互作用（PPI）网络。结果  共鉴定出69个上调的DEG和2个下调的DEG。GO分析结果显示,在生物过程中,DEG在对病毒的防御反应、炎症反应等方面富集;细胞成分中,DEG在细胞外隙、质膜外侧、细胞外区域显著富集;分子功能中,DEG在趋化因子活性、细胞因子活性方面显著富集。KEGG分析结果显示,DEG主要在细胞因子-细胞因子受体相互作用、病毒蛋白与细胞因子和细胞因子受体的相互作用等信号通路中富集。STRING分析结果选出了10个连接度较高的核心基因（STAT1、CXCL10、IRF1、IL6、CXCL9、CCL5、CXCL11、ISG15、CD274、IFIT3）,均在暴露于IL-1β和IFN-γ的人胰岛中显著上调。KEGG再富集发现6个基因（STAT1、CXCL10、CXCL9、CXCL11、CCL5、IL6）,主要在Toll样受体信号通路中显著富集。结论  STAT1、CXCL10、CXCL9、CXCL11、CCL5、IL6为影响人胰岛存活的关键基因,主要在Toll样受体信号通路中富集,是胰岛保护的重要靶点。     

Association of vitamin D status with all‐cause mortality and outcomes among Chinese individuals with diabetic foot ulcers

Aims/IntroductionThe aim of this study was to examine the correlation between serum vitamin D concentrations and prognosis among Chinese individuals with diabetic foot ulcers (DFUs).Materials and MethodsWe retrospectively recruited 488 adults with DFUs in West China Hospital from 1 January 2012 to 31 December 2019. After telephone follow up, 275 patients were finally included. We compared serum vitamin D concentrations among DFUs patients with different prognostic status, and examined the association of vitamin D status with prognostic variables by Kaplan–Meier analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for all‐cause mortality.ResultsThe median concentration of serum vitamin D of patients with DFUs was 37.78 nmol/L (interquartile range 27.91–50.66 nmol/L), with 31.6% having vitamin D deficiency (<30 nmol/L) and 42.2% having insufficient vitamin D (<50 nmol/L). During a median follow‐up period of 52 months, 65 patients died, with an all‐cause mortality of 23.64%. Vitamin D deficiency was independently linked to increased all‐cause mortality after multivariable adjustments (hazard ratio 0.565, 95% confidence interval 0.338–0.946, P = 0.030). There were no significant differences between vitamin D concentrations and other outcomes of DFUs. Patients who suffered amputations had a tendency of lower vitamin D concentrations (34.00 [interquartile range 26.90–41.81] vs 40.21 [interquartile range 29.60–53.96] nmol/L, P = 0.053).ConclusionsVitamin D deficiency was significantly associated with increased all‐cause mortality in Chinese individuals with DFUs. Vitamin D supplementation might be a potential therapy for DFUs to prevent premature death and improve outcomes.     

Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant,New York,New York,USA

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25–December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.     

De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases

PurposeThe purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs).MethodsTo determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist. Panel-based targeted exome sequencing was performed on DNA extracted from blood samples, containing coding regions of 792 IED-causative genes and their flanking exons. All participants underwent genetic testing.ResultsAll proband-parent trios were divided into 22 subgroups, the overall diagnostic yield was 48.67% (605/1243), ranging from 4% to 94.44% for each of the subgroups. A total of 108 IED-causative genes were identified, with the top 24 genes explaining 67% of the 605 genetically solved trios. The genetic etiology of 6.76% (84/1243) of the trio was attributed to disease-causative DNMs, and the top 3 subgroups with the highest incidence of DNM were aniridia (n = 40%), Marfan syndrome/ectopia lentis (n = 38.78%), and retinoblastoma (n = 37.04%). The top 10 genes have a diagnostic yield of DNM greater than 3.5% in their subgroups, including PAX6 (40.00%), FBN1 (38.78%), RB1 (37.04%), CRX (10.34%), CHM (9.09%), WFS1 (8.00%), RP1L1 (5.88%), RS1 (5.26%), PCDH15 (4.00%), and ABCA4 (3.51%). Additionally, the incidence of DNM in offspring showed a trend of correlation with paternal age at reproduction, but not statistically significant with paternal (P = 0.154) and maternal (P = 0.959) age at reproduction.ConclusionsTrios-based genetic analysis has high accuracy and validity. Our study helps to quantify the burden of the full spectrum IED caused by each gene, offers novel potential for elucidating etiology, and plays a crucial role in genetic counseling and patient management.     

Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling

Understanding the regulatory mechanisms of PD-L1 expression in tumors provides key clues for improving immune checkpoint blockade efficacy or developing novel oncoimmunotherapy. Here, we showed that the FDA-approved sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin dramatically suppressed PD-L1 expression and enhanced T cell–mediated cytotoxicity. Mechanistic study revealed that SGLT2 colocalized with PD-L1 at the plasma membrane and recycling endosomes and thereby prevented PD-L1 from proteasome-mediated degradation. Canagliflozin disturbed the physical interaction between SGLT2 and PD-L1 and subsequently allowed the recognition of PD-L1 by Cullin3^SPOP E3 ligase, which triggered the ubiquitination and proteasome-mediated degradation of PD-L1. In mouse models and humanized immune-transformation models, either canagliflozin treatment or SGLT2 silencing significantly reduced PD-L1 expression and limited tumor progression — to a level equal to the PD-1 mAb — which was correlated with an increase in the activity of antitumor cytotoxic T cells. Notably, prolonged progression-free survival and overall survival curves were observed in the group of PD-1 mAb–treated patients with non–small cell lung cancer with high expression of SGLT2. Therefore, our study identifies a regulator of cell surface PD-L1, provides a ready-to-use small-molecule drug for PD-L1 degradation, and highlights a potential therapeutic target to overcome immune evasion by tumor cells.