The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression.     

Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study

ObjectivesThe primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy.MethodsA prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated.ResultsEighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.ConclusionSpent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.     

Synergistic Engineering of Defects and Architecture in Binary Metal Chalcogenide toward Fast and Reliable Lithium–Sulfur Batteries

Lithium–sulfur (Li–S) batteries have great promise to support the next‐generation energy storage if their sluggish redox kinetics and polysulfide shuttling can be addressed. The rational design of sulfur electrodes plays key roles in tacking these problems and achieving high‐efficiency sulfur electrochemistry. Herein, a synergetic defect and architecture engineering strategy to design highly disordered spinel Ni–Co oxide double‐shelled microspheres (NCO‐HS), which consist of defective spinel NiCo₂O_4–x (x = 0.9 if all nickel is Ni²⁺ and cobalt is Co^2.13+), as the multifunctional sulfur host material is reported. The in situ constructed cation and anion defects endow the NCO‐HS with significantly enhanced electronic conductivity and superior polysulfide adsorbability. Meanwhile, the delicate nanoconstruction offers abundant active interfaces and reduced ion diffusion pathways for efficient Li–S chemistry. Attributed to these synergistic features, the sulfur composite electrode achieves excellent rate performance up to 5 C, remarkable cycling stability over 800 cycles and good areal capacity of 6.3 mAh cm^?2 under high sulfur loading. This proposed strategy based on synergy engineering could also inform material engineering in related energy storage and conversion fields.     

In situ proteolysis for protein crystallization and structure determination

We tested the general applicability of in situ proteolysis to form protein crystals suitable for structure determination by adding a protease (chymotrypsin or trypsin) digestion step to crystallization trials of 55 bacterial and 14 human proteins that had proven recalcitrant to our best efforts at crystallization or structure determination. This is a work in progress; so far we determined structures of 9 bacterial proteins and the human aminoimidazole ribonucleotide synthetase (AIRS) domain.     

MicroRNA-194 overexpression protects against hypoxia/reperfusion-induced HK-2 cell injury through direct targeting Rheb

Renal ischemia-reperfusion injury, a major cause of renal failure, always leads to acute kidney injury and kidney fibrosis. MicroRNAs (miRs) have been reported to be associated with renal ischemia-reperfusion injury. miR-194 was downregulated following renal ischemia-reperfusion injury; however, the function and mechanism of miR-194 in renal ischemia-reperfusion injury have not yet been fully understood. In the present study, we constructed renal ischemia-reperfusion injury model in vitro through treatment of human kidney proximal tubular epithelial cells HK-2 by hypoxia/reperfusion (H/R). We observed that miR-194 was decreased in H/R-induced HK-2 cells. miR-194 mimic increased H/R-induced HK-2 cell survival, whereas miR-194 inhibitor further strengthened H/R- inhibited HK-2 cell survival. Also, we observed that miR-194 overexpression suppressed oxidative stress markers, including malondialdehyde, glutathione, and secretion of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α; however, miR-194 inhibitor showed the reverse effects. Results from dual-luciferase analysis confirmed that Ras homology enriched in brain (Rheb) was a direct target of miR-194. Finally, we corroborated that miR-194 affected cell growth, oxidative stress, and inflammation through targeting Rheb in H/R-induced HK-2 cells. In conclusion, our results suggested that miR-194 protect against H/R-induced injury in HK-2 cells through direct targeting Rheb.     

浙江菌类药资源调查及利用研究初报

本文较全面地了浙江菌类药中药资源。其内容包括开展本项目的方法,研究结果。分别对本省自然环境、野生菌类药中药资源的分布进行了重点论述,简要介绍了菌类药调查结果,重点研究种类,并对本省的菌类药现状和展望作了评述;文后列有本项目研究中公开发表的文献,使本方基本能反映本专题的研究内容。     

鳖甲煎丸通过LncRNA-mRNA顺式调控抑制肝癌细胞

为了研究鳖甲煎丸抑制肝癌细胞过程中lncRNA表达谱的变化及lncRNA-mRNA顺式调控在其中的机制,本研究通过CCK8方法检测鳖甲煎丸作用于SMMC-7721细胞后的增殖活性变化,经全细胞转录组学分析lncRNA的表达和特征后构建LncRNA-mRNA顺式调控网络.结果表明鳖甲煎丸含药血清作用肝癌细胞株后其增殖活性受到抑制.全细胞转录组学分析找到差异表达的172个LncRNA.构建lncRNA-mRNA顺式调控网络,对调控基因进行生存分析发现,SCRN1、PLEKHA1、HNRNPM、TMEM107、ETNK1、ISG20L2的表达与肝细胞癌患者生存率显著负相关(P＜0.05).因此得出结论,LncRNA参与鳖甲煎丸抑制肝癌细胞增殖的过程,LncRNA-mRNA顺式调控是其分子机制之一.