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Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s) responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV infection. We found that DNA polymerase κ (POLK), a Y-family DNA polymerase with maximum activity in non-dividing cells, substantially contributes to cccDNA formation during de novo HBV infection. Depleting gene expression of POLK in HepG2-NTCP cells by either siRNA knockdown or CRISPR/Cas9 knockout inhibited the conversion of rcDNA into cccDNA, while the diminished cccDNA formation in, and hence the viral infection of, the knockout cells could be effectively rescued by ectopic expression of POLK. These studies revealed that POLK is a crucial host factor required for cccDNA formation during a de novo HBV infection and suggest that POLK may be a potential target for developing antivirals against HBV.

Salmonids can accumulate lipids in their fillets, creating marbled features with alternate red (Muscle Fibers, MF) and white stripes (Myosepta, MS). To investigate the regulation of this important quality trait, diets with low and high lipid levels were fed to the fish and found that high lipid diet significantly elevated muscular lipid deposition in MS but not in MF. Then, a whole-transcriptome analysis was performed and results showed that the mRNA expression of ACSL1 and GADD45A was downregulated by the lncRNAs MSTRG.19477.1 and XR_005039693.1, resulting in consistent lipid contents in the MF from both groups. The lncRNAs MSTRG.21618.1, XR_005034756.1, XR_002473790.2, XR_002472790.2, and MSTRG43906.1 increased lipid deposition in MS30 by upregulating the mRNA expression of ELOVL2, DGAT2, LCAT, etc. In conclusion, the present study revealed that selective muscular lipid deposition and several lncRNAs may play key roles in regulating the marbling features of rainbow trout.

INTRODUCTION: For enterprises, the results of performance evaluation will be affected by the selected input and output factors, so the indicators of the evaluation system should be representative and characteristic, and the evaluation method should be reasonable.OBJECTIVES: According to the characteristics of science and technology industry, this paper establishes the performance evaluation index system, and the evaluation model of the input-output performance for the science and technology enterprises.METHODS: With the evaluation model, this paper empirically analyses the evaluation index data of 30 science and technology enterprises in recent 3 years, and verifies the effectiveness of the selection of management performance evaluation index of science and technology enterprises.RESULTS: Finally, according to the empirical analysis results of the evaluation model.CONCLUSION: This paper puts forward some countermeasures to improve the business performance of science and technology enterprises.

Acute kidney injury (AKI) occurs in half of patients with septic shock, resulting in unacceptably high mortality. However, effective preventive treatments are still lacking. We hypothesized that pretreatment with lipoxin A4 (LXA4), known to promote inflammation resolution, may attenuate septic AKI via blocking crosstalk between inflammation and cellular senescence. In this study, rats developed AKI following cecal ligation and puncture (CLP), as evidenced by a dynamic increase in serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and pathological injury, accompanied by increased levels of inflammation (IL-6, TNF-α, and HMGB1) and tubular cell senescence. While, on the one hand, inhibition of senescence with rapamycin restored renal function and attenuated septic inflammatory response, on the other hand, LXA4 administration inhibited renal inflammation and tubular epithelial cell senescence after CLP. Ultimately, pretreatment with LXA4 significantly restored renal function and increased the survival rate of rats after CLP. Furthermore, LXA4 inhibited NF-κB-mediated inflammatory response and the p53/p21 senescence pathway in vivo and in vitro . However, the effect was reversed by PPAR-γ siRNA and antagonist. These results indicated that LXA4 exerted its renoprotective effects by blocking the crosstalk between inflammation and premature senescence in a PPAR-γ-dependent manner. Our findings also suggested that premature senescence plays a critical role in septic AKI and that inhibition of the crosstalk between inflammation and premature senescence may represent a new and major mechanism through which LXA4 attenuates septic AKI.

The TCP family genes are plant-specific transcription factors and play important roles in plant development. TCPs have been evolutionarily and functionally studied in several plants. Although common wheat ( L.) is a major staple crop worldwide, no systematic analysis of TCPs in this important crop has been conducted. Here, we performed a genome-wide survey in wheat and found 66 TCP genes that belonged to 22 homoeologous groups. We then mapped these genes on wheat chromosomes and found that several TCP genes were duplicated in wheat including the ortholog of the maize . Expression study using both RT-PCR and hybridization assay showed that most wheat TCP genes were expressed throughout development of young spike and immature seed. -acting element survey along promoter regions suggests that subfunctionalization may have occurred for homoeologous genes. Moreover, protein-protein interaction experiments of three TCP proteins showed that they can form either homodimers or heterodimers. Finally, we characterized two mutants from tetraploid wheat. Each of these two mutant lines contained a premature stop codon in the A subgenome homoeolog that was dominantly expressed over the B subgenome homoeolog. We observed that mutation caused increased spike and grain lengths. Together, our analysis of the wheat TCP gene family provides a start point for further functional study of these important transcription factors in wheat.

The kidney function of patients with chronic kidney disease (CKD) is impaired irreversibly. Organ transplantation is the only treatment to restore kidney function in CKD patients. The assessment of new potential therapeutic procedures relies heavily on experimental animal models, but it is limited by its human predictive capacity. In addition, the frequently used two-dimensional in vitro human renal cell models cannot replicate all the features of the in vivo situation. In this study, we developed a three-dimensional (3D) in vitro human renal organoid model from whole kidney cells as a promising drug screening tool. At present, the renal tissue generated from human pluripotent stem cells (hPSCs) exhibits intrinsic tumorigenicity properties. Here we first developed a 3D renal organoid culture system that originated from adult differentiated cells without gene modification. Renal organoids composed of multiple cell types were created under optimal experimental conditions and evaluated for morphology, viability and erythropoietin production. As a novel screening tool for renal toxicity, 3D organoids were exposed to three widely used drugs: aspirin, penicillin G and cisplatin. The study results showed this 3D renal organoid model can be used as a drug screening tool, a new in vitro 3D human kidney model, and provide hope for potential regenerative therapies for CKD.

Background Postinduction hypotension caused by propofol remains a non-negligible problem for anesthesiologists, and is especially severe in chronic hypertensive patients with long-term vasoconstriction and decreased vascular elasticity. The functional change in gap junctions composed of Cx43 (Cx43-GJs) is reported as the biological basis of synchronized contraction or relaxation of blood vessels. Thus, we investigated the role of Cx43-GJs in propofol-induced dramatic blood pressure fluctuations in chronic hypertensive patients, and their internal mechanisms. Methods Human umbilical artery smooth muscle cells (HUASMCs) were pretreated with long-term angiotensin II (Ang II), with or without propofol, to simulate the contraction and relaxation of normal and hypertensive VSMCs during anesthesia induction. The levels of F-actin polymerization and MLC2 phosphorylation were used as indicators to observe the contraction and relaxation of HUASMCs. Different specific activators, inhibitors and siRNAs were used to explore the role of Cx43-GJs and Ca 2+ as well as the RhoA/ LIMK2/cofilin and RhoA/MLCK signaling pathways in the contraction and relaxation of normal and hypertensive HUASMCs. Results Both F-actin polymerization and MLC2 phosphorylation were significantly enhanced in Ang II-pretreated HUASMCs, along with higher expression of Cx43 protein and stronger function of Cx43-GJs than in normal HUASMCs. However, with propofol administration, similar to Gap26 and Cx43-siRNA, the function of Cx43-GJs in Ang II-pretreated HUASMCs was inhibited compared with that in normal HUASMCs, accompanied by a larger decrease in intracellular Ca 2+ and the RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways. Eventually F-actin polymerization and MLC2 phosphorylation were more dramatically decreased. However, these effects could be reversed by RA with enhanced Cx43-GJ function. Conclusion Long-term exposure to Ang II significantly enhanced the expression of the Cx43 protein and function of Cx43-GJs in HUASMCs, resulting in the accumulation of intracellular Ca 2+ and the activation of its downstream RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways, which maintained HUASMCs in a state of excessive-contraction. With inhibition of Cx43-GJs by propofol in Ang II-pretreated HUASMCs, intracellular Ca 2+ and its downstream signaling pathways were dramatically inhibited, which ultimately excessively relaxed HUASMCs. This is the reason why the blood pressure fluctuation of patients with chronic hypertension was more severe after receiving propofol induction. 9gEgDUsF4_-ddhb1iAhQGK Video Abstract

To avoid recurrent variceal bleeding, transjugular intrahepatic portosystemic shunt (TIPS) in conjunction with variceal embolization is considered to be an effective strategy. However, due to changes in conditions and variations in the patient's state, individuals undergoing TIPS may face challenges and limitations during procedures. The transjugular technique and combined transsplenic portal venous recanalization (PVR) with TIPS were not effective in this case due to a blocked portal vein and a previous splenectomy. With an abdominal incision, we successfully punctured the mesenteric venous system and navigated the occluded segment of the portal vein through the mesenteric approach. TIPS was then performed under balloon guidance. This study aims to explore the management of risks and complications during surgical operations and propose multiple preoperative surgical techniques to improve the success rate of the procedure.

Background Organoids play an important role in basic research, drug screening, and regenerative medicine. Here, we aimed to develop a novel kind of three-dimensional (3D) organoids generated from urine-derived stem cells (USCs) and to explore whether kidney-specific extracellular matrix (kECM) could enable such organoids for renal function in vitro. Methods USCs were isolated from human urine samples and cultured with kECM extraction to generate 3D organoids in vitro. Eight densities from 1000 to 8000 cells per organoids were prepared, and both ATP assay and Live/Dead staining were used to determine the optimal USC density in forming organoids and kECM additive concentration. The morphology and histology of as-made organoids were evaluated by hematoxylin and eosin (H.E.) staining, immunofluorescence staining and whole mount staining. Additionally, RT-qPCR was implemented to detect renal-related gene expression. Drug toxicity test was conducted to evaluate the potential application for drug screening. The renal organoids generated from whole adult kidney cells were used as a positive control in multiple assessments. Results The optimized cell density to generate ideal USC-derived organoids (USC-organoids) was 5000 cells/well, which was set as applying density in the following experiments. Besides, the optimal concentration of kECM was revealed to be 10%. On this condition, Live/Dead staining showed that USC-organoids were well self-organized without significant cell death. Moreover, H.E. staining showed that compact and viable organoids were generated without obvious necrosis inside organoids, which were very close to renal organoids morphologically. Furthermore, specific proximal tubule marker Aquaporin-1 (AQP1), kidney endocrine product erythropoietin (EPO), kidney glomerular markers Podocin and Synaptopodin were detected positively in USC-organoids with kECM. Nephrotoxicity testing showed that aspirin, penicillin G, and cisplatin could exert drug-induced toxicity on USC-organoids with kECM. Conclusions USC-organoids could be developed from USCs via an optimal procedure. Combining culture with kECM, USC-organoid properties including morphology, histology, and specific gene expression were identified to be similar with real renal organoids. Additionally, USC-organoids posed kECM in vitro showed the potential to be a drug screening tool which might take the place of renal organoids to some extent in the future.

Objective This review aimed to confirm the association between ambient temperature and incidence of urolithiasis and evaluate the impact thereof. Methods A systematic literature review was performed up to September 2019 using multiple databases. The effect of temperature on urolithiasis risk was assessed using risk ratio (RR). Pearson correlation coefficient (Pearson's r) was used to evaluate the linear association between ambient temperature and urolithiasis incidence. The non-linear association between climatic temperature and the urolithiasis incidence was also evaluated. Results Twenty-four studies related to the temperature and urolithiasis risk in 14 different countries or regions of five continent involving over 2.5 million cases were included in the meta-analysis. High climatic or workplace temperature was a significant risk factor of urolithiasis. The weighted correlation coefficient (Pearson's r) of monthly temperature and urolithiasis risk was 0.49 [95% confidence interval (CI) 0.40-0.57], a moderate correlation (0.4

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