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The large yellow croaker (Larimichthyscrocea) is one of the most economically valuable marine fish in China and is a notable species in ecological studies owing to a serious collapse of wild germplasm in the past few decades. The stock division and species distribution, which have important implications for ecological protection, germplasm recovery, and fishery resource management, have been debated since the 1960s. However, it is still uncertain even how many stocks exist in this species. To address this, we evaluated the fine-scale genetic structure of large yellow croaker populations distributed along the eastern and southern Chinese coastline based on 7.64 million SNP markers. Compared with the widely accepted stock boundaries proposed in the 1960s, our results revealed that a climate-driven habitat change probably occurred between the Naozhou (Nanhai) Stock and the Ming-Yuedong (Mindong) Stock. The boundary between these two stocks might have shifted northwards from the Pearl River Estuary to the northern area of the Taiwan Strait, accompanied by highly asymmetric introgression. In addition, we found divergent landscapes of natural selection between the stocks inhabiting northern and southern areas. The northern population exhibited highly agminated signatures of strong natural selection in genes related to developmental processes, whereas moderate and interspersed selective signatures were detected in many immune-related genes in the southern populations. These findings establish the stock status and genome-wide evolutionary landscapes of large yellow croaker, providing a basis for conservation, fisheries management and further evolutionary biology studies.

Boron-doped carbon materials (BCs), low-cost and environmentally friendly carbocatalysts, were prepared for the activation of persulfate (PS) for the removal of bisphenol A (BPA). Compared with B-free carbon materials (Cs), the adsorption and catalytic activity were significantly enhanced by the boron modification. Fast and efficient removal of BPA was achieved using the BCs/PS system. The BPA removal rate constant increased linearly with the adsorption capacity of BCs. Electron paramagnetic resonance (EPR) spectroscopy and radical quenching experiments indicated that the degradation mechanisms in the BCs/PS system were different from conventional radical-based oxidation pathways. On the contrary, nonradical pathways were demonstrated to dominate the oxidation processes in the removal of BPA using the BCs/PS system. Herein, a mechanism is proposed where PS is activated by the carbon material to form a reactive electron-deficient carbocatalyst ([BCs]*) complex with a high redox potential, driving a nonradical oxidation pathway to achieve BPA removal. Through experimental investigation and the use of electrochemical techniques (cyclic voltammetry, Tafel corrosion analysis and open circuit voltages), B-doped carbon materials for the activation of PS elevate the potential of the derived nonradical [BCs]* complexes, and then accelerate the BPA removal efficiency

Renal ischemia-reperfusion injury (IRI) is the main cause of acute kidney injury (AKI), yet therapeutic approaches to alleviate IRI remain limited. PIM1 (provirus integration site for Moloney murine leukemia virus 1) is a constitutive serine threonine kinase that phosphorylates various substrates to regulate cell death and survival. However, the role of PIM1 in renal IRI remains unclear. This study aims to investigate the effect of PIM1 on renal IRI and explore its downstream regulatory mechanism. In this study, we inhibited or overexpressed PIM1 in mice and cultured proximal tubular cells, and then induced renal IRI model in vivo and hypoxia reoxygenation (HR) model in vitro. Renal function, renal structure injuries and cellular death were assessed to reflect the extent of IRI. The expression of PIM1 and the levels of ASK1, MAPK and their phosphorylated forms were detected by immunoblot. RNA sequencing of kidney cortex was performed to analyze downstream pathway of PIM1 in renal IRI. The results showed that PIM1 expression was significantly upregulated in renal IRI mouse model and in renal tubular cell HR model. AZD1208 (a PIM1 inhibitor) aggravated renal IRI, while PIM1 overexpression ameliorated renal IRI. This was involved in the regulation of the ASK1-MAPK pathway. Moreover, results demonstrated that ASK1 was a downstream target of PIM1 by administering Selonsertib (an inhibitor of ASK1 activity), and inhibiting ASK1 alleviated cell death after HR in PIM1 knockdown cells by reducing JNK/P38 activation. In conclusion, this study elucidated the protective effect of PIM1 on renal IRI, and the underlying mechanism may be related to ASK1-JNK/P38 signaling pathway. Taken together, PIM1 may be a potential therapeutic target for renal IRI.

8-Oxoguanine DNA glycosylase (OGG1) is a repair protein for 8-oxoguanine (8-oxoG) in eukaryotic atopic DNA. Through the initial base excision repair (BER) pathway, 8-oxoG is recognized and excised, and subsequently, other proteins are recruited to complete the repair. OGG1 is primarily located in the cytoplasm and can enter the nucleus and mitochondria to repair damaged DNA or to exert epigenetic regulation of gene transcription. OGG1 is involved in a wide range of physiological processes, such as DNA repair, oxidative stress, inflammation, fibrosis, and autophagy. In recent years, studies have found that OGG1 plays an important role in the progression of kidney diseases through repairing DNA, inducing inflammation, regulating autophagy and other transcriptional regulation, and governing protein interactions and functions during disease and injury. In particular, the epigenetic effects of OGG1 in kidney disease have gradually attracted widespread attention. This study reviews the structure and biological functions of OGG1 and the regulatory mechanism of OGG1 in kidney disease. In addition, the possibility of OGG1 as a potential therapeutic target in kidney disease is discussed.

Recent studies suggest that Poly(ADP-ribose) polymerase 1 (PARP1) acts as an RNA-binding protein in a majority of renal diseases with tubular cell injury. However, detailed knowledge of RNA targets and the RNA-binding regions for PARP1 is unknown. Herein, mapping of iRIP-seq reads in HK-2 renal tubular epithelial cells showed a biased distribution at coding sequence (CDS) and intron regions that is specific to these cells. A total of 1708 differentially expressed genes were identified after PARP1 knockdown using RNA-seq. Furthermore, transcriptome analysis also showed that selective variable splicing was globally regulated by PARP1 in HK-2 cells. By comparison of PARP1 RNA-seq and iRIP-seq data, we found 68 overlapping genes that are enriched in 'extracellular matrix' pathway. Follow-up identification of their interactions may contribute vital insights into the regulatory role of PARP1 as an RNA-binding protein in HK-2 cells.

Renal ischemia-reperfusion injury (IRI) is one of the underlying causes of acute kidney injury and also an unavoidable problem in renal transplantation. Lots of miRNAs and targets have been found to participate in some post-transcriptional processes in renal IRI, however, the detailed knowledge of miRNA targets and mechanism is unknown. In this study, miR-124 was found inhibited and PARP1 was overexpressed in renal IRI cells and mouse models. Dual-luciferase reporter assay revealed that miR-124 post-transcriptionally regulated PAPR1 3'UTR activity. Our results also demonstrated miR-124 negatively regulated PARP1 which played a role in necroptosis of renal ischemia-reperfusion injury by activating TNFα. TNFα induced the RIP1/RIP3 necroptosis signaling pathway to aggravate the renal injury. Collectively, these studies identified PARP1 as a direct target of miR-124 and activated RIP1/RIP3 necroptosis signaling pathway through TNFα. It elucidated the protective effect of miR-124 in renal ischemia-reperfusion injury, which demonstrated the regulatory mechanism of miR-124/PARP1 in renal injury and exhibited the potential as a novel therapeutic for the treatment of renal IRI.

Oxygen is an essential molecule for animal respiration, growth, and survival. Unlike in terrestrial environments, contamination and climate change have led to the frequent occurrence of hypoxia in aquatic environments, thus impacting aquatic animal survival. However, the adaptative mechanisms underlying fish responses to environmental hypoxia remain largely unknown. Here, we used large yellow croaker ( Larimichthys crocea) and large yellow croaker fry (LYCF) cells to investigate the roles of the Hif-1α/Hsf1/Hsp70 signaling pathway in the regulation of cellular redox homeostasis, and apoptosis. We confirmed that hypoxia induced the expression of Hif-1α, Hsf1, and Hsp70 in vivo and in vitro. Genetic Hsp70 knockdown/overexpression indicated that Hsp70 was required for maintaining redox homeostasis and resisting oxidative stress in LYCF cells under hypoxic stress. Hsp70 inhibited caspase-dependent intrinsic apoptosis by maintaining normal mitochondrial membrane potential, enhancing Bcl-2 mRNA and protein expression, inhibiting Bax and caspase3 mRNA expression, and suppressing caspase-3 and caspase-9 activation. Hsp70 suppressed caspase-independent intrinsic apoptosis by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and disturbed extrinsic apoptosis by inactivating caspase-8. Genetic knockdown/overexpression of Hif-1α and dual-luciferase reporter assay indicated that Hif-1α activated the Hsf1 DNA promoter and enhanced Hsf1 mRNA transcription. Hsf1 enhanced Hsp70 mRNA transcription in a similar manner. In summary, the Hif-1α/Hsf1/Hsp70 signaling pathway plays an important role in regulating redox homeostasis and anti-apoptosis in L. crocea under hypoxic stress.

The large yellow croaker (Larimichthys crocea), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in L. crocea and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in L. crocea and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability in vitro. Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish.

Purpose To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI. Methods In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500-mg qd orally for 3–5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10–14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit. Results At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p > .05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p > .05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events. Conclusions Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI.KEY MESSAGE:Oral sitafloxacin showed similar clinical cure rate and bacterial eradication rate as levofloxacin for treatment of complicated and uncomplicated urinary tract infections (UTIs) in a randomized, active-controlled, multicentre clinical trial.Oral sitafloxacin is safe and well-tolerated in treating acute uncomplicated and complicated UTIs in Chinese adults.Sitafloxacin is a promising alternative treatment option for UTIs in adults.

This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators.Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

BACKGROUND: Renal ischemic reperfusion injury (RIRI) is the most hackneyed cause of acute renal injury with high incidence. As a slit diaphragm (SD), TRPC6 (transient receptor potential channel 6) can maintain the structure and function of glomerular podocytes, and its activation has been reported to prominently alleviate ischemia reperfusion (I/R). However, the specific mechanism of TRPC6 in RIRI is uncertain. METHODS: The TRPC6 specific shRNA or overexpressing plasmid was used to decrease or increase TRPC6 level in HK-2 cells, respectively. Subsequently, the OGD/R (oxygen-glucose deprivation and re-oxygenation) HK-2 cells and RIRI model rats was established to examine the effect of TRPC6 in RIRI in vitro. After processing, viability was confirmed with MTT; cell necrosis was analyzed with flow cytometry; necrosis and autophagy-related proteins were verified with Western blot; free Zn(2+) was tested with an Zn(2+) fluorescent probe; and cell autophagy was monitored with MDC (monodansylcadaverine) method. Furthermore, TRPC6 agonist (OGA) or TRPC6 inhibitor (SKF96365) were introduced to increase or inhibit the activity of TRPC6 in RIRI model rats, and the kidney injury was assessed with H&E staining and RIP1 and PARP-1 expressions were examined with IHC (immunohistochemistry) staining. RESULTS: Our results verified TRPC6 could markedly enhance viability, Zn(2+) influx, and autophagy, and suppressed necrosis in OGD/R HK-2 cells. In addition, increase of Zn(2+) or autophagy activation produced similar results to TRPC6 overexpression in viability, autophagy, and necrosis of OGD/R HK-2 cells. Rescue experiment results also showed TRPC6 could prevent necrosis and facilitate Zn(2+) influx and autophagy of OGD/R HK-2 cells by inducing Zn(2+) influx and autophagy. Moreover, TRPC6 could ameliorate kidney injury, block necrosis, and enhance autophagy in RIRI model rats by promoting Zn(2+) influx and autophagy. CONCLUSIONS: TRPC6 could prevent necrosis and induce autophagy to alleviate RIRI by accelerating Zn(2+) influx and autophagy. This shows TRPC6/Zn(2+) influx/autophagy might be a novel therapeutic strategy for RIRI.

The large yellow croaker (Larimichthys crocea) is an important marine economic fish in China, however, its intolerance to hypoxia causes widespread mortality. To understand the molecular mechanisms underlying hypoxia tolerance in L. crocea, the transcriptome gene expression profiling of three different tissues (blood, gills, and liver) of L. crocea exposed to hypoxia and reoxygenation stress were performed. In parallel, the gene relationships were investigated based on weighted gene co-expression network analysis (WGCNA). Accordingly, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several pathways (e.g., energy metabolism, signal transduction, oxygen transport, and osmotic regulation) may be involved in the response of L. crocea to hypoxia and reoxygenation stress. In addition, also, four key modules (darkorange, magenta, saddlebrown, and darkolivegreen) that were highly relevant to the samples were identified by WGCNA. Furthermore, some hub genes within the association module, including RPS16, EDRF1, KCNK5, SNAT2, PFKL, GSK-3β, and PIK3CD, were found. This is the first study to report the co-expression patterns of a gene network after hypoxia stress in marine fish. The results provide new clues for further research on the molecular mechanisms underlying hypoxia tolerance in L. crocea.

Background Primary hyperoxaluria (PH) is a rare inherited autosomal recessive disease caused by disturbed glyoxylate metabolism. The disease is characterized by calcium oxalate crystal deposition in various organs, especially in the kidney. Due to the lack of current understanding of PH, nearly all patients are only initially diagnosed with PH when recurrent lithiasis and progressive end-stage renal disease occur. Many cases are not diagnosed in patients until renal allograft insufficiency occurs after renal transplantation. This case report and literature review aim to emphasize the need for careful pre-transplant PH screening of patients with bilateral nephrocalcinosis or nephrolithiasis. Case presentation Renal allograft insufficiency was diagnosed as PH after kidney transplantation. Here, we detail the complete clinical course, including computed tomography images of the original kidney and renal graft, histopathological images of a biopsy of the transplanted kidney, the results of laboratory and molecular genetic tests, and the treatment. In addition, we reviewed the literature from 2000 to 2021 and analyzed 19 reported cases of PH diagnosed after kidney transplantation, and provide a summary of the characteristics, complications, treatment, and prognosis of these cases. Conclusions By reviewing and analyzing these cases, we concluded that patients with a history of nephrocalcinosis or nephrolithiasis in both kidneys need preoperative screening for PH and appropriate treatment before kidney transplantation. Delayed graft function caused by PH is easily misdiagnosed as acute rejection, and needle biopsy should be performed at an early stage.

The circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is a novel identified abnormally upregulated circRNA in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. The expression of circ-RNF13, microRNA (miR)-424-5p, and TGFβ-induced factor homeobox 2 (TGIF2) were detected by real-time quantitative PCR and western blotting, and their interaction was confirmed by dual-luciferase reporter assay. Functional assays were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model, along with real-time quantitative PCR. Circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGIF2 upregulation and miR-424-5p downregulation. Blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells but inhibited cell viability, colony formation, migration, and invasion, along with suppressed tumor growth in vivo. Besides, HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells in vitro. Consistently, TGIF2 restoration partially abrogated the role of miR-424-5p upregulation in Huh7-HBV and Hep3B-HBV cells. The circ-RNF13 sponged miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.

The neuroendocrine system of fish responds to low temperature via regulating hormones. To explore the adaptability of Larimichthys crocea to low temperature, the levels of the plasma cortisol, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), total cholesterol (TC), and glucose were determined after exposure to low temperature and during subsequent rewarming. Furthermore, the mRNA expression of the glucocorticoid receptor (GR) gene was analyzed under the stress. We found that the levels of the plasma cortisol, TSH, T3, glucose, and TC increased under the low temperature stress, suggesting that elevated hormones may be conducive to promoting the mobilization of the glucose and lipid in L. crocea exposed to low temperature. During the rewarming period, the plasma cortisol level decreased, whereas the T3 level was still significantly higher than that in the control group. Notably, the plasma T4 level was unaffected by the temperature changes. Furthermore, the sequence alignment and phylogenetic tree analysis revealed that the GR protein of L. crocea had high homology and a similar protein structure with those from other teleosts. Under the low temperature stress, the GR mRNA expression increased in the brain and head kidney, whereas it basically returned to the control level following rewarming. These findings revealed the changes of the hormones and the potential function of the GR gene in L. crocea following exposure to low temperature, providing some insights into breeding low temperature-resistant varieties of L. crocea.

Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion in vitro, along with suppressed tumor growth in vivo. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells in vitro; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.

Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identified 12,979 novel lncRNAs in mouse. The expression profiles of both mRNAs and lncRNAs were differed significantly between LN and control mice. In particular, there were more upregulated lncRNAs and mRNAs than downregulated ones in the kidney tissues of LN mice. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response-associated pathways. KEGG analysis showed that both downregulated and upregulated genes were enriched in a number of pathways, including the SLE pathway, and approximately half of these SLE-associated genes encoded inflammatory factors. Moreover, we observed that 2,181 DElncRNAs may have targeted and regulated the expression of 778 mRNAs in LN kidney tissues. The results of this study showed that 11 DElncRNAs targeted and were co-expressed with six immune and SLE-associated genes. qPCR analysis confirmed that lncRNA Gm20513 positively regulated the expression of the SLE-associated gene H2-Aa. In conclusion, the results of our study demonstrates that lncRNAs influence the progression of LN and provide some cues for further study of lncRNAs in LN. These results regarding the lncRNA-mRNAregulatory network may have important value in LN diagnosis and therapy.

Deep learning (DL) has been successfully applied to many cutting-edge applications, e.g., image processing, speech recognition, and natural language processing. As more and more DL software is made open-sourced, publicly available, and organized in model repositories and stores (Model Zoo, ModelDepot), there comes a need to understand the relationships of these DL models regarding their maintenance and evolution tasks. Although clone analysis has been extensively studied for traditional software, up to the present, clone analysis has not been investigated for DL software. Since DL software adopts the data-driven development paradigm, it is still not clear whether and to what extent the clone analysis techniques of traditional software could be adapted to DL software. In this paper, we initiate the first step on the clone analysis of DL software at three different levels, i.e., source code level, model structural level, and input/output (I/0)-semantic level, which would be a key in DL software management, maintenance and evolution. We intend to investigate the similarity between these DL models from clone analysis perspective. Several tools and metrics are selected to conduct clone analysis of DL software at three different levels. Our study on two popular datasets (i.e., MNIST and CIFAR-10) and eight DL models of five architectural families (i.e., LeNet, ResNet, DenseNet, AlexNet, and VGG) shows that: 1). the three levels of similarity analysis are generally adequate to find clones between DL models ranging from structural to semantic; 2). different measures for clone analysis used at each level yield similar results; 3) clone analysis of one single level may not render a complete picture of the similarity of DL models. Our findings open up several research opportunities worth further exploration towards better understanding and more effective clone analysis of DL software.