RNF26-mediated ubiquitination of TRIM21 promotes bladder cancer progression.

RNF26 is an important E3 ubiquitin ligase that has been associated with poor prognosis in bladder cancer. However, the underlying mechanisms of RNF26 in bladder cancer tumorigenesis are not fully understood. In the present study, we found that RNF26 expression level was significantly upregulated in the bladder cancer tissues, and higher RNF26 expression is closely associated with poorer prognosis, lower immune cell infiltration, and more sensitive to immune checkpoint blockade drugs and chemotherapy drugs, including cisplatin, VEGFR-targeting drugs and MET-targeting drugs. RNF26 knockdown in UMUC3 and T24 cell lines inhibited cell growth, colony formation and migratory capacity. Meanwhile, RNF26 overexpression had the opposite effects. Mechanistically, RNF26 exerts its oncogenic function by binding to TRIM21 and promoting its ubiquitination and subsequent degradation. Moreover, we revealed ZHX3 as a downstream target of RNF26/TRIM21 pathway in bladder cancer. Taken together, we identified a novel RNF26/TRIM21/ZHX3 axis that promotes bladder cancer progression. Thus, the RNF26/TRIM21/ZHX3 axis constitutes a potential efficacy predictive marker and may serve as a therapeutic target for the treatment of bladder cancer.

FTO promotes the progression of bladder cancer via demethylating m6A modifications in PTPN6 mRNA.

Bladder cancer (BC), a highly prevalent malignancy of the urinary system, necessitates further investigation into its progression mechanisms. N6-methyladenosine (m6A) RNA methylation, a prevalent modification in cellular RNA, has been implicated in the tumorigenesis and metastasis of various cancers. In this study, the upregulation of FTO in human BC samples and its association with poor prognosis were demonstrated using immunohistochemistry (IHC) on tissue sections collected from BC patients. The functional role of FTO in promoting the proliferation and metastasis abilities of BC cells was determined using a combination of in vitro and in vivo assays. In vitro, we conducted cell proliferation assays, such as the Cell Counting Kit-8 (CCK-8) assay, and metastasis assays, including the wound healing assay and transwell invasion assay. In vivo, we employed xenograft models to assess tumor growth and metastasis. Furthermore, our investigation into potential FTO targets in BC cells revealed that FTO modifies PTPN6 mRNA, leading to increased stability and expression of PTPN6, thereby enhancing proliferation and metastasis abilities. In conclusion, our findings indicate that FTO serves as an oncogenic factor in BC, suggesting its potential utility as a diagnostic or prognostic biomarker for bladder cancer.

A retrospective study revealing complex viral diversity and a substantial burden of HPV infection in SARS-CoV-2 positive individuals, Sierra Leone.

BACKGROUND: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. METHODS: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. RESULTS: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. CONCLUSIONS: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes.

Astragaloside â £ mediates the effect and mechanism of KPNB1 on biological behavior and tumor growth in prostate cancer.

Background: and purpose Prostate cancer is an comparatively prevalent clinical malignant tumor in men, impacting the lives of millions of men globally. This study measured the expression of Karyopherin Subunit Beta 1 (KPNB1) in prostate cancer cells, and made an effort to investigate how astragaloside IV affects the biological behavior, tumor growth, and mechanism of action of prostate cancer through KPNB1. Methods: Human prostate cancer and normal cells were obtained and KPNB1 expression levels in the two cells were determined using qPCR and WB. Prostate cancer cells were grouped according to the addition of astragaloside IV, KPNB1 inhibitor (importazole) alone and in combination. KPNB1, NF-κB, and cycle-related proteins were detected to be expressed at different levels in each group's cells by WB. MTT to assess the viability of the cells. To identify the cell cycle, use flow cytometry, and sphere formation experiment to observe sphere formation ability. Nude mice were purchased and subcutaneously inoculated with prostate cancer cells to establish a prostate cancer model, and grouped by tail vein injection of astragaloside IV and importazole. Tumor size was measured. KPNB1 and NF-κB expression in tumor tissues were detected by WB. The expression of proteins relevant to the cycle is observed by immunohistochemical methods. TUNEL was used to detect apoptosis of tissue cells. Results: KPNB1 expression was upregulated in prostate cancer cells (P < 0.05). KPNB1, NF-κB, and cycle-related protein levels were decreased by astragaloside IV and importazole both separately and together. Decreased viability of the cells and a higher percentage of cell cycle arrest in the G0 phase, apoptosis was increased, and sphere formation was decreased (P < 0.05). In vitro implantation experiments found that the application of astragaloside IV and importazole resulted in tumor growth inhibition, decreased KPNBI, NF-κB, and cyclin expression in tumor tissues, and promoted apoptosis in tumor tissues (P < 0.05). Conclusion: Prostate cancer cells' expression of KPNB1 is downregulated by astragaloside IV, which also prevents the cells from proliferating. It offers a conceptual framework for the use of astragaloside IV in the management of prostate cancer.

Exploring the prognostic implications of cuproptosis-associated alterations in clear cell renal cell carcinoma via in vitro experiments.

This study investigated the impact of novel copper ionophores on the prognosis of clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME). The differential expression of 10 cuproptosis and 40 TME-pathway-related genes were measured in 531 tumor samples and 71 adjacent kidney samples in The Cancer Genome Atlas database. A risk score model was constructed with LASSO cox to predict the prognosis of ccRCC patients. Forest plot and function enrichment were used to study the biological function of the key genes in depth. The study found that the risk score model accurately predicted the prognosis of ccRCC patients. Patients with high scores had higher immune responses with a higher proportion of anti-tumor lymphocytes and a lower proportion of immunosuppressive M2-like macrophages. However, the high-score group also exhibited a higher proportion of T follicular helper cells and regulatory T cells. These results suggest that cuproptosis-based therapy may be worth further investigation for the treatment of ccRCC and TME. Subsequently, by using RNAi, we established the stable depletion models of FDX1 and PDHB in ccRCC cell lines 786-O and ACHN. Through CCK8, colony formation, and Transwell assays, we observed that the knockdown of FDX1 and PDHB could significantly reduce the capabilities of proliferation and migration in ccRCC cells. In conclusion, this study illuminates the potential effectiveness of copper ionophores in the treatment of ccRCC, with higher risk scores correlating with better TME immune responses. It sets the stage for future cuproptosis-based therapy research in ccRCC and other cancers, focusing on copper's role in TME.

Ezetimibe ketone protects against renal ischemia-reperfusion injury and attenuates oxidative stress via activation of the Nrf2/HO-1 signaling pathway.

Recently, ezetimibe (EZM) has been suggested to be a potent Nrf2 activator that is important for preventing oxidative stress. Interestingly, we found that its metabolite ezetimibe ketone (EZM-K) also has antioxidant effects. Thus, we investigated the role of EZM-K in preventing renal ischemia‒reperfusion injury (RIRI). Cultured NRK-52E cells were subjected to simulated IR with or without EZM-K. Rats were used to simulate in vivo experiments. EZM-K alleviated H2O2-induced apoptosis and reactive oxygen species (ROS) and upregulated Nrf2 and HO-1 levels in NRK-52E cells. A HO-1 and a Nrf2 inhibitor reversed the protective effects of EZM-K. In the rat RIRI model, pretreatment with EZM-K activated the Nrf2/HO-1 signaling pathway, suppressed tubular injury and inflammation, and improved renal function. EZM-K significantly prevented renal injury caused by ischemia‒reperfusion via the Nrf2/HO-1 signaling axis both in vivo and in vitro. The other metabolite of EZM, ezetimibe glucuronide (EZM-G) had no protective effects against ROS in RIRI. EZM-G also had no antioxidant effects and could not activate Nrf2/HO-1 signal pathway. Our findings also indicated the therapeutic potential of EZM-K in preventing RIRI.

Cdk1/p53/p21 feedback loop mechanisms in the pathogenesis of interstitial cystitis/bladder pain syndrome.

PURPOSE: This study aimed to elucidate the role of the Cdk1/p53/p21 feedback loop in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). MATERIALS AND METHODS: An IC/BPS cell model was established. Cell viability was determined using the CCK-8 assay. Flow cytometry was adopted to assess cell apoptosis rates. ELISA was employed to measure secretion levels of inflammatory factors (IL-6, IL-8, and TNF-α). Gene expressions were assessed using PCR, while protein expressions were analyzed through Western blotting analysis. Epithelial permeability was demonstrated using the phenol red leakage experiment and FITC-dextran permeability assay. The interaction between proteins was determined using co-immunoprecipitation, and protein localization was investigated using immunofluorescence. RESULTS: The CCK-8 assay revealed a significantly reduced viability of IC/BPS cells compared to normal epithelial cells (p < 0.05). Elevated levels of IL-6, IL-8, and TNF-α were detected in IC/BPS cells. Changes in the expressions of E-cadherin and ZO-1 were evident, leading to increased epithelial permeability in IC/BPS cells. Furthermore, within IC/BPS cells, Cdk1 phosphorylated p53 in the nucleus. The Cdk1/p53/p21 feedback loop was established to influence urothelial permeability. Both p21 and Cdk1 inhibitors notably reduced the epithelial permeability in IC/BPS cells. CONCLUSION: The Cdk1/p53/p21 feedback loop was instrumental in IC/BPS, acting as a regulator of urothelial permeability. This discovery offered a novel therapeutic approach for IC/BPS management.

Genomic Surveillance for SARS-CoV-2 Variants: Dominance of XBB Replacement - China, January-June 2023.

Introduction: In the first half of 2023, a global shift was observed towards the predominance of XBB variants. China faced a significant epidemic between late 2022 and early 2023 due to Omicron subvariants BA.5.2 and BF.7. This study aims to depict the evolving variant distribution among provincial-level administrative divisions (PLADs) in China and explore the factors driving the predominance of XBB replacement. Methods: Sequences from local and imported coronavirus disease 2019 (COVID-19) cases recorded between January 1 and June 30, 2023, were included. The study analyzed the changing distribution of viral variants and assessed how the prior dominance of specific variants, XBB subvariants, and imported cases influenced the prevalence of the XBB replacement variant. Results: A total of 56,486 sequences were obtained from local cases, and 8,669 sequences were from imported cases. Starting in April, there was a shift in the prevalence of XBB from imported to local cases, with varying dominance among PLADs. In PLADs previously high in BF.7, the rise of XBB was delayed. A positive correlation was found between XBB proportions in imported cases from January to March and local cases in April. The distribution pattern of XBB subvariants differed between local and imported cases within the same PLAD. No significant differences were noted in the replacement rates of XBB subvariants. Conclusions: The timing of XBB dominance differed among various PLADs in China in the first half of 2023, correlating closely with the prevalence of XBB variants among imported cases.

Value of ultra-high b-value diffusion-weighted imaging for the evaluation of renal ischemia-reperfusion injury.

To explore the feasibility of ultra-high b-value diffusion-weighted imaging (ubDWI) in assessment of renal IRI. Thirty-five rabbits were randomized into a control group (n = 7) and a renal IRI group (n = 28). The rabbits in the renal IRI group underwent left renal artery clamping for 60 min. Rabbits underwent axial ubDWI before and at 1, 12, 24, and 48 h after IRI. Apparent diffusion coefficient (ADCst) were calculated from ubDWI with two b-values (b = 0, 1000 s/mm2). Triexponential fits were applied to calculate the pure diffusion coefficients (D), perfusion-related diffusion coefficient (D⁎), and ultra-high ADC (ADCuh). The interobserver reproducibility were evaluated. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. The ADCst, D, and ADCuh values showed good reproducibility. The ADCst, D, and D⁎ values of renal Cortex (CO) and outer medulla (OM) significantly decreased after IRI (all P < 0.05). The ADCuh values significantly increased from pre-IRI to 1 h after IRI (P < 0.05) and significantly declined at 24 h and 48 h after IRI (all P < 0.05). ADCuh was strongly positively correlated with AQP-1 in the renal CO and OM (ρ = 0.643, P < 0.001; ρ = 0.662, P < 0.001, respectively). ubDWI can be used to non-invasively evaluate early renal IRI, ADCuh may be adopted to reflect AQP-1 expression.

Patient Readmission for Ischemic Stroke: Risk Factors and Impact on Mortality.

Patient readmission for ischemic stroke significantly strains the healthcare and medical insurance systems. Current understanding of the risk factors associated with these readmissions, as well as their subsequent impact on mortality within China, remains insufficient. This is particularly evident in the context of comprehensive, contemporary population studies. This 4-year retrospective cohort study included 125 397 hospital admissions for ischemic stroke from 838 hospitals located in 22 regions (13 urban and 9 rural) of a major city in western China, between January 1, 2015 and December 31, 2018. The Chi-square tests were used in univariate analysis. Accounting for intra-subject correlations of patients' readmissions, accelerated failure time (AFT) shared frailty models were used to examine readmission events and pure AFT models for mortality. Risk factors for patient readmission after ischemic stroke include frequent admission history, male gender, employee's insurance, advanced age, residence in urban areas, index hospitalization in low-level hospitals, extended length of stay (LOS) during index hospitalization, specific comorbidities and subtypes of ischemic stroke. Furthermore, our findings indicated that an additional admission for ischemic stroke increased patient mortality by 16.4% (P < .001). Stroke readmission contributed to an increased risk of hospital mortality. Policymakers can establish more effective and targeted policies to reduce readmissions for stroke by controlling these risk factors.

NAT10 promotes renal ischemia-reperfusion injury via activating NCOA4-mediated ferroptosis.

Ischemia-reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI) and is associated with substantial morbidity and mortality rates. In this study, we aimed to investigate the role of NAT10 and its ac4C RNA modification in IRI-induced renal injury. Our findings revealed that both the expression level of NAT10 and the RNA ac4C level in the kidneys were elevated in the IRI group compared to the sham group. Functionally, we observed that inhibition of NAT10 activity with Remodelin or the specific knockout of NAT10 in the kidney led to a significant attenuation of IRI-induced renal injury. Furthermore, in vitro experiments demonstrated that NAT10 inhibition and specific knockout of NAT10 in the kidney markedly suppressed global ac4C RNA modification, providing protection against hypoxia/reoxygenation-induced tubular epithelial cell injury and ferroptosis. Mechanistically, our study uncovered that NAT10 promoted ac4C RNA modification of NCOA4 mRNA, thereby enhancing its stability and contributing to IRI-induced ferroptosis in tubular epithelial cells (TECs). These findings underscore the potential of NAT10 and ac4C RNA modification as promising therapeutic targets for the treatment of AKI. Overall, our study sheds light on the critical involvement of NAT10 and ac4C RNA modification in the pathogenesis of IRI-induced renal injury, offering valuable insights for the development of novel AKI treatment strategies.

METTL3 facilitates renal cell carcinoma progression by PLOD2 m6A-methylation under prolonged hypoxia.

N6-methyladenosine (m6A) is the most prevalent reversible modification in eukaryotic mRNA, and it plays a critical role in tumor progression. The purpose of this study was to investigate the function and regulatory mechanisms of the methyltransferase METTL3 in renal cell carcinoma (RCC). METTL3 expression was upregulated and predicted a poor prognosis in patients with advanced RCC. METTL3 facilitated the proliferation, migration, and invasion of RCC cells, depending on its methylase activity. METTL3 positively regulated the expression of PLOD2, and both genes were triggered under prolonged hypoxia. Mechanistically, hypoxia-induced the binding of HIF-1α to the METTL3 promoter, which enhanced its transcriptional activity. METTL3-mediated m6A modifications of PLOD2 mRNA at 3'UTR region, promoting the translation of PLOD2 protein. Furthermore, silencing METTL3 impaired RCC progression in vitro. In vivo, administration of highly potent and selective METTL3 inhibitor STM2457 showed anti-tumor effects, whereas AAV9-mediated re-transduction of PLOD2 largely abolished the above phenomenon in a subcutaneous mouse model. These findings reveal that hypoxia and HIF-driven METTL3 transcription promote RCC progression by increasing PLOD2 expression in an m6A-dependent manner, suggesting that METTL3 may serve as a novel pharmaceutical intervention for RCC.

Big Data-Enabled Analysis of Factors Affecting Medical Expenditure in the Cerebral Infarction of a Developing City in Western China.

Purpose: Cerebral infarction (CI) has been one of the leading causes of death in China since 2017, and controlling the medical expenses of this disease is an urgent issue for the Chinese government. This study aims to explore the important factors that affect the hospitalization expenses of CI patients and to provide a scientific basis for establishing a reasonable reimbursement mechanism and hospitalization expense standard for CI patients. Methods: Data from 109,314 inpatients from the Healthcare Security Administration of Chengdu in western China from January 2016 to December 2018 were utilized. Descriptive statistical analysis was used for variable characteristic analysis. The Mann-Whitney test and Kruskal-Wallis test were used for single-factor analysis, and multiple linear stepwise regression was used for single-factor analysis and multiple-factor analysis. Results: This study found that the average direct economic burden of CI in Chengdu was approximately 10,569 Chinese yuan (CNY), about 1450 US dollars, the average length of stay (LOS) was 14.47 days, the indirect economic burden was approximately 2817 CNY, and the total economic burden was 13,386 CNY for a CI inpatient. Gender, insurance type, grade of medical institution, the level of payment type, age, LOS, and complications and comorbidities (CCs) are the most important factors affecting CI medical costs. Conclusion: Citizens should improve their lifestyle habits to reduce disease risk to avoid the associated medical and economic burdens. Hospitals should improve their medical technology to decrease the LOS and reduce direct medical costs. The government should actively promote the hierarchical diagnosis and treatment policy to reduce the waste of medical resources caused by low-acuity patients going to high-level hospitals for treatment. The National Healthcare Security Administration should optimize the medical insurance payment method and establish a corresponding mechanism to reduce the occurrence of excessive medical treatments such as overuse.

RNA-sequencing-based detection of human viral pathogens in cerebrospinal fluid and serum samples from children with meningitis and encephalitis.

Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the Anelloviridae was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.

DNA methylation role in subgenome expression dominance of Juglans regia and its wild relative J. mandshurica.

Subgenome expression dominance plays a crucial role in the environmental adaptation of polyploids. However, the epigenetic molecular mechanism underlying this process has not been thoroughly investigated, particularly in perennial woody plants. Persian walnut (Juglans regia) and its wild relative, Manchurian walnut (Juglans mandshurica), are woody plants of great economic importance and are both paleopolyploids that have undergone whole-genome duplication events. In this study, we explored the characteristics of subgenome expression dominance in these 2 Juglans species and examined its epigenetic basis. We divided their genomes into dominant subgenome (DS) and submissive subgenome (SS) and found that the DS-specific genes might play critical roles in biotic stress response or pathogen defense. We comprehensively elucidated the characteristics of biased gene expression, asymmetric DNA methylation, transposable elements (TEs), and alternative splicing (AS) events of homoeologous gene pairs between subgenomes. The results showed that biased expression genes (BEGs) in 2 Juglans species were mainly related to external stimuli response, while non-BEGs were related to complexes that might be involved in signal transduction. DS genes had higher expression and more AS events while having less DNA methylation and TEs than homoeologous genes from the SS in the 2 Juglans species. Further studies showed that DNA methylation might contribute to the biased expression of gene pairs by modifying LTR/TIR/nonTIR TEs and improving the AS efficiency of corresponding precursor mRNAs in a particular context. Our study contributes to understanding the epigenetic basis of subgenome expression dominance and the environmental adaptation of perennial woody plants.

A rapid and highly sensitive multiple detection of human adenovirus type 3, type 7 and respiratory syncytial virus by recombinase-aided reverse transcription PCR.

BACKGROUND: Polymerase chain reaction (PCR) has been widely used for many pathogen detection. However, PCR technology still suffers from long detection time and insufficient sensitivity. Recombinase-aided amplification (RAA) is a powerful nucleic acid detection tool with high sensitivity and amplification efficiency, but its complex probes and inability of multiplex detection hinder the further application of this technology. METHODS: In this study, we developed and validated the multiplex reverse transcription recombinase-aided PCR (multiplex RT-RAP) assay for human adenovirus 3 (HADV3), human adenovirus 7 (HADV7), and human respiratory syncytial virus (HRSV) within 1 h with Human RNaseP protein as a reference gene to monitor the whole process. RESULTS: Using recombinant plasmids, the sensitivity of multiplex RT-RAP for the detection of HADV3, HADV7, and HRSV was 18, 3, and 18 copies per reaction, respectively. The multiplex RT-RAP showed no cross-reactivity with other respiratory viruses, demonstrating its good specificity. A total of 252 clinical specimens were tested by multiplex RT-RAP and the results were found to be consistent with those of corresponding RT-qPCR assays. After testing serial dilutions of selected positive specimens, the detection sensitivity of multiplex RT-RAP was two to eightfold higher than that of corresponding RT-qPCR. CONCLUSION: We conclude the multiplex RT-RAP is a robust, rapid, highly sensitive, and specific assay with the potential to be used in the screening of clinical samples with low viral load.

Silencing LINC00491 inhibits prostate cancer development through the miR-384/TRIM44 axis.

Accumulating evidence has demonstrated the key role of long noncoding (lnc)RNAs in tumorigenesis. Prostate cancer (PCa) is a cancer with high mortality that requires further exploration of the underlying molecular mechanisms. In the present study, we aimed to discover novel potential biomarkers for diagnosing PCa and targeting treatment. Overexpression of the lncRNA, LINC00491, was verified in PCa tumor tissues and cell lines using the real-time polymerase chain reaction. Cell proliferation and invasion were then analyzed via the Cell Counting Kit-8, colony formation, and transwell assays in vitro, and tumor growth in vivo. The interaction of miR-384 with LINC00491, as well as TRIM44, was investigated via bioinformatics analyses, subcellular fractionation, luciferase reporter gene assays, radioimmunoprecipitation, pull-down, and western blot analyses. LINC00491 was overexpressed in PCa tissues and cell lines. LINC00491 knockdown resulted in impaired cell proliferation and invasion in vitro and decreased tumor growth in vivo. Moreover, LINC00491 acted as a sponge for miR-384 and its downstream target, TRIM44. Additionally, miR-384 expression was downregulated in PCa tissues and cell lines, and its expression was negatively correlated with LINC00491. A miR-384 inhibitor restored the inhibitory effects of LINC00491 silencing on PCa cell proliferation and invasion. LINC00491 is a tumor promoter in PCa via enhancing TRIM44 expression by sponging miR-384 to facilitate the development of PCa. LINC00491 plays a significant role in PCa and could serve as both a biomarker for early diagnosis and a novel treatment target.

Genomic Surveillance for SARS-CoV-2 - China, September 26, 2022 to January 29, 2023.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated 2,431 variants over the course of its global transmission over the past 3 years. To better evaluate the genomic variation of SARS-CoV-2 before and after the optimization of coronavirus disease 2019 (COVID-19) prevention and control strategies, we analyzed the genetic evolution branch composition and genomic variation of SARS-CoV-2 in both domestic and imported cases in China (the data from Hong Kong and Macau Special Administrative Regions and Taiwan, China were not included) from September 26, 2022 to January 29, 2023. Methods: Analysis of the number of genome sequences, sampling time, dynamic changes of evolutionary branches, origin, and clinical typing of SARS-CoV-2 variants submitted by 31 provincial-level administrative divisions (PLADs) and Xinjiang Production and Construction Corps (XPCC) was conducted to assess the accuracy and timeliness of SARS-CoV-2 variant surveillance. Results: From September 26, 2022 to January 29, 2023, 20,013 valid genome sequences of domestic cases were reported in China, with 72 evolutionary branches. Additionally, 1,978 valid genome sequences of imported cases were reported, with 169 evolutionary branches. The prevalence of the Omicron variants of SARS-CoV-2 in both domestic and imported cases was consistent with that of international epidemic variants. Conclusions: This study provides an overview of the prevalence of Omicron variants of SARS-CoV-2 in China. After optimizing COVID-19 prevention and control strategies, no novel Omicron variants of SARS-CoV-2 with altered biological characteristics or public health significance have been identified since December 1, 2022.

Surveillance of SARS-CoV-2 at the Huanan Seafood Market.

SARS-CoV-2, the causative agent of COVID-19, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases had a history of contact with the Huanan Seafood Market. Here we present the results of surveillance for SARS-CoV-2 within the market. From January 1st 2020, after closure of the market, 923 samples were collected from the environment. From 18th January, 457 samples were collected from 18 species of animals, comprising of unsold contents of refrigerators and freezers, swabs from stray animals, and the contents of a fish tank. Using RT-qPCR, SARS-CoV-2 was detected in 73 environmental samples, but none of the animal samples. Three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.99% to 100% with the human isolate HCoV-19/Wuhan/IVDC-HB-01/2019. SARS-CoV-2 lineage A (8782T and 28144C) was found in an environmental sample. RNA-seq analysis of SARS-CoV-2 positive and negative environmental samples showed an abundance of different vertebrate genera at the market. In summary, this study provides information about the distribution and prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stages of the COVID-19 outbreak.