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SARS-CoV-2 pandemic has caused a continuing health crisis affecting the public health system globally. Population-based serological surveys are a highly valuable and recommended method to measure population exposure and spread of pandemic, given the existence of asymptomatic cases and little access to diagnostic testing. This national population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in all parts of Ethiopia and determine potential risk factors and burden of infection. A nationwide seroprevalence survey was done among 12,756 households (HHs) across the country using three-stage stratified sampling technique from April 15, 2021 to May 16, 2021 among population of Ethiopia above 15 years of age. One member of each of the selected HHs, who fulfilled the eligibility criteria, was randomly selected. We captured data using interviews and finger prick blood samples to test for anti-SARS-CoV-2 antibodies using high specificity rapid diagnostic tests (RDTs). A questionnaire was used to capture all necessary data on demographics, social exposure, and history of vaccination for SARS-CoV-2, symptoms compatible with SARS-CoV-2, and any known medical conditions. The data were collected using an open data kits (ODK) software and imported into STATA version 17 for analysis. Descriptive statistics (frequencies and proportions) were used to summarize data on the study variables. Forest plots and maps were used to visualize the seroprevalence of SARS-CoV-2 across various individual and environmental factors. The study sample was weighted, and the survey set command in Stata (svy) was used in the analyses to account for the survey design. Adjusted Odd ratio (AOR) was used to determine higher risk factors of having been infected at least once, 95% confidence interval to assess precision of the estimates, and a P value ≤  0.05 to determine statistically significant. This study indicated the overall national prevalence of seropositivity was 9.3% that suggests nearly one in ten individuals in Ethiopia was exposed to SARS-CoV-2 infection by May 2021. All regional states in the country are affected with SARS-CoV-2 infection although infection was more common in densely populated regions. Seroprevalence was significantly higher among, individual, aged 35-44, 55-64 and 65 and over years had more odds of being infected by SARS-CoV-2 compared with those aged 15-24 years. The seroprevalence is also high among professional/technical occupations, and among those having at least one comorbidity. The participants who had seven and more members had higher odds of infection compared with those who had two or less members. The odds of infection among respondents, who reported having ever tested for COVID-19 and being sick since March 2020, were higher compared with their counterparts. Among the environmental factors, the odds of SARS-CoV-2 infection in urban residents were higher than in the rural setting. In relation to geographic administration boundaries, participants from Harari Region, Addis Ababa, and Benishangul Gumuz had higher odds of infection compared to those from Afar Regions respective. This study reveals the overall seroprevalence of SARS CoV-2 antibodies in Ethiopia was 10.0% as of May 2021. The seroprevalence of IgG antibodies against COVID-19 is higher than that of IgM antibodies, indicating a past infection. SARS-CoV-2 antibody seroprevalence was varied by regional state, sex, residence area, age, and occupational status. It also suggests that the majority of Ethiopia's have inadequate knowledge of understanding about SARS-CoV-2 antibodies, we recommend strengthening public health and social measures to mitigate the spread of COVID-19 diseases, including increased vaccination coverage and testing capability. All responsible authorities and stakeholders working locally, nationally, and globally need to support strengthening health systems and be prepared to combat morbidity and mortality and to encourage ongoing vaccination efforts. Periodic seroprevalence surveys will aid in monitoring the status and progress of the COVID-19 pandemic.

Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5'-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer.

Resequencing of 302 soybean accessions and GWAS provide a comprehensive resource for soybean geneticists and breeders. Understanding soybean ( Glycine max ) domestication and improvement at a genetic level is important to inform future efforts to further improve a crop that provides the world's main source of oilseed. We detect 230 selective sweeps and 162 selected copy number variants by analysis of 302 resequenced wild, landrace and improved soybean accessions at >11× depth. A genome-wide association study using these new sequences reveals associations between 10 selected regions and 9 domestication or improvement traits, and identifies 13 previously uncharacterized loci for agronomic traits including oil content, plant height and pubescence form. Combined with previous quantitative trait loci (QTL) information, we find that, of the 230 selected regions, 96 correlate with reported oil QTLs and 21 contain fatty acid biosynthesis genes. Moreover, we observe that some traits and loci are associated with geographical regions, which shows that soybean populations are structured geographically. This study provides resources for genomics-enabled improvements in soybean breeding.

Background. Endometriosis (EMs) is a benign chronic condition that tends to recur in women of childbearing age, with an incidence of approximately 10%. It is a multifactorial disease for which the pathogenesis is currently unclear. This study is aimed at investigating the expression and clinical significance of tRNA-derived small RNA (tsRNA), a novel noncoding small RNA with potential regulatory functions, in endometriosis. Methods. The tRF/tiRNA expression profiles in endometrial tissues from three pairs of endometriosis patients and controls were detected by tRF&tiRNA PCR microarray technology and then verified by quantitative real-time polymerase chain reaction (qPCR). The target genes and target sites of TRF396, tiRNA-5030-GlnTTG-3, TRF308, and TRF320 were predicted by miRanda, and the network diagram of their interaction with miRNA was drawn. The impact of tRNA-derived fragments on the pathogenesis of endometriosis was analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results. Two upregulated and 19 downregulated tRNA-derived fragments were identified. The qRT-PCR results of 2 upregulated and 2 downregulated RNA-derived fragments were consistent with the RNA Seq data. The OR2B4 gene related to TRF396, the DGAT1 gene related to tiRNA-5030-GlnTTG-3, the KLF16 gene of TRF308, and the RNF213 gene of TRF320 had significant correlations. Gene Ontology and pathway analysis showed that the target genes of TRF396 and tiRNA-5030-GlnTTG-3 were mainly involved in the intrinsic components of the membrane and the overall composition of the membrane in cell components; molecular functions mainly involve olfactory conduction and G protein-coupled receptor activity. In the biological process, it was mainly involved in the detection of sensory stimuli. The target genes of TRF308 and TRF320 were mainly involved in the intracellular part; molecular functions are mainly related to DNA binding transcription factor activity and protein binding and mainly related to biological regulation of biological processes. Pathway analysis showed that the RAP1 signaling pathway and the AXON GUIDANCE signaling pathway may participate in the progression of endometriosis. Conclusion. The differential expression of tRF/tiRNA in endometriosis may be related to the pathogenesis of endometriosis. Furthermore, tRF/tiRNA may be a biomarker for the diagnosis and treatment of EMs in the future.

The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer. Our results indicate that survivin is one of the key players responsible for the innate chemoresistance of colorectal cancer stem cells. Thus, aptamer-mediated targeting of survivin in cancer stem cells in combination with chemotherapeutic drugs constitutes a new avenue to improve treatment outcome in oncologic clinics.

Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions—from normal prostate epithelium to localized PCa to metastases—in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13 , FOXA1 and NKX3-1 . Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression. Analyses of epigenomic datasets spanning transitions from normal prostate epithelium to localized prostate cancer to metastases show that latent developmental programs are reactivated in metastatic disease and that prostate lineage-specific regulatory elements are strongly enriched for prostate cancer risk heritability.

Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs) could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ) and low metastatic (MOLF/EiJ) mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL) SNPs with disease-free survival, consistent with the mouse studies.

More than 800 million people suffer from kidney disease, yet the mechanism of kidney dysfunction is poorly understood. In the present study, we define the genetic association with kidney function in 1.5 million individuals and identify 878 (126 new) loci. We map the genotype effect on the methylome in 443 kidneys, transcriptome in 686 samples and single-cell open chromatin in 57,229 kidney cells. Heritability analysis reveals that methylation variation explains a larger fraction of heritability than gene expression. We present a multi-stage prioritization strategy and prioritize target genes for 87% of kidney function loci. We highlight key roles of proximal tubules and metabolism in kidney function regulation. Furthermore, the causal role of SLC47A1 in kidney disease is defined in mice with genetic loss of Slc47a1 and in human individuals carrying loss-of-function variants. Our findings emphasize the key role of bulk and single-cell epigenomic information in translating genome-wide association studies into identifying causal genes, cellular origins and mechanisms of complex traits. Genome-wide analyses identify hundreds of loci associated with kidney function. Integrated analyses of expression, methylation and single-cell open chromatin and expression data derived from human kidney samples prioritize genes and mechanisms underlying renal disease.

Currently, mpox virus (MPXV) continues to pose a global public health challenge, with immunocompromised individuals often exhibiting more severe clinical symptoms. This study screens three male mouse models (ICR, IFNAR1 -/- , SCID) and identifies SCID mice as the optimal model for modeling severe patient symptoms, including pneumonia, rash, and localized inflammation, which is applied to evaluate the antiviral efficacy of tecovirimat and cidofovir. Both drugs prevent systemic MPXV spread when administered within two days post virus exposure. Local antiviral efficacy differs between the two drugs, particularly after intradermal infection. Prolonged treatment up to 28 days post infection results in 100% survival of SCID mice but fails to effectively suppress localized rash and inflammatory swelling, suggesting that the drugs have limited impact at later stages of the disease. These findings indicate that the therapeutic efficacy of tecovirimat and cidofovir depends on the timing of intervention initiation and the stage of disease progression. This study establishes MPXV clade IIb-infected SCID mouse models presenting with pneumonia, lesions, and localized inflammation that recapitulate key clinical manifestations observed in high-risk populations, and demonstrates that the timing of treatment initiation and the stage of disease progression critically influence the anti-MPXV efficacy of both tecovirimat and cidofovir.

Soccer, as a high-intensity sport, places significant physical demands on athletes and is associated with a high risk of injury. Electrical muscle stimulation (EMS), a training and rehabilitation technology, has gained attention for its potential benefits in sports settings. This systematic review, conducted under the PRISMA guidelines, rigorously assessed the effectiveness of EMS in improving muscle strength, promoting post-exercise recovery, and facilitating injury rehabilitation among soccer players. A comprehensive search of the PubMed, Scopus, and Web of Science databases identified 10 studies meeting the inclusion criteria. Among these, six studies demonstrated a significant improvement in athletic performance following local or whole-body EMS application. Four studies provided evidence supporting EMS’s efficacy in enhancing post-exercise recovery and reducing recovery time after injuries, with observed reductions in recovery time. However, the majority of the included studies were not double-blind, which limits the strength of the evidence. None of the included studies reported EMS-related adverse effects. Overall, the current results suggest that EMS may be a useful adjunct to improve athletic performance and facilitate recovery in soccer players. This review offers actionable insights for coaches and athletes regarding the safe and effective application of EMS in soccer training and rehabilitation programs.