Macrophage-Related Testicular Inflammation in Individuals with Idiopathic Non-Obstructive Azoospermia: A Single-Cell Analysis.

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which is a type of male infertility with unknown origins that accounts for 10-15% of cases. By using single-cell analysis techniques, we aimed to uncover the mechanisms of iNOA and gain insight into the cellular and molecular changes in the testicular environment. In this study, we performed bioinformatics analysis using scRNA-seq and microarray data obtained from the GEO database. The analysis included techniques such as pseudotime analysis, cell-cell communication, and hdWGCNA. Our study showed a significant difference between the iNOA and the normal groups, indicating a disorder in the spermatogenic microenvironment in iNOA. We observed a reduction in the proportion of Sertoli cells and blocked germ cell differentiation. Additionally, we found evidence of testicular inflammation related to macrophages and identified ODF2 and CABYR as potential biomarkers for iNOA.

The Genetic Structure and East-West Population Admixture in Northwest China Inferred From Genome-Wide Array Genotyping.

Northwest China is a contacting region for East and West Eurasia and an important center for investigating the migration and admixture history of human populations. However, the comprehensive genetic structure and admixture history of the Altaic speaking populations and Hui group in Northwest China were still not fully characterized due to insufficient sampling and the lack of genome-wide data. Thus, We genotyped genome-wide SNPs for 140 individuals from five Chinese Mongolic, Turkic speaking groups including Dongxiang, Bonan, Yugur, and Salar, as well as the Hui group. Analysis based on allele-sharing and haplotype-sharing were used to elucidate the population history of Northwest Chinese populations, including PCA, ADMIXTURE, pairwise Fst genetic distance, f-statistics, qpWave/qpAdm and ALDER, fineSTRUCTURE and GLOBETROTTER. We observed Dongxiang, Bonan, Yugur, Salar, and Hui people were admixed populations deriving ancestry from both East and West Eurasians, with the proportions of West Eurasian related contributions ranging from 9 to 15%. The genetic admixture was probably driven by male-biased migration- showing a higher frequency of West Eurasian related Y chromosomal lineages than that of mtDNA detected in Northwest China. ALDER-based admixture and haplotype-based GLOBETROTTER showed this observed West Eurasian admixture signal was introduced into East Eurasia approximately 700 ∼1,000 years ago. Generally, our findings provided supporting evidence that the flourish transcontinental communication between East and West Eurasia played a vital role in the genetic formation of northwest Chinese populations.

RNF8 deficiency results in neurodegeneration in mice.

The progressive loss of neurons causes neurodegenerative diseases. Because the accumulation of DNA breaks results in neuronal apoptosis, the lack of a variety of DNA damage repair-related proteins contributes to neurodegeneration. The ubiquitin ligase RNF8 plays an important role in DNA double-strand break repair via histone ubiquitination. However, the function of RNF8 in terminally differentiated neurons remains unknown. This study aimed to determine whether RNF8 is involved in the DNA damage response in neurons and contributes to neurodegeneration. Here, we present evidence suggesting that RNF8 deficiency results in DNA damage accumulation and neuronal apoptosis. RNF8(-/-) mice exhibit neuronal degeneration and reactive astrocytosis. Neurons from RNF8(-/-) mice appear to be more susceptible to X-ray-induced DNA damage. These changes were consistent with the behavioral performances of the RNF8-deficient mice, which included impaired performances in the open-field test and step-down avoidance task. Overall, these findings show that RNF8 is required for DNA damage repair in neurons. RNF8 deficiency is sufficient to cause neuronal pathology and cognitive decline, and the loss of RNF8 results in neuron degeneration.

Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo.

Histone deacetylase inhibitors (HDACIs) are a promising class of drugs that act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is an HDACI that has been widely used as an anti-convulsant and shows promise as a chemotherapeutic drug for a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of bladder cancer cells and its synergistic effect with chemotherapeutic agents in vitro and in vivo. The cell viability of human bladder cancer cell lines following treatment with VPA and/or VPA in combination with mitomycin C, cisplatin (DDP) and adriamycin were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst staining was used to observe the morphology of the apoptotic cells. Survivin protein and acetylated histone H3 levels were quantified using western blot analysis. The in vivo tumor growth inhibition of VPA was determined in rats with N-methyl-N-nitrosourea-induced bladder cancer. VPA significantly inhibited the growth of the bladder cancer cells in a concentration- and time-dependent manner. Furthermore, improved results were achieved for tumor inhibition when VPA was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in the bladder cancer cells following the treatment with VPA. Intravesical injections of VPA were able to inhibit tumor progression when combined with DDP. In conclusion, VPA acts as an HDACI that has a direct anticancer effect and markedly enhances the action of several chemotherapy agents. VPA may sensitize bladder cancer to anticancer drugs by downregulating survivin expression.