More than 50% of prostate cancer (PCa) patients have bone metastasis with osteoblastic lesions. MiR-18a-5p is associated with the development and metastasis of PCa, but it remains unclear whether it is involved in osteoblastic lesions. We first found that miR-18a-5p was highly expressed in the bone microenvironment of patients with PCa bone metastases. To address how miR-18a-5p affects PCa osteoblastic lesions, antagonizing miR-18a-5p in PCa cells or pre-osteoblasts inhibited osteoblast differentiation in vitro. Moreover, injection of PCa cells with miR-18a-5p inhibition improved bone biomechanical properties and bone mineral mass in vivo. Furthermore, miR-18a-5p was transferred to osteoblasts by exosomes derived from PCa cells and targeted the Hist1h2bc gene, resulting in Ctnnb1 up-regulation in the Wnt/β-catenin signaling pathway. Translationally, antagomir-18a-5p significantly improved bone biomechanical properties and alleviated sclerotic lesions from osteoblastic metastases in BALB/c nude mice. These data suggest that inhibition of exosome-delivered miR-18a-5p ameliorates PCa-induced osteoblastic lesions.

Di (2-ethylhexyl) phthalate (DEHP), an estrogen-like compound that is a ubiquitous environmental contaminant, has been reported to adversely affect human and mammalian reproduction. Many studies have found that exposure to DEHP during pregnancy perturbs female germ cell meiosis and is detrimental to oogenesis. Previous studies have demonstrated that melatonin (MLT) is beneficial to reproductive endocrinology, oogenesis, and embryonic development as the ability to antioxidative and antiapoptotic. However, whether the meiotic defect of germ cells exposed to DEHP could be rescued by MLT is not clear. Here, we cultured 12.5 days post coitum (dpc) fetal mouse ovaries for 6 days, exposed them to 100 μM DEHP with or without 1 μM MLT in vitro.. The results showed that DEHP exposure induced the abnormal formation of DNA double-strand breaks (DSBs), and inhibited the repair of DSBs during meiotic recombination. In addition, we found defective oocytes were prone to undergo apoptosis. Notably, this defect could be remarkably ameliorated by the addition of MLT via a reduction of the levels of reactive oxygen species and an inhibition of apoptosis. In conclusion, our data revealed that MLT had a protective action against the meiotic deterioration of fetal oocytes induced by DEHP in the mouse in vitro.

With the evolution of the pandemic caused by the Coronavirus disease of 2019 (COVID-19), reverse transcriptase-polymerase chain reactions (RT-PCR) have invariably been a golden standard in clinical diagnosis. Nevertheless, the traditional polymerase chain reaction (PCR) is not feasible for field application due to its drawbacks, such as time-consuming and laboratory-based dependence. To overcome these challenges, a microchip-based ultrafast PCR system called SWM-02 was proposed to make PCR assay in a rapid, portable, and low-cost strategy. This novel platform can perform 6-sample detection per run using multiple fluorescent channels and complete an ultrafast COVID-19 RT-PCR test within 40 min. Here, we evaluated the performance of the microdevice using the gradient-diluted COVID-19 reference samples and commercial PCR kit and determined its limit-of-detection (LoD) as 500 copies/mL, whose variation coefficients for the nucleocapsid (N) gene and open reading frame 1 ab region (ORF1ab) gene are 1.427% and 0.7872%, respectively. The system also revealed an excellent linear correlation between cycle threshold (Ct) values and dilution factors (R² > 0.99). Additionally, we successfully detected the target RNAs and internal gene in the clinical samples by fast PCR, which shows strong consistency with conventional PCR protocol. Hence, with compact dimension, user-friendly design, and fast processing time, SWM-02 has the capability of offering timely and sensitive on-site molecular diagnosis for prevention and control of pathogen transmission.

CPs treatment altered the gut microbiota composition and restored impaired spermatogenesis via the steroid hormone synthesis process.

Recently there has been a continuing worldwide decrease in the quality of human spermatozoa, especially in spermatozoa motility and concentration. Many factors are involved in this decline, and great efforts have been made to rescue spermatogenesis; however, there has been little progress in the improvement of sperm quality. Chestnuts are used in traditional Chinese medicine; their major active components are chestnut polysaccharides (CPs). CPs have many biological activities but their effects on spermatogenesis are unknown. The current investigation was designed to explore the impact of CPs on spermatogenesis and the underlying mechanisms. We demonstrated that CPs significantly increased sperm motility and concentration (4-fold and 12-fold, respectively), and improved seminiferous tubule development by increasing the number of germ cells after busulfan treatment. CPs dramatically rescued the expression of important genes and proteins (STRA8, DAZL, SYCP1, SYCP3, TNP1 etc.) in spermatogenesis. Furthermore, CPs increased the levels of hormone synthesis proteins such as CYP17A1 and HSD17β1. All the data suggested that CPs improved the testicular microenvironment to rescue spermatogenesis. With CPs being natural products, they may be an attractive alternative for treating infertile patients in the future. At the same time, the deep underlying mechanisms of their action need to be explored.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility owing to the absence of sperm during ejaculation as a result of failed spermatogenesis. The molecular mechanisms of NOA have not been well studied. Here, we revealed the dysregulated differentially expressed genes in NOA and related signaling pathways or biological processes. Cluster features of biological processes include spermatogenesis, fertilization, cilium movement, penetration of zona pellucida, sperm chromatin condensation, and being significantly enriched metabolic pathways in proximal tubule bicarbonate reclamation, aldosterone synthesis and secretion, glycolysis and glycogenesis pathways in NOA using Gene Ontology analysis and pathway enrichment analysis. The NOA gene co-expression network was constructed by weighted gene co-expression network analysis to identify the hub genes (CHD5 and SPTBN2). In addition, we used another Gene Expression Omnibus dataset (GSE45887) to validate these hub genes. Furthermore, we used the Seurat package to classify testicular tissue cells from NOA patients and to characterize the differential expression of hub genes in different cell types from different adult males based on the scRNA-seq dataset (GSE106487). These results provide new insights into the pathogenesis of NOA. Of particular note, CHD5 and SPTBN2 may be potential biomarkers for the diagnosis and treatment of NOA.