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Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects. [ABSTRACT FROM AUTHOR]

Background: Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). Methods: A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. Results: 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild. Conclusions: BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ. Trial registration number: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Simple Summary: Traditional musk is a scarce resource of traditional Chinese medicine in China, which is difficult to obtain. Few studies have been reported on the search for alternatives to musk. To this end, we collected muskrat musk, which is widely regarded as a substitute for musk, and performed Gas Chromatography Time-of-Flight Mass Spectrometry (GC–TOF–MS) metabolomics analysis together with musk. The results showed that muskrat musk and musk had certain similarities in terms of their composition, but the important active components of muscone were missing. Analysis of muskrat musk at different ages showed that amino acids, fatty acids, and steroids were significantly enriched, which may affect the function of muskrat scent glands through local enrichment for a short time. Muskrat musk is considered to be a potential substitute for traditional musk. However, little is known about the similarity between muskrat musk and musk, and whether it is related to muskrat age. In this study, muskrat musk (MR1, MR2, and MR3) were from 1, 2, and 3-year-old muskrats, respectively, and white musk (WM) and brown musk (BM) were picked from male forest musk deer. The results indicated that muskrat musk had higher similarity to WM than BM. Further research showed that RM3 had the highest matched degree with WM. By significantly different metabolite analysis, we found that 52 metabolites continue to increase from 1- to 3-year-old muskrats. In total, 7 and 15 metabolites were significantly decreased in RM1 vs. RM2 and RM2 vs. RM3, respectively. Meanwhile, 30 and 17 signaling pathways were observed from increased and decreased metabolites, respectively. The increased metabolites mainly entailed enrichment in amino acid biosynthesis and metabolism, steroid hormone biosynthesis, and fatty acid biosynthesis. In conclusion, muskrat musk from three-year-old muskrat is a relatively good substitute for white musk, and the result also implies that these biological processes of amino acid biosynthesis and metabolism, steroid hormone biosynthesis, and fatty acid biosynthesis are beneficial to the secretion of muskrat musk. [ABSTRACT FROM AUTHOR]

Background: A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance. Methods: A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18–40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin. Results: A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance. Conclusion: Blonanserin significantly improved the symptoms of schizophrenia in female patients aged 18–40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients. [ABSTRACT FROM AUTHOR]

Objectives: Mesoderm, derived from a new layer between epiblast and hypoblast during gastrulation, can differentiate into various tissues, including muscles, bones, kidneys, blood, and the urogenital system. However, systematic elucidation of mesoderm characteristics and specific markers remains a challenge. This study aims to screen and identify candidate genes important for mesoderm development. Materials and Methods: Cells originating from the three germ layers were obtained by laser capture microdissection, followed by microcellular RNA sequencing. Mesoderm‐specific differentially expressed genes (DEGs) were identified by using a combination of three bioinformatics pipelines. Candidate mesoderm‐specific genes expression were verified by real‐time quantitative polymerase chain reaction analysis and immunohistochemistry. Functional analyses were verified by ESCs‐EBs differentiation and colony‐forming units (CFUs) assay. Results: A total of 1962 differentially expressed mesoderm genes were found, out of which 50 were candidate mesoderm‐specific DEGs which mainly participate in somite development, formation of the primary germ layer, segmentation, mesoderm development, and pattern specification process by GO analysis. Representative genes Cdh2, Cdh11, Jag1, T, Fn‐1, and Pcdh7 were specifically expressed in mesoderm among the three germ layers. Pcdh7 as membrane‐associated gene has hematopoietic‐relevant functions identified by ESCs‐EBs differentiation and CFUs assay. Conclusions: Spatial transcriptomic profiling with multi‐method analysis and confirmation revealed candidate mesoderm progenitors. This approach appears to be efficient and reliable and can be extended to screen and validate candidate genes in various cellular systems. [ABSTRACT FROM AUTHOR]

RING finger protein 135 has an important role in the occurrence of many cancers; however its regulation and function of RNF135 in hepatocellular carcinoma remains unknown. The promoter methylation status and mRNA expression of RNF135 was evaluated by methylation-specific PCR, semi-quantitative RT-PCR, and real-time quantitative PCR in HCC tissues and cell lines, and further analyzed from The Cancer Genome Atlas database. Wound healing assay, transwell migration, cell viability, and colony formation assay were performed to investigate the function of RNF135. GSEA analysis, TIMER database, and ESTIMATE algorithm were used to decipher the associated pathway and immune infiltration. The survival analysis was applied to assess the prognostic value of RNF135. RNF135 expression was downregulated in HCC tissues and 5 of 8 HCC cell lines, and was negatively correlated with its promoter hypermethylation. Demethylating regent decitabine restored RNF135 expression on the cellular level. Knockdown of RNF135 expression enhanced the migration of HCC cells, while RNF135 overexpression and decitabine treatment repressed cell migration. Bioinformatics analysis and immunohistochemistry revealed a positive relationship between RNF135 expression and six immune cell infiltrates (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells). Survival analysis disclosed that RNF135 hypermethylation is independently associated with poor clinical outcomes in HCC. Decreased RNF135 expression driven by promoter hypermethylation frequently occurred in HCC and associated with prognosis of HCC. RNF135 functions as a tumor suppressor and is involved in tumor immune microenvironment in HCC. [ABSTRACT FROM AUTHOR]

Animal gut microbiota begins to colonize after birth and is functionally indispensable for maintaining the health of the host. It has been reported that gender and age influence the composition of the intestinal microbiome. However, the effects of gender and age on the intestinal microorganism of forest musk deer (FMD) remain unclear. The aim of this study was to establish the relationship between the structure and composition of fecal microbiota of male and female forest musk deer with age. Here, Illumina Miseq 300PE sequencing platform targeting 16S rRNA V3–V4 hypervariable region applied to define the fecal microbiota of male and female FMD with two age groups, juvenile (age 1–2 years) and adult (age 4–10 years). Alpha diversity index did not show significant difference in bacterial diversity between the males and females or among age groups. The intestinal microbiota of FMD was dominated by three phyla, the Firmicutes, Proteobacteria and Bacteroidetes regardless of gender and different ages. Higher proportions of Proteobacteria were found in adult male and juvenile female individuals. The composition of Bacteroidetes was stable with the gender and age of FMD. Interestingly, the relative abundance of genera Clostridiales and Bacteroidales were higher in the juvenile FMD. Conversely, proportions of Pseudomonas and Lachnospiraceae were abundant in the adult FMD. Higher proportions of Ruminococcaceae, Dore, and 5-7N15 were found in the juvenile male groups. They may reflect the different immune resistance of male and female individuals at different stages of development. This study explored the fecal microbiota composition of forest musk deer in relation to gender and age, which may provide an effective strategy for developing intestinal microecological preparations and potential musk deer breeding. [ABSTRACT FROM AUTHOR]

The organizational properties of complex lipid mixtures can give rise to functionally important structures in cell membranes. In model membranes, ternary lipid-cholesterol (CHOL) mixtures are often used as representative systems to investigate the formation and stabilization of localized structural domains (“rafts”). In this work, we describe a self-consistent mean-field model that builds on molecular dynamics simulations to incorporate multiple lipid components and to investigate the lateral organization of such mixtures. The model predictions reveal regions of bimodal order on ternary plots that are in good agreement with experiment. Specifically, we have applied the model to ternary mixtures composed of dioleoylphosphatidylcholine:18:0 sphingomyelin:CHOL. This work provides insight into the specific intermolecular interactions that drive the formation of localized domains in these mixtures. The model makes use of molecular dynamics simulations to extract interaction parameters and to provide chain configuration order parameter libraries. [ABSTRACT FROM AUTHOR]

The Chinese forest musk deer (Moschus berezovskii) is an economically important species distributed throughout southwest China and northern Vietnam. Occurrence and development of disease are aggravated by inbreeding and genetic diversity declines in captive musk deer populations. Deep transcriptomics investigation may provide a promising way to improve genetic health of captive and wild FMD population. MicroRNAs (miRNAs), which regulate gene expression by targeting and suppressing of mRNAs, play an important role in physiology and organism development control. In this study, RNA-seq technology was adopted to characterize the miRNA transcriptome signature among six tissues (heart, liver, spleen, lung, kidney, and muscle) in Chinese forest musk deer at two years of age. Deep sequencing generated a total of 103,261,451 (~87.87%) good quality small RNA reads; of them 6,622,520 were unique across all six tissues. A total of 2890 miRNAs were identified, among them 1129 were found to be expressed in all tissues. Moreover, coexpression of 20 miRNAs (>2000RPM) in all six tissues and top five highly expressed miRNAs in each tissue implied the crucial and particular function of them in FMD physiological processes. Our findings of forest musk deer miRNAs supplement the database of transcriptome information for this species and conduce to our understanding of forest musk deer biology. [ABSTRACT FROM AUTHOR]

Research of epithelial cells in musk gland is lacking. There are no good characterized epithelial cell lines that can provide complementary in vitro models for in vivo research. We successfully cultivated epithelial cells of musk gland for the first time. The protocol described here produces epithelial cell lines from the mature secreting musk gland. Based on morphological observation, epithelial cells of musk gland were isolated and cultured in vitro. After the third passage, the musk gland-derived cells were filled with many lipid droplets and proliferated well. We used gas chromatography and mass spectrometry to explore the chemical composition of lipid droplets in the musk gland-derived cells. The main components of secreted lipid droplet were alkanes, esters, amines, alcohols, ketones, organic acids, and aldehydes. Muscone, which is the main active compound of musk, was not found. This is a new attempt in the field of animal musk to obtain naturally secreted animal musk in vitro by cloning specialized cells. In conclusion, this study provides a reference at the cellular level to further analyze the biology and physiology of the musk gland epithelium and secretion mechanism of musk deer. [ABSTRACT FROM AUTHOR]

A structure‐based statistical potential is developed for transcription factor binding site (TFBS) prediction. Besides the direct contact between amino acids from TFs and DNA bases, the authors also considered the influence of the neighbouring base. This three‐body potential showed better discriminate powers than the two‐body potential. They validate the performance of the potential in TFBS identification, binding energy prediction and binding mutation prediction. [ABSTRACT FROM AUTHOR]

Herein, aptamer-based quantum-dot detectors of K^+ made of two-different K^+ aptamers are compared. These deoxyribonucleic acid-based aptamers are TBA (5^\prime GGT TGG TGT GGT TGG 3^\prime) and AG3 (5^\prime GGG TTA GGG TTA GGG TTA GGG 3^\prime). The nanoscale aptamer-quantum-dot-based detectors described in this paper are synthesized and tested in DI water aliquots that contain KCl. The results including data suggest that beacons made of AG3 and TBA serve better as an ion indicator in different potassium level regions. As a result, aptamer beacon made of AG3 has better potential in the design of take-home diagnostic devices for hyperkalemia and hypokalemia. [ABSTRACT FROM PUBLISHER]

Epicauta apteraKaszab(E. aptera), an endangered species used to extract cantharidin in Chinese traditional medicine, has a limited geographical distribution in the southwest China. The complete mitochondrial genome ofE. apterais 15 645bp which contains an A + T rich region and 37 genes, including 13 protein-coding genes, 22 tRNA genes and two rRNA genes (GenBank accession No. KX023302). All protein-coding genes are initiated by ATN start codon. Moreover, the largest non-coding A + T-rich region with a length of 1039 bp is at the end of 12S rRNA. It is the first report involved in the complete mitochondrial genome ofE. aptera. [ABSTRACT FROM PUBLISHER]