Effects of treatment with Astragalus Membranaceus on function of rat leydig cells

Background Astragalus membranaceus (AM) is a Chinese traditional herb which has been reported to have broad positive effects on many diseases, including hepatitis, heart disease, diabetes and skin disease. AM can promote cell proliferation, increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and inhibit apoptosis by regulating the transcription of proto-oncogenes controlling cell death. While AM is included in some commercially available “testosterone boosting supplements”, studies directly testing ability of AM to modulate testosterone production are lacking. In the present study, we examined the effects of AM on Leydig cell function in vitro. Methods Rat Leydig cells were purified and treated with AM at different concentrations (0 μg/mL, 10 μg/mL, 20 μg/mL, 50 μg/mL, 100 μg/mL and 150 μg/mL) and cell counting-8 (CCK-8) assay, Enzyme-linked immunosorbent assay, quantitative real time PCR and analysis of activities of SOD and GPx were done respectively. Results Treatment with 100 μg/mL (P \u3c 0.05) and 150 μg/mL AM (P \u3c 0.01) significantly increased Leydig cell numbers. Treatment with AM (20 μg/mL, 50 μg/mL and 100 μg/mL) significantly increased testosterone production (P \u3c 0.01). In addition, increased Leydig cell SOD and GPx activities were observed in response to 20 μg/mL and 50 μg/mL AM treatment (P \u3c 0.01). Furthermore, expression of Bax mRNA was significantly decreased (P \u3c 0.01), and the ratio of Bcl-2/Bax mRNA was significantly increased in response to 20 μg/mL AM in the culture medium (P \u3c 0.05). Conclusions Results supported a beneficial effect of AM on multiple aspects of rat Leydig cell function in vitro including testosterone production

An Investigation of Noise Robustness for Flow-Matching-Based Zero-Shot TTS

Recently, zero-shot text-to-speech (TTS) systems, capable of synthesizing any speaker's voice from a short audio prompt, have made rapid advancements. However, the quality of the generated speech significantly deteriorates when the audio prompt contains noise, and limited research has been conducted to address this issue. In this paper, we explored various strategies to enhance the quality of audio generated from noisy audio prompts within the context of flow-matching-based zero-shot TTS. Our investigation includes comprehensive training strategies: unsupervised pre-training with masked speech denoising, multi-speaker detection and DNSMOS-based data filtering on the pre-training data, and fine-tuning with random noise mixing. The results of our experiments demonstrate significant improvements in intelligibility, speaker similarity, and overall audio quality compared to the approach of applying speech enhancement to the audio prompt.Comment: Accepted to INTERSPEECH202

Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One‐sample Mendelian randomization (MR) and summary data‐based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one‐sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65–0.90; p = 0.001) and CCB use (0.83; 0.72–0.95; p = 0.007), equivalent to a 10‐mm Hg reduction in systolic BP, was significantly associated with lower risk of pre‐frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39–1.33; p = 0.296) or thiazides variants (0.74; 0.53–1.03; p = 0.072) on pre‐frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta −0.02, p = 2.87 × 10−4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty

Alveolar type 2 cells marker gene SFTPC inhibits epithelial-to-mesenchymal transition by upregulating SOX7 and suppressing WNT/β-catenin pathway in non-small cell lung cancer

IntroductionSurfactant Protein C gene (SFTPC) is a marker gene of alveolar type 2 cells (AT2), which are the key structures of alveoli. Mutations or deletions in SFTPC cause idiopathic pulmonary fibrosis (IPF). Importantly, IPF is an independent risk factor for non-small cell lung cancer (NSCLC). It suggests that abnormal expression of SFTPC may be relevant to development of NSCLC. However, the function and mechanism of SFTPC in NSCLC are still poor understood until now.MethodsThe expression of SFTPC and the relationship between SFTPC and prognosis of NSCLC were analyzed in TCGA database and our collected clinical NSCLC tissues. Subsequently, the function and mechanism of SFTPC in NSCLC were explored by RNA-sequence, qRT-PCR, Western blot, Immunohistochemical, Wound-healing, Millicell, Transwell assays and mouse tumor xenograft model.ResultsSFTPC was dramatically downregulated in NSCLC tissues from TCGA database and 40 out of 46 collected clinical LUAD tissues compared with adjacent non-tumor tissues. Low expression of SFTPC was associated with poor prognosis of LUAD by TCGA database. Importantly, we confirmed that overexpression of SFTPC significantly inhibited Epithelial-to-Mesenchymal Transition (EMT) process of NSCLC cells by upregulating SOX7 and then inactivating WNT/β-catenin pathway in vitro and in vivo. Particularly, we discovered that low expression of SFTPC was associated with EMT process and low expression of SOX7 in NSCLC tissues.ConclusionOur study revealed a novel mechanism of SFTPC in NSCLC development. Meanwhile, it also might provide a new clue for exploring the molecular mechanism about NSCLC development in patients with IPF in the future

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions—a case report

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient’s gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient’s symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms

Children neuropsychological and behavioral scale-revision 2016 in the early detection of autism spectrum disorder

BackgroundThe Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) is a widely used developmental assessment tool for children aged 0–6 years in China. The communication warning behavior subscale of CNBS-R2016 is used to assess the symptoms of autism spectrum disorder (ASD), and its value of >30 points indicates ASD based on CNBS-R2016. However, we observed that children with relatively lower values were also diagnosed with ASD later on in clinical practice. Thus, this study aimed to identify the suitable cutoff value for ASD screening recommended by the communication warning behavior of CNBS-R2016.Materials and methodsA total of 90 typically developing (TD) children and 316 children with developmental disorders such as ASD, developmental language disorder (DLD), and global developmental delay (GDD; 130 in the ASD group, 100 in the DLD group, and 86 in the GDD group) were enrolled in this study. All subjects were evaluated based on the CNBS-R2016. The newly recommended cutoff value of communication warning behavior for screening ASD was analyzed with receiver operating curves.ResultsChildren in the ASD group presented with lower developmental levels than TD, DLD, and GDD groups in overall developmental quotient assessed by CNBS-R2016. We compared the consistency between the scores of communication warning behavior subscale and Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Diagnostic Observation Schedule, second edition (ADOS-2), and clinical diagnosis for the classification of ASD at a value of 30 based on the previously and newly recommended cutoff value of 12 by the CNBS-R2016. The Kappa values between the communication warning behavior and ABC, CARS, ADOS-2, and clinical diagnosis were 0.494, 0.476, 0.137, and 0.529, respectively, with an agreement rate of 76.90%, 76.26%, 52.03%, and 82.27%, respectively, when the cutoff point was 30. The corresponding Kappa values were 0.891, 0.816, 0.613, and 0.844, respectively, and the corresponding agreement rate was 94.62%, 90.82%, 90.54%, and 93.10%, respectively, when the cutoff point was 12.ConclusionThe communication warning behavior subscale of CNBS-R2016 is important for screening ASD. When the communication warning behavior score is 12 points or greater, considerable attention and further comprehensive diagnostic evaluation for ASD are required to achieve the early detection and diagnosis of ASD in children

Development of a colloidal gold immunochromatographic assay strip using monoclonal antibody for rapid detection of porcine deltacoronavirus

Porcine deltacoronavirus (PDCoV) cause diarrhea and dehydration in newborn piglets and has the potential for cross-species transmission. Rapid and early diagnosis is important for preventing and controlling infectious disease. In this study, two monoclonal antibodies (mAbs) were generated, which could specifically recognize recombinant PDCoV nucleocapsid (rPDCoV-N) protein. A colloidal gold immunochromatographic assay (GICA) strip using these mAbs was developed to detect PDCoV antigens within 15 min. Results showed that the detection limit of the GICA strip developed in this study was 103 TCID50/ml for the suspension of virus-infected cell culture and 0.125 μg/ml for rPDCoV-N protein, respectively. Besides, the GICA strip showed high specificity with no cross-reactivity with other porcine pathogenic viruses. Three hundred and twenty-five fecal samples were detected for PDCoV using the GICA strip and reverse transcription-quantitative real-time PCR (RT-qPCR). The coincidence rate of the GICA strip and RT-qPCR was 96.9%. The GICA strip had a diagnostic sensitivity of 88.9% and diagnostic specificity of 98.5%. The specific and efficient detection by the strip provides a convenient, rapid, easy to use and valuable diagnostic tool for PDCoV under laboratory and field conditions

Current landscape of fecal microbiota transplantation in treating depression

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies