Paraprobiotics are potential agents for improving animal health and performance. This experiment investigated the effect of dietary supplementation of yeast (Saccharomyces cerevisiae) culture (YC) on the growth performance, nutrient digestibility, rumen development and microbiome of fattening sheep. Ninety male Hu sheep weighed 38 ± 1.47 kg were randomly assigned to three treatments: CON diet (basal diet), LYC diet (basal diet supplied with 10 and 20 g/d yeast culture at the early and late stages, respectively), and HYC diet (basal diet supplied with 20 and 40 g/d yeast culture at the early and late stages, respectively). Treatments (LYC or HYC) were sprinkled on the feed surface according to the required dosage before feeding the basal diet to each sheep throughout the trial. The trial included early (60 days) and later (30 days) fattening periods. The results showed that average daily gain and feed efficiency were higher (p < 0.05) in the LYC group compared with CON in later and whole stages. Digestibility of DM, OM, CP, NDF and ADF were higher (p < 0.05) in LYC and HYC compared with CON. The retained N, the utilization efficiency of N and the biological value of N were higher (p < 0.05) in LYC compared with CON and HYC. Rumen NH₃-N was higher (p < 0.05) in LYC and HYC. The papillary height of the rumen was higher (p < 0.05) in LYC when compared with CON and HYC, whereas rumen wall thickness and muscular layer thickness were higher (p < 0.05) in HYC compared with CON and LYC. The dressing percentage of LYC and HYC was higher (p < 0.05) compared with CON. The diversity, richness and structure of rumen microbiota showed no significant difference (p > 0.05); however, still observed remarkable increases in the relative abundance of several specific genera including Succiniclasticum and Fibrobacter with increasing doses of yeast culture. In addition, at the ASV level, ASV83, ASV123 (Succiniclasticum), and ASV148, ASV250 (Fibrobacter) were increased in YC groups. In conclusion, we confirmed that the supplementation of YC in diet could improve the growth and slaughter performance of fattening Hu sheep through improving nutrient digestion, especially nitrogen utilization, rumen microbial environment and the development of rumen epithelium, which proves the benefits of paraprobiotics in animal production.

Background: Osteogenesis imperfecta (OI) is marked by clinical and genetic heterogeneity, and the genotype–phenotype correlation remains not very clear. We conducted a clinical and genetic study in a Chinese OI cohort to determine the spectra of phenotypes and pathogenic variants. Methods: In this study, 298 Chinese families were recruited from 2019 to 2024. Clinical phenotypes including fractures, short stature, skeletal deformities, blue sclera, dentinogenesis imperfecta, and hearing loss were recorded and analyzed. Next-generation sequencing combined with PCR-based techniques was used to detect candidate pathogenic variants. Variant pathogenicity was evaluated via conservation analysis, bioinformatics analysis, and functional studies at the cellular level. In this OI cohort, the spectra of pathogenic variants, clinical phenotypes, and genotype–phenotype correlations were analyzed. Results: Our OI cohort included 71 type I (23.83%), 122 type III (40.94%), 90 type IV (30.20%), and 15 type V (5.03%) probands. The cohort consisted of 196 children (65.77%) and 102 adults (34.23%). For the first time, phenotypic differences between different age groups were confirmed. In total, we identified 231 variants, including 47 novel pathogenic variants. Notable variants include two atypical splicing variants, one small deletion, two small duplications, one gross deletion, and one gross duplication. New genotype–phenotype correlations were observed: patients with SERPINF1 variants had the highest fracture frequency, followed by those with WNT1 variants, compared to patients with other gene variants. Conclusions: We performed the clinical and genetic analysis in a large Chinese OI cohort. The expanded spectra of genetic variants and clinical phenotypes were constructed by identifying 47 novel pathogenic variants and summarizing the skeletal and extra-skeletal manifestations. The current paper will provide important evidence for the precise diagnosis of the disease.

Background This article reports and discusses the biochemical and genetic characteristics of four very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD.Methods Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS) and high-throughput sequencing technology. New mutations were analyzed for pathogenicity using bioinformatics software. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of very-long-chain acyl-CoA dehydrogenase (VLCAD)protein.Result A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10 and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and neonatal period,respectively. Seven kinds of mutations were detected, including four novel mutations. The bioinformatics software revealed that the mutations were harmful, and the Swiss PDB Viewer results suggest that variation affects protein conformation.Conclusions This study identified four novel ACADVL gene mutations. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.

Objectives Iodide transport defect (ITD) is one of the principal causes of congenital hypothyroidism (CH) and its primary molecular mechanism is a mutation of the sodium/iodide symporter (NIS) gene. This study aims to analyse the clinical characteristics and genetic mutations of ITD. Methods The participants were a pair of siblings diagnosed with congenital hypothyroidism. Inductively coupled plasma mass spectrometry was used to determine the concentration of salivary iodine and serum iodine and to calculate their ratio. At the same time, next-generation sequencing (NGS) was applied to detect all exons of congenital hypothyroidism-related genes. All suspicious variants were further validated in the patients and their parents by PCR and Sanger sequencing. Results Both patients were conclusively diagnosed with thyroid iodine transport defect (ITD). NGS identified two variants of the NIS gene in the siblings: c.1021G>A (p.Gly341Arg) with paternal origin and c.1330-2A>C with maternal origin. Both of these variants have not been reported to date. They are predicted to be pathogenic based on these clinical symptoms and comprehensive software analysis. Conclusions This is the first reported family study of congenital hypothyroidism with SLC5A5 mutation in China. Next-generation sequencing technology is an effective means of studying the genetics of congenital hypothyroidism. The therapeutic effect of potassium iodide needs to be further evaluated.