Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis.

Obesity has been reported to promote disordered folliculogenesis, but the exact molecular mechanisms are still not fully understood. In this study, we find that miR-133a is involved in obesity-induced follicular development disorder. After feeding with a high-fat diet (HFD) and fructose water for nine weeks, the mouse body weight is significantly increased, accompanied by an inflammatory state and increased expression of miR-133a in the adipose tissues and ovaries as well as accelerated follicle depletion. Although miR-133a is increased in the fat and ovaries of HFD mice, the increased miR-133a in the HFD ovaries is not derived from exosome transferred from obese adipose tissues but is synthesized by ovarian follicular cells in response to HFD-induced inflammation. In vivo experiments show that intrabursal injection of miR-133a agomir induces a decrease in primordial follicles and an increase in antral follicles and atretic follicles, which is similar to HFD-induced abnormal folliculogenesis. Overexpression of miR-133a modestly promotes granulosa cell apoptosis by balancing the expression of anti-apoptotic proteins such as C1QL1 and XIAP and pro-apoptotic proteins such as PTEN. Overall, this study reveals the function of miR-133a in obesity-induced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.

Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.

Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including 3 AGOs and 3 DICER-like proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.

Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways.

BACKGROUND: Glabridin (Glab) is a bioactive component of licorice that can ameliorate diabetes, but its role in diabetic nephropathy (DN) has seldom been reported. Herein, we explored the effect and underlying mechanism of Glab on DN. METHODS: The bioactive component-target network of licorice against DN was by a network pharmacology approach. The protective effect of Glab on the kidney was investigated by a high-fat diet with streptozotocin induced-diabetic rat model. High glucose-induced NRK-52E cells were used for in vitro studies. The effects of Glab on ferroptosis and VEGF/Akt/ERK pathways in DN were investigated in vivo and in vitro using qRT-PCR, WB, and IHC experiments. RESULTS: Bioinformatics analysis constructed a network comprising of 10 bioactive components of licorice and 40 targets for DN. 13 matching targets of Glab were mainly involved in the VEGF signaling pathway. Glab treatment ameliorated general states and reduced FBG, HOMA-ß, and HOMA-insulin index of diabetic rats. The renal pathological changes and the impaired renal function (the increased levels of Scr, BUN, UREA, KIM-1, NGAL, and TIMP-1) were also improved by Glab. Moreover, Glab repressed ferroptosis by increasing SOD and GSH activity, and GPX4, SLC7A11, and SLC3A2 expression, and decreasing MDA and iron concentrations, and TFR1 expression, in vivo and in vitro. Mechanically, Glab significantly suppressed VEGF, p-AKT, p-ERK1/2 expression in both diabetic rats and HG-induced NRK-52E cells. CONCLUSIONS: This study revealed protective effects of Glab on the kidney of diabetic rats, which might exert by suppressing ferroptosis and the VEGF/Akt/ERK pathway.

A Comparison of the Performances of Artificial Intelligence System and Radiologists in the Ultrasound Diagnosis of Thyroid Nodules.

AIMS: The purpose of this paper is to prospectively evaluate the performance of an artificial intelligence (AI) system in diagnosing thyroid nodules and to assess its potential value in comparison with the performance of radiologists with different levels of experience, as well as the factors affecting its diagnostic accuracy. BACKGROUND: In recent years, medical imaging diagnosis using AI has become a popular topic in clinical application research. OBJECTIVE: This study aimed to evaluate the performance of an AI system in diagnosing thyroid nodules and compare it with the performance levels of different radiologists. METHODS: This study involved 426 patients screened for thyroid nodules at the First Affiliated Hospital of Guangzhou Medical University between July 2017 and March 2019. All of the nodules were evaluated by radiologists with various levels of experience and an AI system. The diagnostic performances of two junior and two senior radiologists, an AI system, and an AI-assisted junior radiologist were compared, as were their diagnostic results with respect to nodules of different sizes. RESULTS: The senior radiologists, the AI system, and the AI-assisted junior radiologist performed better than the junior radiologist (p < 0.05). The area under the curves of the AI system and the AI-assisted junior radiologist were similar to the curve of the senior radiologists (p > 0.05). The diagnostic results concerning the two nodule sizes showed that the diagnostic error rates of the AI system, junior radiologists, and senior radiologists for nodules with a maximum diameter of ≤1 cm (Dmax ≤ 1 cm) were higher than those for nodules with a maximum diameter of 1 cm (Dmax > 1 cm) (23.4% vs. 12.1%, p = 0.002; 26.6% vs. 7.3%, p < 0.001; and 38.3% vs. 14.6%, p < 0.001). CONCLUSION: The AI system is a decision-making tool that could potentially improve the diagnostic efficiency of junior radiologists. Micronodules with Dmax ≤ 1cm were significantly correlated with diagnostic accuracy; accordingly, more micronodules of this size, in particular, should be added to the AI system as training samples. Other: The system could be a potential decision-making tool for effectively improving the diagnostic efficiency of junior radiologists in the community.

Occurrence and Molecular Characterization of Abundant tet(X) Variants Among Diverse Bacterial Species of Chicken Origin in Jiangsu, China.

Many novel tigecycline-inactivating enzymes encoded by tet(X) variants from different bacteria were discovered since the plasmid-mediated tet(X3) and tet(X4) genes conferring high-level resistance to tigecycline in Enterobacterales and Acinetobacter were reported. However, there have been no comprehensive studies of the prevalence of different tet(X) variants in poultry farms. In this study, we collected 45 chicken fecal samples, isolated tet(X)-positive strains, and performed antimicrobial susceptibility testing, conjugation assay, whole-genome sequencing, and bioinformatics analysis. A total of 15 tet(X)-bearing strains were isolated from 13 samples. Species identification and tet(X) subtyping analysis found that the 15 strains belonged to eight different species and harbored four different tet(X) variants. Genomic investigation showed that transmission of tet(X) variants was associated with various mobile genetic elements, and tet(X4) was the most prevalent variant transferred by conjugative plasmids. Meanwhile, we characterized a plasmid co-harboring tet(X6) and bla OXA-58 in Acinetobacter baumannii. In summary, we demonstrated that different tet(X) variants were widely disseminated in the chicken farming environment and dominated by tet(X4). This finding expands the understanding of the prevalence of tet(X) among different animal sources, and it was advocated to reduce the usage of antibiotics to limit the emergence and transmission of novel tet(X) variants in the poultry industry.