Insm1 regulates mTEC development and immune tolerance.

The expression of self-antigens in medullary thymic epithelial cells (mTECs) is essential for the establishment of immune tolerance, but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood. Here, we show that Insm1, a zinc finger protein with known functions in neuroendocrine and neuronal cells, is broadly coexpressed with an autoimmune regulator (Aire) in mTECs. Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells. Mutation of Insm1 in mice downregulated Aire expression, dysregulated the gene expression program of mTECs, and altered mTEC subpopulations and the expression of tissue-restricted antigens. Consistent with these findings, loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues. We found that Insm1 regulates gene expression in mTECs by binding to chromatin. Interestingly, the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions. Together, our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.

Bibliometric and Correlation Analysis of Bariatric Surgery Researches in Asia-Pacific from 2000 to 2021.

INTRODUCTION: Bariatric surgery has grown in popularity over the past two decades, especially in the Asia-Pacific. Correspondingly, researchers' interest in this field has also increased. This study aims to perform a bibliometric analysis of publications from Asia-Pacific represented by the International Federation for the Surgery of Obesity and Metabolic Disorders Asia-Pacific Chapter (IFSO-APC) and investigate the relevant factors that might affect the publications. METHODS: The search terms for bariatric surgery were searched in Web of Science focusing on the period 2000-2021. Bibliometric analysis was performed after screening the search results. Univariate and multivariate regression analyses were performed on the number of publications and corresponding indicators obtained from official agencies. RESULTS: A total of 9,547 publications in IFSO-APC were retrieved, of which China had the largest number with 2,782 publications. Authors and journals with major contributions were listed. The authors' or affiliations' cooperation networks mainly were limited to domestic. "Bariatric surgery" was the most frequent keyword with 2,063 times and also the largest cluster. "Morbid obesity" was the strongest citation bursts. Multivariate analysis found that the number of publications in each country/region was associated with body mass index ≥25 kg/m2, gross domestic product, and total population. CONCLUSION: Generally, Asia-Pacific represented by IFSO-APC scientific publications on bariatric surgery has grown significantly in the last two decades, but cooperation between countries/regions should be strengthened. "Morbid obesity" is the focus and frontier of research in this field.

A Retrospective Evaluation of Pregnancy Outcomes Following Bariatric Surgery: A Single-Center Experience.

Background: Bariatric and metabolic surgery (BMS) is an effective treatment for obesity and its complications, but its effect on pregnancy outcomes is inconclusive. The present study aimed to investigate women's pregnancy status and outcomes as well as the impact of pregnancy intervals after BMS. Methods: The menstrual cycle and fertility status of women who underwent BMS in our centre between July 2010 and January 2021 were retrospectively analyzed and followed up until one-year post-delivery. The pregnancy outcomes after BMS were observed, including changes in weight, pregnancy interval, pregnancy complications, weight and health status of the newborn (premature birth, admission to neonatology, or deformity). Results: We identified 31 women who were successfully conceived after BMS. There were statistical differences in weight and menstrual status before and post-operation (P < 0.05), and 77.97% of them had remission or recovery of obesity-related comorbidities. Eighteen patients delivered successfully after BMS, but there were still 12 cases of spontaneous abortion and 1 case of induced abortion. The abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years (P = 0.045). Of the women who delivered successfully, 5 had pregnancy-specific complications, including gestational diabetes mellitus and hypertensive disorder of pregnancy. However, the growth and development of the newborn are normal since the birth follow-up. Conclusion: The present results suggest that the abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years. It is recommended that postoperative patients avoid pregnancy until their weight is stable to reduce the risk of adverse pregnancy outcomes.

Field-effect transistor bioassay for ultrasensitive detection of folate receptor 1 by ligand-protein interaction.

A miniaturized and integrated bioassay was developed based on molybdenum disulfide (MoS2) field-effect transistor (FET) functionalized with bovine serum albumin-folic acid (BSA-FA) for monitoring FOLR1. We performed the electrical test of FOLR1 within the range 100 fg/mL to 10 ng/mL, and the limit of detection was 0.057 pg/mL. The ultrahigh sensitivity of the bioassay was realized by ligand-protein interaction between FA and FOLR1, with a ligand-protein binding ratio of 3:1. The formation of FA-FOLR1 was confirmed with ELISA. The binding affinity dissociation constant KD was 12 ± 6 pg/mL. This device can work well for FOLR1 detection in human serum, which presents its promising application in point-of-care diagnosis. This study supports the future applications of such ligand-protein-based bioassays in the clinical practices. Graphical abstract MoS2-based FET device for detecting folate receptor 1 (FOLR1) was fabricated. The molecular folic acid as a probe can specifically bound to FOLR1 with a high affinity.

Developing chemically modified redox-responsive proteins as smart therapeutics.

The conditional control of protein function in response to the physiological changes of diseased cells is essential to develop smart protein therapeutics. Herein, we report a redox-responsive chemical modification of a protein by conjugating an intracellular glutathione (GSH)-cleavable ligand, NSA, onto a protein residue. We demonstrated that the NSA conjugation of Ribonuclease A (RNase A) enabled the control of the protein function by GSH in an aqueous solution and living cells, with extended applications for targeted cancer therapy using a lipid nanoparticle-based intracellular protein delivery strategy.

The Learning Curve for Surgeons Regarding Endoscopic Thyroidectomy via the Oral-vestibular Approach.

BACKGROUND: For selected patients, endoscopic thyroidectomy via the oral-vestibular approach (ETOVA) can be used to achieve a very good esthetic effect. This study aimed to assess the learning curve for ETOVA and identify improvements. PATIENTS AND METHODS: This retrospective study evaluated the outcomes of 101 patients who underwent ETOVA by surgeons A and B. The patients were classified according to whether they had undergone surgery during the primary or advanced stage of the learning curve, respectively. Proficiency with the procedure in various types of cases and the operation time, operative blood loss, hospital stay length, and postoperative complications were analyzed. RESULTS: In total, 56 and 45 patients were treated by surgeons A and B, respectively. For both surgeons, the operation times decreased considerably after 20 cases. Statistically significant differences with respect to stage were observed in terms of operation time (P<0.05) and drainage tube reservation (P<0.05). By contrast, significant differences were not observed between stages in terms of operative blood loss (P>0.05) or postoperative hospital stay length (P>0.05). The total postoperative complication rate was low and comparable with that of open surgery. CONCLUSIONS: The specific learning curve identified for ETOVA suggests that surgeons with sufficient endoscopic surgery experience could achieve a stable proficiency after ∼20 cases. A standardized training program and exposure to more cases would reduce the learning curve.