Sirtuin 6 maintains epithelial STAT6 activity to support intestinal tuft cell development and type 2 immunity

Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD+-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection

Design and characterization of the SPT-3G receiver

The SPT-3G receiver was commissioned in early 2017 on the 10-meter South Pole Telescope (SPT) to map anisotropies in the cosmic microwave background (CMB). New optics, detector, and readout technologies have yielded a multichroic, high-resolution, low-noise camera with impressive throughput and sensitivity, offering the potential to improve our understanding of inflationary physics, astroparticle physics, and growth of structure. We highlight several key features and design principles of the new receiver, and summarize its performance to date

Effect of Delaminated MXene (Ti3C2) on the Performance of Cement Paste

Delaminated MXene was incorporated into cement to improve the properties of cement composites, and its effects on the hydration process, microstructures, and mechanical properties were investigated, respectively. The investigation results showed that delaminated MXene was well-dispersed in the cement matrix and significantly reinforced the compressive strength of cement, especially when the addition is 0.01 wt%. Meanwhile, the total hydration heat of cement hydration and the quantity of hydration products were increased with the addition of delaminated MXene. In addition, the formation of HD C-S-H gel was promoted, and the microstructure of hydrated cement became more compact

Voluntary Medical Male Circumcision and Incident HIV Infection Among Men Who Have Sex With Men in China (The CoM Study): Protocol for a Randomized Controlled Trial

BackgroundSystematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. ObjectiveThe primary objective of this study is to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. MethodsA multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. ResultsRecruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. ConclusionsThis study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. Trial RegistrationChinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369 International Registered Report Identifier (IRRID)DERR1-10.2196/4716