Increased Expression and Altered Methylation of HERVWE1 in the Human Placentas of Smaller Fetuses from Monozygotic, Dichorionic, Discordant Twins

<div><h3>Background</h3><p>The human endogenous retroviral family W, Env(C7), member 1 gene (<em>HERVWE1</em>) is thought to participate in trophoblast cell fusion, and its expression is diminished in the placentas of singleton intrauterine growth-retarded pregnancies. However, there is limited information about the role of <em>HERVWE1</em> in discordant fetal growth in twins. This study was to compare <em>HERVWE1</em> gene expression between the placentas of discordant monozygotic twins and to identify its regulation by methylation.</p> <h3>Methodology/Principal Findings</h3><p>Fetuses from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked as “smaller” or “larger” according to birth weight. Placental <em>HERVWE1</em> mRNA and protein expression profiles were analyzed using quantitative RT-PCR and immunohistochemistry (IHC) staining. Methylation profiles of the <em>HERVWE1</em> promoter region were analyzed using a pyrosequencing assay. DNA methyltransferase (<em>DNMT</em>) transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained using an immunohistochemical assay. There was a significant negative correlation between <em>HERVWE1</em> mRNA levels and birth weight in twins (<em>P</em><0.01). Whereas the mean methylation level of the <em>HERVWE1</em> promoter region was diminished in the smaller group in discordant twins(<em>P</em><0.01), increased mRNA and protein levels of <em>HERVWE1</em> were found in smaller fetuses compared with larger fetuses in discordant twins(<em>P</em><0.01). There was no significant difference in 5-MC staining intensity between discordant twins (<em>P</em>>0.05). The <em>DNMT3b3</em> mRNA levels in the smaller group were significantly downregulated compared with the larger group in discordant twins(<em>P</em><0.05), whereas the <em>DNMT3b7</em> mRNA levels in the smaller group were significantly upregulated compared with the larger group in discordant twins(<em>P</em><0.05).</p> <h3>Conclusions/Significance</h3><p>In discordant, monozygotic, dichorionic twins, <em>HERVWE1</em> expression was higher in smaller fetuses and lower in larger fetuses. Methylation of the <em>HERVWE1</em> gene promoter region may participate in the regulation of <em>HERVWE1</em> gene expression in discordant twin pregnancies.</p> </div

SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense

Abstract Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose‐6‐phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH‐producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS. SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5‐dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation

Indigo: a natural molecular passivator for efficient perovskite solar cells

Organic–inorganic hybrid lead halide perovskite solar cells have made unprecedented progress in improving photovoltaic efficiency during the past decade, while still facing critical stability challenges. Herein, the natural organic dye Indigo is explored for the first time to be an efficient molecular passivator that assists in the preparation of high-quality hybrid perovskite film with reduced defects and enhanced stability. The Indigo molecule with both carbonyl and amino groups can provide bifunctional chemical passivation for defects. In-depth theoretical and experimental studies show that the Indigo molecules firmly binds to the perovskite surfaces, enhancing the crystallization of perovskite films with improved morphology. Consequently, the Indigo-passivated perovskite film exhibits increased grain size with better uniformity, reduced grain boundaries, lowered defect density, and retarded ion migration, boosting the device efficiency up to 23.22%, and ˜21% for large-area device (1 cm2). Furthermore, the Indigo passivation can enhance device stability in terms of both humidity and thermal stress. These results provide not only new insights into the multipassivation role of natural organic dyes but also a simple and low-cost strategy to prepare high-quality hybrid perovskite films for optoelectronic applications based on Indigo derivatives.Peer ReviewedPostprint (author's final draft

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

peer reviewedCurrent therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC

Investigation of co-pyrolysis characteristics and kinetics of municipal solid waste and paper sludge through TG-FTIR and DAEM

In order to explore a harmless and resource-based way to treat municipal solid waste (MSW) and paper sludge (PS), the co-pyrolysis MSW and PS was studied in this paper. Firstly, MSW and PS had the lower residue mass, and MSW had higher pyrolysis index under CO2 atmosphere, compared with the one under N-2 atmosphere. Hence, the CO2 was used as the carrier gas in the following study. Secondly, under CO2 atmosphere, the co-pyrolysis of MSW and PS with and without MgO were researched. With the increasing of PS ratio, the pyrolysis performance of the blends decreased constantly. MgO act as catalyst could improve the pyrolysis characteristic index of the blends. However, MgO was an inorganic salt and it would affect the synergistic effect of MSW and PS. The curves of online evolutions of all the gas products and the functional groups had an obvious peak at around 500 degrees C. The activation energy of the blends in the first step (<600.) were around 170 kJ/mol and reached more than 300 kJ/mol of the second step (600-1000.). In addition, the adding of MgO could decrease the activation energy of MSW, 50M50P and PS. Finally, 50M50P-M was suitable for treating more sludge. And these results could offer some referential information for designing and optimizing the co-pyrolysis technology for MSW and PS

Assessment of the temporal trend and daily profiles of the dietary purine intake among Chinese residents during 2014 to 2021

The incidence of hyperuricemia is on the rise in China, primarily due to dietary habits. However, limited data exists regarding dietary purine intake in the country. This study aimed to estimate the daily dietary purine intake among Chinese residents from 2014 to 2021 and evaluate the temporal trend using joinpoint regression analysis. The analysis revealed an annual percentage change (APC) of 0.8% (95% CI: 0.1–1.5%) in dietary purine intake prior to the joinpoint (2014–2019). Following the joinpoint (2019–2021), the APC significantly increased to 6.5% (95% CI: 3.3–9.8%), indicating a noteworthy upward trend (p = 0.045). Furthermore, the average daily purine intake varied significantly among different regions of China, with the southern region showing the highest dietary intake of purines. Considering the diverse contributions of various food sources to dietary purine intake, it was observed that meat consumption had the greatest impact, accounting for 36.2% of purine intake, followed by cereals consumption (25.3%) and vegetables and edible fungi (24.2%). These findings hold significance for dietary intervention and management strategies aimed at reducing purine intake among the population

Therapeutic Effects of Traditional Chinese Exercises on Musculoskeletal Pain: A Systematic Review and Meta-Analysis

Background. The number of patients with musculoskeletal pain, which seriously affects people’s quality of life, has increased. Traditional Chinese exercises are accepted and practiced to strengthen the body. Objective. This study aims to explore the efficacy of traditional Chinese exercises for the treatment of musculoskeletal pain. Methods. A comprehensive search of randomized controlled trials (RCTs) related to traditional Chinese exercises on patients with musculoskeletal pain was completed using PubMed, SinoMed, CNKI, VIP, and Wanfang Med Online databases. All RCTs published until February 2021 were considered. Two researchers independently screened the literature according to the predesigned inclusion and exclusion criteria, and data was extracted and assessed for their risk of bias via the Cochrane collaboration tool. Meta-analysis was performed using RevMan5.2 and Rx64 4.0.2 software. Results. A total of 45 RCT studies with 3178 patients were included. Traditional Chinese exercises were able to effectively alleviate patients with musculoskeletal pain (MD = −1.54, 95% confidence interval (−1.88, −1.19), P < 0.01). Among them, the Yi Jin Jing exercise was superior to other exercises, while Wu Qin Xi showed no significant effects. Besides, traditional Chinese exercises had significant positive effects on the dysfunction and stiffness of the waist and knee joints. Traditional Chinese exercises could effectively relieve the clinical symptoms of patients with musculoskeletal pain. Particularly, the Yi Jin Jing exercise presented the most significant positive effect on pain reduction

Nitrogen migration in sewage sludge chemical looping gasification using copper slag modified by NiO as an oxygen carrier

In view of the high cost and failure of resource utilization of waste copper slag, the copper slag modified by NiO is used as an oxygen carrier in the chemical looping gasification, where the sewage sludge is converted into syngas through the oxidation of copper slag. Additionally, current studies on nitrogen migration in chemical looping are limited to the detection of nitrogen compounds in gas products, and there is little research on nitrogen migration from raw materials to solid-liquid-gas products. Therefore, under different oxygen equivalent coefficients (Omega), steam contents, reaction times, and cycle number, the nitrogen changes in gas (Gas-N), tar (Tar-N) and char (Char-N) were investigated in this paper. With increasing of Omega (0-0.78), the oxidation and catalytic cracking reactions of the NOx precursors, Char-N and Tar-N were promoted, and the yield of N-2 increased from 52.49% to 91.98%. The addition of steam would lead to a significant increase in the yield of NOx precursors. The release of NH3 and HCN was mainly concentrated in the first 5 min. As the numbers of cycle increased, NH3-N and HCN-N both gradually decreased. Based on the above results, the distribution and migration mechanism of nitrogen species were also summarized. (C) 2021 Elsevier Ltd. All rights reserved

Investigation of the nitrogen migration characteristics in sewage sludge during chemical looping gasification

Increasing attention has been given to the control of nitrogen pollutants during the process of using sewage sludge. In this paper, the gasification characteristics and the law of nitrogen migration in the process of chemical looping gasification (CLG) of sewage sludge were explored. Copper slag calcined at 1100 degrees C (1100CS), FeAl (Fe2O3+Al2O3), NiFeAl (NiFe2O4+Al2O3), and NiAl (NiO + Al2O3) were used as oxygen carrier. The addition of an oxygen carrier could increase the carbon conversion rate and decrease the low heating value. NOx precursors (HCN and NH3) were the main nitrogen-containing gas pollutants (similar to 40%). The sum yield of char nitrogen and tar nitrogen was only similar to 10%. Nitrile nitrogen, heterocyclic nitrogen and amide nitrogen were the main nitrogenous compounds in tar nitrogen. Increasing the oxidative activity of the oxygen carrier could significantly promote the oxidative transformation of N-2 from the NOx precursors, tar nitrogen, char nitrogen. Additionally, the migration of fuel nitrogen includes synchronous autothermal pyrolysis (stage I) and oxidative pyrolysis of the three-phase product under the action of [O] (stage II). Finally, this research realizes the energy utilization of sludge and reduces the release of nitrogen pollutants. (C) 2020 Elsevier Ltd. All rights reserved