The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.

Proper RPA acetylation promotes accurate DNA replication and repair.

The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair. We show that yeast RPA is acetylated on multiple conserved lysines by the acetyltransferase NuA4 upon DNA damage. Mimicking constitutive RPA acetylation or blocking its acetylation causes spontaneous mutations with the signature of micro-homology-mediated large deletions or insertions. In parallel, improper RPA acetylation/deacetylation impairs DNA double-strand break (DSB) repair by the accurate gene conversion or break-induced replication while increasing the error-prone repair by single-strand annealing or alternative end joining. Mechanistically, we show that proper acetylation and deacetylation of RPA ensure its normal nuclear localization and ssDNA binding ability. Importantly, mutation of the equivalent residues in human RPA1 also impairs RPA binding on ssDNA, leading to attenuated RAD51 loading and homologous recombination repair. Thus, timely RPA acetylation and deacetylation likely represent a conserved mechanism promoting high-fidelity replication and repair while discriminating the error-prone repair mechanisms in eukaryotes.

RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.

The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1-H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial-temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability.

The Effects of Six Weeks of Fasted Aerobic Exercise on Body Shape and Blood Biochemical Index in Overweight and Obese Young Adult Males.

Background/Objective: The effects of fasted aerobic exercise on body composition and whether it causes adverse effects remain controversial. This study was to compare the effects of fasted and non-fasted aerobic exercise on body shape and blood biochemical indexes in overweight and obese young adult males, and observe whether FAE triggers adverse reactions. Methods: Thirty overweight and obese young adult males were randomly divided into fasted aerobic exercise (FAE) group, non-fasted aerobic exercise (NFAE) group, and control group. They were subjected to indoor treadmill intervention five days a week combined with diet control for six weeks. The FAE group had breakfast 0.5 h after exercise, and the NFAE group exercised 1 h after breakfast. Both groups filled out adverse reaction questionnaires during exercise, and the control group did not have any intervention. Height, weight, body mass index (BMI), and body fat percentage of the three groups of subjects before and after the experiment were measured by the GAIA KIKO bio-resistance antibody composition analyzer in Korea; waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were measured by the tape measure method; fasting plasma glucose (FPG), fasting insulin (FINs), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), and HDL-C/LDL-C were measured by Roche C8000 automatic biochemical analysis instrument. Results: Weight, BMI, body fat percentage, WC, HC, WHR, WHtR, TG, TC, LDL-C and VLDL decreased very significantly (P < 0.01) in the FAE and NFAE groups after the 6-week experiment. The decrease in FINS was significant in the FAE group (P < 0.05) and the decrease in HDL-C was very significant in the NFAE group (P < 0.01). There was no significant difference in the frequency of adverse reactions between two groups (P > 0.05). Conclusion: Six-week FAE and NFAE significantly improved body shape in overweight and obese young adult males, while FAE significantly reduced fasting insulin levels and increased tissue cell sensitivity to insulin. And compared to NFAE, 30 min of FAE in the morning did not increase adverse effects.

Value of transvaginal three-dimensional ultrasound in evaluating the curative effect of Yangmo decoction in the treatment of uterine adhesion. / ç»é˜´é“ä¸‰ç»´è¶ å£°åœ¨åˆ¤æ–­å »è†œæ–¹æ²»ç–—å®«è ”ç²˜è¿žæ•ˆæžœä¸­çš„ä»·å€¼.

OBJECTIVES: Intrauterine adhesions (IUA) is the damage of the basal layer of the endometrium caused by various reasons, resulting in adhesion of the uterine muscle walls to each other, which is manifested as clinical symptoms such as spanomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis (HA) is the main treatment, for patients with moderate or severe adhesion or angular adhesion, the incidence of postoperative adhesion is high. Traditional Chinese medicine "Yangmo decoction" can promote endometrial growth. Three-dimensional transvaginal ultrasonography (3D-TVUS) can judge IUA and evaluate uterine receptivity through three-dimensional imaging. This study aims to investigate the value of 3D-TVUS in judging the efficacy of Yangmo decoction in the treatment of intrauterine adhesions. METHODS: The clinical data of patients who underwent HA at two different centers in department of Gynecology of Third Xiangya Hospital of Central South University and Changsha Jiangwan Hospital from January 2021 to August 2021 were retrospectively collected. A total of 275 eligible patients were included. According to the postoperative management measures, the selected patients were divided into two groups. Yangmo decoction group (n=138): the use of Yangmo decoction and uterine-shaped silicon stent post HA; Hormone group (n=137): the use of estrogen, progesterone and uterine-shaped silicon stent post HA. The preoperative general data, preoperative and postoperative 3D-TVUS parameters of the two groups were analyzed. RESULTS: The endometrial thickness of Yangmo decoction group was thicker than that of hormone group (P<0.001), the intercornual distance was wider (P=0.016), the endometrial echo was more homogeneous (P=0.018), the percentage of bilaterally visible tubal opening was higher (P<0.001), the endometrial morphology was better (P=0.012), and endometrial blood flow, endometrial motility and uterine motion were better in Yangmo decoction group than that in the hormone group (all P<0.001). CONCLUSIONS: The endometrial thickness, echo, blood flow, and peristalsis, the number of visible tubal opening, uterine motion, and the intercornual distance obtained by 3D-TVUS examination are important factors to evaluate the prognosis of postoperative drug treatment for IUA. 3D-TVUS is of great significance in evaluating the efficacy of Yangmo decoction in the treatment of IUA.

Playing Ant Forest to promote online green behavior: A new perspective on uses and gratifications.

The popularity of Internet technology has resulted in people's lives being increasingly embedded in this network. The rise in usage of environmental protection apps has become a powerful tool in driving offline environmental protection activities and green lifestyles. However, little is known about the public's online green behavior. To fill this gap, we took Ant Forest, the most influential online environmental protection project in China, as a case study to explore the driving psychology of Ant Forest users' continuous use behaviors (CUBs) by expanding the use and gratifications theory. The proposed hypotheses were tested using a structural equation model based on data from 951 Ant Forest users. The results showed that users' gratification is an important psychological motivation that encourages CUBs in Ant Forest, and the different dimensions of gratification have significant differences in the driving intensity of the three types of CUBs. Moreover, emotional dependence moderates the relationships between gratifications and CUBs. Finally, from the perspective of cultivating gratification, this study suggests promoting the continuous use of Ant Forest as it provides a reference for understanding and developing online green behavior.

Evaluating Whether and How Public Health Event Information Frameworks Promote Pro-Environmental Behavior.

The major public health emergencies (PHEs) represented by the COVID-19 pandemic, while posing a serious threat to human health, have led people to rethink about the harmonious relationship between humans and nature. It is worthy to explore whether and how the framework effect of event information can be used to turn crises into opportunities to promote public pro-environmental behavior (PEB). Through a pre-and post-test control experiment, this study took the COVID-19 pandemic as a case, to explore the effects of four PHE information frameworks on promoting PEB, coupled with two information loss-gain frameworks and two information content frameworks. The results showed that all four information frameworks contribute to the public PEB. However, there are differences: only the environmental gain information effect is significant for PEB in the private sphere. The environmental loss and health gain information are effective for PEB in organizations. However, in the public sphere, all four information frameworks significantly motivate PEB. Further factorial analysis revealed that the interaction between the information content and loss-gain framework was not significant, with the latter playing the dominant role. These findings provide a new approach to how to develop the information framework effect and turn crises into opportunities to promote public PEB in the context of major PHEs.

Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Comparison of high-intensity focused ultrasound ablation and uterine artery embolization in the management of cervical pregnancy.

Background: Cervical pregnancy (CP) is an uncommon type of ectopic pregnancy with a rising risk to life. Currently, there is no universal protocol for the safe and effective management of CP. This study aimed to investigate the clinical efficacy of high-intensity focused ultrasound ablation (HIFU) vs. uterine artery embolization (UAE) in the management of CP to develop a standard for the treatment of CP. Methods: From January 2015 to October 2021, 36 patients with CP were diagnosed, treated, and followed up at the Department of Gynecology of Third Xiangya Hospital of Central South University. A total of 11 patients were treated with HIFU followed by suction curettage under hysteroscopic guidance, and 25 patients were treated with UAE followed by suction curettage under hysteroscopic guidance. Medical records and pregnancy outcomes were retrospectively analyzed. Results: Compared to the UAE group, the HIFU group had a shorter interval time (1.5 ± 0.21 days vs. 2.6 ± 0.26 days), shorter duration of hospitalization (5.5 ± 0.31 days vs. 6.6 ± 0.21 days), shorter recovery time of menstruation (30.6 ± 7.09 days vs. 36.9 ± 5.54 days), fewer adverse reactions (0/11 vs. 9/25), and fewer postoperative complications (1/11 vs. 8/25). There were no significant differences in age, gravidity, parity, abortion, gestational age, cardiac pulsation, admission symptoms, hemoglobin level, largest diameter of the sac/mass, serum human chorionic gonadotropin (hCG) level at admission, hospitalization expenses, hospitalization days, blood loss during curettage, degree of hCG decline, residue after curettage, fertility requirement, and pregnancy outcomes. Conclusion: Both HIFU and UAE are safe and effective in the treatment of patients with CP. Compared to UAE, HIFU treatment for CP is a safer and more effective therapeutic schedule owing to the advantages of being more minimally invasive, shorter interval time, shorter hospitalization days and recovery time of menstruation, fewer adverse reactions, and fewer postoperative complications.

Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.

Histone acetylation is a key histone post-translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl-lysines, are located in the center of the histone acetylation-signaling network. How they regulate DNA repair and genome stability remains poorly understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is reported in promoting DNA double-stranded break repair by homologous recombination (HR). Depletion of either yeast BDF1 or human TAF1, or disruption of their BRDs impairs DNA end resection, Replication Protein A (RPA) and Rad51 loading, and HR repair, causing genome instability and hypersensitivity to DNA damage. Mechanistically, it is shown that Bdf1 preferentially binds the DNA damage-induced histone H4 acetylation (H4Ac) via the BRD motifs, leading to its chromatin recruitment. Meanwhile, Bdf1 physically interacts with RPA, and this interaction facilitates RPA loading in the chromatin context and the subsequent HR repair. Similarly, TAF1 also interacts with H4Ac or RPA. Thus, Bdf1 and TAF1 appear to share a conserved mechanism in linking the HR repair to chromatin acetylation in preserving genome integrity.

Assessing the effect of non-financial information intervention on promoting group-level energy savings.

Increasing attention has been paid to information intervention in stimulating household energy conservation. However, for group-level energy users who have no financial motivation to save energy, little is known about which types of non-financial information intervention (NFII) strategies can effectively motivate group-level energy conservation. A 14-week controlled field experiment was conducted to test the energy-saving effect of 4 types of NFII strategies. The results show that compared with the control group, the experimental group receiving normative information and group-contrast feedback decreased electricity consumption by 24.23%. Followed by the group receiving normative information and self-contrast feedback and the group receiving environmental education information and group-contrast feedback. The group receiving environmental education information and self-contrast feedback showed no significant energy savings. Analysis of variance further showed that normative information had a better energy-saving effect than environmental education information, and the energy-saving effects produced by group-contrast feedback were better than that of self-contrast feedback. These conclusions provide insights and recommendations on how to use NFII to motivate group-level energy conservation.

Promoting Employee Green Behavior Through the Person-Organization Fit: The Moderating Effect of Psychological Distance.

The importance of employee green behavior (EGB) to an enterprise's green development goal is increasingly emphasized in many industries. However, to date promoting EGB through interaction, namely between individuals and organizations, has not been a central concern. Therefore, from the perspective of the person-organization fit, this study considers the psychological distance between employees and the organization as a moderating variable, exploring the mechanisms of values fit, needs-supplies fit, and demands-abilities fit on green behaviors as within and outside the scope of employee responsibility. After collecting the results of questionnaires from 412 employees, our hypotheses were tested using the Structural Equation Model (SEM). The results show that (1) person-organization fit can effectively promote EGB in the workplace. However, different types of person-organization fit have different influencing paths and effect-strengths on employees' task-related green behavior and proactive green behavior. (2) Values fit has the greatest incentive effect on EGB, followed by demands-abilities fit, while needs-supplies fit promotes only eco-helping behavior. (3) Psychological distance has a significant moderating effect on the relationship between the person-organization fit and EGB. The effect of person-organization fit on EGB is enhanced when employees are close with less emotional distance, while the effect is weakened in the case of close expectation distance. Finally, this study provides suggestions for enterprise managers providing ways to motivate EGB through the selection and allocation of human resources.