Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair.

The tumor-suppressor breast cancer 1 (BRCA1) in complex with BRCA1-associated really interesting new gene (RING) domain 1 (BARD1) is a RING-type ubiquitin E3 ligase that modifies nucleosomal histone and other substrates. The importance of BRCA1-BARD1 E3 activity in tumor suppression remains highly controversial, mainly stemming from studying mutant ligase-deficient BRCA1-BARD1 species that we show here still retain significant ligase activity. Using full-length BRCA1-BARD1, we establish robust BRCA1-BARD1-mediated ubiquitylation with specificity, uncover multiple modes of activity modulation, and construct a truly ligase-null variant and a variant specifically impaired in targeting nucleosomal histones. Cells expressing either of these BRCA1-BARD1 separation-of-function alleles are hypersensitive to DNA-damaging agents. Furthermore, we demonstrate that BRCA1-BARD1 ligase is not only required for DNA resection during homology-directed repair (HDR) but also contributes to later stages for HDR completion. Altogether, our findings reveal crucial, previously unrecognized roles of BRCA1-BARD1 ligase activity in genome repair via HDR, settle prior controversies regarding BRCA1-BARD1 ligase functions, and catalyze new efforts to uncover substrates related to tumor suppression.

miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.

Genomic characterization of dryland adaptation in endangered Anxi cattle in China.

Local species exhibit distinctive indigenous characteristics while showing unique productive and phenotypic traits. However, the advent of commercialization has posed a substantial threat to the survival of indigenous species. Anxi cattle, an endangered native breed in China, have evolved unique growth and reproductive characteristics in extreme desert and semidesert ecosystems. In this study, we conducted a genomic comparison of 10 Anxi cattle genomes with those of five other global populations/breeds to assess genetic diversity and identify candidate genomic regions in Anxi cattle. Population structure and genetic diversity analyses revealed that Anxi cattle are part of the East Asian cattle clade, exhibiting higher genetic diversity than commercial breeds. Through selective sweep analysis, we identified specific genetic variations linked to the environmental adaptability of Anxi cattle. Notably, we identified several candidate genes, including CERS3 involved in regulating skin permeability and antimicrobial functions, RBFOX2 associated with cardiac development, SLC16A7 participated in the regulation of pancreatic endocrine function, and SPATA3 related to reproduction. Our findings revealed the distinctive genomic features of Anxi cattle in dryland environments, provided invaluable insights for further research and breed preservation, and had important significance for enriching the domestic cattle breeding gene bank.

Increased level of RAB39B leads to neuronal dysfunction and behavioural changes in mice.

Duplications of the Xq28 region are a common cause of X-linked intellectual disability (XLID). The RAB39B gene locates in Xq28 and has been implicated in disease pathogenesis. However, whether increased dosage of RAB39B leads to cognitive impairment and synaptic dysfunction remains elusive. Herein, we overexpressed RAB39B in mouse brain by injecting AAVs into bilateral ventricles of neonatal animals. We found that at 2 months of age, neuronal overexpression of RAB39B impaired the recognition memory and the short-term working memory in mice and resulted in certain autism-like behaviours, including social novelty defect and repetitive grooming behaviour in female mice. Moreover, overexpression of RAB39B decreased dendritic arborization of primary neurons in vitro and reduced synaptic transmission in female mice. Neuronal overexpression of RAB39B also altered autophagy without affecting levels and PSD distribution of synaptic proteins. Our results demonstrate that overexpression of RAB39B compromises normal neuronal development, thereby resulting in dysfunctional synaptic transmission and certain intellectual disability and behavioural abnormalities in mice. These findings identify a molecular mechanism underlying XLID with increased copy numbers of Xq28 and provide potential strategies for disease intervention.

TGF-ß signaling promotes cervical cancer metastasis via CDR1as.

BACKGROUND: Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-ß pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear. METHODS: After agonist of TGF-ß treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed. RESULTS: CDR1as was found upregulated obviously following TGF-ß activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-ß signaling factors known to promote EMT, including P-Smad2 and P-Smad3. CONCLUSIONS: Our study proved TGF-ß signaling may promote cervical cancer metastasis via CDR1as.

Development and evaluation of a culturally adapted digital-platform integrated multifaceted intervention to promote the utilization of maternal healthcare services: a single-arm pilot study.

BACKGROUND: The utilization of hospital delivery and antenatal care (ANC) is essential for improving maternal and newborn outcomes. However, social and cultural barriers in underdeveloped rural areas hindered maternal care utilization. This study aims to design and evaluate the effectiveness of a culturally adapted digital-platform intervention to promote maternal care utilization among women in ethnic minority communities in China. METHODS: From January 1st, 2020, to December 31st, 2021, all pregnant women in Mianshan town, Liangshan Autonomous Prefecture, were invited to participate in the intervention. The multifaceted intervention included participatory and cultural-tailored health education on a popular social media platform, transportation subsidies, and capacity building and economic incentives for healthcare providers. The effectiveness of the intervention was evaluated by comparing two groups: mothers who gave live birth before the intervention (January 1st to December 31st, 2019) and mothers whose entire pregnancy period was covered by the intervention. The primary outcomes were the rate of hospital delivery and ANC utilization. Data on pregnant women were retrospectively collected through telephone surveys and the maternal and newborn's health monitoring system. RESULTS: A total of 237 intervention sample and 138 pre-intervention sample were included. The intervention group demonstrated significantly higher rates of hospital delivery (97.5% vs. 87.7%, p < 0.001), timely initiation of ANC (73.0% vs. 62.3%, p = 0.031), and timely completion of five-time ANC visits (37.1% vs.4.3%, p < 0.001) compared to the pre-intervention group. The intervention group was more likely to utilize hospital delivery (OR = 9.26, 95%CI [2.83-30.24], p < 0.001) and ANC, including timely initiation of ANC (OR = 2.18, 95%CI [1.31-3.62], p = 0.003), completion of five ANC visits (OR = 1.72, 95%CI [1.05-2.83], p = 0.032), and timely completion of five ANC visits (OR = 15.12, 95%CI [6.24-36.64], p < 0.001). CONCLUSIONS: The culturally adapted digital-platform integrated multifaceted intervention effectively promoted the utilization of hospital delivery, timely initiation of ANC, and completion of ANC visits in the Yi ethnic community in China. This study provides valuable insights for future interventions targeting maternal healthcare services in underdeveloped ethnic minority communities worldwide. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300073219. Registered 4 July 2023 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=199202 .

Cigarette Gifting Among Nonsmokers in China: Findings From the International Tobacco Control China Survey.

INTRODUCTION: Cigarette gifting is commonly practiced in China and has contributed to the social acceptability and high prevalence of cigarette smoking in the country. As a result, nonsmokers in China are particularly susceptible to smoking. While previous studies have examined cigarette gifting behaviors among smokers, little is known about cigarette gifting among nonsmokers. AIMS AND METHODS: This study aimed to examine the percentage and correlates of giving and receiving cigarettes as gifts among adult nonsmokers in China. We analyzed nonsmokers (N = 1813) aged ≥18 years using data from the International Tobacco Control China Wave 5 Survey. Descriptive statistics summarized the characteristics of those who gave and received cigarettes as gifts. Multivariable logistic regression models were used to identify factors associated with the two behaviors. RESULTS: Among nonsmokers, 9.9% reported giving cigarettes as gifts to family or friends in the last 6 months. A higher level of knowledge about smoking harms was associated with lower adjusted odds of gifting cigarettes. Nonsmokers aged 25-39 years, with middle income, positive attitude toward cigarette gifts, exposure to anti-smoking information, and exposure to smoking promotion, and those who reported receiving cigarettes as gifts from family or friends were more likely to give cigarettes as gifts. A total of 6.6% of nonsmokers reported receiving cigarettes as gifts in the last 6 months. High education, neutral or positive attitude toward cigarette gifts, exposure to anti-smoking information, exposure to smoking promotion, and having smoking friends were associated with receiving cigarettes as gifts. CONCLUSIONS: It is concerning that Chinese cultural norms that support cigarette gifting have extended to giving nonsmokers cigarettes as gifts. Effective anti-smoking messages are needed. Changing the norms around cigarette gifting and increasing knowledge about smoking harms should help reduce cigarette gifting among nonsmokers. IMPLICATIONS: Easy access to cigarettes received as gifts, along with the wide acceptance of smoking in China, places Chinese nonsmokers in a risky position. More educational campaigns targeting nonsmokers to proactively prevent them from smoking are called for. The ineffectiveness of existing anti-smoking information highlights the need for more effective anti-smoking messages. That attitude toward cigarette gifts is the strongest predictor of giving cigarettes as gifts suggests the need for interventions to reverse the positive attitude about cigarette gifting to decrease the popularity of this activity.

Healthcare utilisation and expenditures attributable to current e-cigarette use among US adults.

AIMS: This study estimated annual healthcare expenditures attributable to current e-cigarette use among US adults, including current exclusive and dual/poly e-cigarette use. METHODS: Analysing the 2015-2018 National Health Interview Survey data, we estimated the impacts of e-cigarette use on healthcare utilisation among adults aged 18+ years. Healthcare utilisation outcomes were hospital nights, emergency room (ER) visits, doctor visits and home visits. Current e-cigarette use was categorised as exclusive and dual/poly e-cigarette use. The econometric model included two equations: health status as a function of e-cigarette use and other independent variables, and healthcare utilisation as a function of health status, e-cigarette use, and other independent variables. Using an 'excess utilisation' approach, we multiplied the e-cigarette-attributable fraction derived from the model by annual health expenditures to calculate healthcare expenditures attributable to current exclusive and dual/poly e-cigarette use, the sum of which were expenditures attributable to all current e-cigarette use. RESULTS: Current exclusive and dual/poly e-cigarette use, with 0.2% and 3.5% prevalence in 2015-2018, were associated with higher odds of reporting poor health status than never tobacco users. Poor health status was associated with higher odds of using the four healthcare services and a greater number of ER and doctor visits. Annual healthcare expenditures attributable to all current e-cigarette use was $15.1 billion ($2024 per user) in 2018, including $1.3 billion attributable to exclusive e-cigarette use ($1796 per user) and $13.8 billion attributable to dual/poly e-cigarette use ($2050 per user). CONCLUSION: Adult current e-cigarette use was associated with substantial excess healthcare utilisation and expenditures.

Association between e-cigarette use and food insecurity among low-income adults.

INTRODUCTION: Previous research quantifying the relationship between tobacco use and food insecurity has focused on cigarette smoking. E-cigarette use has become popular in recent years. Drawing on large, population-based survey data, this study augments the previous research, considering the association of e-cigarette use with food insecurity among low-income adults. METHODS: We analysed data from the California Health Interview Survey in 2014-2019. The study sample consisted of 25 948 respondents aged 18-64 who lived in low-income (<200% of the Federal Poverty Level) households. Multivariable logistic regression models were estimated to examine the associations of e-cigarette use as well as dual use of e-cigarettes and cigarettes with food insecurity. RESULTS: Of California low-income adults, 6.4% identified as current e-cigarette users (3.0% dual users of e-cigarettes and cigarettes, and 3.4% sole e-cigarette users) and 43.0% reported food insecurity. After controlling for confounding factors, food insecurity was significantly more likely to be reported among current e-cigarette users (adjusted OR (AOR)=1.67; 95% CI 1.25 to 2.23) compared with never e-cigarette users, and among dual users (AOR=2.21; 95% CI 1.63 to 3.00), current sole e-cigarette users (AOR=1.66; 95% CI 1.15 to 2.40), and current sole cigarette smokers (AOR=1.46; 95% CI 1.22 to 1.76) compared with never tobacco users. The odds of food insecurity among dual users were significantly greater than sole cigarette smokers but not statistically different from sole e-cigarette users. CONCLUSIONS: Using e-cigarette is an associated risk factor for food insecurity among low-income adults. Dual use of e-cigarettes and cigarettes has a significantly greater risk of food insecurity compared with smoking cigarettes alone.

Structural basis for the activation and inhibition of the UCH37 deubiquitylase.

The UCH37 deubiquitylase functions in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler. We have performed biochemical characterization and determined crystal structures of UCH37 in complexes with RPN13 and NFRKB, which mediate its recruitment to the proteasome and INO80, respectively. RPN13 and NFRKB make similar contacts to the UCH37 C-terminal domain but quite different contacts to the catalytic UCH domain. RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop. In contrast, NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. These findings reveal remarkable commonality in mechanisms of recruitment, yet very different mechanisms of regulating enzyme activity, and provide a foundation for understanding the roles of UCH37 in the unrelated proteasome and INO80 complexes.

Clear cell carcinoma arising in an ovarian remnant 19 years after oophoerctomy: case report.

BACKGROUND: Ovarian remnant syndrome (ORS) is a rare complication that occurs after oophorectomy, characterized by residual ovarian tissue causing pelvic pain, masses, and various symptoms. The clinical manifestations of ORS are nonspecific, and its diagnosis relies on histological examination. Since ORS typically represents a benign ovarian lesion, there have been few reported cases of malignant transformation. In this report, we presented a unique case of ovarian clear cell carcinoma (OCCC) arising from an ovarian remnant following salpingo-oophorectomy. CASE PRESENTATION: Our patient was a 47-year-old female initially diagnosed with uterine myoma. She had previously undergone cesarean section and unilateral salpingo-oophorectomy. Transvaginal ultrasound and computed tomography (CT) scans revealed a soft tissue mass adjacent to the right lateral wall of the myometrium. The patient opted for transabdominal hysterectomy, left adnexal resection, laparoscopic omentectomy, appendectomy, and pelvic and abdominal lymphadenectomy. The final pathology results confirmed the diagnosis of OCCC, consistent with ORS. The patient subsequently received six cycles of intravenous chemotherapy using the carboplatin/paclitaxel (TC) regimen (paclitaxel liposomes 175 mg/m², carboplatin AUC 5). After 3 years of follow-up, the patient's condition remained normal. CONCLUSION: ORS can significantly impact patients' quality of life and pose challenges for clinicians. Complete excision of ovarian tissue during the initial surgery is crucial in preventing ORS recurrence and potential malignant transformation of ovarian remnants.

Optimization of screening strategies for colorectal cancer based on fecal DNA and occult blood testing.

BACKGROUND: Fecal DNA and occult blood testing have been gradually developed for colorectal cancer (CRC) screening. Comparison of different testing strategies for these methods in CRC screening is in urgent need. This study aims to examine the efficacy of different testing strategies including multi-target fecal DNA testing, qualitative and quantitative fecal immunoassay tests (FITs). METHODS: Fecal samples were collected from patients diagnosed by colonoscopy. Tests using fecal DNA, quantitative FIT or qualitative FIT were performed on same fecal samples. Efficiency of different testing strategies within different populations was investigated. RESULTS: For high-risk populations (CRC and advanced adenoma), the positive rate of the three methods alone was 74.3-80%; the positive predictive values (PPVs) ranged from 37.3% to 77.8%, and the negative predictive values (NPVs) ranged from 86.3% to 92.2%. For combined testing strategies, the positive rate was 71.4-88.6%, PPVs ranged from 38.3% to 86.2%, and NPVs ranged from 89.6% to 92.9%. Parallel fecal multi-target DNA test and quantitative FIT appears to be superior when using a combined testing strategy. For the normal population, no significant difference was identified in efficacy between these methods when used alone and in combination. CONCLUSIONS: Single testing strategy among the three methods is more suitable for the general population screening, and the combined testing strategy is more suitable for high-risk populations screening. The use of different combination strategies may have superiority in CRC high-risk population screening, but cannot conclude significant differences which may be attributed to the small sample size, large samples controlled trials are needed.

Identifying and Removing the Interfacial States in Metal-Oxide-Semiconductor Schottky Si Photoanodes for the Highest Fill Factor.

A critical bottleneck for realizing an efficient Schottky type Si photoelectrode is minimizing the charge extraction losses across the heterointerface via reducing the unfavorite defects. This requires a clear microscopic insight into the correlation between interfacial features and photoconversion. Herein, by taking the n-Si/oxide (MOx)/Ni as the prototype, the heterointerface with the different characteristics and its effects on charge transportation and the corresponding photoelectric/photoelectrochemical (PEC) behaviors were clarified. An ultra-thin AlOx layer can effectively diminish the interfacial pinning of n-Si/Ni and significantly facilitate the photoconversion; meanwhile, it results in some unexpected donor-like deep defects at around 0.59 eV below the conduction band of n-Si, which could be ionized under a reverse bias and cause about 10% photogenerated charge recombination. Fortunately, these deep defects can be further eliminated by cooperating AlOx with a thin Au layer. The AlOx/Au dual-interlayer can remove almost all unexpected defects and maximize the efficiency of the electric field for charge extraction from semiconductor Si for the surface catalytic reaction. Eventually, the n-Si/SiOx/AlOx/Au/Ni/NiFeOx photoanode exhibited a record fill factor of 0.75 for the corresponding photoelectric device and an applied bias photon-to-current efficiency of 3.71% for PEC water oxidation. This study provides definite insights into interfacial electronic states and elaborates their crucial role in solar photoelectric conversion.

High-affinity free ubiquitin sensors for quantifying ubiquitin homeostasis and deubiquitination.

Ubiquitin (Ub) conjugation is an essential post-translational modification that affects nearly all proteins in eukaryotes. The functions and mechanisms of ubiquitination are areas of extensive study, and yet the dynamics and regulation of even free (that is, unconjugated) Ub are poorly understood. A major impediment has been the lack of simple and robust techniques to quantify Ub levels in cells and to monitor Ub release from conjugates. Here, we describe avidity-based fluorescent sensors that address this need. The sensors bind specifically to free Ub, have dissociation constant Kd values down to 60 pM and, together with a newly developed workflow, allow us to distinguish and quantify the pools of free, protein-conjugated and thioesterified forms of Ub from cell lysates. Alternatively, free Ub in fixed cells can be visualized microscopically by staining with a sensor. Real-time assays using the sensors afford unprecedented flexibility and precision to measure deubiquitination of virtually any (poly)Ub conjugate.

CircCASC15-miR-100-mTOR may influence the cervical cancer radioresistance.

BACKGROUND: Cervical cancer has ranked the top one in gynecological malignancies for incidence. Radioresistance is now becoming a leading reason of recurrence. METHODS: Our microRNA array data indicated that the miRNA-100 level decreased significantly during radioresistance. In this study, we up-regulated miR-100 in Hela and Siha cells by using miR-100 mimics and observed proliferation and invasion. RESULTS: It turned out that with overexpression of miR-100, the cells had less invasiveness as well as proliferation. It may target gene mTOR, and it deed reduced EMT. To examine the role of miR-100 in radioresistance, there was no significant result showed by BSP. While the circCASC15 has been identified with sponge function according to RNA pull down and ISH. CONCLUSION: The conclusions indicate miR-100 is a tumor suppressor gene and could be a therapeutic target in radio-resistant cervical cancers.

An innovative endoscopic management strategy for postoperative fistula after laparoscopic sleeve gastrectomy.

BACKGROUND: Postoperative fistula is a life-threatening complication that lacks a standard treatment strategy after laparoscopic sleeve gastrectomy (LSG). This observational study is the first to report the efficacy and safety of endoscopic full-thickness resection (EFTR) combined with purse-string sutures in treating this complication. PATIENTS AND METHODS: The old fistula was resected by EFTR, cut radially, and then sutured with a purse-string. The primary endpoint was complete fistula closure within two months. Endoscopic procedure-related complications were also recorded. RESULTS: Eight of 788 LSG patients developed fistulas with an incidence of 1.01%, primarily under the gastroesophageal junction, and the average distance from the center of the fistula to the cardia was 30 ± 6.3 mm. Two patients were cured by conservative treatment, and six received endoscopic sutures. The time from LSG to fistula diagnosis was 12.3 ± 14.4 days. The time from fistula diagnosis to endoscopic repair was 43.8 ± 55.8 days and 21.4 ± 10.0 days after eliminating the data of first case. The average fistula size was 12 ± 10 mm, the average endoscopic procedure duration was 40 ± 16 min, and the average number of endoscopic procedures required was 1.6 ± 0.8. Five patients achieved the primary endpoint, and one patient refused a third endoscopic suture after two sutures. The endoscopy success rate was 83.3%. No endoscopic procedure-related complications occurred. CONCLUSIONS: EFTR combined with purse-string sutures is an innovative, safe, and effective endoscopic strategy for postoperative fistula after LSG, avoiding reoperation and allowing early oral feeding.

Sexual Behavior Transition and Acute and Early HIV Infection Among Men Who Have Sex With Men: Evidence from an Open Cohort in China, 2011-2019.

The present study examined how sexual behaviors transit over time among men who have sex with men (MSM) and whether these transitions were associated with acute and early HIV (AEH) infection. An open cohort study was conducted using snowball sampling to recruit MSM via physical venues and Internet venues from 2011 to 2019, in China. Cox models were used to estimate the correlates of risk factors and AEH infection. We used Latent Transition Analysis (LTA) to describe behavioral profile and explore latent behavioral "trans-phenotypes," then examined the effect between different "trans-phenotypes" and AEH infection risk and explored the effect of characteristics as possible predictors of sexual behavior transition. Of 6502 MSM, a total of 1974 individuals with negative human immunodeficiency virus (HIV) tests at baseline and at least 2 visit records were included in the final analysis from 2011 to 2019. During an average 1.84 years of follow-up, 64 AEH infections were documented. In the multivariable Cox model, the association between condom use in last anal sex (HR: 0.095, 0.038-0.205), fewer sexual partners (HR: 0.375, 0.205-0.712), low frequency of condom use (HR: 3.592, 1.186-11.272), and AEH acquisition were found. The percentage of MSM with "maintain/develop safety-profile," "consistent risky-profile," and "safety-profile to risky-profile" were 52.48, 40.17, and 7.35%, respectively. Compared with "maintain\develop safety-profile," "consistent or develop risky-profile" had an increasing likelihood of AEH infection. Meanwhile, male sex workers (MSWs) or older MSM were more likely to consist or transit in "risky-profile." Having middle education is a risk factor to transit in "risky-profile" for MSM with "safety-profile" at baseline. In addition, MSM who accept health services in the past year engaged in higher proportion of developing safety-profile. Approximately half of MSM maintain or develop risky behavior with the increasing likelihood of AEH acquisition in China, which suggested that targeted and intensive interventions should be prioritized to maintain safety-profile. Clinical Trial Number: ChiCTR2000039500.

Ubiquitin signals proteolysis-independent stripping of transcription factors.

Ubiquitination of transcription activators has been reported to regulate transcription via both proteolytic and nonproteolytic routes, yet the function of the ubiquitin (Ub) signal in the nonproteolytic process is poorly understood. By use of the heterologous transcription activator LexA-VP16 in Saccharomyces cerevisiae, we show that monoubiquitin fusion of the activator prevents stable interactions between the activator and DNA, leading to transcription inhibition without activator degradation. We identify the AAA(+) ATPase Cdc48 and its cofactors as the Ub receptor responsible for extracting the monoubiquitinated activator from DNA. Our results suggest that deubiquitination of the activator is critical for transcription activation. These findings with LexA-VP16 extend in both yeast and mammalian cells to native transcription activators Met4 and R-Smads, respectively, that are known to be oligo-ubiquitinated. The results illustrate a role for Ub and Cdc48 in transcriptional regulation and gene expression that is independent of proteolysis.

Role for autophagy-related markers Beclin-1 and LC3 in endometriosis.

BACKGROUND: Endometriosis is a common and challenging disease in women of childbearing age with high personal and social costs. Many molecular differences between ectopic and eutopic endometrium present difficulties in the development of new drug therapies and therapies. Autophagy is a response to stress and has recently been studied in human cancers. Two important autophagy genes, Beclin-1 and LC3, have been reported in several human cancers. However, the reports of Beclin-1 and LC3 in endometriosis are limited and controversial. METHODS: In this study, we investigated the expression of Beclin-1 and LC3 by Immunohistochemistry. RESULTS: We found their downregulation in endometriosis. We also found these two autophagy gene expression are negatively correlated with the stage of endometriosis. CONCLUSIONS: Decreased expression of Beclin-1 and LC3 may be related to the occurrence and development of endometriosis.

High risks of HIV transmission for men sex worker - a comparison of profile and risk factors of HIV infection between MSM and MSW in China.

BACKGROUND: Although men who have sex with men (MSM) and male sex workers (MSWs) both represent the high-risk groups for the transmission of HIV/AIDS and syphilis, the comparison between them have not yet been well studied in China. We aimed to evaluate the prevalence of HIV among MSM and MSW, and then identify the difference of risk factors of HIV infection. METHODS: A snowball sampling was employed to recruit patrons attending the Tianjin bathhouse from March 2011 to October 2018. A questionnaire covering sociodemographic characteristics, sexual behaviors, HIV-related and HIV awareness was completed by 5166 patrons from all parts of China. Bivariate analyses were done using the Chi-square test to investigate the association between factors and HIV infection among MSM and MSWs. Subsequently, we studied the different impact of risk factors on HIV infections among the two groups using multiple logistic regression with the adjusted odds ratio (aOR) being derived. RESULTS: From 2011 to 2018, 235 MSWs and 4931 MSM were included into our study. HIV prevalence among the MSWs was 17.8% (95%CI: 13.2% ~ 23.4%) while 6.5% (95%CI: 5.8% ~ 7.2%) for MSM (P < 0.01). MSWs tends to be younger (26.50% in MSWs vs. 8.64% in MSM, P < 0.05), live alone (84.68% in MSWs vs. 47.98 in MSM, P < 0.05), get poor education (41.28% in MSWs vs. 28.45 in MSM, P < 0.05), use drug (8.09% in MSWs vs. 0.89% in MSM, P < 0.05), have more proportion of always use condom during anal sex (56.50% in MSWs vs. 41.95% in MSM, P < 0.05) but less proportion during commercial sex (81.28% in MSWs vs. 98.48% in MSM, P < 0.05), access HIV-related health services (65.96% in MSWs vs. 47.80% in MSM, P < 0.05) and have a HIV test last year(60.85% in MSWs vs. 41.27% in MSM, P < 0.05). The significant associations between risk factors with HIV infection in MSM were not observed in MSWs and vice versa. CONCLUSIONS: High HIV prevalence needs urgent intervention targeting MSWs as a higher susceptible to HIV in comparison to MSM owing to their unique characteristics. The discrepancies of profiles and risk factors between MSM and MSWs should be consider in design and development of strategies.