Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

Slope Micrometeorological Analysis and Prediction Based on an ARIMA Model and Data-Fitting System.

The rapid development of highway engineering has made slope stability an important issue in infrastructure construction. To meet the needs of green vegetation growth, ecological recovery, landscape beautification and the economy, long-term monitoring research on high-slope micrometeorology has important practical significance. Because of that, we designed and created a new slope micrometeorological monitoring and predicting system (SMMPS). We innovatively upgraded the cloud platform system, by adding an ARIMA prediction system and data-fitting system. From regularly sensor-monitored slope micrometeorological factors (soil temperature and humidity, slope temperature and humidity, and slope rainfall), a data-fitting system was used to fit atmospheric data with slope micrometeorological data, the trend of which ARIMA predicted. The slope was protected in time to prevent severe weather damage to the slope vegetation on a large scale. The SMMPS, which upgrades its cloud platform, significantly reduces the cost of long-term monitoring, protects slope stability, and improves the safety of rail and road projects.

One-Pot Transformation of Hypervalent Iodines into Diversified Phenoxazine Analogues as Promising Photocatalysts.

A facile and efficient quinoline-fused 4H-benzo[b][1,4]oxazine has been successfully fabricated through an oxidative O-arylation, Pd-catalyzed double N-arylation of 4-hydroxyquinoline derivatives and trivalent aryl iodides. Diversified fused heterocycles could be easily constructed in overall high isolated yields with great substrate scope. The afforded heteroatom-"doped" phenoxazine 3 demonstrated high molar absorptivities and excellent stability and redox reversibility. These phenoxazine analogues therefore could be utilized as promising catalysts in the photoredox catalyzed perfluoroalkylation of heteroarenes and photopromoted radical polymerization (OATRP).

Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases.

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.

Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer.

BACKGROUND: Primary or acquired resistance to cetuximab often occurs during targeted therapy in metastatic colorectal cancer (mCRC) patients. In many cancers, the key role of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in anticancer drug resistance has been confirmed. Emerging evidence has shown that specific exosomal lncRNAs may serve as meaningful biomarkers. In this study, we hypothesize that exosomal UCA1 might predict the response to cetuximab in CRC patients. METHODS: First, acquired cetuximab-resistant cell lines were generated, and UCA1 expressions in these cells and their exosomes were compared. We also systematically evaluate the stability of exosomal UCA1. Thereafter, the predictive value of exosomal UCA1 in CRC patients treated with cetuximab was evaluated. Finally, through cell apoptosis assays and immunofluorescence staining, we analyzed the role of UCA1-containing exosomes in conferring cetuximab resistance. RESULTS: UCA1 expression was markedly higher in cetuximab-resistant cancer cells and their exosomes. Exosomal UCA1 was shown to be detectable and stable in serum from CRC patients. In addition, circulating UCA1-containing exosomes could predict the clinical outcome of cetuximab therapy in CRC patients, and UCA1 expression was considerably higher in the progressive disease/stable disease patients than in the partial response/complete response patients. Furthermore, exosomes derived from cetuximab-resistant cells could alter UCA1 expression and transmit cetuximab resistance to sensitive cells. CONCLUSIONS: We discovered a novel role of UCA1-containing exosomes, showed their capability to transmit drug resistance and investigated their potential clinical use in predicting cetuximab resistance.

Phenotypic switching of vascular smooth muscle cells in the 'normal region' of aorta from atherosclerosis patients is regulated by miR-145.

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to an adverse proliferative phenotype is a hallmark of atherosclerosis or vascular restenosis. However, the genetic modulators responsible for this switch have not been fully elucidated in humans nor have they been correlated with clinical abnormalities. This study investigated genetic mechanisms involved in phenotypic switching of VSMCs at non-defect areas of the aorta in patients with atherosclerosis. Aortic wall samples were obtained from patients with (N = 53) and without (N = 27) atherosclerosis undergoing cardiovascular surgery. Vascular smooth muscle cell cultures were generated, and expression of microRNA-145 (miR-145), its target gene Kruppel-Like Factor 5 (KLF5) and Myocardin (MYOCD, a smooth muscle-specific transcriptional coactivator) were analysed using RT-qPCR, along with expression of relevant proteins. Vascular smooth muscle cells were transduced with miR-145 inhibitor and mimic to determine the effect of miR-145 expression on VSMC proliferation. miR-145 expression decreased while KLF5 expression increased in atherosclerotic aortas. Atherosclerotic samples and VSMCs had decreased expression of contractile markers calponin and alpha smooth muscle actin (α-SMA) and MYOCD. miR-145 inhibitor-transduced VSMCs from non-atherosclerotic patients showed decreased expression of calponin and α-SMA and increased proliferation compared with non-transduced controls, and these levels were close to those of atherosclerotic patients. miR-145 mimic-transduced VSMCs from atherosclerotic patients showed increased expression of calponin and α-SMA and decreased proliferation compared with non-transduced controls, and these levels were close to those found in non-atherosclerotic patients. These data demonstrate that miR-145 modulates the phenotypic switch of VSMCs from a contractile to a proliferative state via KLF5 and MYOCD in atherosclerosis.

Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress.

Sirtuin3 (SIRT3) is an important member of the sirtuin family of protein deacetylases that is localized to mitochondria and linked to lifespan extension in organisms ranging from yeast to humans. As aged cells have less regenerative capacity and are more susceptible to oxidative stress, we investigated the effect of ageing on SIRT3 levels and its correlation with antioxidant enzyme activities. Here, we show that severe oxidative stress reduces SIRT3 levels in young human mesenchymal stromal/stem cells (hMSCs). Overexpression of SIRT3 improved hMSCs resistance to the detrimental effects of oxidative stress. By activating manganese superoxide dismutase (MnSOD) and catalase (CAT), SIRT3 protects hMSCs from apoptosis under stress. SIRT3 expression, levels of MnSOD and CAT, as well as cell survival showed little difference in old versus young hMSCs under normal growth conditions, whereas older cells had a significantly reduced capacity to withstand oxidative stress compared to their younger counterparts. Expression of the short 28 kD SIRT3 isoform was higher, while the long 44 kD isoform expression was lower in young myocardial tissues compared with older ones. These results suggest that the active short isoform of SIRT3 protects hMSCs from oxidative injury by increasing the expression and activity of antioxidant enzymes. The expression of this short isoform decreases in cardiac tissue during ageing, leading to a reduced capacity for the heart to withstand oxidative stress.

Sexual communication and condom use among Chinese men who have sex with men in Beijing.

This study collected cross-sectional data from 307 young Chinese men who have sex with men (MSM) to explore the characteristics of sexual communications, including target of communication (stable partners, casual partners), topics of communication (condom use, HIV/STDs prevention, and sexual history), and the associations between sexual communication characteristics and condom use. A variety of measures were employed to assess respondents' condom use with different sexual partners over different recall periods. Chi-square tests were employed to examine the relationships between sexual communication characteristics and condom use. This study found that sexual communications with regular partners about topics, such as condom use, HIV/STDs prevention, and current and past sexual relationship were associated with condom use with regular partners. Respondents who had sexual communications with both regular and casual partners were more likely to use condoms with their regular partners. The findings in the current study provided empirical evidence for the importance of frequent sexual communication between Chinese MSM and their sex partners.

Online sex-seeking behaviors among men who have sex with men: implications for investigation and intervention.

To investigate factors associated with online sex-seeking behaviors among men who have sex with men (MSM) in Beijing, China. MSM participants were recruited from two cohort studies with multiple enrollment methods from November 2006 to February 2007 and from March to June 2008, respectively. Data collected included demographics and sexual behaviors. Of the 901 participants, 68.1% were single; 69.3% were non-Beijing residents; 94.4% considered themselves to be homosexual; 65.2% received college or higher levels of education; the median age was 26 years; 73.0% sought male sex partners via the Internet in the past 3 months; 66.2% had ≥2 sex partners. Younger age, higher levels of education and having had ≥2 male sex partners in the past 3 months were independently associated with seeking sex partners on the Internet. These findings indicate that Internet-based intervention programs could encourage younger high-risk MSM to use condoms and reduce their numbers of sexual partners.

Correlates of consistent condom use among young migrant men who have sex with men (MSM) in Beijing, China.

OBJECTIVES: The prevalence of sexually transmitted infections (STIs), including HIV, among men who have sex with men (MSM) has risen in China, mainly due to unprotected sexual intercourse. Migrant MSM might be more vulnerable to the risk of STIs/HIV because of their low socioeconomic status. This study aims at exploring the correlates of consistent condom use among young migrant MSM (aged 18-29 years) in Beijing. METHODS: Multivariate logistic regression analysis. RESULTS: The mean age of the sample was 23.7 years. Rural-to-urban migrant MSM accounted for 46% of the sample, and urban-to-urban migrant MSM for 54%. Of 307 migrant MSM, 178 (54%) reported having used a condom every time in the last three sexual episodes with both stable and casual sexual partners. Multivariate logistic regression analysis showed that MSM who had a low monthly income, had often experienced alcohol intoxication, did not use a condom at first sex, and had fewer lifetime male sexual partners were less likely to use condoms consistently. CONCLUSIONS: Consistent condom use among young migrant MSM was relatively low and was associated with socioeconomic status and alcohol use. Future STIs/HIV prevention programmes should strengthen empowerment, access to condoms, and reduction of alcohol consumption within this socio-economically marginalised group.

[The sexual behavior characteristics and STD infection status of women who have sex with women in Beijing].

OBJECTIVE: To study sexual behavioral characteristics, infection status of HIV and sexually transmitted infections (STDs) among women who have sex with women (WSW) in Beijing. METHODS: A total of 150 WSWs were recruited by snowball sampling in several main types of activity sites of WSW (including NGOs, salons, bars, etc.) in Beijing during September 2010 to April 2011. Information on demographic factors, sexual behavioral characteristics, infection status of STDs, and use of medical care were collected by questionnaire investigation. Serum samples, vaginal and cervical swabs were taken for each subject to test HIV, hepatitis B (HBV), hepatitis C (HCV), syphilis, herpes simplex virus (HSV), neisseria gonorrhoeae, chlamydia trachoma, bacterial vaginosis, trichomonas vaginalis and mycotic vaginitis. RESULTS: The age range of the subjects was from 19 to 46 years old. Approximately 82.67% (124/150) of them aged 20 to 29 years old, and 54.00% (81/150) were unmarried. Approximately 76.67% (115/150) had an education level of college degree or above, and 70.67% (106/150) were migrants. Approximately 66.66% (100/150) of the subjects considered themselves as homosexual, 28.00% (42/150) as bisexual. The age at first homosexual sex ranged from 11 to 30 years old. The median of number of female sex partners in last 1 year was 1, and 33.78% (50/148) of the subjects had 2 or more female sex partners. Approximately 20.27% (30/148) of the subjects applied sex instruments, of which 66.67% (20/30) never or seldom used condoms. Hand-clitoris and hand-vagina contacts were the main types of woman-to-woman sex, accounting for 91.22% (135/148). 12.00% (18/150) of the subjects had sex with men during last year. Among them, 50.00% (9/18) used condoms at last heterosexual sex, and 66.67% (12/18) never or seldom used condoms at last heterosexual sex in past 1 year. One subject provided paid sex service for men, and used condoms every time. In the past one year, 45.33% (68/150) of the subjects had symptoms of STDs, but only 36.76% (25/68) of them sought medical care. The infection rate of STDs was 34.67% (52/150). The infection rates of NG and GV were both 16.11% (24/149), and those of mycotic vaginitis, chlamydia trachoma, and TV were 8.72% (13/149), 4.03% (6/149), and 0.67% (1/150), respectively. The numbers of subjects tested positive for HBV, HCV, and syphilis were all 1. No subjects were found HIV positive or HSV-2 positive. CONCLUSION: Multiple sexual partners and heterosexual sex behavior were common among WSW in Beijing. More than 1/3 of the subjects were infected with STD.

Demographic and behavioral determinants of self-reported history of sexually-transmitted diseases (STDs) among young migrant men who have sex with men (MSM) in Beijing, China.

BACKGROUND: Sexually-transmitted disease (STD) is a facilitating cofactor that contributes to human immunodeficiency virus (HIV) transmission. Previous studies indicated a high prevalence of STDs among men who have sex with men (MSM) in China. To date, limited data are available for correlates of STD infection among young migrant MSM in China. The current study intends to examine the association between demographic and behavioral factors and STD infection. METHODS: Data were collected from a sample of 307 migrant MSM aged 18-29 years in Beijing in 2009. Multivariate logistic regression analysis was employed to examine the factors associated with a history of STDs. RESULTS: Results showed that about 13% of MSM reported a history of STDs. The average number of lifetime sexual partners was 15.0. About 56.7% of MSM did not use a condom at the first sexual encounter. The percentage of MSM who used a condom consistently was 47.4%. Multivariate logistic regression results showed that STD history was positively associated with education, income, the number of lifetime male sexual partners, and negatively associated with the frequency of properly using a condom. CONCLUSION: STD history was associated with socioeconomic status and sexual risk behaviors. The results suggested that HIV prevention intervention programs need to educate MSM to reduce the number of sexual partners and to use a condom properly. Furthermore, HIV prevention intervention programs among MSM need to be tailored to meet the needs of different socioeconomic groups of MSM.

A retrospective cohort study of intensive gastric variceal ligation versus endoscopic gastric variceal obturation in the management of gastric variceal bleeding.

BACKGROUND: Gastric variceal bleeding is often more serious and can be fatal. Currently, international consensus recommendations for the treatment of gastric variceal bleeding vary according to endoscopic classification. Few studies have investigated ligation versus gastric variceal obturation (GVO) for the treatment of gastric varices. METHODS: The study included 79 patients with cirrhosis-induced bleeding from esophageal and fundal varices who were treated at the Second Hospital of Hebei Medical University between January 2016 and December 2020 and who met the inclusion criteria. Among them, 42 patients were included in the intensive gastric varices ligation (IGVL) group, and 37 were included in the GVO group. We conducted a retrospective cohort study to analyze the effectiveness and safety of these 2 treatments. RESULTS: The rebleeding rate after initial treatment was significantly lower in the IGVL group than in the GVO group (23.8% vs. 48.6%, P<0.05). No significant between-group difference was observed in overall mortality (14.3% vs. 32.4%), 6-week mortality (0.0% vs. 2.7%), or 1-year mortality (11.9% vs. 13.5%, all P>0.05). The >1-year mortality and bleeding-related mortality rates were significantly higher in the GVO group than in the IGVL group (23.3% vs. 2.7%, P<0.05; 27.0% vs. 9.5%, P<0.05). The incidence of adverse events was 57.1% in the IGVL group and 48.6% in the GVO group, with no significant difference (P>0.05). Independent predictors for rebleeding after initial treatment were the use of GVO as endoscopic treatment, total bilirubin >17.1 µmol/L, liver cancer, and diabetes. For mortality, the independent predictors were male sex, liver cancer, ascites, and rebleeding after initial treatment. CONCLUSIONS: Rebleeding after initial treatment was lower after IGVL than GVO. Independent predictors for rebleeding after initial treatment were endoscopic treatment method, total bilirubin >17.1 µmol/L, liver cancer, and diabetes. For mortality, the independent predictors were male sex, liver cancer, ascites, and rebleeding after initial treatment.

[Characteristics of sexual behaviors and infection status of AIDS and other sexually transmitted diseases among men who have sex with men in 2009 in Beijing].

OBJECTIVE: To analyze sexual behavior characteristics and sexually transmitted diseases such as AIDS infections in man who have sex with men (MSM) of Beijing Chaoyang district. METHODS: Through selecting 10 MSM as seed in Chaoyang district of the existing education member companion in its main activity place, using snowball sampling to select 1008 people that 16 years old or above, nearly a year had sex with male in Chaoyang to conduct an investigation.Questionnaires were used to investigate the general conditions, characteristics of sexual behaviors, condom usage, AIDS knowledge awareness and sexually transmitted diseases history. Each participant was asked to exsanguinated 5 ml peripheral blood for applying ELISA for HIV, syphilis helicoids detection and HIV positive samples confirm test. Using χ(2) test on the statistical analysis of the data. RESULTS: In the 1008 MSM, most of them were with the age of 20 - 29 years old (66.6%, 671/1008), giving priority to unmarried (79.1%, 797/1008), college degree and above culture during accounted for 43.3% (436/1008), 56.2% (566/1008) had both male and female sexual partners; the rate of temporary sexual partners who were one-night stand objects or friends or guest was 72.2% (226/313). The forever condom utilization rate was 29.0% (170/587) in MSM who had both male and female sexual partners, lower than that who had both male and female sexual partners (47.2%, 345/731). That the study objects of HIV infection who can use condom correctly rate was 3.6% (16/442), and that who never or occasionally used condom rate was 8.5% (24/228). AIDS, gonorrhea and other sexually transmitted diseases (to give priority to the acuteness wet wart) infection rates were 4.8% (6/124), 10.5% (13/124) and 8.9% (11/124) in those who had the history of group sex, and that was 5.9% (52/884), 1.9% (17/884) and 2.3% (20/884) in those who without the history of group sex. The research object's gonorrhea and other sexually transmitted diseases (to give priority to the acuteness wet wart) who provided commercial sex service infection rates were 7.7% (9/117) and 6.8% (8/117), significantly higher than those who did not provide a commercial sex service object of study subject (2.4% (21/891)and 2.6% (23/891)). CONCLUSION: HIV infection is high among MSM population. Types and identification of sexual partners, and condom use are associated with HIV and STD infection.

[Incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men in Beijing].

OBJECTIVE: To study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing. METHODS: A total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test. RESULTS: A total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion. CONCLUSION: The seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.

Sirtuin 3 Ameliorates Lung Senescence and Improves Type II Alveolar Epithelial Cell Function by Enhancing the FoxO3a-Dependent Antioxidant Defense Mechanism.

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.

Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering.

Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR2, and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.

MicroRNA-421 promotes proliferation and invasion of non-small cell lung cancer cells through targeting PDCD4.

Recent evidence highlights that microRNAs serve as crucial regulators of tumorigenesis, including non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression profile, clinical significance and biological role of miR-421 in NSCLC. The results showed that miR-421 expression was markedly increased in NSCLC tissues and cell lines. Further experimental data indicated that knockdown of miR-421 significantly inhibited NSCLC cell proliferation and induced cell cycle arrest in vitro. The migratory and invasive abilities of NSCLC cells were also attenuated following miR-421 knockdown. Furthermore, PDCD4 was identified as a direct target of miR-421, and its expression was inversely correlated with miR-421 expression in NSCLC tissues. PDCD4 also abrogated the oncogenic role of miR-421 in NSCLC cells. Collectively, our study revealed that miR-421 is significantly upregulated in NSCLC and might represent a potential therapeutic target for NSCLC patients.

Rgnef promotes ovarian tumor progression and confers protection from oxidative stress.

Ovarian cancer is the fifth-leading cause of cancer death among women. The dissemination of ovarian tumors and growth as spheroids accompanies late-stage disease. In cell culture, ovarian tumor cell spheroids can exhibit elevated resistance to environmental stressors, such as reactive oxygen species. Homeostatic balance of the antioxidant response is a protective mechanism that prevents anoikis, a form of programmed cell death. Signaling pathways activated by integrin receptors suppress anoikis. Rgnef (ARHGEF28/p190RhoGEF) is a guanine nucleotide exchange factor that is activated downstream of integrins. We find that Rgnef protein levels are elevated in late-stage serous ovarian cancer, high Rgnef mRNA levels are associated with decreased progression-free and overall survival, and genomic ARHGEF28 loss is associated with increased patient survival. Using transgenic and transplantable Rgnef knockout mouse models, we find that Rgnef is essential for supporting three-dimensional ovarian spheroid formation in vitro and tumor growth in mice. Using RNA-sequencing and bioinformatic analyses, we identify a conserved Rgnef-supported anti-oxidant gene signature including Gpx4, Nqo1, and Gsta4; common targets of the NF-kB transcription factor. Antioxidant treatment enhanced growth of Rgnef-knockout spheroids and Rgnef re-expression facilitated NF-κB-dependent tumorsphere survival. These studies reveal a new role for Rgnef in ovarian cancer to facilitate NF-κB-mediated gene expression protecting cells from oxidative stress.