Insights into sunlight-driven transformation of tetracycline by iron (hydr)oxides: The dominating role of self-generated hydrogen peroxide.

Iron (hydr)oxides are abundant in surface environment, and actively participate in the transformation of organic pollutants due to their large specific surface areas and redox activity. This work investigated the transformation of tetracycline (TC) in the presence of three common iron (hydr)oxides, hematite (Hem), goethite (Goe), and ferrihydrite (Fh), under simulated sunlight irradiation. These iron (hydr)oxides exhibited photoactivity and facilitated the transformation of TC with the initial phototransformation rates decreasing in the order of: Hem > Fh > Goe. The linear correlation between TC removal efficiency and the yield of HO• suggests that HO• dominated TC transformation. The HO• was produced by UV-induced decomposition of self-generated H2O2 and surface Fe2+-triggered photo-Fenton reaction. The experimental results indicate that the generation of HO• was controlled by H2O2, while surface Fe2+ was in excess. Sunlight-driven H2O2 production in the presence of the highly crystalline Hem and Goe occurred through a one-step two-electron reduction pathway, while the process was contributed by both O2-induced Fe2+ oxidation and direct reduction of O2 by electrons on the conduction band in the presence of the poorly crystalline Fh. These findings demonstrate that sunlight may significantly accelerate the degradation of organic pollutants in the presence of iron (hydr)oxides.

Associations between atmospheric PM2.5 exposure and carcinogenic health risks: Surveillance data from the year of lowest recorded levels in Beijing, China.

Scant research has pinpointed the year of minimum PM2.5 concentration through extensive, uninterrupted monitoring, nor has it thoroughly assessed carcinogenic risks associated with analyzing numerous components during this nadir in Beijing. This study endeavored to delineate the atmospheric PM2.5 pollution in Beijing from 2015 to 2022 and to undertake comprehensive evaluation of carcinogenic risks associated with the composition of atmospheric PM2.5 during the year exhibiting the lowest concentration. PM2.5 concentrations were monitored gradually in 9 districts of Beijing for 7 consecutive days per month from 2015 to 2022, and 32 kinds of PM2.5 components collected in the lowest PM2.5 concentration year were analyzed. This comprehensive dataset served as the basis for carcinogenic risk assessment using Monte Carlo simulation. And we applied the Positive Matrix Factorization (PMF) method to identity the sources of atmospheric PM2.5. Furthermore, we integrated this source appointment model with risk assessment model to discern the origins of these risks. The findings revealed that the annual average PM2.5 concentration in 2022 stood at 43.1 µg/m3, marking the lowest level recorded. The mean carcinogenic risks of atmospheric PM2.5 exposure calculated at 6.30E-6 (empirical 95% CI 1.09E-6 to 2.25E-5) in 2022. The PMF model suggested that secondary sources (35.4%), coal combustion (25.6%), resuspended dust (15.1%), biomass combustion (14.1%), vehicle emissions (7.1%), industrial emissions (2.0%) and others (0.7%) were the main sources of atmospheric PM2.5 in Beijing. The mixed model revealed that coal combustion (2.41E-6), vehicle emissions (1.90E-6) and industrial emissions (1.32E-6) were the main sources of carcinogenic risks with caution. Despite a continual decrease in atmospheric PM2.5 concentration in recent years, the lowest concentration levels still pose non-negligible carcinogenic risks. Notably, the carcinogenic risks associated with metals and metalloids exceeded that of PAHs. And the distribution of risk sources did not align proportionally with the distribution of PM2.5 mass concentration.

Seneca valley virus 3C protease blocks EphA2-Mediated mTOR activation to facilitate viral replication.

The Seneca Valley virus (SVV) is a recently discovered porcine pathogen that causes vesicular diseases and poses a significant threat to the pig industry worldwide. Erythropoietin-producing hepatoma receptor A2 (EphA2) is involved in the activation of the AKT/mTOR signaling pathway, which is involved in autophagy. However, the regulatory relationship between SVV and EphA2 remains unclear. In this study, we demonstrated that EphA2 is proteolysed in SVV-infected BHK-21 and PK-15 cells. Overexpression of EphA2 significantly inhibited SVV replication, as evidenced by decreased viral protein expression, viral titers, and viral load, suggesting an antiviral function of EphA2. Subsequently, viral proteins involved in the proteolysis of EphA2 were screened, and the SVV 3C protease (3Cpro) was found to be responsible for this cleavage, depending on its protease activity. However, the protease activity sites of 3Cpro did not affect the interactions between 3Cpro and EphA2. We further determined that EphA2 overexpression inhibited autophagy by activating the mTOR pathway and suppressing SVV replication. Taken together, these results indicate that SVV 3Cpro targets EphA2 for cleavage to impair its EphA2-mediated antiviral activity and emphasize the potential of the molecular interactions involved in developing antiviral strategies against SVV infection.

Jolkinolide B synergistically potentiates the antitumor activity of GPX4 inhibitors via inhibiting TrxR1 in cisplatin-resistant bladder cancer cells.

Glutathione peroxidase 4 (GPX4) is a promising anticancer therapeutic target; however, the application of GPX4 inhibitors (GPX4i) is limited owing to intrinsic or acquired drug resistance. Hence, understanding the mechanisms underlying drug resistance and discovering molecules that can overcome drug resistance are crucial. Herein, we demonstrated that GPX4i killed bladder cancer cells by inducing lipid reactive oxygen species-mediated ferroptosis and apoptosis, and cisplatin-resistant bladder cancer cells were also resistant to GPX4i, representing a higher half-maximal inhibitory concentration value than that of parent bladder cancer cells. In addition, thioredoxin reductase 1 (TrxR1) overexpression was responsible for GPX4i resistance in cisplatin-resistant bladder cancer cells, and inhibiting TrxR1 restored the sensitivity of these cells to GPX4i. In vitro and in vivo studies revealed that Jolkinolide B (JB), a natural diterpenoid and previously identified as a TrxR1 inhibitor, potentiated the antiproliferative efficacy of GPX4i (RSL3 and ML162) against cisplatin-resistant bladder cancer cells. Furthermore, GPX4 knockdown and inhibition could augment JB-induced paraptosis and apoptosis. Our results suggest that inhibiting TrxR1 can effectively improve GPX4 inhibition-based anticancer therapy. A combination of JB and GPX4i, which is well-tolerated and has several anticancer mechanisms, may serve as a promising therapy for treating bladder cancer.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma.

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma. On laser irradiation, Ce6 can generate reactive oxygen species (ROS) to kill cancer cells directly and induces immunogenic tumor cell death (ICD), which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47. Moreover, both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages, promote antigen presentation, and eventually induce T lymphocyte-mediated antitumor immunity. Overall, the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma, which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Association between air pollution and male sexual function: A nationwide observational study in China.

This study aimed to explore the associations between air pollution and male sexual function. A total of 5047 male subjects in China were included in this study. The average air pollution exposure (PM2.5, PM10, SO2, CO, NO2, and O3) for the preceding 1, 3, 6, and 12 months before the participants' response was assessed. Male sexual function was evaluated using the International Index of Erectile Function-5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT). Generalized linear models were utilized to explore the associations between air pollution and male sexual function. K-prototype algorithm was conducted to identify the association among specific populations. Significant adverse effects on the IIEF-5 score were observed with NO2 exposure during the preceding 1, 3, and 6 months (1 m: ß = -5.26E-05; 3 m: ß = -4.83E-05; 6 m: ß = -4.23E-05, P < 0.05). PM2.5 exposure during the preceding 12 months was found to significantly negatively affect the PEDT after adjusting for confounding variables. Our research indicated negative correlations between air pollutant exposures and male sexual function for the first time. Furthermore, these associations were more pronounced among specific participants who maintain a normal BMI, exhibit extroverted traits, and currently engage in smoking and alcohol consumption.

Risk factors of developmental dysplasia of the hip in infants: A meta-analysis based on cohort studies.

INTRODUCTION: Developmental dysplasia of the hip (DDH) is a prevalent condition in children. Currently, the exact etiology of DDH remains uncertain. The objective of this study was to conduct a meta-analysis to investigate the risk factors associated with DDH in infants. The findings would provide a theoretical foundation for targeted early screening and diagnosis. HYPOTHESIS: Several indicators, such as gender, intrauterine position, family history of DDH, gestational age, delivery mode, amniotic fluid levels, swaddling, parity, fetus number, combined musculoskeletal deformities, birth weight, and physical examination results, may serve as risk factors for DDH. MATERIALS AND METHODS: Cohort studies investigating the risk factors of DDH in infants through logistic regression analysis were searched in the Wanfang, VIP citation, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, Excerpta Medica Database (Embase), PubMed, and Cochrane Library databases up to May 2023. After extracting the data from eligible literature and assessing them using the Newcastle-Ottawa Scale (NOS), articles were selected based on pre-established inclusion and exclusion criteria. RESULTS: A total of eleven literature reports covering 979,757 infants were included in this meta-analysis. The publication bias did not significantly influence the results. The incidence rate of DDH was 47.99‰ among infants with risk factors compared to 3.21‰ in the general population. Risk factors for DDH included being female (OR=6.97, 95% CI: 5.18-9.39, p<0.001), breech delivery (OR=4.14, 95% CI: 3.09-5.54, p<0.001), positive family history (OR=4.07, 95% CI: 2.20-7.52, p<0.001), cesarean section (OR=1.11, 95% CI: 1.01-1.21, p=0.032), oligohydramnios (OR=3.93, 95% CI: 1.29-12.01, p=0.016), swaddling (OR=6.74, 95% CI: 1.25-36.31, p=0.026), firstborn status (OR=1.84, 95% CI: 1.49-2.53, p<0.001), combined musculoskeletal malformations (OR=2.27, 95% CI: 1.58-3.27, p<0.001), and physical signs of DDH (OR=8.71, 95% CI: 2.44-31.07, p=0.001). Premature delivery (OR=0.91, 95% CI: 0.88-0.95, p<0.001) was a protective factor for DDH. The relationship between multiple pregnancies (OR=0.58, 95% CI: 0.33-1.02, p=0.060) and low birth weight (OR=0.62, 95% CI: 0.14-2.76, p=0.529) in relation to DDH remained uncertain. DISCUSSION: This meta-analysis shows that female, breech delivery, positive family history, cesarean section, firstborn status, oligohydramnios, swaddling and combined musculoskeletal malformations are associated with DDH. Premature delivery appeared to be a protective factor against DDH. Nevertheless, the other factors need more research to reach more conclusive results. LEVEL OF EVIDENCE: III; meta-analysis.

ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.

A Receptor Integrin ß1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif.

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin ß1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host factor benefiting aMPV/C attachment or internalization. The transient expression of avian ITGB1-rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) is susceptible to aMPV/C infection. Kinetic replication of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to efficiently infect human non-small cell lung cancer (A549) cells. This may be a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells, facilitating aMPV/C infection.

Pandemic Fatigue and Vaccine Hesitancy among People Who Have Recovered from COVID-19 Infection in the Post-Pandemic Era: Cross-Sectional Study in China.

At present, the COVID-19 pandemic is still ongoing globally and the virus is constantly mutating. The herd immunity barrier established by past infections or vaccinations is gradually weakening and reinfections are occurring. To evaluate the pandemic fatigue and vaccine hesitancy among people who have recovered from COVID-19 in the post-pandemic era, we conducted an anonymous cross-sectional survey study in China from 4 July to 11 August 2023, nearly 6 months after the last large-scale nationwide infection. Basic sociodemographic characteristics, health-related factors (smoking, drinking, and chronic disease history), COVID-19 vaccination history, and self-reported long COVID were obtained as potential covariates. A series of logistic regression models were performed to examine the association between pandemic fatigue and vaccine hesitancy toward the next dose of COVID-19 vaccines via crude relative risks (cORs) and adjusted relative risks (aORs) with 95% CIs. According to our results, of the 2942 participants, 1242 (42.2%) were hesitant (unwilling or not sure) to receive the next dose of COVID-19 vaccines. The average score on the Pandemic Fatigue Scale was 21.67 ± 8.86, in which the scores of all items in the vaccine-hesitant group were significantly higher than those in the vaccine-accepting group. Additionally, the higher the pandemic fatigue level among people who have recovered from COVID-19, the more likely they were to be hesitant to receive the next dose of the COVID-19 vaccines (moderate: aOR = 2.94, 95% CI: 2.46-3.53; high: aOR = 6.88, 95% CI: 5.49-8.64). Overall, more than 40% of the recovered participants were unwilling or uncertain about the next vaccine dose, with varying degrees of pandemic fatigue. Pandemic fatigue is a potentially relevant factor for vaccine hesitancy and may hinder the translation of vaccination intention into behavior. Considering the ongoing reinfection situation, implementing a health education plan to reduce pandemic fatigue and prioritizing vaccination issues for people who have recovered from COVID-19 may be key to promoting the reduction of the COVID-19 disease burden and ensuring the health and well-being of the population.

Prevalence of Intimate Partner Violence and Associated Factors Among People With HIV: A Large-Sample Cross-Sectional Study in China.

To assess the prevalence and exacerbating factors of intimate partner violence in people with human immunodeficiency virus (PWH) in China, we conducted a cross-sectional study, involving 2792 PWH in 4 provinces in China from 1 September 2020 to 1 June 2021. The categories of intimate partner violence (IPV) included physical violence, sexual violence, emotional abuse, and controlling behavior. The severity of a violent act was divided into mild, moderate, and severe. Among PWH, the prevalence of IPV was 15.4% (95% confidence interval, 14.1%-16.8%). The severity of physical violence was mainly moderate, and the severity of sexual violence, emotional abuse, and controlling behavior was mainly mild. The prevalence of IPV in men was higher than that in women. Results from the multivariable logistic regression showed that age, ethnic, registered residence, education, and duration of HIV antiretroviral therapy were factors related to IPV in PWH (P < .05).

Trends of underweight, overweight, and obesity among older adults in China from 2008 to 2018: a national observational survey.

OBJECTIVE: This study aims to investigate the 10-year trends and disparities in underweight, overweight, and obesity among older adults aged 65 years and older in China from 2008 to 2018. METHODS: We used four waves (2008, 2011, 2014, and 2018) of data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national community-based cross-sectional survey conducted every 2-3 years. Body weight and height were measured by trained assessors following standardized procedures. BMI was calculated and divided into underweight (< 18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (≥ 30.0 kg/m2) according to WHO reference. Multinomial logistic regression models were used to examine factors related with abnormal BMI groups, after adjusting for potential confounders. RESULTS: Among 46,543 older adults in China, the prevalence rates of underweight decreased with each survey year from 2008 to 2018, declining from 20.05 to 7.87% (p < 0.001). In contrast, the prevalence rates of overweight and obesity showed an increasing trend (all p < 0.001). Specifically, the prevalence of overweight rose from 12.82% to 2008 to 28.45% in 2018, and the prevalence of obesity increased from 1.62% to 2008 to 4.95% in 2018. In the multinomial logistic regression model, survey year, gender, residence, marital status, economic status, numbers of chronic diseases, smoking status, sleep quality, and functional disability were factors related with obesity. CONCLUSION: The prevalence rates of overweight and obesity were increasing while the prevalence of underweight and normal weight significantly decreased from 2008 to 2018 among older adults in China, which poses a huge challenge for chronic disease. There is an urgent need for intervention policy planning and early prevention of abnormal body weight for the preparation of an aging society.

Global, Regional, and National Trends in Incidence and Mortality of Primary Liver Cancer and Its Underlying Etiologies from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

OBJECTIVE: Primary liver cancer is not only one of the most common causes of cancer deaths but also the second most common cause of premature death worldwide. Understanding the trends in incidence and mortality of primary liver cancer and its etiologies is crucial for development of effective prevention and mitigation strategies. This study aimed to quantify the trends in incidence and mortality of primary liver cancer and its etiologies at the global, regional and national levels using data from Global Burden of Disease (GBD) study. METHOD: Annual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of primary liver cancer and its etiologies, including hepatitis B, hepatitis C, alcohol use, nonalcoholic steatohepatitis, and other causes, between 1990 and 2019 were collected from GBD study 2019. Percentage changes in incident cases and deaths and estimated annual percentage changes (EAPCs) in ASIRs and ASMRs of primary liver cancer and its etiologies were calculated to quantify their temporal trends. Correlations of EAPC in ASIRs and ASMRs with socio-demographic index (SDI) and universal health coverage index (UHCI) in 2019 were separately evaluated by Pearson correlation analyses. RESULTS: Globally, the incident cases and deaths of primary liver cancer increased by 43.11% from 373 393 in 1990 to 534 365 in 2019 and 32.68% from 365 213 in 1990 to 484 584 in 2019, respectively. ASIR and ASMR of primary liver cancer decreased by an average of 2.23% (95% CI 1.83%, 2.63%) and 1.93% (95% CI 1.55%, 2.31%) per year between 1990 and 2019 worldwide, respectively. ASIRs and ASMRs of primary liver cancer varied between regions, with an increasing trend in ASIR (EAPC = 0.91; 95% CI 0.47, 1.35) and a stable trend in ASMR (EAPC = 0.42, 95% CI - 0.01, 0.85) of primary liver cancer in high SDI region between 1990 and 2019. Nearly half (91/204) of the countries suffered an increasing trend in ASIR of primary liver cancer and more than one-third (71/204) of the countries suffered an increasing trend in ASIRs of primary liver cancer from all etiologies between 1990 and 2019 worldwide. Positive correlations of EAPC in ASIR and ASMR of primary liver cancer with SDI and UHCI were observed in nations with SDI ≥ 0.7 or UHCI ≥ 70. CONCLUSION: Primary liver cancer remains a major public health concern globally, with an increasing trend in the numbers of incident cases and deaths in the past three decades. We observed an increasing trend in ASIR of primary liver cancer in nearly half of the countries and an increasing trend in ASIRs of primary liver cancer by etiology in more than one-third of the countries worldwide. In line with the Sustainable Development Goals, the identification and elimination of risk factors for primary liver cancer will be required to achieve a sustained reduction in liver cancer burden.

Heme Oxygenase-1 and Its Metabolites Carbon Monoxide and Biliverdin, but Not Iron, Exert Antiviral Activity against Porcine Circovirus Type 3.

Porcine circovirus type 3 (PCV3) is a newly discovered pathogen that causes porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, multisystemic inflammation, and reproductive failure. Heme oxygenase-1 (HO-1), a stress-inducible enzyme, exerts protective functions by converting heme into carbon monoxide (CO), biliverdin (BV), and iron. However, the effects of HO-1 and its metabolites on PCV3 replication remain unknown. In this study, experiments involving specific inhibitors, lentivirus transduction, and small interfering RNA (siRNA) transfection revealed that active PCV3 infection reduced HO-1 expression and that the expression of HO-1 negatively regulated virus replication in cultured cells, depending on its enzymatic activity. Subsequently, the effects of the HO-1 metabolites (CO, BV, and iron) on PCV3 infection were investigated. The CO inducers (cobalt protoporphyrin IX [CoPP] or tricarbonyl dichloro ruthenium [II] dimer [CORM-2]) mediate PCV3 inhibition by generating CO, and this inhibition is reversed by hemoglobin (Hb; a CO scavenger). The inhibition of PCV3 replication by BV depended on BV-mediated reactive oxygen species (ROS) reduction, as N-acetyl-l-cysteine affected PCV3 replication while reducing ROS production. The reduction product of BV, bilirubin (BR), specifically promoted nitric oxide (NO) generation and further activated the cyclic GMP/protein kinase G (cGMP/PKG) pathway to attenuate PCV3 infection. Both the iron provided by FeCl3 and the iron chelated by deferoxamine (DFO) with CoPP treatment failed to affect PCV3 replication. Our data demonstrate that the HO-1-CO-cGMP/PKG, HO-1-BV-ROS, and HO-1-BV-BR-NO-cGMP/PKG pathways contribute crucially to the inhibition of PCV3 replication. These results provide important insights regarding preventing and controlling PCV3 infection. IMPORTANCE The regulation of host protein expression by virus infection is the key to facilitating self-replication. As an important emerging pathogen of swine, clarification of the interaction between PCV3 infection and the host enables us to understand the viral life cycle and pathogenesis better. Heme oxygenase-1 (HO-1) and its metabolites carbon monoxide (CO), biliverdin (BV), and iron have been demonstrated to involve a wealth of viral replications. Here, we, for the first time, demonstrated that HO-1 expression decreases in PCV3-infected cells and negatively regulates PCV3 replication and that the HO-1 metabolic products CO and BV inhibit PCV3 replication by the CO- or BV/BR/NO-dependent cGMP/PKG pathway or BV-mediated ROS reduction, but the iron (the third metabolic product) does not. Specifically, PCV3 infection maintains normal proliferation by downregulating HO-1 expression. These findings clarify the mechanism by which HO-1 modulates PCV3 replication in cells and provide important targets for preventing and controlling PCV3 infection.

The global, regional, and national burden and its trends of inguinal, femoral, and abdominal hernia from 1990 to 2019: findings from the 2019 Global Burden of Disease Study - a cross-sectional study.

BACKGROUND: Inguinal, femoral, and abdominal hernia repairs are the most common surgical procedure worldwide. However, studies on hernia disease burden are notably limited, in both developed and low-income and middle-income countries (LMICs). We investigated temporal trends in the incidence and prevalence of inguinal, femoral, and abdominal hernias at global, regional, and national levels in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). MATERIALS AND METHODS: Annual incident cases, prevalent cases, age-standardized incidence rates (ASIRs), and age-standardized prevalence rates (ASPRs) of inguinal, femoral, and abdominal hernias between 1990 and 2019 were extracted from the GBD 2019 study and stratified by sex, age, and location. Percentage changes in incident cases and prevalent cases, and the estimated annual percentage changes of ASIRs and ASPRs were calculated to quantify the trends in the incidence and prevalence of inguinal, femoral, and abdominal hernias. Data analysis for the present study was conducted from 15 June 2022 to 15 July 2022. RESULTS: Globally, there were 32.53 million [95% uncertainty interval (UI): 27.71-37.79] prevalent cases and 13.02 million (10.68-15.49) incident cases of inguinal, femoral, and abdominal hernias in 2019, which increased by 36.00% and 63.67%, respectively, compared with 1990. Eighty-six percent of the incident cases were males, the male-to-female ratio was 6 : 1, and most patients were aged 50-69 years. India (2.45 million), China (1.95 million), and Brazil (0.71 million) accounted for more than one-third (39%) of the incident cases worldwide. From 1990 to 2019, the ASIR and ASPR showed a decreasing trend worldwide, except in Central Sub-Saharan Africa, which had an increasing trend in ASIR and ASPR. CONCLUSION: The global incident cases and prevalent cases of inguinal, femoral, and abdominal hernias increased substantially from 1990 to 2019, with a heavier burden observed in males, older adults, and in LMICs such as India and China. In addition, the ASIR and ASPR increased substantially in Central Sub-Saharan Africa. More efforts are warranted for hernia management to reduce the burden of inguinal, femoral, and abdominal hernias, such as by providing safe hernia surgical treatment for males, older adults, and LMICs.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.

Avian Metapneumovirus Subgroup C Phosphoprotein Suppresses Type I Interferon Production by Blocking Interferon Regulatory Factor 3 Nuclear Translocation.

Avian metapneumovirus subgroup C (aMPV/C) is an important pathogen that causes upper respiratory symptoms and egg production decline in turkeys and chickens. aMPV/C infection leads to inhibition of the host antiviral immune response. However, our understanding of the molecular mechanisms underlying host immune response antagonized by aMPV/C infection is limited. In this study, we demonstrated that the aMPV/C phosphoprotein (P) inhibits the IFN antiviral signaling pathway triggered by melanoma differentiation gene 5 (MDA5) and reduces interferon ß (IFN-ß) production and IFN-stimulated genes (ISGs) by targeting IFN regulatory factor 7 (IRF7) but not nuclear factor κB (NF-κB) in DF-1 cells. Moreover, we found that aMPV/C P protein only blocks the nuclear translocation of IRF3 by interacting with IRF3 in HEK-293T cells, instead of affecting IRF3 phosphorylation and inducing IRF3 degradation, which suppresses IRF3 signaling activation and results in a decrease in IFN-ß production. Collectively, these results reveal a novel mechanism by which aMPV/C infection disrupts IFN-ß production in the host. IMPORTANCE The innate immune response is the first defense line of host cells and organisms against viral infections. When RNA viruses infect cells, viral RNA induces activation of retinoic acid-induced gene I and melanoma differentiation gene 5, which initiates downstream molecules and finally produces type I interferon (IFN-I) to regulate antiviral immune responses. The mechanism for avian metapneumovirus (aMPV) modulating IFN-I production to benefit its replication remains unknown. Here, we demonstrate that phosphoprotein of aMPV subgroup C (aMPV/C) selectively inhibits the nuclear translocation of interferon regulatory 3 (IRF3), instead of affecting the expression and phosphorylation of IRF3, which finally downregulates IFN-I production. This study showed a novel mechanism for aMPV/C infection antagonizing the host IFN response.

Interpretable machine learning to identify important predictors of birth weight: A prospective cohort study.

Background: Predicting birth weight and identifying its risk factors are clinically important. This study aims to use interpretable machine learning to predict birth weight and identity important predictors. Methods: This prospective cohort study was conducted in Tongzhou Maternal and Child Health Care Hospital of Beijing, China, recruiting pregnant women between June 2018 and February 2019. We used 24 features to predict infant birth weight, including gestational age, mother's age, parity, history of macrosomia delivery, pre-pregnancy body mass index (BMI), height, father's BMI, lifestyle (diet, physical activity, smoking), and biomarker (fasting glucose and lipids) features. Study outcome was birth weight of infant. We used 8 supervised learning models including 4 individual [linear regression, ridge regression, lasso regression, support vector machines regression (SVR)], and 4 ensemble estimators (random forest, AdaBoost, gradient boosted trees, and voting ensemble for regression) to predict birth weight. Model accuracy was measured by root mean squared error (RMSE) of 10-fold cross validation on the training set and RMSE of prediction on the test set. We used permutation importance algorithm to understand the prediction from the models and what affected them. Result: This study included 4,754 mother-child dyads. RMSEs were lower in voting ensemble for regression, linear regression, and SVR than random forest, AdaBoost, and gradient boosted tree. The 5 most important predictors for infant birth weight were gestational age, fetal sex, preterm birth, mother's height, and pre-pregnancy BMI. After adding ultrasound-measured indicators of fetal growth into predictors, mother's height and pre-pregnancy BMI remained the most important predictors in predicting the outcome. Conclusion: Mother's height and pre-pregnancy BMI were identified as important predictors for infant birth weight. Interpretable machine learning is a promising tool in the prediction of birth weight.