Exploring mother-daughter communication and social media influence on HPV vaccine refusal for daughters aged 9-17 years in a cross-sectional survey of 11,728 mothers in China.

This study investigated the influences of mother-daughter communication and social media on mothers' HPV vaccine refusal for their daughters aged 9-17. A cross-sectional online survey among 11,728 mothers of girls aged 9-17 in Shenzhen, China was implemented between July and October 2023. Multi-level logistic regression models were fitted. Among 11,728 participants, 43.2% refused to have their daughters receive an HPV vaccination. In multivariate analysis, more openness in the mother-daughter communication (AOR: 0.99, 95%CI: 0.98, 0.99), perceived more positive outcomes of mother-daughter communication (AOR: 0.77, 95%CI: 0.75, 0.79), higher frequency of exposure to testimonials about daughters' HPV vaccination (AOR: 0.81, 95%CI: 0.78, 0.85) and information encouraging parents to vaccinate their daughters against HPV on social media (AOR: 0.76, 95%CI: 0.73, 0.79), and thoughtful consideration of the veracity of the information specific to HPV vaccines (AOR: 0.80, 95%CI: 0.77, 0.83) were associated with lower vaccine refusal. Mothers who were not the main decision-makers of daughters' HPV vaccination (AOR: 1.28 to 1.46), negative outcome expectancies of mother-daughter communication (AOR: 1.06, 95%CI: 1.04, 1.08), and mothers' HPV vaccine refusal (AOR: 2.81, 95%CI: 2.58, 3.06) were associated with higher vaccine refusal for their daughters. The level of mothers' HPV vaccine refusal for their daughters was high in China. Openness and outcome expectancies of mother-daughter communication and information exposure on social media were considered key determinants of HPV vaccine refusal for daughters. Future HPV vaccination programs should consider these interpersonal factors.

Integrating a Biomineralized Nanocluster for H2S-Sensitized ROS Bomb against Breast Cancer.

Nanomaterial-assisted chemodynamic therapy (CDT) has received considerable attention in recent years. It outperforms other modalities by its distinctive reactive oxygen species (ROS) generation through a nonexogenous stimulant. However, CDT is limited by the insufficient content of endogenous hydrogen peroxide (H2O2). Herein, a biodegradable MnS@HA-DOX nanocluster (MnS@HA-DOX NC) was constructed by in situ biomineralization from hyaluronic acid, to enlarge the ROS cascade and boost Mn2+-based CDT. The acid-responsive NCs could quickly degrade after internalization into endo/lysosomes, releasing Mn2+, H2S gas, and anticancer drug doxorubicin (DOX). The Fenton-like reaction catalyzed by Mn2+ was amplified by both H2S and DOX, producing a mass of cytotoxic ·OH radicals. Through the combined action of gas therapy (GT), CDT, and chemotherapy, oxidative stress would be synergistically enhanced, inducing irreversible DNA damage and cell cycle arrest, eventually resulting in cancer cell apoptosis.

Coverage with the First Dose of Human Papillomavirus Vaccination among Females Aged 9-50 Years in Shenzhen, China: A Surveillance Based on Administrative Health Records in 2023.

China started to offer human papillomavirus (HPV) vaccines to females aged 9-45 years in 2016. However, there was a lack of reports about HPV vaccination coverage in a representative sample of females in China. Therefore, this study aimed to examine the current HPV coverage and associated factors among females aged 9-50 years in Shenzhen, China, based on administrative health records kept by community health centers. A multistage random sampling approach was used. The research team randomly selected 18 community health centers in Shenzhen, and 3118 health records of females aged 9-50 years were then randomly selected from these health centers. Among all participants, 18.7% received at least one dose of HPV vaccination. The highest coverage was observed among females aged 18-26 years (23.4%), followed by those aged 27-35 years (22.0%) and 36-45 years (20.2%). Such coverage was very low among females aged 9-17 years (4.6%) and those aged 46-50 years (3.2%). Among females aged 18 years or above, higher education level, having a family doctor, and permanent residency in Shenzhen were associated with higher HPV vaccination coverage, while older age and being married/divorced were negatively associated with coverage. The HPV vaccination coverage in Shenzhen was 18.7% and there is a strong need for improvement.

Heat accumulation and phase transition induction in a VO2 thin film by a femtosecond pulse-periodic radiation.

The kinetics of optical switching due to the insulator-metal phase transition in a VO2 thin film is studied experimentally at different laser pulse repetition frequencies (PRFs) in the NIR range and compared with temperature kinetics obtained through the thermal conductance calculations. Two switching processes have been found with characteristic times <2 ms and <15 ms depending on the PRF; the former is explained by the accumulation of metallic domains remaining after a single-pulse phase transition, and the latter is referred to the heat accumulation in the film. Consequently, the dynamics of the microscopic domains is leading in the initiation of phase transition under pulse-periodic conditions compared to the macroscopic heat transfer. The reverse transition at the radiation turn-off depends on the PRF with a time coefficient of 17.5 µs/kHz and is determined by the metallic domains' decay in the film. The results are important for understanding the nature of the insulator-metal transition in thin films of VO2 as well as using them in all-optical switches of pulse-periodic laser radiation.

A Mechanism Underpinning the Bioenergetic Metabolism-Regulating Function of Gold Nanocatalysts.

Bioenergetic deficits are known to be significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the energy metabolism-regulating function of colloidal Au nanocrystals, referred to as CNM-Au8, that are synthesized electrochemically in the absence of surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and neurite network preservation across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic cofactor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized counterpart (NAD+ ), which promotes bioenergy production by regulating the intracellular level of adenosine triphosphate. Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. Photoexcited charge carriers and photothermal effect, which result from optical excitations and decay of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, are further harnessed as unique leverages to modulate reaction kinetics. As exemplified by this work, Au nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.

A comprehensive analysis of the role of QPRT in breast cancer.

To explore the clinical role of QPRT in breast cancer. The gene expression, methylation levels and prognostic value of QPRT in breast cancer was analyzed using TCGA data. Validation was performed using the data from GEO dataset and TNMPLOT database. Meta analysis method was used to pool the survival data for QPRT. The predictive values of QPRT for different drugs were retrieved from the ROC plot. The expression differences of QPRT in acquired drug-resistant and sensitive cell lines were analyzed using GEO datasets. GO and KEGG enrichment analysis were conducted for those genes which were highly co-expressed with QPRT in tissue based on TCGA data and which changed after QPRT knockdown. Timer2.0 was utilized to explore the correlation between QPRT and immune cells infiltration, and the Human Protein Atlas was used to analyse QPRT's single-cell sequencing data across different human tissues. The expression of QPRT in different types of macrophages, and the expression of QPRT were analysed after coculturing HER2+ breast cancer cells with macrophages. Additionally, TargetScan, Comparative Toxicogenomics and the connectivity map were used to research miRNAs and drugs that could regulate QPRT expression. Cytoscape was used to map the interaction networks between QPRT and other proteins. QPRT was highly expressed in breast cancer tissue and highly expressed in HER2+ breast cancer patients (P < 0.01). High QPRT expression levels were associated with worse OS, DMFS, and RFS (P < 0.01). Two sites (cg02640602 and cg06453916) were found to be potential regulators of breast cancer (P < 0.01). QPRT might predict survival benefits in breast cancer patients who received taxane or anthracycline. QPRT was associated with tumour immunity, especially in macrophages. QPRT may influence the occurrence and progression of breast cancer through the PI3K-AKT signalling pathway, Wnt signalling pathway, and cell cycle-related molecules.

Concerns related to the interactions between COVID-19 vaccination and cancer/cancer treatment were barriers to complete primary vaccination series among Chinese cancer patients: A multicentre cross-sectional survey.

COVID-19 vaccination is effective for cancer patients without safety concerns. However, COVID-19 vaccination hesitancy is common among cancer patients. This study investigated factors affecting primary COVID-19 vaccination series completion rate among cancer patients in China. A multicentre cross-sectional study was conducted in four Chinese cities in different geographic regions between May and June 2022. A total of 893 cancer inpatients provided written informed consent and completed the study. Logistic regression models were fitted. Among the participants, 58.8% completed the primary COVID-19 vaccination series. After adjusting for background characteristics, concerns about interactions between COVID-19 vaccination and cancers/cancer treatment (adjusted odds ratios [AOR]: 0.97, 95%CI: 0.94, 0.99) were associated with lower completion of primary vaccination series. In addition, perceived higher risk of COVID-19 infection comparing to people without cancers (AOR: 0.46, 95%CI: 0.24, 0.88), perceived a high chance of having severe consequences of COVID-19 infection (AOR: 0.68, 95%CI: 0.51, 0.91) were also associated with lower completion rate. Being suggested by significant others (AOR: 1.32, 95%CI: 1.23, 1.41) and perceived higher self-efficacy to receive COVID-19 vaccination (AOR: 1.48, 95%CI: 1.31, 1.67) were positively associated with the dependent variable. Completion rate of primary COVID-19 vaccination series was low among Chinese cancer patients. Given the large population size and their vulnerability, this group urgently needs to increase COVID-19 vaccination coverage. Removing concerns about interactions between COVID-19 vaccination and cancers, using fear appeal approach, involving significant others, and facilitating patients to make a plan to receive COVID-19 vaccination might be useful strategies.

Hesitancy to Receive the Booster Doses of COVID-19 Vaccine Among Cancer Patients in China: A Multicenter Cross-Sectional Survey - Four PLADs, China, 2022.

What is already known about this topic?: Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population; however, coverage for booster doses of the coronavirus disease 2019 (COVID-19) vaccine was low among cancer patients in China. What is added by this report?: Overall, 32.0% and 56.4% of cancer patients from four Provincial Level Administrative Divisions (PLADs) expressed hesitancy toward the first and second booster doses, respectively. Factors negatively associated with hesitancy to receive booster doses included positive attitudes, perceived support, and higher exposure to COVID-19 vaccination information. Conversely, postvaccination fatigue was positively associated with vaccine hesitancy. What are the implications for public health practice?: Improved COVID-19 vaccination coverage is needed to promote health for cancer patients.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study.

BACKGROUND: Lugol chromoendoscopy (LCE) has served as a standard screening technique in high-risk patients with esophageal cancer. Nevertheless, LCE is not suitable for general population screening given its side effects. Linked color imaging (LCI) is a novel image-enhanced endoscopic technique that can distinguish subtle diff-erences in mucosal color. AIM: To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions. METHODS: In this prospective study, we enrolled 543 patients who underwent white light imaging (WLI), LCI and LCE successively. We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions. Clinicopathological features and color analysis of lesions were assessed. RESULTS: In total, 43 patients (45 neoplastic lesions) were analyzed. Among them, 36 patients (38 neoplastic lesions) were diagnosed with LCI, and 39 patients (41 neoplastic lesions) were diagnosed with LCE. The sensitivity of LCI was similar to that of LCE (83.7% vs 90.7%, P = 0.520), whereas the specificity of LCI was greater than that of LCE (92.4% vs 87.0%, P = 0.007). The LCI procedure time in the esophageal examination was significantly shorter than that of LCE [42 (34, 50) s vs 160 (130, 189) s, P < 0.001]. The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI. However, the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer. CONCLUSION: LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions, and LCI represents a promising screening strategy for general populations.

Reprogramming efficiency and pluripotency of mule iPSCs over its parents†.

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.

Low Behavioral Intention to Use Any Type of HIV Testing and HIV Self-Testing among Migrant Male Factory Workers Who Are at High Risk of HIV Infection in China: A Secondary Data Analysis.

This study investigated the prevalence of and factors associated with behavioral intention to take up any type of HIV testing and HIV self-testing (HIVST) in the next six months among male migrant workers, who were at high risk of HIV infection, in Shenzhen, China. This was a secondary data analysis. A total of 363 subjects who had sexual intercourse with non-regular female sex partners and/or female sex workers in the past six months were selected. Logistic regression models were fitted for data analysis. About 16.5% of participants reported having used HIV testing in their lifetime and 12.7% for HIVST. Among the participants, 25.6% and 23.7% intended to take up any type of HIV testing and HIVST in the next six months, respectively. Significant factors associated with the behavioral intention to take up HIV testing and HIVST included individual-level factors based of the Health Belief Model (e.g., perceived benefit, perceived cue to action, perceived self-efficacy) and interpersonal-level factors (e.g., frequency of exposure to health-related content or HIV and STI-related content on short video apps). This study provided practical implications for designing interventions to increase the uptake of HIV testing and HIVST among migrant workers.

Self-help inflatable balloon versus autologous skin-grafting surgery for preventing esophageal stricture after complete circular endoscopic submucosal dissection: a propensity score matching analysis.

BACKGROUND: The self-help inflatable balloon (SHIB) and autologous skin-grafting surgery (ASGS) were used to prevent stricture after esophageal complete circular endoscopic submucosal dissection (cESD) with promising clinical results. We aim to evaluate which method is more suitable for patients who underwent esophageal cESD. METHODS: From October 2017 to July 2021, patients whose mucosal defect length were between 30 and 100 mm after esophageal cESD were retrospectively reviewed from two prospective studies. They were enrolled once SHIB or ASGS was used as preventive methods to prevent stricture. Propensity score matching (PSM) was used to balance the baseline characteristics between the two groups. Comparisons were made between the two groups, including operation time, the longitudinal length of ulceration, fasting time, hospitalization days, and the incidence of stricture. RESULTS: A total of 41 patients who met the inclusion criteria were enrolled in the study. The numbers of patients in SHIB group and ASGS group were 25 and 16, respectively. Fifteen patients in each group were selected after performing PSM. The basic baseline characteristics were comparable between the two groups. The stricture rates were 20% (3/15) in SHIB group and 40% (6/15) in ASGS group, while the difference was not statistically significant (p = 0.427). The SHIB group showed significantly shorter operation time, shorter hospitalization days, lower cost, and longer removing balloon/stent time compared with ASGS group (p < 0.001). Comparison of relevant stricture factors between the stricture group and non-stricture group revealed that longer longitudinal length of ulceration (> 60 mm) accounted for a higher proportion in stricture groups (p = 0.035). CONCLUSION: Both the SHIB and ASGS had high efficacy and safety in preventing strictures in patients with mucosal defects no longer than 100 mm in length after esophageal cESD. The longitudinal length of ulceration > 60 mm was the independent factor for predicting stricture.

Effect of Ascosphaera apis Infestation on the Activities of Four Antioxidant Enzymes in Asian Honey Bee Larval Guts.

Ascosphaera apis infects exclusively bee larvae and causes chalkbrood, a lethal fungal disease that results in a sharp reduction in adult bees and colony productivity. However, little is known about the effect of A. apis infestation on the activities of antioxidant enzymes in bee larvae. Here, A. apis spores were purified and used to inoculate Asian honey bee (Apis cerana) larvae, followed by the detection of the host survival rate and an evaluation of the activities of four major antioxidant enzymes. At 6 days after inoculation (dpi) with A. apis spores, obvious symptoms of chalkbrood disease similar to what occurs in Apis mellifera larvae were observed. PCR identification verified the A. apis infection of A. cerana larvae. Additionally, the survival rate of larvae inoculated with A. apis was high at 1−2 dpi, which sharply decreased to 4.16% at 4 dpi and which reached 0% at 5 dpi, whereas that of uninoculated larvae was always high at 1~8 dpi, with an average survival rate of 95.37%, indicating the negative impact of A. apis infection on larval survival. As compared with those in the corresponding uninoculated groups, the superoxide dismutase (SOD) and catalase (CAT) activities in the 5- and 6-day-old larval guts in the A. apis−inoculated groups were significantly decreased (p < 0.05) and the glutathione S-transferase (GST) activity in the 4- and 5-day-old larval guts was significantly increased (p < 0.05), which suggests that the inhibition of SOD and CAT activities and the activation of GST activity in the larval guts was caused by A. apis infestation. In comparison with that in the corresponding uninoculated groups, the polyphenol oxidase (PPO) activity was significantly increased (p < 0.05) in the 5-day-old larval gut but significantly reduced (p < 0.01) in the 6-day-old larval gut, indicating that the PPO activity in the larval guts was first enhanced and then suppressed. Our findings not only unravel the response of A. cerana larvae to A. apis infestation from a biochemical perspective but also offer a valuable insight into the interaction between Asian honey bee larvae and A. apis.

Emission factors and source profiles of volatile organic compounds from typical industrial sources in Guangzhou, China.

Volatile organic compounds (VOCs) are important precursors of ozone (O3) and fine particulate matter (PM2.5). An accurate depiction of the emission characteristics of VOCs is the key to formulating VOC control strategies. In this study, the VOC emission factors and source profiles in five industrial sectors were developed using large-scale field measurements conducted in Guangzhou, China (100 samples for the emission factors and 434 samples for the source profile measurements). The emission factors based on the actual measurement method and the material balance method were 1.6-152.4 kg of VOCs per ton of raw materials (kg/t) and 3.1-242.2 kg/t, respectively. The similarities between the emission factors obtained using these two methods were examined, which showed a coefficient of divergence (CD) of 0.34-0.72. Among the 33 subdivided VOC source profiles developed in this study, sources including light guide plate (LGP), photoresist mask, and plastic products were the first time developed in China. Due to regional diversities in terms of production technologies, materials, and products, the emission characteristics of the VOCs varied, even in the same sector, thereby demonstrating the importance of developing localized source profiles of VOCs. The ozone formation potential (OFP) of the shipbuilding and repair sector from fugitive emissions was the highest value among all the industrial sectors. Controlling the emissions of aromatics and OVOCs was critical to reducing the O3 growth momentum in industrial sectors. In addition, 1,2-dibromoethane showed high carcinogenic risk potentials (CRPs) during most of the industrial sectors and should be prioritized for controlling.

Incidence trends and disparities in Helicobacter pylori related malignancy among US adults, 2000-2019.

Background: Helicobacter pylori (H. pylori) is closely related to the carcinogenesis of gastric cancer (GC) and gastric non-Hodgkin lymphoma (NHL). However, the systemic trend analysis in H. pylori-related malignancy is limited. We aimed to determine the national incidence trend in non-cardia GC, cardia GC, and gastric NHL in the US during 2000-2019. Method: In this population-based study, we included 186,769 patients with a newly diagnosed H. pylori-related malignancy, including non-cardia GC, cardia GC, and gastric NHL from the Surveillance, Epidemiology, and End Results (SEER) Registry from January 1, 2000 to December 31, 2019. We determined the age-adjusted incidence of three H. pylori-related malignancies respectively. Average annual percentage change (AAPC) in 2000-2019 was calculated to describe the incidence trends. Analyses were stratified by sex, age, race and ethnicity, geographic location and SEER registries. We also determined the 5-year incidence (during 2015-2019) by SEER registries to examine the geographic variance. Results: The incidence in non-cardia GC and gastric NHL significantly decreased during 2000-2019, while the rate plateaued for cardia GC (AAPCs, -1.0% [95% CI, -1.1%-0.9%], -2.6% [95% CI, -2.9%-2.3%], and -0.2% [95% CI, -0.7%-0.3%], respectively). For non-cardia GC, the incidence significantly increased among individuals aged 20-64 years (AAPC, 0.8% [95% CI, 0.6-1.0%]). A relative slower decline in incidence was also observed for women (AAPC, -0.4% [95% CI, -0.6%-0.2%], P for interaction < 0.05). The incidence of cardia GC reduced dramatically among Hispanics (AAPC, -0.8% [95% CI, -1.4%-0.3%]), however it increased significantly among nonmetropolitan residents (AAPC, 0.8% [95% CI, 0.4-1.3%]). For gastric NHL, the decreasing incidence were significantly slower for those aged 20-64 years (AAPC, -1.5% [95% CI, -1.9-1.1%]) and Black individuals (AAPC, -1.3% [95% CI, -1.9-1.1%]). Additionally, the highest incidence was observed among Asian and the Black for non-cardia GC, while Whites had the highest incidence of cardia GC and Hispanics had the highest incidence of gastric NHL (incidence rate, 8.0, 8.0, 3.1, and 1.2, respectively) in 2019. Geographic variance in incidence rates and trends were observed for all three H. pylori-related malignancies. The geographic disparities were more pronounced for non-cardia GC, with the most rapid decline occurring in Hawaii (AAPC, -4.5% [95% CI, -5.5-3.6%]) and a constant trend in New York (AAPC 0.0% [95% CI, -0.4-0.4%]), the highest incidence in Alaska Natives, and the lowest incidence among Iowans (14.3 and 2.3, respectively). Conclusion: The incidence of H. pylori-related cancer declined dramatically in the US between 2000 and 2019, with the exception of cardia GC. For young people, a rising trend in non-cardia GC was noted. Existence of racial/ethnic difference and geographic diversity persists. More cost-effective strategies of detection and management for H. pylori are still in demand.

Parental Willingness and Associated Factors of Pediatric Vaccination in the Era of COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

A significant decline in pediatric vaccination uptake due to the COVID-19 pandemic has been documented. Little is known about the parental willingness and associated factors of pediatric vaccination during the COVID-19 pandemic. An extensive literature search in the databases of PubMed, Scopus, Web of Science, and EBSCOhost were conducted. A total of 20 eligible studies published from 2020-2022 were included for systematic summary by a thematic analysis, among which 12 studies were included in a meta-analysis conducted with R-4.2.1. The prevalence of parental willingness to childhood/routine vaccination and seasonal influenza vaccination was 58.6% (95%CI 2.8-98.6%) and 47.3% (95%CI 25.3-70.5%). Moreover, there is no sufficient evidence of significant change in parental willingness to childhood/routine vaccination, human papillomavirus vaccination, or pneumococcal conjugate vaccination during the pandemic. However, a significant increase in parental willingness to vaccinate their children against seasonal influenza was found. In addition to the factors of parental vaccination willingness/hesitancy that are well-studied in literature, children/parents' history of COVID-19 and children's perceived vulnerability to COVID-19 were associated with parental willingness. Developing synergetic strategies to promote COVID-19 vaccination together with other pediatric vaccination is warranted during the pandemic. This may help to improve and/or catch up the vaccine uptake of children during and/or after the COVID-19 pandemic.

Tumor-polarized GPX3+ AT2 lung epithelial cells promote premetastatic niche formation.

The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3+ AT2 cells inhibited CD4+ T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3+ AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1α) and promoting HIF-1α-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3+ AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.

Would Chinese Men Who Have Sex With Men Take Up Human Papillomavirus (HPV) Screening as an Alternative Prevention Strategy to HPV Vaccination?

Background: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection. A community-based organization (CBO)-private clinic service model promoting HPV vaccination among MSM was implemented in Hong Kong. The aim of this study was to evaluate the effectiveness of this service model in increasing HPV screening among MSM. Methods: This was a secondary analysis of the CBO-private clinic service model in increasing HPV screening among MSM. Participants were Hong Kong Chinese-speaking MSM aged 18-45 years who had never received HPV vaccination. All participants completed a telephone survey at baseline before receiving online intervention promoting HPV vaccination and completed another telephone survey 12 months afterward. Results: A total of 350 participants completed a baseline telephone survey and received interventions promoting HPV vaccination. Among 274 participants being followed up at Month 12, 33 (12.0%) received any type of HPV screening during the study period. Such uptake rate was similar to the prevalence of HPV screening in the past year measured at baseline (12.0 vs. 9.9%, p = 0.43). More MSM preferred HPV vaccination or HPV vaccination plus HPV screening, and very few preferred HPV screening alone. After adjusting for significant baseline characteristics, higher perceived susceptibility to HPV (adjusted odds ratio (AOR): 1.16, 95% confidence interval (CI): 1.00-1.34) and receiving HPV vaccination during the study period (AOR: 7.03, 95% CI: 3.07-16.13) were significantly associated with higher HPV screening uptake. Conclusions: The CBO-private clinic service model promoting HPV vaccination had limited impact in increasing HPV screening among MSM in Hong Kong. MSM in Hong Kong may not use HPV screening as an alternative prevention strategy to HPV vaccination. Future programs preventing HPV-related diseases among MSM in Hong Kong should focus on HPV vaccination promotion.

Relationship between HER2 overexpression and long-term outcomes of early gastric cancer: a prospective observational study with a 6-year follow-up.

BACKGROUND: Studies have confirmed the prognostic value of the expression status of human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer. However, its role in early gastric cancer (EGC) remains largely unknown. This study explored the association between HER2 overexpression and clinical outcomes of patients with EGC. METHODS: A total of 211 patients who had undergone endoscopic treatment for pN0 EGC were enrolled. The HER2 expression status was assessed using immunohistochemistry (IHC). RESULTS: The prevalence of HER2 overexpression was 14.2%. HER2 overexpression showed a significant correlation with tumor location (P = 0.033). Multivariate analysis showed that HER2 overexpression was significantly associated with an increased risk of tumor recurrence in pN0 EGC (hazard ratio [HR] = 3.97; 95% confidence interval [CI] 1.30-12.14; P = 0.016) but not overall survival (OS) or disease-specific survival (DSS). Of the included patients, age was associated with OS (HR = 1.11; 95% CI 1.04-1.18; P = 0.002], whereas lymphovascular invasion was significantly associated with poor DSS (HR = 33.66; 95% CI 3.05-371.25; P = 0.004). CONCLUSION: This study shows that HER2 overexpression is significantly associated with tumor recurrence in pN0 EGC. Hence, Her2 testing at diagnosis is important and differential treatment and/or follow up strategies for patients with Her2 overexpression may merit future study.

Opposite regulation of F508del-CFTR biogenesis by four poly-lysine ubiquitin chains In vitro.

As a misfolding protein, almost all of F508del-CFTR is degraded by the ubiquitin-proteasome system before its maturation, which results in no membrane expression of cystic fibrosis transmembrane conductance regulator (CFTR) and therefore, no chloride secretion across epithelial cells of cystic fibrosis (CF) patients. The conjugation of ubiquitin (Ub) chains to protein substrates is necessary for the proteasomal degradation of F508del-CFTR. Ubiquitin contains seven lysine (K) residues, all of which can be conjugated to one another, forming poly-ubiquitin chains on substrates, either by mixing together, or by only one type of lysine providing sorting signals for different pathways. Here, we report that four lysine-linked poly-Ub chains (LLPUCs) were involved in F508del-CFTR biogenesis: LLPUCs linked by K11 or K48 facilitated F508del-CFTR degradation, whereas the other two linked by K63 and K33 protected F508del-CFTR from degradation. LLPUC K11 is more potent for F508del-CFTR degradation than K48. F508del-CFTR utilizes four specific lysine-linked poly-Ub chains during its biogenesis for opposite destiny through different identification by proteasomal shuttle protein or receptors. These findings provide new insights into the CF pathogenesis and are expected to facilitate the development of therapies for this devastating disease.