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Abstract Objective Socioeconomic status (SES) has been previously associated with children’s early development, health, and nutrition; however, evidence about the potential role of caregiver-child interaction in such associations was limited. This study aimed to explore the effect of caregiver-child interaction on the associations of SES with child developmental outcomes, including early neurodevelopment and social-emotional behavior. Methods A cross-sectional survey was conducted among 2078 children aged 0–6 in a rural county that just lifted out of poverty in 2020 in Central China. The Ages & Stages Questionnaires-Chinese version (ASQ-C) and the Social-Emotional (ASQ: SE) questionnaire were used to assess children's early neurodevelopment and social-emotional behavior, respectively. Caregiver-child interaction was evaluated with the Brigance Parent–Child Interactions Scale. Regression-based statistical mediation and moderation effect were conducted with the PROCESS macro of SPSS. Results Children with low SES had an increased risk of suspected neurodevelopmental delay [OR = 1.92, 95% CI: 1.50, 2.44] and social-emotional developmental delay [OR = 1.31, 95% CI: 1.04, 1.66]. The caregiver-child interaction partially mediated the associations of SES with child developmental outcomes; the proportion of the indirect effect was 14.9% for ASQ-C total score and 32.1% for ASQ: SE score. Moreover, the caregiver-child interaction had a significant moderation effect on the association of SES with ASQ-C total score (P

The transmission and prevalence of Hand, Foot and Mouth Disease (HFMD) are affected by a variety of natural and socio-economic environmental factors. This study aims to quantitatively investigate the non-stationary and spatially varying associations between various environmental factors and HFMD risk. We collected HFMD surveillance cases and a series of relevant environmental data from 2013 to 2021 in Xi'an, Northwest China. By controlling the spatial and temporal mixture effects of HFMD, we constructed a Bayesian spatiotemporal mapping model and characterized the impacts of different driving factors into global linear, non-stationary and spatially varying effects. The results showed that the impact of meteorological conditions on HFMD risk varies in both type and magnitude above certain thresholds (temperature: 30 °C, precipitation: 70 mm, solar radiation: 13000 kJ/m2, pressure: 945 hPa, humidity: 69%). Air pollutants (PM2.5, PM10, NO2) showed an inverted U-shaped relationship with the risk of HFMD, while other air pollutants (O3, SO2) showed nonlinear fluctuations. Moreover, the driving effect of increasing temperature on HFMD was significant in the 3-year period, while the inhibitory effect of increasing precipitation appeared evident in the 5-year period. In addition, the proportion of urban/suburban/rural area had a strong influence on HFMD, indicating that the incidence of HFMD firstly increased and then decreased during the rapid urbanization process. The influence of population density on HFMD was not only limited by spatial location, but also varied between high and low intervals. Higher road density inhibited the risk of HFMD, but higher night light index promoted the occurrence of HFMD. Our findings further demonstrated that both ecological and socioeconomic environmental factors can pose multiple driving effects on increasing the spatiotemporal risk of HFMD, which is of great significance for effectively responding to the changes in HFMD epidemic outbreaks.

Abstract Multiple tumors are synergistically promoted by c-Met and TRK, and blocking their cross-signalling pathway may give better effects. In this study, we developed a tyrosine kinase inhibitor 1D228, which exhibited excellent anti-tumor activity by targeting c-Met and TRK. Models in vitro, 1D228 showed a significant better inhibition on cancer cell proliferation and migration than the positive drug Tepotinib. Models in vivo, 1D228 showed robust anti-tumor effect on gastric and liver tumor growth with 94.8% and 93.4% of the TGI, respectively, comparing 67.61% and 63.9% of Tepotinib. Importantly, compared with the combination of Larotrectinib and Tepotinib, 1D228 monotherapy in MKN45 xenograft tumor models showed stronger antitumor activity and lower toxicity. Mechanistic studies showed that 1D228 can largely inhibit the phosphorylation of TRKB and c-Met. Interestingly, both kinases, TRKs and c-Met, have been found to be co-expressed at high levels in patients with gastric cancer through IHC. Furthermore, bioinformatics analysis has revealed that both genes are abnormally co-expressed in multiple types of cancer. Cell cycle analysis found that 1D228 induced G0/G1 arrest by inhibiting cyclin D1. Additionally, vascular endothelial cells also showed a pronounced response to 1D228 due to its expression of TRKB and c-Met. 1D228 suppressed the migration and tube formation of endothelial cells, which are the key functions of tumor angiogenesis. Taken together, compound 1D228 may be a promising candidate for the next generation of c-Met and TRK inhibitors for cancer treatment, and offers a novel potential treatment strategy for cancer patients with abnormal expressions of c-Met or NTRK, or simultaneous of them.

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic β cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in β cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in β cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

Background In mainland China, HPV vaccines have been available to the public. However, only a few related studies among health care providers, as the key information providers, were reported although public concerns on HPV vaccines still exist. In this study, we aim to assess the knowledge of HPV, its vaccines, and attitudes toward HPV vaccines among the three most important groups of health care providers in Western China. Method This was a cross-sectional questionnaire-based study. Health care providers including obstetrician-gynecologists (OB-GYNs), pediatricians, and immunization service providers in Western China were investigated regarding their knowledge of HPV and its vaccines and their attitudes toward HPV vaccines. Results Of 1079 health care providers completing the survey, 1015 (94.1%) knew HPV infection is the primary cause of cervical cancer. However, lower knowledge levels of other HPV-related diseases were also found (43.2%). About three-quarters (74.1%) of practitioners interviewed would be willing to recommend HPV vaccination, which was found to be lower among the OB-GYNs (69.6%) and the pediatricians (73.2%). “Lack of relevant knowledge,” “concerns on safety and efficacy” and price were the three most important concerns surrounding HPV vaccination. Conclusion The interviewed practitioners did not have adequate knowledge of HPV and its vaccines in depth. Education interventions are highly recommended to the health care providers, especially for OB-GYNs and pediatricians, to increase the coverage of HPV vaccination among the population. For the currently high price of vaccines, a future co-sharing mechanism between the government, the providers, and the individuals might be a solution.

Abstract Background Chest radiograph (CXR) is still one of the most commonly used diagnostic tools for chest diseases. In this cohort study, we attempted to investigate the magnitude and temporal pattern of lung cancer risk following abnormal CXR findings. Methods We conducted an extended follow‐up of an occupational screening cohort in Yunnan, China. The associations between abnormal CXR results from baseline screening, the first four consecutive rounds of CXR screening, all previous rounds of screening and lung cancer risk were analyzed using time‐varying coefficient Cox regression model. The associations of lung cancer risk and previous CXR‐screening results according to histology were also considered. Sensitivity analyses were conducted to assess the robustness of the previous abnormal CXR findings on subsequent lung cancer risk. Results Abnormal CXR findings were associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared to negative screening results, the adjusted hazard ratios (HR) of baseline abnormal CXR results, and at least one abnormal result in the first four consecutive screening rounds during the first 5 years of follow‐up were 17.06 (95% CI: 11.74–24.79) and 13.77 (95%: 9.58–17.79), respectively. This significantly increased lung cancer risk continued over the next 5 years. These associations were stronger for persistent abnormal findings, and abnormal findings identified in recent screening rounds. Conclusions The increased risk was significant for both squamous cell carcinoma and adenocarcinoma. Although decreased over time, an increased lung cancer risk relative to abnormal CXR findings can continue for 10 years.

Cholesterol metabolism in the brain plays a crucial role in normal physiological function, and its aberrations are associated with cognitive dysfunction. The present study aimed to determine which cholesterol-related genes play a vital role in cognitive dysfunction and to dissect its underlying molecular mechanisms using a systems genetics approach in the BXD mice family. We first systematically analyzed the association of expression of 280 hippocampal genes related to cholesterol metabolism with cognition-related traits and identified lipoprotein lipase (Lpl) as a critical regulator. This was further confirmed by phenome-wide association studies that indicate Lpl associated with hippocampus volume residuals and anxiety-related traits. By performing expression quantitative trait locus mapping, we demonstrate that Lpl is strongly cis-regulated in the BXD hippocampus. We also identified ∼3,300 genes significantly (p < 0.05) correlated with the Lpl expression. Those genes are mainly involved in the regulation of neuron-related traits through the MAPK signaling pathway, axon guidance, synaptic vesicle cycle, and NF-kappa B signaling pathway. Furthermore, a protein–protein interaction network analysis identified several direct interactors of Lpl, including Rab3a, Akt1, Igf1, Crp, and Lrp1, which indicates that Lpl involves in the regulation of cognitive dysfunction through Rab3a-mediated synaptic vesicle cycle and Akt1/Igf1/Crp/Lrp1-mediated MAPK signaling pathway. Our findings demonstrate the importance of the Lpl, among the cholesterol-related genes, in regulating cognitive dysfunction and highlighting the potential signaling pathways, which may serve as novel therapeutic targets for the treatment of cognitive dysfunction.

Developing facile methods for the synthesis of active and stable electrocatalysts is vitally important to realize overall water splitting. Here, we demonstrate a practical method to obtain FeNiOOH nanosheets on nickel foam (NF) as bifunctional electrocatalyst by growing a FeCo Prussian blue analog with further in situ oxidation under ambient conditions. The binder-free, self-standing FeNiOOH/NF electrode with hierarchical nanostructures requires low overpotentials of 260 mV and 240 mV at a current density of 50 mA cm−2 for oxygen evolution reaction and hydrogen evolution reaction, respectively, in 1.0 M KOH solution. Therefore, an alkaline water electrolyzer constructed by bifunctional FeNiOOH/NF electrode as both anode and cathode delivers 50 mA cm−2 under a cell voltage of 1.74 V with remarkable stability, which outperforms the IrO2-Pt/C-based electrolyzer. The excellent performance could be ascribed to the superior FeNiOOH intrinsic activity and the hierarchical structure. This work provides a cost-efficient surface engineering method to obtain binder-free, self-standing bifunctional electrocatalyst on commercial NF, which could be further extended to other energy and environment applications.

Lung cancer which represents characteristics of a heavy disease burden, a large proportion of advanced lung cancer and a low five-year survival rate is a threat to human health. It is essential to implement population-based lung cancer screening to improve early detection and early treatment. The National Lung Screening Trial (NLST) demonstrated that screening with low dose helical computed tomography (LDCT) may decrease lung cancer mortality, which brings hope for the early diagnosis and treatment of lung cancer. In recent years, great progresses have been made on research of lung cancer screening with LDCT. However, whether LDCT could be applied to large population-based lung cancer screening projects is still under debate. In this paper, we review the recent progresses on history of lung cancer screening with LDCT, selection of high-risk individuals, management of pulmonary nodules, performance of screening, acceptance of LDCT and cost-effectiveness.

PurposeOur understanding of breast cancer in very young women (≤35 years old) remains limited. We aimed to assess the clinicopathological characteristics, molecular subtype, and treatment distribution and prognosis of these young patients compared with patients over 35 years.MethodsWe retrospectively analyzed non-metastatic female breast cancer cases treated at three Chinese academic hospitals between January 1, 2008, and December 31, 2018. Local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were compared between different age groups and stratified with distinct molecular subtypes.ResultsA total of 11,671 women were eligible for the final analyses, and 1,207 women (10.3%) were ≤35 years at disease onset. Very young breast cancer women were more likely to be single or childless, have higher-grade disease, have more probability of lymphovascular invasion (LVI) in tumor and triple-negative subtype, and be treated by lumpectomy, chemotherapy especially more anthracycline- and paclitaxel-based chemotherapy, endocrine therapy plus ovarian function suppression (OFS), anti-HER2 therapy, and/or radiotherapy than older women (P < 0.05 for all). Very young women had the lowest 5-year LRFS and DFS among all age groups (P < 0.001 for all). When stratified by molecular subtype, very young women had the worst outcomes vs. women from the 35~50-year-old group or those from >50-year-old group for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) subtype, including LRFS, DFS, and OS (P < 0.05 for all). In terms of LRFS and DFS, multivariate analyses showed similar results among the different age groups.ConclusionOur study demonstrated that very young women with breast cancer had higher-grade tumors, more probability of LVI in tumor, and more triple-negative subtype, when compared with older patients. They had less favorable survival outcomes, especially for patients with the HR+/HER2− subtype.

Background: Sputum cytologic atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk. Methods: An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and 7 annual screenings since enrollment. The associations between sputum cytologic results from baseline screening, the first 4 consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model. Results: A moderate or worse cytologic result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared with negative screening results, the adjusted hazard ratios of baseline-moderate or worse atypia, at least one moderate or worse atypia in the first 4 consecutive screening rounds during the first 10 years of follow-up were 3.11 [95% confidence interval (CI): 2.37-4.07], 3.25 (95% CI: 2.33-4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio = 17.55, 95% CI: 8.32-37.03); atypia identified in the recent screening rounds (adjusted HR = 4.14, 95% CI: 2.70-6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer. Conclusions: Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years. Impact: Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance, or chemoprevention of lung cancer. [ABSTRACT FROM AUTHOR]