Microfluidic device reveals new insights into impairment of neutrophil transmigration in patients with sepsis.

Neutrophils need to migrate through tight tissue spaces to eliminate pathogens, but their movement is often hindered by their large and stiff nuclei. Neutrophil migration is impaired in sepsis patients, but it is unclear whether this defect is related to the deformability of their nuclei. Herein, we designed microfluidic devices with micron-scale narrow slits to simulate biological barriers. This setup allowed us to observe and record neutrophil movement and nuclear deformation in real-time. We also developed a method for morphological analysis to quantify nucleus deformation in numerous individual cells. Our studies showed that neutrophils from healthy individuals could adjust their nuclear shape to squeeze through these constrictions, whereas those from sepsis patients demonstrated less flexibility. Neutrophils with rigid nuclei struggled to pass through narrow gaps and were more likely to rupture under pressure. These findings suggest that the migration defects of neutrophils observed in sepsis may be attributed to the inability of neutrophils to deform their nuclei, highlighting the crucial role of microfluidic technologies in offering new insights into migration defects under pathological conditions.

Effects of physical activity patterns on myopia among children and adolescents: A latent class analysis.

BACKGROUND: The daily physical activity (PA) patterns of children and adolescents are intricate and ambiguous, with varying effects on myopia resulting from different combinations of PA. This study aims to scrutinize the spectrum of PA patterns among children and adolescents and assess their impact on myopia. METHODS: Data sourced from the 2014 National Student Physical Fitness Survey (Tianjin segment) encompassed PA records and visual acuity measurements of participants. Latent Class Analysis and a generalized linear model were employed to investigate the relationship between PA categories and visual acuity across different educational stages. RESULTS: The study comprised 6465 primary and middle school students, among whom 50.13% were male. PA patterns were categorized into high (27.16%), medium (29.88%) and low visual acuity regulation groups (13.97%) and the nonmainstream group (28.99%). Following adjustments for sex, age, region and BMI, the medium visual acuity regulation group exhibited a lower risk of myopia (OR = 0.617, 95% CI = 0.424-0.897, p = 0.012; OR = 0.654, 95% CI = 0.438-0.976, p = 0.038) compared to the nonmainstream group among junior and senior middle school students. CONCLUSION: The efficacy of diverse PA patterns in mitigating myopia risk varies across educational stages and is influenced by sex-specific factors. It is imperative to advance myopia management strategies by emphasizing tailored PA interventions, discerning between PA patterns and delivering timely guidance and interventions tailored to distinct educational stages and sexes.

Influence of eye-related behavior on myopia among junior middle school students under the background of double reduction during the COVID-19 pandemic.

BACKGROUND: To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. METHODS: Data were obtained from the 2019-2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. RESULTS: A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203-1.787; P < 0.001). CONCLUSIONS: The dual reduction policy has a positive effect on improving unhealthy eye-related behaviors, and the prevention and control of myopia through the use of different combinations of eye-related behaviors are heterogeneous among junior middle school students. In the post-COVID-19 period, we should continue to implement a double reduction policy and formulate targeted eye-related behavior strategies to provide an important reference for the prevention and control of myopia among children and adolescents during public health emergencies in the future.

Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling.

Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor ß (TGF-ß) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of activin A on NK cell migration. In vitro, activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, activin A increased Ca2+, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca2+ chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that activin A induces NK cell migration through AKT signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.

Salinity decreases methane concentrations in Chinese lakes.

Lakes are important sources of methane (CH4), and understanding the influence of environmental factors on CH4 concentration in lake water is crucial for accurately assessing CH4 emission from lakes. In this study, we investigated CH4 concentration in two connected Tibetan Plateau lakes, Lake Keluke (an open freshwater lake) and Lake Tuosu (a closed saline lake), through in-situ continuous measurements taken in different months from 2021 to 2023. The results show substantial spatial and seasonal variations in CH4 concentrations in the two lakes, while the CH4 concentrations in Lake Keluke are consistently higher than those in Lake Tuosu for each month. Despite sharing similar environmental conditions due to connected (e.g. pH, water temperature, dissolved oxygen content, and total organic carbon content), the critical difference between the two lakes is their salinity. This implies that salinity is the critical factor contributing to the decrease in CH4 concentrations in Lake Tuosu, possibly due to the changes in microbial species between freshwater and brackish/saline lakes. Additionally, to further validate the effect of salinity on CH4 concentrations in lake water, we compared the CH4 concentrations of 33 lakes (including 5 saline lakes and 28 freshwater lakes) from the Tibetan Plateau, Chinese Loess Plateau, and Yangtze Plain, and found that saline lakes consistently exhibit lower CH4 concentrations (avg. 0.08 µmol/L), while freshwater lakes generally display higher CH4 concentrations (avg. 1.25 µmol/L) with considerable fluctuations. Consequently, freshwater and saline lakes exhibit distinct CH4 emissions, which could be used for more accurate estimation of global CH4 emission from lakes.

Cenozoic Indo-Pacific warm pool controlled by both atmospheric CO2 and paleogeography.

The Indo-Pacific warm pool (IPWP) is crucial for regional and global climates. However, the development of the IPWP and its effect on the regional climate during the Cenozoic remain unclear. Here, using a compilation of sea surface temperature (SST) records (mainly since the middle Miocene) and multimodel paleoclimate simulations, our results indicated that the extent, intensity and warmest temperature position of the IPWP changed markedly during the Cenozoic. Specifically, its extent decreased, its intensity weakened, and its warmest temperature position shifted from the Indian to western Pacific Ocean over time. The atmospheric CO2 dominated its extent and intensity, while paleogeography, by restricting the distribution of the Indian Ocean and the width of the tropical seaways, controlled the shift in its warmest temperature position. In particular, the eastward shift to the western Pacific Ocean from the middle to late Miocene inferred from compiled SST records likely resulted from the constriction of tropical seaways. Furthermore, by changing the atmospheric thermal structure and atmospheric circulation, the reduced extent and intensity of the IPWP decreased the annual precipitation in the western Indian Ocean, eastern Asia and Australia, while the shift in the warmest temperature position from the Indian to western Pacific Ocean promoted aridification in Australia. Qualitative model-data agreements are obtained for both the IPWP SST and regional climate. From the perspective of past warm climates with high concentrations of atmospheric CO2, the expansion and strengthening of the IPWP will occur in a warmer future and favor excessive precipitation in eastern Asia and Australia.

Modifying effects of green space on the relationships between air pollution and ischemic cerebrovascular event recurrence in Tianjin, China.

This study aimed to explore how air pollution and green space influence ICE recurrence and whether they might interact with each other. A case-cross design was used in this study, which was carried out in Tianjin, China. A total of 8306 patients with recurrent ICE were collected from 2019 to 2020. The maximum effects of PM2.5, PM10, SO2, NO2, CO were 1.012 (95%CI: 1.004, 1.019), 1.010 (95%CI: 1.004, 1.016), 1.035 (95%CI: 0.982, 1.091), 1.067 (95%CI: 1.043, 1.091) and 1.012 (95%CI: 1.004, 1.021) , respectively, and the risk was higher in males and in the 50-60 age group. In the stratification of greening, it was found that air pollution except O3 had the highest risk of ICE recurrence for those with lower green space. Our study found that air pollution (except O3) can increase the risk of ICE recurrence, and this risk can be reduced by increasing green space.

Spatial patterns of Holocene temperature changes over mid-latitude Eurasia.

The Holocene temperature conundrum, the discrepancy between proxy-based Holocene global cooling and simulated global annual warming trends, remains controversial. Meanwhile, reconstructions and simulations show inconsistent spatial patterns of terrestrial temperature changes. Here we report Holocene alkenone records to address spatial patterns over mid-latitude Eurasia. In contrast with long-term cooling trends in warm season temperatures in northeastern China, records from southwestern Siberia are characterized by colder conditions before ~6,000 years ago, thus long-term warming trends. Together with existing records from surrounding regions, we infer that colder airmass might have prevailed in the interior of mid-latitude Eurasian continent during the early to mid-Holocene, perhaps associated with atmospheric response to remnant ice sheets. Our results challenge the proposed seasonality bias in proxies and modeled spatial patterns in study region, highlighting that spatial patterns of Holocene temperature changes should be re-considered in record integrations and model simulations, with important implications for terrestrial hydroclimate changes.

Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway.

Activin A, a member of the transforming growth factor­ß (TGF­ß) superfamily, has been implicated in the tumorigenesis and progression of various cancers. However, it remains unclear whether activin A induces apoptosis in human lung adenocarcinoma cells through the endoplasmic reticulum (ER) stress pathway. In the present study, BrdU, flow cytometry and western blotting were used to examine cell proliferation, apoptosis and protein expression, respectively. The present study revealed that activin A inhibited human lung adenocarcinoma A549 cell proliferation, induced apoptosis, and upregulated the protein levels of C/EBP homologous protein (CHOP), growth arrest and DNA damage­inducible protein 34 (GADD34), cleaved­caspase­3 and caspase­12. Furthermore, the administration of activin A did not alter the levels of suppressor of mothers against decapentaplegic 3 (Smad3) or phosphorylated (p)­Smad3 proteins, whereas, it significantly elevated the levels of ActRIIA and p­extracellular signal regulated kinase proteins 1 and 2 (ERK1/2) proteins in A549 cells. The apoptotic effects of activin A on A549 cells were attenuated by the ERK inhibitor FR180204, which also downregulated CHOP and caspase­12 protein levels. Additionally, activin A increased intracellular calcium flux in A549 cells, and the calcium ion chelator BAPTA acetoxymethyl ester (BAPTA­AM) inhibited activin A­induced A549 cell apoptosis, whereas the calcium agonist ionomycin significantly increased apoptosis of A549 cells induced by activin A. These findings indicated that the activation of the ER stress pathway resulting in apoptosis of A549 cells triggered by activin A is facilitated by the ActRIIA­ERK1/2 signaling and calcium signaling. The present findings suggest that the agonists of ERK and calcium signaling exhibit promising clinical therapeutic potential for the induction of apoptosis in lung adenocarcinoma.

Unraveling FOXO3a and USP18 Functions in Idiopathic Pulmonary Fibrosis through Single-Cell RNA Sequencing of Mouse and Human Lungs.

Background Idiopathic pulmonary fibrosis (IPF) is identified as a chronic, progressive lung disease, predominantly marked by enhanced fibroblast proliferation and excessive deposition of extracellular matrix. The intricate interactions between diverse molecular pathways in fibroblasts play a crucial role in driving the pathogenesis of IPF. Methods This research is focused on elucidating the roles of FOXO3a, a transcription factor, and USP18, a ubiquitin-specific protease, in modulating fibroblast functionality in the context of IPF. FOXO3a is well-known for its regulatory effects on cellular responses, including apoptosis and oxidative stress, while USP18 is generally associated with protein deubiquitination. Results Our findings highlight that FOXO3a acts as a critical regulator in controlling fibroblast activation and differentiation, illustrating its vital role in the pathology of IPF. Conversely, USP18 seems to promote fibroblast proliferation and imparts resistance to apoptosis, thereby contributing to the exacerbation of fibrotic processes. The synergistic dysregulation of both FOXO3a and USP18 in fibroblasts was found to significantly contribute to the fibrotic alterations characteristic of IPF. Conclusion Deciphering the complex molecular interactions between FOXO3a and USP18 in fibroblasts provides a deeper understanding of IPF pathogenesis and unveils novel therapeutic avenues, offering a promising potential for not just halting but potentially reversing the progression of this debilitating disease.

Source apportionment of heavy metals in PM2.5 samples and effects of heavy metals on hypertension among schoolchildren in Tianjin.

The prevalence of hypertension in children has increased significantly in recent years in China. The aim of this study was to provide scientific support to control ambient heavy metals (HMs) pollution and prevent childhood hypertension. In this study, ambient HMs in PM2.5 were collected, and 1339 students from Tianjin were randomly selected. Positive matrix factorization (PMF) was used to identify and determine the sources of HMs pollution. The generalized linear model, Bayesian kernel machine regression (BKMR) and the quantile g-computation method were used to analyze the relationships between exposure to HMs and the risk of childhood hypertension. The results showed that HMs in PM2.5 mainly came from four sources: soil dust, coal combustion, incineration of municipal waste and the metallurgical industry. The positive relationships between As, Se and Pb exposures and childhood hypertension risk were found. Coal combustion and incineration of municipal waste were important sources of HMs in the occurrence of childhood hypertension. Based on these accomplishments, this study could provide guidelines for the government and individuals to alleviate the damaging effects of HMs in PM2.5. The government must implement policies to control prime sources of HMs pollution.

iEarth: an interdisciplinary framework in the era of big data and AI for sustainable development.

The Intelligent Earth (iEarth) framework, composed of four major themes: iEarth data, science, analytics, and decision, is proposed to define and build an interdisciplinary and synergistic framework for research, practice, and education that simultaneously safeguards the sustainable development of our living planet.

Study on the mesh size determination method of blast wave numerical simulation with strong applicability.

With the rapid development of computer hardware and software technology, numerical simulations have become one of the most important tools for studying propagation law of blast wave. Results of numerical simulations of explosion events greatly depend on the mesh size. The mesh size determination methods in the literature are relatively weak in generality. In this paper, a mesh size determination method with strong applicability is proposed. According to this method, the mesh size is the product of the scale coefficient and the third root of the equivalent TNT mass. The scale coefficient is related to the model dimension, scaled distance and simulation accuracy, and is independent of the TNT shape and the location of the detonation point. A large number of numerical simulation results confirm the accuracy of this method. The recommended scale coefficient to meet the engineering accuracy requirements is related to the model dimension and scaled distance. In general, when the scaled distance and model dimension are larger, the recommended scale coefficient will be larger. In this paper, the figures and tables of the recommended scale coefficients of 1D, 2D and 3D models varying with the scaled distance are given, and their rationality is verified by the existing numerical simulation events of blast wave. They can be used as a reference to determine the mesh size in numerical simulation of blast wave.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Transgastric Single-Incision Laparoscopic Resection for a Gastric Submucosal Tumor Located at the Cardia.

INTRODUCTION: Surgical treatment of gastric submucosal tumors (SMTs) located near the gastroesophageal junction can be technically challenging, especially regarding preservation of the integrity and function of the lower esophageal sphincter. We introduce a novel minimally invasive surgery, successfully performed in a patient with a gastric SMT located at the cardia. A 24-year-old lady presenting with acid reflux for 1 year underwent esophagogastroscopy that showed a gastric SMT located at the cardia. Endoscopic ultrasonography showed a 20×19 mm homogeneous hypoechoic lesion originating from the muscularis propria layer. Transgastric single-incision laparoscopic resection of the tumor was performed. CONCLUSION: Transgastric single-incision laparoscopic resection of gastric SMTs is technically feasible and safe. This presents an alternative surgical choice for resection for gastric SMTs located in difficult regions such as the fundus, cardia, or prepyloric antrum.

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling.

Follistatin (FST) and activin A as gonadal proteins exhibit opposite effects on follicle-stimulating hormone (FSH) release from pituitary gland, and activin A-FST system is involved in regulation of decidualization in reproductive biology. However, the roles of FST and activin A in migration of decidualized endometrial stromal cells are not well characterized. In this study, transwell chambers and microfluidic devices were used to assess the effects of FST and activin A on migration of decidualized mouse endometrial stromal cells (d-MESCs). We found that compared with activin A, FST exerted more significant effects on adhesion, wound healing and migration of d-MESCs. Similar results were also seen in the primary cultured decidual stromal cells (DSCs) from uterus of pregnant mouse. Simultaneously, the results revealed that FST increased calcium influx and upregulated the expression levels of the migration-related proteins MMP9 and Ezrin in d-MESCs. In addition, FST increased the level of phosphorylation of JNK in d-MESCs, and JNK inhibitor AS601245 significantly attenuated FST action on inducing migration of d-MESCs. These data suggest that FST, not activin A in activin A-FST system, is a crucial chemoattractant for migration of d-MESCs by JNK signalling to facilitate the successful uterine decidualization and tissue remodelling during pregnancy.

Analysis of epidemiological characteristics and influencing factors of scoliosis among middle school students in Tianjin / 中国学校卫生

Objective@#To understand the prevalence and influencing factors of scoliosis among middle school students in Tianjin, and to provide scientific basis for the prevention and treatment of scoliosis.@*Methods@#Based on stratified cluster random sampling method, 21 679 middle school students from 62 middle schools (35 middle schools and 27 high schools) in Tianjin were selected for scoliosis screening and completed relevant questionnaires.@*Results@#The prevalence of scoliosis in middle school students in Tianjin was 4.00%, with girls (5.13%) higher than that in boys (2.94%), vocational high school (5.96%) higher than that in ordinary senior high school (4.98%) and junior high school (3.00%), the differences were statistically significant ( χ 2=67.56, 71.46 , P <0.01). Multivariate Logistic regression showed that gender, district, school segment, number of physical educaiotn(PE) classes per week, outdoor activity time per day, and days of 60 minutes or more of moderate and vigorous exercise per day in a week were related to the detection rate of scoliosis( OR=0.12-1.95, P <0.05).@*Conclusion@#The detection rate of scoliosis among middle school students in Tianjin varies in gender, resident area and school level, so more attention should be paid to girls, high school students and students in middle economic area. Comprehensive efforts should incorporate duration, intensity and type of physical exercise.

Association between latent classes of health risk behaviors and depressive symptoms among junior middle school students in Tianjin / 中国学校卫生

Objective@#To investigate the prevalence of depressive symptoms among junior middle school students in Tianjin, and to explore the association between latent classes of health risk behaviors and depressive symptoms, so as to provide clues for identifying high risk groups of depressive symptoms and a scientific basis for comprehensive intervention measures.@*Methods@#By using a multistage stratified cluster sampling method, 8 175 students in 16 districts of Tianjin were investigated with demographic characteristics, depressive symptoms, and health risk behaviors. Latent class analysis was performed by Mplus 8.3. SPSS 23.0.@*Results@#The prevalence of depressive symptoms among junior high school students in Tianjin was 17.8%,the prevalence of depressive symptoms in urban(19.4%) areas was higher than that in rural areas(16.5%),and that of female students( 20.2 %) was higher than that of male students(15.5%)( χ 2=11.62,30.58, P <0.01). Health risk behaviors were classified into three groups: healthy group (84.0%), poor diet group ( 3.8 %) and multiple risk behaviors group (12.2%). After adjusting for region, grade, gender, and family type, multivariate Logistic regression analysis showed that the poor diet group ( OR=2.82, 95%CI =2.17-3.66) and the multiple risk behaviors group ( OR=4.31, 95%CI =3.67-5.05) had a higher risk of depressive symptoms compared with the healthy group ( P ＜0.01).@*Conclusion@#Depressive symptoms are prevalent among junior middle school students in Tianjin. Different latent classes of health risk behaviors have different correlations with depressive symptoms. It is important to ensure early detection and personalized intervention for different types of health risk behavior among junior middle school students to maximize cost effectiveness.

Relationship between physical activity, sleep duration and overweight, obesity with depressive symptoms among middle school students in Tianjin / 中国学校卫生

Objective@#To investigate the relationship between physical activity, sleep duration, overweight, obesity and depressive symptoms among middle school students in Tianjin, and to provide the evidence for targeted prevention of depression.@*Methods@#In September 2019 to 2021, the stratified cluster sampling method was used to select 52 747 middle school students from 16 districts in Tianjin for questionnaire survey, including demographics, depressive symptom, sleep status and physical activity. The χ 2 test and multivariate Logistic regression were used to analyze the data.@*Results@#The prevalence of depressive symptoms among middle school students in Tianjin was 19.07%, with higher prevalence in female, urban areas, resident students and left behind students ( χ 2=128.44, 155.77, 35.29, 19.15, P <0.05). The prevalence of overweight and obesity were 20.64% and 22.13%, the proportion of students who met physical activity, outdoor activity, sleep duration guideline were 49.54%, 33.64%, 25.77%, respectively. Logistic regression results showed that meeting the guidelines on physical activity, outdoor activity, sleep duration and BMI were negatively correlated with depression symptoms, with sleep duration showed the highest protective effects on depressive symptoms( OR=0.60, 95%CI =0.57-0.63, P <0.05). Compared with students who did not meet any guidelines, students who met 4 guidelines had a lower risk of depression symptoms( OR=0.39, 95%CI =0.34-0.46, P <0.05).@*Conclusion@#The prevalence of depressive symptoms of middle school students in Tianjin is in moderate level, and the intervention should be comprehensively administered in terms of sleep duration, physical activity, outdoor activities, as well as overweight and obesity to reduce the occurrence of depression symptoms among middle school students.