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.

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.

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.

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.

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.

Exceptional terrestrial warmth around 4200-2800 years ago in Northwest China.

One of the Holocene abrupt events around 4200 years ago, lasting for âˆ¼ 200 years, is thought to have caused cultural disruptions, yet terrestrial climatic status right after the cold/dry event remains poorly defined and is often presumed that a generally cool condition prevailed during the Bronze Age (∼ 4000-2200 years ago). Here we report an alkenone-based summer temperature record over the past âˆ¼ 12,000 years, in addition to two updated alkenone records, from Northwest China, providing new insights into the climatic status right after the event. Our results indicate that exceptional terrestrial warmth, up to âˆ¼ 6 °C, occurred around 4200-2800 years ago during the Bronze Age, superimposed on the long-term Holocene cooling trend. The exceptional warmth in Northwest China, together with other climate anomalies elsewhere, suggests an unusual large-scale climatic reorganization at 4200-2800 years ago when solar activity remained high, with important implications to the climate background for cultural developments during the Bronze Age.

Follistatin Is a Novel Chemoattractant for Migration and Invasion of Placental Trophoblasts of Mice.

Follistatin (FST) as a gonadal protein is central to the establishment and maintenance of pregnancy. Trophoblasts' migration and invasion into the endometrium are critical events in placental development. This study aimed to elucidate the role of FST in the migration and invasion of placental trophoblasts of mice. We found that FST increased the vitality and proliferation of primary cultured trophoblasts of embryonic day 8.5 (E8.5) mice and promoted wound healing of trophoblasts. Moreover, FST significantly induced migration of trophoblasts in a microfluidic device and increased the number of invasive trophoblasts by Matrigel-coated transwell invasion assay. Being treated with FST, the adhesion of trophoblasts was inhibited, but intracellular calcium flux of trophoblasts was increased. Western blotting results showed that FST had no significant effects on the level of p-Smad3 or the ratio of p-Smad3/Smad3 in trophoblasts. Interestingly, FST elevated the level of p-JNK; the ratio of p-JNK/JNK; and expression of migration-related proteins N-cadherin, vimentin, ezrin and MMP2 in trophoblasts. Additionally, the migration of trophoblasts and expression of N-cadherin, vimentin, and MMP2 in trophoblasts induced by FST were attenuated by JNK inhibitor AS601245. These findings suggest that the elevated FST in pregnancy may act as a chemokine to induce trophoblast migration and invasion through the enhanced JNK signaling to maintain trophoblast function and promote placental development.

Surgery versus radiotherapy in octogenarians with stage Ia non­small cell lung cancer: propensity score matching analysis of the SEER database.

OBJECTIVES: To compare overall survival (OS) and cancer-specific survival (CSS) outcomes of surgery with radiotherapy in octogenarians with stage Ia non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients aged ≥ 80 years with clinical stage Ia (T1N0M0) NSCLC between 2012 and 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned into surgery and radiotherapy groups. Multivariate Cox regression analysis was used to identify survival-associated factors. Treatment groups were adjusted by propensity score matching (PSM) analysis while OS and CSS outcomes were compared among groups by Kaplan-Meier analysis. RESULTS: A total of 1641 patients were identified, with 46.0% in the surgical group and 54.0% in the radiotherapy group. Compared to surgery, radiotherapy-treated patients were older, later diagnosed, had more often unmarried, more squamous cell carcinoma, more unknown grade and increased tumor sizes. Radiotherapy was associated with a significantly worse OS, compared to surgery (hazard ratio 2.426; 95% CI 2.003-2.939; P < .001). After PSM, OS (P < 0.001) and CSS (P < 0.001) were higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgical and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgical and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. There were no survival differences between the matched surgery without lymph node examination (LNE) and radiotherapy group, as well as between the matched surgery and radiotherapy who were recommended but refused surgery group. CONCLUSIONS: In octogenarians with stage Ia NSCLC, surgery with lymph node dissection offers better OS and CSS outcomes than radiotherapy.

Intrachromosomal Looping and Histone K27 Methylation Coordinately Regulates the lncRNA H19-Fetal Mitogen IGF2 Imprinting Cluster in the Decidual Microenvironment of Early Pregnancy.

Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of longnoncoding RNAs (lncRNAs) in the decidual microenvironment where the crosstalk at the fetal-maternal interface occurs. By exploring RNA-seq data from RSA patients, we identified H19, a noncoding RNA that exhibits maternal monoallelic expression, as one of the most upregulated lncRNAs associated with RSA. The paternally expressed fetal mitogen IGF2, which is reciprocally coregulated with H19 within the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in some decidual tissues. This loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 repressive histone marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR), and the loss of CTCF-mediated intrachromosomal looping. These data suggest that dysregulation of the H19/IGF2 imprinting pathway may be an important epigenetic factor in the decidual microenvironment related to poor decidualization.