Search

Abstract Background PI3K/AKT signaling pathway plays important role in tumorigenesis of human cancer. Protein phosphorylation is crucial for signaling transduction of this pathway. PIK3CA, encoding the catalytic subunit p110α of PI3K complex, is one of the most frequently mutated oncogenes in human cancers. However, phosphorylation sites of PIK3CA/p110α and their underlying mechanism in tumorigenesis are largely unknown. Methods Tyrosine phosphorylation sites of PIK3CA/p110α are identified with Mass-Spectrum. Crispr/CAS9 strategy is applied to generate Y317F and Y508F mutant knock-in cell clones. The growth and metastasis abilities of cells are evaluated in vitro and in vivo. Phospho-proteomics analysis and Western blots are used to demonstrate downstream signaling pathways of PIK3CA/p110α tyrosine phosphorylation. In vitro kinase assay is applied to identify the kinase of PIK3CA/p110α tyrosine phosphorylation. Results Tyrosine phosphorylation of PIK3CA/p110α is stimulated by growth factors such as EGF, HGF and PDGF. Two tyrosine residues, Y317 and Y508, are identified on PIK3CA/p110α. Either Y317 or Y508 phosphorylation is essential for tumorigenesis of CRC. Mutation at Y317 of p110α reduces the proliferation, migration, and invasion of cancer cells through Src-MLC2 pathway, while mutation at Y508 of p110α impairs AKT signaling. Moreover, Src interacts with and phosphorylates p110α. Conclusions PIK3CA/p110α phosphorylation at Y317 and Y508 play important role in tumorigenesis of colorectal cancer through two independent pathways.

How PD-L1 expression is regulated in cancer is poorly understood. Here, we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers (CRCs). ERBB3 is one of the four members of the EGF receptor family, all with protein tyrosine kinase domains. ERBB3 is a pseudokinase with a high binding affinity to ATP. We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines. The ERBB3 ATP-binding mutant cells dramatically reduce IFN-γ-induced PD-L1 expression. Mechanistically, ERBB3 regulates IFN-γ-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells. Knockin of a tumor-derived ERBB3 mutation located in the kinase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy, suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune checkpoint therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy by reinvigorating antitumor immune responses, but their efficacy remains limited in most patients. To address this challenge and optimize Immune check inhibitor treatment, understanding the underlying molecular intricacies involved is crucial. The emergence of CRISPR-Cas9 technology has empowered researchers to precisely investigate gene function and has introduced transformative shifts in identifying key genes for various physiological and pathological processes. CRISPR screenings, particularly in vivo CRISPR screenings, have become invaluable tools in deciphering molecular networks and signaling pathways governing suppressive immune checkpoint molecules. In this review, we provide a comprehensive overview of in vivo CRISPR screenings in cancer immunotherapy, exploring how this cutting-edge technology has unraveled potential novel therapeutic targets and combination strategies. We delve into the latest findings and advancements, shedding light on immune checkpoint regulation and offering exciting prospects for the development of innovative and effective treatments for cancer patients.

Background: Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown. Methods: A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran’s Q statistics were employed to assess the heterogeneity of the instrumental variables. Results: Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family Bacteroidaceae (β = −0.072; 95% CI: −0.143, −0.001; p = 0.047), Genus Parabacteroides (β = −0.112; 95% CI: −0.184, −0.039; p = 0.002), and Genus Bacteroides (β = −0.072; 95% CI: −0.143, −0.001; p = 0.047). In addition, the gut microbiota (Family Bacteroidaceae (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047), Genus Parabacteroides (OR = 0.915; 95% CI: 0.858, 0.975; p = 0.007), and Genus Bacteroides (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found. Conclusion: This two-sample Mendelian randomization study found that Family Bacteroidaceae, Genus Parabacteroides, and Genus Bacteroides were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.

The mechanisms behind the oncogenic role of the PIK3CA helical domain mutant is poorly understood. Here, the authors show that its oncogenic function depends on the release of p85β from mutated p110α, its translocation to the nucleus and the consequent increased activity of EZH proteins.

Abstract Background We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. Methods A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. Results In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12–0.35 and OR: 0.22, 95%CI: 0.12–0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02–3.55), 2.91 (95%CI: 1.75–4.85), and 2.01 (95%CI: 1.47–2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02–0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05–0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42–8.09 and OR: 2.45, 95%CI: 1.53–3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42–3.19). Conclusions Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.

Abstract Background We investigated college students’ attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). Methods We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. Results A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. Conclusions Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

The relationship between body mass index (BMI) and cognitive impairment remains controversial, especially in older people. This study aims to confirm the association of phenotypic and genetic obesity with cognitive impairment and the benefits of adhering to a healthy lifestyle. This prospective study included 10,798 participants (aged ≥ 50 years) with normal cognitive function from the Health and Retirement Study in the United States. Participants were divided into low (lowest quintile), intermediate (quintiles 2–4), and high (highest quintile) groups according to their polygenic risk score (PRS) for BMI. The risk of cognitive impairment was estimated using Cox proportional hazard models. Higher PRS for BMI was associated with an increased risk, whereas phenotypic obesity was related to a decreased risk of cognitive impairment. Never smoking, moderate drinking, and active physical activity were considered favourable and associated with a lower risk of cognitive impairment compared with current smoking, never drinking, and inactive, respectively. A favourable lifestyle was associated with a low risk of cognitive impairment, even in subjects with low BMI and high PRS for BMI. This study suggest that regardless of obesity status, including phenotypic and genetic, adhering to a favourable lifestyle is beneficial to cognitive function.

Background: There was growing interest in endocrine disrupting chemicals that might have effect on the obesity epidemic, but few studies on the association of phthalates (PAEs) with childhood overweight and obesity in China based on longitudinal cohort study were available, which was the purpose of the present study. Methods: A nested case-control study was conducted in a prospective cohort of 2298 children aged 7–13 years from October 2017 to October 2020 with five waves visits in Xiamen city, China. A total of 829 children remained in the first wave of follow up with collection of urine for measuring seven PAEs metabolites, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate (MiBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), utilizing ultra high performance liquid chromatography-triple quadrupole mass spectrometry. Overweight and obesity, defined by WHO classifications, were allocated to the cases group, and those of all normal weight and matched cases with normal weight in each wave of follow-up as two control groups. Logistic regression models after adjusting for confounders were utilized to analyze the effect of PAEs on overweight and obesity in children with divided four groups based on the quartile distribution of each and total PAEs concentration. Results: The detection rates of children for each PAEs metabolite were 99.4% for MMP, 99.4% for MEP, 99.8% for MBP, 54.5% for MEHP, 84.4% for MEOHP, 99.9% for MEHHP, and 97.2% for MiBP. The geometric mean of concentrations of PAEs, MMP, MEP, MBP, MEHP, MEHHP, and MiBP were 310.085, 34.658, 9.127, 166.347, 7.043, 3.400, 18.571, and 24.093 (ng/ml), respectively. The total PAEs and seven metabolites concentrations were positively associated with childhood BMI Z-Scores with statistically significant slope rates and correlation coefficients, and were higher in the cases group than those in two controls groups in each wave of follow-up. The PAEs concentrations in the cases group was 5.90 (95 %CI: 5.79, 6.01) ng/ml in the first wave of survey, which was higher than those normal controls group (5.68 (95 %CI: 5.61, 5.75) ng/ml, P

DNA methyltransferase I plays the central role in maintenance of CpG DNA methylation patterns across the genome and alteration of CpG methylation patterns is a frequent and significant occurrence across many cancers. Cancer cells carrying hypomorphic alleles of Dnmt1 have become important tools for understanding Dnmt1 function and CpG methylation. In this study, we analyse colorectal cancer cells with a homozygous deletion of exons 3 to 5 of Dnmt1, resulting in reduced Dnmt1 activity. Although this cell model has been widely used to study the epigenome, the effects of the Dnmt1 hypomorph on cell signalling pathways and the wider proteome are largely unknown. In this study, we perform the first quantitative proteomic analysis of this important cell model and identify multiple signalling pathways and processes that are significantly dysregulated in the hypomorph cells. In Dnmt1 hypomorph cells, we observed a clear and unexpected signature of increased Epithelial-to-Mesenchymal transition (EMT) markers as well as reduced expression and sub-cellular re-localization of Beta-Catenin. Expression of wild-type Dnmt1 in hypomorph cells or knock-down of wild-type Dnmt1 did not recapitulate or rescue the observed protein profiles in Dnmt1 hypomorph cells suggesting that hypomorphic Dnmt1 causes changes not solely attributable to Dnmt1 protein levels. In summary, we present the first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells and identify redistribution of Dnmt1 and its interaction partner Beta-Catenin.

Introduction: The association patterns of hemoglobin (HB) concentrations with mortality among the longevity older adults are unclear. We aimed to evaluate the relationship among older adults form Chinese longevity regions.Methods: We included 1,785 older adults aged ≥65 years (mean age, 86.7 years; 1,002 women, 783 men) from the community-based Chinese Longitudinal Healthy Longevity Survey. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline.Results: In total, 999 deaths occurred during a median follow-up of 5.4 years from 2011 to 2017. Restricted cubic spline analysis found no non-linear association between HB concentrations and all-cause mortality after a full adjustment for covariates among the older adults form longevity regions (p > 0.05 for non-linearity). The risk for all-cause mortality was significantly higher in the groups with HB concentration of

Some patients retested positive for SARS-CoV-2 following negative testing results and discharge. However, the potential risk factors associated with redetectable positive testing results in a large sample of patients who recovered from COVID-19 have not been well-estimated. A total of 745 discharged patients were enrolled between January 30, 2020, and September 9, 2020, in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Patients who tested positive for SARS-CoV-2 after discharge were confirmed by guidelines issued by China. The repositive rate in different settings was calculated. Among 745 discharged patients, 157 (21.1%; 95% CI, 18.2–24.0%) tested repositive and the repositive rate was 16.8% (95% CI, 14.1–24.0%) for nasopharyngeal swabs and 9.7% (95% CI, 7.0–12.5%) for anal swabs. Among them, 55 (35.0%) were asymptomatic, 15 (9.6%) had mild symptoms, 83 (52.9%) had moderate symptoms, and 4 (2.6%) had severe symptoms at the first admission. The days from discharge to repositivity was 8.0 (IQR, 8.0–14.0). Most repositive patients were without clinical symptoms, and lymphocyte cell counts were higher than before being discharged. The likelihood of repositive testing for SARS-CoV-2 RNA was significantly higher among patients who were of younger age (OR, 3.88; 95% CI, 1.74–8.66, 0–17 years old), had asymptomatic severity (OR, 4.36; 95% CI, 1.47–12.95), and did not have clinical symptoms (OR, 1.89; 95% CI, 1.32–2.70, without fever). No other positive patients emerged within the families or close contacts of repositive patients. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon; we need to familiarize with the possibility that the virus will remain endemic.

Background: Air pollution has been associated with elevated blood pressure in adults. However, epidemiological evidence from children and adolescents is limited. We investigated the associations between long-term exposure to particulate matter (PM) air pollution and blood pressure in a large population of children and adolescents. Methods: A cross-sectional analysis was performed in a nationally representative sample consisting of 43,745 children and adolescents aged 7 to 18 years in seven provinces in China. Exposure to ambient fine particles (PM2.5) and thoracic particles (PM10) was estimated using spatiotemporal models based on satellite remote sensing, meteorological data and land use information. Mixed-effects (two-level) linear and logistic regression models were used to investigate the associations between PM exposure and systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. Results: After adjustment for a wide range of covariates, every 10 μg/m3 increment in PM2.5 and PM10 concentration was associated with 1.46 [95% confidence interval (CI): 0.05, 2.88] and 1.36 (95% CI: 0.34, 2.39) mmHg increases in SBP, respectively. PM10 was also associated with higher prevalence of hypertension [odds ratio per 10 μg/m3 increment: 1.45 (95% CI: 1.07, 1.95)]. Conclusions: Long-term exposure to ambient PM air pollution was associated with increased blood pressure and higher prevalence of hypertension in children and adolescents. Our findings support air pollution reduction strategies as a prevention measure of childhood hypertension, a well-recognized risk factor of future cardiovascular health. Keywords: Air pollution, Particulate matter, Blood pressure, Hypertension, Children, Adolescents

Abstract Background Current evidence on the health effects of passive smoking on childhood blood pressure is limited and inconsistent. We investigated the associations between exposure to parental smoking and blood pressure in children and adolescents. Methods A cross-sectional analysis was performed in a national sample of 42,745 children and adolescents (50.2% boys) aged 7–18 years from seven provinces in China. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Information on parental smoking was collected through questionnaire. Multivariable linear regression and logistic regression was used to investigate the associations of parental smoking with blood pressure and prevalent hypertension, respectively. Results The reported parental smoking rates were 49.7 and 50.2% in boys and girls, respectively. After adjustment for a range of potential confounders, exposure to parental smoking was associated with 0.44 [95% confidence interval (CI): 0.16, 0.72] mmHg and 0.26 (95% CI: 0.04, 0.47) mmHg higher SBP and DBP in girls. Girls exposed to parental smoking were also more likely to have hypertension compared with those without exposure (odds ratio = 1.11, 95% CI: 1.02, 1.20). No significant associations were found in boys. Conclusions Exposure to parental smoking was associated with increased blood pressure and higher prevalence of hypertension in girls, but not in boys. Urgent strategies are needed for the promotion of smoking-free environment, especially for children and adolescents.

Abstract Background The associations of famine exposure with diabetes risk in adulthood are still unclear. This study aimed to explore the association between famine exposure in early life and risk of diabetes in adulthood. Methods A total of 4138 subjects were selected from the data of the China Health and Retirement Longitudinal Study (CHARLS) 2011–2012. Diabetes was diagnosed as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated haemoglobin (HbA1C) > 6.5%, or self-reported diabetes. Birthdates of subjects were used to categorize famine exposure groups. The association of fetal-stage famine exposure with diabetes risk in adults was assessed using logistics regression model. Results The prevalence of diabetes in the non-exposed, fetal-stage exposed, infant-stage exposed, and preschool-stage exposed groups were 9.0, 13.6, 12.7 and 10.8%, respectively. Compared with the age-balanced control group, the fetal-stage exposed group was associated with the elevated risk of diabetes in later life after adjusting for covariates (OR = 1.37; 95%CI: 1.09–1.72; P = 0.008). Stratified analysis showed that the association between prenatal famine exposure and diabetes risk in adulthood was comparable between severely affected areas and less severely affected areas (P for interaction =0.153). Conclusions Famine exposure in fetal stages was associated with the elevated diabetes risk in adults, which could be the critical periods for relative intervention.

This study aimed to examine the impact of short-term adiposity change on risk of high blood pressure (HBP), and to assess the low limit range of body mass index (BMI) and waist-to-height ratio (WHtR) reduction proposed to decrease the HBP risk in children. Children were longitudinally surveyed at baseline and after a short-term follow-up. General obesity (GOB) is categorized by age and gender-specific BMI cut-off points, abdominal obesity (AOB) by WHtR. Logistic regression model was used to estimate relations between adiposity change and HBP risk with adjustment of covariates. A total of 28,288 children (median of baseline age:10 years) were involved with follow-up of 6.88±1.20 months. After the follow-up, 9.4% of the children had persistent general obesity (GOB), 2.8% converted from GOB to non-GOB, 0.9% had newly developed GOB. When compared with children remained non-GOB, children with continuous GOB status, newly developed GOB, converting from GOB to non-GOB had 5.03-fold (95%CI: 4.32~5.86), 3.35-fold (95%CI: 1.99~5.65), 2.72-fold (2.03~3.63) HBP risk, respectively. Similar findings were observed for abdominal obesity (AOB). Reduction of 0.21-0.88 kg/m2 of baseline BMI (0.86-3.59%) or 0.009-0.024 of baseline WHtR (1.66-4.42%) in GOB or AOB children, respectively, was associated with significant decrease in HBP risk. Children with persistent obesity, newly developed obesity, or converting from obese to non-obese had significantly higher HBP risk. For children with GOB or AOB, reduction of

Aiming at the large heat loss inside the traditional trough-type vacuum solar heat collecting tube, a new type of spiral three-blade rotor structure was designed and inserted into the inner tube side of the heat collecting tube. Based on the principle of fluid dynamics and field synergy, a mathematical model of the three governing equations of the fluid in the tube was established. Numerical simulations of the heat transfer and flow in the flow field in the two types of collector tubes with or without interpolated rotors were performed. Performance comparisons were made in terms of velocity field, pressure field, temperature field, and field synergy coupling ability. The results of the comprehensive evaluation index of heat transfer performance were finally given. The research shows that the PEC value continues to become larger with the increase in the inlet flow rate, from an initial value of 1.63 to a final value of 2.69. The heat transfer performance enhancement advantage of the new type vacuum heat collector tube is obviously greater than the disadvantage of flow resistance, and the comprehensive performance is better.

Abstract Background Little is known regarding the nutritional burden in Chinese ethnic minority children. This study aimed to investigate the epidemiological characteristics of excess body weight and underweight for 26 ethnic groups. Methods Data on 80,821 participants aged 7–18 years across 26 minorities, with completed records from a large national cross-sectional survey, were obtained from Chinese National Survey on Students’ Constitution and Health (CNSSCH) in 2014. Excess body weight, underweight and their components were classified according to Chinese national BMI references. Results The overall prevalence of excess body weight and underweight among ethnic groups were 12.0% and 14.5%, in which 4.4% and 4.1% of the participants were classified as obese and severe wasting, respectively. Compared with girls, boys showed a higher prevalence of underweight, severe wasting and obesity, but a lower prevalence of excess body weight (P

Abstract Background To explore the associations between the Chinese famine exposure in early life and the dyslipidemia in adulthood. Methods We selected 2752 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011–2012 to evaluate the associations of early life the Chinese famine exposure with risk of dyslipidemia in adulthood. Dyslipidemia was defined as TC (Total Cholesterol): HDL-C (High-Density Lipoprotein Cholesterol) ratio ≥ 5.0 or use cholesterol lowering drugs. Famine exposure cohorts were categorized by birthdates of participants. Binary logistics regression model was used to examine the associations of early-life famine exposure with the risk of dyslipidemia. Results The dyslipidemia prevalence of the non-exposed cohort, fetal stage-, infant stage-, and preschool stage-exposed cohorts in adulthood was 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusted for age. The risks of dyslipidemia in fetal (OR = 1.58; 95% CI: 1.23–2.03; P

Cancer cells rely on glutamine to replenish the TCA cycle. Here, the authors show that oncogenic PIK3CAmutations drive this metabolic rewiring in colorectal cancer cells by up-regulating glutamate pyruvate transaminase expression, thus increasing sensitivity to glutamine starvation.

Abstract Background Early-life developmental adaptations in response to severe malnutrition may play a crucial role in susceptibility to hypertension. This study aimed to explore the associations between exposure to the Chinese famine (1959–1961) at fetal, infant and preschool stages during fetal life or childhood and the risk of hypertension in adulthood. Methods We used the data of 1,966 adults born between 1956 and 1964 in selected families from the China Health and Retirement Longitudinal Study (CHARLS) national survey. Results Prevalence of hypertension among adults in non-exposed, fetal-exposed, infant-exposed, and preschool-exposed cohorts was 18.9, 20.7, 28.7, and 23.4 %, respectively. In severely affected famine areas, only infant-exposed cohort had a significant increased risk of hypertension compared with non-exposed cohort (OR 2.12; 95 % CI 1.19, 3.79; P = 0.011), and the significance remained after adjusted gender, smoking, and drinking (OR 2.11; 95 % CI 1.18, 3.77; P = 0.012). After stratification by BMI and economic status, the risk of hypertension was higher for subjects with BMI ≥ 24 kg/m2(OR 2.09; 95 % CI 1.09, 4.01; P = 0.026) or high economic status(OR 2.26; 95 % CI 1.19, 4.31; P = 0.013) than those with BMI

We recently reported that PIK3CA mutant colorectal cancers (CRCs) are addicted to glutamine through up-regulation of glutamate pyruvate transaminase 2 (GPT2). A GPT2 inhibitor suppresses in vivo growth of PIK3CA mutant, but not wild-type, CRCs. This study indicates that targeting glutamine may be an effective approach to treat CRCs with PIK3CA mutations.

Tumor tissues are chronically exposed to hypoxia owing to aberrant vascularity. Lipid droplet (LD) accumulation is a hallmark of hypoxic cancer cells, yet how LDs form and function during hypoxia remains poorly understood. Herein, we report that in various cancer cells upon oxygen deprivation, HIF-1 activation down-modulates LD catabolism mediated by adipose triglyceride lipase (ATGL), the key enzyme for intracellular lipolysis. Proteomics and functional analyses identified hypoxia-inducible gene 2 (HIG2), a HIF-1 target, as a new inhibitor of ATGL. Knockout of HIG2 enhanced LD breakdown and fatty acid (FA) oxidation, leading to increased ROS production and apoptosis in hypoxic cancer cells as well as impaired growth of tumor xenografts. All of these effects were reversed by co-ablation of ATGL. Thus, by inhibiting ATGL, HIG2 acts downstream of HIF-1 to sequester FAs in LDs away from the mitochondrial pathways for oxidation and ROS generation, thereby sustaining cancer cell survival in hypoxia.

The association between vegetable intake and blood pressure (BP) in adolescents is still inconsistent, and the description of the recommended daily vegetable consumption is abstract and nonfigurative. Here we aimed to investigate the association between vegetable consumption and BP and further look for a simple way to describe a satisfactory level of daily vegetable consumption for adolescents. We recruited 18,757 adolescents, aged 13–17 years, from seven provinces in China in 2013. A standard physical examination, including height, weight and BP was conducted. Information regarding vegetable intake was collected by questionnaire, and one serving of vegetables was defined as the size of an adult’s fist. Multivariable linear and logistic regression models were used for analysis after adjusting for covariates. Approximately 12.2%, 38.0%, 28.7%, and 21.1% of the adolescents reported daily vegetable consumption of

Obesity is a risk factor for many human diseases. However, the underlying molecular causes of obesity are not well understood. Here, we report that protein tyrosine phosphatase receptor T (PTPRT) knockout mice are resistant to high-fat diet-induced obesity. Those mice avoid many deleterious side effects of high-fat diet-induced obesity, displaying improved peripheral insulin sensitivity, lower blood glucose and insulin levels. Compared to wild type littermates, PTPRT knockout mice show reduced food intake. Consistently, STAT3 phosphorylation is up-regulated in the hypothalamus of PTPRT knockout mice. These studies implicate PTPRT-modulated STAT3 signaling in the regulation of high-fat diet-induced obesity.