Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.

Phosphorylation at tyrosine 317 and 508 are crucial for PIK3CA/p110α to promote CRC tumorigenesis.

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.

Development and Validation of Small-Size Mechanism for RP-3 Aviation Fuel with High Precision.

In this study, a kerosene surrogate model fuel containing 73% n-dodecane, 14.7% 1,3,5-trimethylcyclohexane, and 12.3% n-propylbenzene (percentage in mass) is developed by considering both the physical and chemical characteristics of practical aviation kerosene. By combining the small-size C0-C4 (carbon number) core mechanism and the large hydrocarbon submechanisms, a low- and high-temperature chemical kinetic mechanism including 43 species and 136 reactions is constructed for the kerosene surrogate model fuel. The performance of the 43-species mechanism is validated by examining various experimental ignition delay times and laminar flame speeds of single component of n-dodecane and practical kerosene. The predicted main species concentrations during the oxidation process in the jet-stirred reactor by this small-size mechanism exhibit generally acceptable performance with the corresponding experimental data of RP-3 kerosene. The results of brute force sensitivity analysis indicate that the mechanism retains key reaction paths. This relatively small size can be applied to the simulation of computational fluid dynamics to further explore the practical problems of aviation fuel application in engine.

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain.

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.

The association of phthalate metabolites with childhood waist circumference and abdominal obesity.

The association between phthalates exposure and childhood abdominal obesity is still unclear. This study aimed to assess phthalates (PAEs) exposure level and explore the association between PAEs metabolites exposure and the risk of abdominal obesity in Chinese students aged 7-10 years. A total of 798 students aged 7-10 years were selected from the baseline survey of the cohort of Childhood Blood Pressure and Environmental Factors (CBPEF), which was established in Xiamen City, Fujian province, East China, from August to November in 2018. Urine samples were collected from these students to analyze the concentrations of seven PAEs metabolites using the method of high-performance liquid chromatography-tandem triple quadrupole mass spectrometry. Waist circumference was used to define abdominal obesity. The logistic regression model was used to analyze the association of urinary creatinine-adjusted PAEs metabolites with childhood abdominal obesity risk. The prevalence of childhood abdominal obesity is 12.0% (96/798). Apart from mono(2-ethylhexyl) phthalate (62.5% for boys and 47.0% for girls), the detection rate of the others PAEs metabolites ranged from 82.6 to 100%. Boys had higher concentrations of PAEs metabolites than girls (P < 0.05), except for monoethyl phthalate. Compared with the Q1 group of PAEs metabolites, the risk of childhood abdominal obesity increased to 429% (OR = 5.29; 95% CI: 2.09, 13.39) and 273% (OR = 3.73; 95% CI: 1.57, 8.86) for the Q4 group of monoethyl phthalate and monoisobutyl phthalate, respectively. CONCLUSION: The detection rate of PAEs metabolites is common, and the exposure level of PAEs metabolites was associated with the risk of abdominal obesity in Chinese students aged 7-10 years. WHAT IS KNOWN: • The prevalence of childhood abdominal obesity had increased sharply from 4.9% in 1993 to 17.5% in 2014 in China. More than 80% of the Chinese children and adolescents have measurable level of several PAEs metabolites in the urine. Previous studies with limited sample had explored the association between DEHP metabolites exposure and childhood abdominal obesity risk, however, the association were inconsistent. WHAT IS NEW: • The detection rate of PAEs metabolites is common among Chinese children aged 7-10 years. Boys had higher concentrations of PAEs metabolites than girls (P < 0.05), except for monoethyl phthalate. Compared with the Q1 group of PAEs metabolites, the risk of childhood abdominal obesity increased to 429% and 273% for the Q4 group of monoethyl phthalate and monoisobutyl phthalate, respectively.

Unveiling immune checkpoint regulation: exploring the power of in vivo CRISPR screenings in cancer immunotherapy.

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.

The Causal Relationship between the Morning Chronotype and the Gut Microbiota: A Bidirectional Two-Sample Mendelian Randomization Study.

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 (ß = -0.072; 95% CI: -0.143, -0.001; p = 0.047), Genus Parabacteroides (ß = -0.112; 95% CI: -0.184, -0.039; p = 0.002), and Genus Bacteroides (ß = -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.

Does a Healthy Lifestyle Lower the Elevated Risk of Obesity Caused by Caesarian Section Delivery in Children and Adolescents?

Background: Both caesarean section (CS) and lifestyle were linked with child adiposity. This study aimed to investigate whether CS delivery is linked with elevated risk of child adiposity regardless of a healthy lifestyle. Methods: All the subjects in this study came from a baseline survey of a national school-based program on healthy lifestyle interventions against adiposity among Chinese children and adolescents. A questionnaire was used to collect the information on delivery mode and lifestyle. According to the weighted lifestyle score, subjects were categorized into healthy, intermediate, and unhealthy lifestyle. Results: A total of 44,961 children aged 6−18 years were enrolled in the current study. Overall, 41.9% (18,855/44,961) of children were delivered by CS. Compared with children delivered by vaginal delivery, children delivered by CS had a higher adiposity risk (OR = 1.56; 95%CI: 1.46−1.66; p < 0.001) after adjustment for age, sex, region, mother adiposity, ethnicity, and weighted lifestyle factors. Compared with children with a healthy lifestyle, children with an unhealthy lifestyle had a higher risk of child adiposity (OR = 1.31; 95%CI: 1.19−1.44). Children delivered by CS who had an unhealthy lifestyle had a 106% higher (OR = 2.06; 95%CI: 1.79−2.37) risk of child adiposity compared with children delivered by vaginal delivery who had a healthy lifestyle. However, keeping a healthy lifestyle in later life seems not to offset the increased risk of child adiposity caused by CS (OR = 1.59; 95%CI: 1.39−1.82). Conclusions: Both CS and unhealthy lifestyle were linked with child adiposity risk. Keeping a healthy lifestyle did not counteract the elevated risk of child adiposity caused by CS.

Comparative Analysis of Combustion Behaviors and Emission Characteristics of Diesel Engines Fueled with Biodiesel or Biodiesel Blends.

In this study, we carried out an experimental analysis of combustion behaviors and emission characteristics of pure biodiesel and biodiesel-dimethyl ether (DME) blends and determined the impacts of the biodiesel ratio and the nozzle parameter on the combustion pressure characteristics in the time domain/frequency domain and emission characteristics. The findings show that with a decrease in the biodiesel proportion in biodiesel-DME blends, the maximum combustion pressure and fuels in the premixed combustion stage decrease with a retarded maximum value phase, but the maximum heat release in diffusive combustion increases and the maximum amplitude of pressure rise acceleration decreases. All of the pressure level curves of BD100, BD80, and BD50 contain a rapid decrease stage 1, a slow decrease stage 2, and a fluctuating stage 3. With a decrease in the biodiesel proportion, the exhaust gas temperature, NO x emissions, and smoke emissions of BD100, BD80, and BD50 decrease gradually. Compared with a 5 × 0.43 mm nozzle, the maximum combustion pressure and maximum heat release rate of BD50 for a 4 × 0.35 mm nozzle were higher and the phase of the maximum value was advanced. Soot emissions for the 4 × 0.35 mm nozzle were lower, which is especially obvious under a high brake mean effective pressure (BMEP).

Effects of Ethanol and Methanol on the Combustion Characteristics of Gasoline with the Revised Variation Disturbance Method.

This paper proposes a revised variation disturbance method to provide valuable information and reference for fuel design or optimization of internal combustion engines to realize the comprehensive and quantitative evaluation of the effects of blending agents on the combustion performance of primary fuels. In this method, methanol and ethanol are blended into gasoline to form six kinds of alcohol-gasoline (E10, E20, E30, M10, M20, and M30). Then, the ignition delay, adiabatic flame temperature, component concentration, fuel-burning rate, extinction strain rate, and CO emission of gasoline and alcohol-gasoline are studied by system simulation in a wide range of operating conditions. Based on the new variation disturbance method, the effects of methanol and ethanol on the combustion performance of gasoline are next analyzed globally and characterized quantitatively. The comprehensive results of ethanol and methanol on the gasoline's combustion are visually presented. The method proposed in this paper is preliminarily validated based on the analysis of the microscopic mechanism of combustion. The results show that the blending of ethanol and methanol has positive effects on gasoline combustion, and ethanol can rapidly ignite the gasoline in a wide range of operating conditions and is superior to methanol in terms of fuel combustion, stability, and pollutant discharge. Based on the treatment of simulated values of six combustion characteristics selected in this paper and the calculations of the variation disturbance method, the total disturbance values of ethanol and methanol to gasoline combustion are obtained as 0.8493 and 0.2605, respectively. That is, ethanol has a more significant effect on improving the combustion performance of gasoline than methanol. In addition, based on the analysis results of the combustion, it is found that the blending of ethanol enlarges the reaction of notable components in gasoline. This finding also proves the effectiveness and validity of the scientific method utilized in this paper.

Favourable Lifestyle Protects Cognitive Function in Older Adults With High Genetic Risk of Obesity: A Prospective Cohort Study.

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.

Nuclear translocation of p85ß promotes tumorigenesis of PIK3CA helical domain mutant cancer.

PI3Ks consist of p110 catalytic subunits and p85 regulatory subunits. PIK3CA, encoding p110α, is frequently mutated in human cancers. Most PIK3CA mutations are clustered in the helical domain or the kinase domain. Here, we report that p85ß disassociates from p110α helical domain mutant protein and translocates into the nucleus through a nuclear localization sequence (NLS). Nuclear p85ß recruits deubiquitinase USP7 to stabilize EZH1 and EZH2 and enhances H3K27 trimethylation. Knockout of p85ß or p85ß NLS mutant reduces the growth of tumors harboring a PIK3CA helical domain mutation. Our studies illuminate a novel mechanism by which PIK3CA helical domain mutations exert their oncogenic function. Finally, a combination of Alpelisib, a p110α-specific inhibitor, and an EZH inhibitor, Tazemetostat, induces regression of xenograft tumors harboring a PIK3CA helical domain mutation, but not tumors with either a WT PIK3CA or a PIK3CA kinase domain mutation, suggesting that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors.

Liver Endothelium Promotes HER3-Mediated Cell Survival in Colorectal Cancer with Wild-Type and Mutant KRAS.

We previously identified that human epidermal growth factor receptor 3 (HER3, also known as ERBB3) is a key mediator in liver endothelial cell (EC) promoting colorectal cancer growth and chemoresistance, and suggested HER3-targeted therapy as a strategy for treating patients with metastatic colorectal cancer in the liver. Meanwhile, KRAS mutations occur in 40%-50% of metastatic colorectal cancer and render colorectal cancer resistant to therapies targeting the other HER family protein epidermal growth factor receptor (EGFR). It is necessary to elucidate the roles of KRAS mutation status in HER3-mediated cell survival and colorectal cancer response to HER3 inhibition. In the present study, we used primary ECs isolated from non-neoplastic liver tissues to recapitulate the liver EC microenvironment. We demonstrated that liver EC-secreted factors activated colorectal cancer-associated HER3, and increased colorectal cancer cell survival in vitro and promoted colorectal cancer patient-derived xenograft tumor growth in vivo. Moreover, we determined that blocking HER3, either by siRNA knockdown or the humanized antibody seribantumab, blocked EC-induced colorectal cancer survival in vitro in both KRAS wild-type and mutant colorectal cancer cells, and the HER3 antibody seribantumab significantly decreased colorectal cancer tumor growth and sensitized tumors to chemotherapy in an orthotopic xenograft model with colorectal cancer tumors developed in the liver. In summary, our findings demonstrated that blocking HER3 had significant effects on attenuating liver EC-induced colorectal cancer cell survival independent of the KRAS mutation status. IMPLICATIONS: This body of work highlighted a potential strategy of using HER3 antibodies in combination with standard chemotherapy agents for treating patients with either KRAS wild-type or KRAS mutant metastatic colorectal cancer.

Effect of childhood phthalates exposure on the risk of overweight and obesity: A nested case-control study in China.

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 < 0.001) and matched controls group (5.72 (95 %CI: 5.61, 5.84) ng/ml, P = 0.018). The prevalence and ORs of overweight and obesity increased with quartile group of each and total PAEs concentrations accompanying a dose-response relationship. Compared with the quartile1 reference group with lowest total PAEs concentrations, the ORs of overweight and obesity in quartile2, quartile3 and quartile4 group increased gradually and reached at 1.20 (0.74-1.95), 1.49 (0.93-2.38) and 2.22 (1.41-3.48), respectively (Ptrend < 0.001). The strength of the associations between PAEs and overweight and obesity was sex-specific in children. DISCUSSION: Children in China were extensively exposed to PAEs, and the exposure to PAEs during childhood could significantly increase the risk of overweight and obesity with a dose-response relationship, particularly in girls. While limiting the exposure of PAEs products, the determination of exposure limit of plasticizer should be further strengthened.

Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Is Hemoglobin Concentration a Linear Predictor of Mortality in Older Adults From Chinese Longevity Regions?

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 <11.0 g/dL (HR: 1.37, 95% CI: 1.10-1.70) and 11.0-12.0 g/dL (HR: 1.25, 95% CI: 1.01-1.54); the risk of all-cause mortality was significantly lower in the groups with HB concentration ≥14.0 g/dL (HR: 0.76, 95% CI: 0.60-0.97) compared with the reference group (13.0-13.9 g/dL). Conclusions: Among older adults form Chinese longevity regions, HB concentrations were found to be inversely and linearly associated with all-cause mortality. Further prospective intervention trials are needed to confirm whether higher HB concentrations had a lower risk of mortality in these older adults.

A Healthy Lifestyle Offsets the Increased Risk of Childhood Obesity Caused by High Birth Weight: Results From a Large-Scale Cross-Sectional Study.

Objective: To investigate whether a healthy lifestyle is associated with the lower childhood obesity regardless of birth weight. Methods: Participants were selected from a large-scale cross-sectional study conducted in the seven provinces across China. Birth weight and lifestyle factors were collected through a questionnaire. A weighted healthy lifestyle score was calculated and categorized into favorable, intermediate, and unfavorable lifestyles. Results: A total of 47,768 participants were enrolled in this study. Overall, 16.4% of the participants followed a favorable lifestyle, 62.8% followed an intermediate lifestyle, and 20.8% followed an unfavorable lifestyle. Compared with the participants who were born normal birth weight (NBW), participants who were born high birth weight (HBW) (OR = 1.58; 95% CI 1.48-1.77) and very high birth weight (VHBW) (OR = 1.79; 95% CI: 1.47-2.18) had higher obesity risk, however, the participants who were born low birth weight (LBW) had lower obesity risk (OR = 0.81; 95% CI: 0.68-0.96). Participants with an unfavorable lifestyle were associated with a higher risk of childhood obesity compared with the participants with favorable lifestyle (OR = 1.25; 95%CI: 1.14-1.38). Participants who were born VHBW and with an unfavorable lifestyle had 2.76 times (95% CI: 1.78-4.28) further risk of childhood obesity compared with the participants who were born NBW and with a favorable lifestyle. However, adherence to a favorable lifestyle seems to counteract the elevated risk of childhood obesity by VHBW (OR = 1.37; 95% CI: 0.84-2.24). Conclusion: Both the HBW and unfavorable lifestyle were significantly associated with risk of childhood obesity. Adherence to a favorable lifestyle decreased the risk of childhood obesity among the participants with VHBW. A more longitudinal study is required to repeat the finding to inform tailored prevention programs.