Fujian cytoplasmic male sterility and the fertility restorer gene OsRf19 provide a promising breeding system for hybrid rice.

Cytoplasmic male sterility (CMS) determined by mitochondrial genes and restorer of fertility (Rf) controlled by nuclear-encoded genes provide the breeding systems of many hybrid crops for the utilization of heterosis. Although several CMS/Rf systems have been widely exploited in rice, hybrid breeding using these systems has encountered difficulties due to either fertility instability or complications of two-locus inheritance or both. In this work, we characterized a type of CMS, Fujian Abortive cytoplasmic male sterility (CMS-FA), with stable sporophytic male sterility and a nuclear restorer gene that completely restores hybrid fertility. CMS is caused by the chimeric open reading frame FA182 that specifically occurs in the mitochondrial genome of CMS-FA rice. The restorer gene OsRf19 encodes a pentatricopeptide repeat (PPR) protein targeted to mitochondria, where it mediates the cleavage of FA182 transcripts, thus restoring male fertility. Comparative sequence analysis revealed that OsRf19 originated through a recent duplication in wild rice relatives, sharing a common ancestor with OsRf1a/OsRf5, a fertility restorer gene for Boro II and Hong-Lian CMS. We developed six restorer lines by introgressing OsRf19 into parental lines of elite CMS-WA hybrids; hybrids produced from these lines showed equivalent or better agronomic performance relative to their counterparts based on the CMS-WA system. These results demonstrate that CMS-FA/OsRf19 provides a highly promising system for future hybrid rice breeding.

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Inhibition of 14-3-3 proteins increases the intrinsic excitability of mouse hippocampal CA1 pyramidal neurons.

14-3-3 proteins are a family of regulatory proteins that are abundantly expressed in the brain and enriched at the synapse. Dysfunctions of these proteins have been linked to neurodevelopmental and neuropsychiatric disorders. Our group has previously shown that functional inhibition of these proteins by a peptide inhibitor, difopein, in the mouse brain causes behavioural alterations and synaptic plasticity impairment in the hippocampus. Recently, we found an increased cFOS expression in difopein-expressing dorsal CA1 pyramidal neurons, indicating enhanced neuronal activity by 14-3-3 inhibition in these cells. In this study, we used slice electrophysiology to determine the effects of 14-3-3 inhibition on the intrinsic excitability of CA1 pyramidal neurons from a transgenic 14-3-3 functional knockout (FKO) mouse line. Our data demonstrate an increase in intrinsic excitability associated with 14-3-3 inhibition, as well as reveal action potential firing pattern shifts after novelty-induced hyperlocomotion in the 14-3-3 FKO mice. These results provide novel information on the role 14-3-3 proteins play in regulating intrinsic and activity-dependent neuronal excitability in the hippocampus.

Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study.

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

Associations of body mass index trajectory, waist circumference trajectory, or both with type 2 diabetes mellitus risk in Chinese adults: The China-PAR project.

AIMS: To identify the trajectories of body mass index (BMI) and waist circumference (WC), and assess the associations of BMI trajectory, WC trajectory, or the two combined, with type 2 diabetes mellitus (T2DM) risk in Chinese adults. MATERIALS AND METHODS: This study was based on a prospective project-the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). A total of 54 434 participants (39.21% men) who were measured on at least two occasions were included. Three slowly increasing trajectory patterns were identified for BMI, and four for WC, by latent mixed modelling. A nine-category variable was derived by combining the WC trajectory (low, moderate, moderate-high/high) and the BMI trajectory (low, moderate, high). Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of developing T2DM increased with elevated BMI or WC trajectory levels (all ptrend <0.001). The risks were 2.85 (2.59-3.14) for high BMI trajectory and 4.34 (3.78-4.99) for high WC trajectory versus low trajectory groups, respectively. The association was more pronounced among younger individuals (pinteraction <0.001). In the joint analysis, compared to participants with low WC and BMI trajectory, those with moderate-high/high WC combined with high BMI trajectory had the highest risk of T2DM (OR 3.96, 95% CI 3.48-4.50); even those who maintained moderate-high/high WC but low BMI trajectory showed a higher T2DM risk (OR 3.00, 95% CI 2.31-3.91). CONCLUSIONS: This study suggests that simultaneous dynamic and continuous monitoring of BMI and WC may contribute more than single measurements to predicting T2DM risk and determining preventive strategies.

Association between Mediterranean diet and periodontitis among US adults: The mediating roles of obesity indicators.

OBJECTIVE: This study aimed to assess the association between the Mediterranean diet (MedDiet) and periodontitis in US adults and to further explore the mediating roles of obesity indicators in this association. BACKGROUND DATA: The relationship between MedDiet and periodontitis is controversial. And it is unclear whether obesity indicators are potential mediators of this relationship. METHODS: Using data derived from the National Health and Nutrition Examination Survey (2009-2014). Weighted binary logistic regression and restricted cubic spline were used to assess the association between MedDiet and periodontitis. Weighted ordinal logistic regression was performed to evaluate the relationship between MedDiet and periodontitis severity. The mediating roles of body mass index (BMI) and waist circumference in the relationship between the MedDiet and periodontitis were explored. Association analyses were further performed using mean clinical attachment loss (CAL) or mean periodontal probing depth (PPD) as dependent variables. The false discovery rate method was used to correct the p-values in the regression analyses. RESULTS: A total of 8290 eligible participants (4159 participants with periodontitis and 4131 without periodontitis) were included. A negative association between the MedDiet adherence score and periodontitis was observed in the binary logistic regression model (adjusted odds ratio = 0.94, 95% confidence interval: 0.90-0.97, p = .001). Restricted cubic spline regression revealed a dose-response relationship between the MedDiet adherence score and periodontitis. BMI and waist circumference significantly mediate this association, with mediation proportions of 9.7% (p = .032) and 9.3% (p = .012), respectively. Multivariable ordinal logistic regression showed that the MedDiet adherence score was negatively associated with the severity of periodontitis (all p < .05). Additionally, the MedDiet adherence score was negatively associated with mean PPD or mean CAL (all p < .05). CONCLUSIONS: This study suggests a significant negative association between adherence to the MedDiet and periodontitis and a possible mediating role of obesity indicators in this association. Furthermore, studies are still warranted to confirm our findings.

Association between polycyclic aromatic hydrocarbons and periodontitis: Results from a large population-based study.

AIM: To explore the association between polycyclic aromatic hydrocarbons (PAHs) (measured using urinary metabolites) and periodontitis using data from the National Health and Nutrition Examination Survey 2009-2014. MATERIALS AND METHODS: Weighted binary logistic regression, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to evaluate independent and joint associations between the six urinary monohydroxylated metabolites of PAHs (OH-PAHs) and periodontitis. RESULTS: In all, 3413 participants were included in this study. All six urinary OH-PAHs were present at higher levels in the periodontitis group compared with the non-periodontitis group (p < .001). Fully adjusted multivariable logistic regressions showed positive associations between the six urinary OH-PAHs and periodontitis (p < .05). Higher concentrations of OH-PAHs were also positively associated with attachment loss, periodontal pocket depth (PPD) and the number of tooth loss. BKMR and WQS regression yielded similar positive associations between OH-PAH mixtures and periodontitis. CONCLUSIONS: PAHs and their mixture are positively associated with periodontitis, which may provide novel insights into periodontitis prevention from an environmental exposure perspective.

Dose-response associations of triglyceride to high-density lipoprotein cholesterol ratio and triglyceride-glucose index with arterial stiffness risk.

BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. METHODS: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. RESULTS: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01-1.23) and 1.78 (1.38-2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14-1.39) and 1.57 (1.36-1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with ß of 0.09 (95% CI 0.04-0.14) and 0.57 (95% CI 0.35-0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. CONCLUSIONS: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.

Obesity and risk of depressive disorder in children and adolescents: A meta-analysis of observational studies.

PURPOSE: This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. METHODS: We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random-effects models. The Newcastle-Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality. RESULTS: Finally, for this meta-analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case-control study article and 16 cross-sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09-1.60, I2 = 79.90%, Pheterogeneity < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00-1.35, I2 = 25.0%, Pheterogeneity = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression. CONCLUSION: Evidence from this meta-analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms.

Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones.

OBJECTIVES: To investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association. METHODS: We extracted data from National Health and Nutrition Examination Survey (NHANES) 2009-2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones. RESULTS: Participants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01-1.39; PR = 1.17 for PFNA, 95% CI: 1.02-1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables. CONCLUSIONS: These findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.

Advances on novel iron saccharide-iron (III) complexes as nutritional supplements.

Iron deficiency is prevalent worldwide, and iron supplementation is a promising strategy to address iron needs of the body. However, traditional oral supplements such as ferrous sulfate, ferrous succinate, and ferrous gluconate are absorbed in the form of ferrous ions, leading to lipid peroxidation and side effects due to other reasons. In recent years, saccharide-iron (III) complexes (SICs) as novel iron supplements have aroused attention for the high iron absorption rate and no gastrointestinal irritation at oral doses. In addition, research on the biological activities of SICs revealed that they also exhibited good abilities in treating anemia, eliminating free radicals, and regulating the immune response. This review focused on the preparation, structural characterization, and bioactivities of these new iron supplements, as promising candidates for the prevention and treatment of iron deficiency.

Sugar intake and risk of hypertension: a systematic review and dose-response meta-analysis of cohort and cross-sectional studies.

Several epidemiological studies have investigated the association between sugar intake, the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the risk of hypertension, but findings have been inconsistent. We carried out a systematic review and meta-analysis of observational studies to examine the associations between sugar intake, hypertension risk, and BP levels. Articles published up to February 2, 2021 were sourced through PubMed, EMBASE and Web of Science. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a fixed- or random-effects model. Restricted cubic splines were used to evaluate dose-response associations. Overall, 35 studies were included in the present meta-analysis (23 for hypertension and 12 for BP). Sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) were positively associated with hypertension risk: 1.26 (95% CI, 1.15-1.37) and 1.10 (1.07-1.13) per 250-g/day increment, respectively. For SBP, only SSBs were significant with a pooled ß value of 0.24 mmHg (95% CI, 0.12-0.36) per 250 g increase. Fructose, sucrose, and added sugar, however, were shown to be associated with elevated DBP with 0.83 mmHg (0.07-1.59), 1.10 mmHg (0.12-2.08), and 5.15 mmHg (0.09-10.21), respectively. Current evidence supports the harmful effects of sugar intake for hypertension and BP level, especially SSBs, ASBs, and total sugar intake.

Association of triglyceride-glucose index and its 6-year change with risk of hypertension: A prospective cohort study.

BACKGROUND AND AIM: We aimed to investigate the association of triglyceride-glucose (TyG) index and its dynamic change with risk of hypertension in rural Chinese and, further, to explore whether the TyG index mediates the obesity-related hypertension. METHODS AND RESULTS: A prospective cohort study, including 10,309 subjects without hypertension at baseline, was conducted in 2007-2008 and followed up in 2013-2014. TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis was performed to examine the contribution of the TyG index to the association of obesity-hypertension incidence. During a median follow-up of 6 years, 2073 subjects developed hypertension. In multivariate logistic model adjusted for age, sex, alcohol drinking, smoking, physical activity and education, monthly income, family history of hypertension, TC, and HDL-C, the risk of hypertension was 1.14 (1.07-1.22) for per-SD increase in TyG. After additional controlling for obesity, this association was nonsignificant (1.06, 0.99-1.13) and (1.05, 0.99-1.13) for BMI and WC, respectively. Increasing trends were found for hypertension incidence as the TyG change increased, with or without adjustment for obesity (all Ptrend < 0.05). With per-SD increment in TyG change, the risks of hypertension incidence were 1.14 (1.07-1.22) for absolute TyG change, and 1.15 (1.08-1.22) for relative TyG change in multivariate logistic model; the results were significant after further adjustment for BMI or WC, respectively. The TyG index partially mediated the obesity-incident hypertension association: 6.84% for BMI and 6.68% for WC, respectively. CONCLUSIONS: Elevated TyG index and its dynamic change were positively associated with risk of incident hypertension in rural Chinese population, and the TyG index may play a partially mediating role in obesity-related incident hypertension.

Association of remnant cholesterol with hypertension, type 2 diabetes, and their coexistence: the mediating role of inflammation-related indicators.

PURPOSE: Cholesterol metabolism is a risk factor for cardiovascular disease, and recent studies have shown that cholesterol metabolism poses a residual risk of cardiovascular disease even when conventional lipid risk factors are in the optimal range. The association between remnant cholesterol (RC) and cardiovascular disease has been demonstrated; however, its association with hypertension, type 2 diabetes mellitus (T2DM), and the concomitance of the two diseases requires further study. This study aimed to evaluate the association of RC with hypertension, T2DM, and both in a large sample of the U.S. population, and to further explore the potential mechanisms involved. METHODS: This cross-sectional study used data from the 2005-2018 cycles of the National Health and Nutrition Examination Survey (N = 17,749). Univariable and multivariable logistic regression analyses were performed to explore the relationships of RC with hypertension, T2DM, and both comorbidities. A restricted cubic spline regression model was used to reveal the dose effect. Mediation analyses were performed to explore the potential mediating roles of inflammation-related indicators in these associations. RESULTS: Of the 17,749 participants included (mean [SD] age: 41.57 [0.23] years; women: 8983 (50.6%), men: 8766 (49.4%)), the prevalence of hypertension, T2DM, and their co-occurrence was 32.6%, 16.1%, and 11.0%, respectively. Higher RC concentrations were associated with an increased risk of hypertension, T2DM, and their co-occurrence (adjusted odds ratios for per unit increase in RC were 1.068, 2.259, and 2.362, and 95% confidence intervals were 1.063-1.073, 1.797-2.838, and 1.834-3.041, respectively), with a linear dose-response relationship. Even when conventional lipids were present at normal levels, positive associations were observed. Inflammation-related indicators (leukocytes, lymphocytes, monocytes, and neutrophils) partially mediated these associations. Among these, leukocytes had the greatest mediating effect (10.8%, 14.5%, and 14.0%, respectively). CONCLUSION: The results of this study provide evidence that RC is associated with the risk of hypertension, T2DM, and their co-occurrence, possibly mediated by an inflammatory response.

Independent and interactive effect of sedentary time and physical activity on risk of all-cause mortality: A prospective cohort study.

OBJECTIVES: Sedentary behavior (SB) and physical inactivity have been associated with an increased risk of all-cause mortality. Evidence in China is scarce, and it is unclear whether physical activity (PA) attenuates or even eliminates the harmful effects of prolonged SB in the Chinese population. METHODS: We conducted a prospective cohort study of 17 084 Chinese adults. PA and sitting time (ST) were assessed using the IPAQ. Cox proportional hazards models were used to estimate the risk of PA and ST with all-cause mortality. Interaction plots were used to visualize the interaction effects. RESULTS: During a median follow-up of 6.01 years, a total of 1106 deaths occurred. PA level was inversely associated with the incidence of all-cause mortality, while ST showed a detrimental association (all ptrend < 0.05). In the stratified analysis, ST was associated with all-cause mortality in the low PA, while the association was attenuated in the moderate PA group: the HRs (95% CI) comparing ST of 4-8, 8-11, and ≥11 to <4 h/day were 1.15 (0.73-1.81), 1.55 (0.92-2.59), and 2.70 (1.52-4.80), respectively. In the high PA group, no significant association was found across all ST levels. In the joint analysis, compared with the high PA and ST <4 h/day, the harmful effect was found only in the combined low PA and moderate PA groups with ST ≥11 h/day (HR:2.71, 95% CI:1.69-4.35). In addition, a significant interaction association was found. CONCLUSION: Our study, based on a prospective cohort, suggests that the detrimental effect of ST on all-cause mortality is attenuated or eliminated by high PA levels in the Chinese population.

Effect of transoral laser microsurgery vs open partial laryngectomy on the prognosis of patients with early laryngeal carcinoma: propensity score-based analysis.

OBJECTIVE: To evaluate the effect of surgical procedures (transoral laser microsurgery (TLM) and open partial laryngectomy (OPL)) on the prognosis of patients with early laryngeal cancer. METHODS: A total of 760 patients diagnosed with early laryngeal cancer (T1-2N0M0) and treated with TLM (n = 416) or OPL (n = 344) between 2004 and 2015 were abstracted from the SEER database. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (SIPTW) were performed to obtain comparable cohorts. The survival rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. Univariate and multivariate Cox regression analyses with a false discovery rate (FDR) correction were applied to contrast the association between two surgical approaches and overall survival (OS) and disease-specific survival (DSS). RESULTS: The 5-year OS for the TLM group was 79.5% versus 77.7% for the OPL group (P = 0.619). Similar results were revealed for the comparison of 5-year DSS rates (91.1% versus 91.5%, P = 0.891). After PSM and SIPTW balance the confounding factors, no significant difference was observed in the OS and DSS of patients treated with TLM compared to patients treated with OPL. The consistent results were still yielded (all P > 0.05), when stratified by gender, age, year of diagnosis, residence, household income, tumor site, T stage, differentiation, and adjuvant therapy. CONCLUSION: This study provides strong evidence that there is no significant difference in the prognosis of early laryngeal carcinoma between the treatment of TLM and OPL, which may be helpful to guide the clinical decision-making of these patients.

Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN.

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.

Correlation of heavy metals' exposure with the prevalence of coronary heart disease among US adults: findings of the US NHANES from 2003 to 2018.

We sought to explore the association between heavy metal exposure and coronary heart disease (CHD) based on data from the US National Health and Nutrition Examination Survey (NHANES, 2003-2018). In the analyses, participants were all aged > 20 and had participated in heavy metal sub-tests with valid CHD status. The Mann-Kendall test was employed to assess the trends in heavy metals' exposure and the trends in CHD prevalence over 16 years. Spearman's rank correlation coefficient and a logistics regression (LR) model were used to estimate the association between heavy metals and CHD prevalence. 42,749 participants were included in our analyses, 1802 of whom had a CHD diagnosis. Total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine, and cadmium, lead, and total mercury in blood all showed a substantial decreasing exposure level tendency over the 16 years (all Pfor trend < 0.05). CHD prevalence varied from 3.53 to 5.23% between 2003 and 2018. The correlation between 15 heavy metals and CHD ranges from - 0.238 to 0.910. There was also a significant positive correlation between total arsenic, monomethylarsonic acid, and thallium in urine and CHD by data release cycles (all P < 0.05). The cesium in urine showed a negative correlation with CHD (P < 0.05). We found that exposure trends of total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine and blood decreased. CHD prevalence fluctuated, however. Moreover, total arsenic, monomethylarsonic acid, and thallium in urine all showed positive relationships with CHD, while cesium in urine showed a negative relationship with CHD.

Crosstalk of FGFR1 signaling and choline metabolism promotes cell proliferation and survival in prostate cancer cells.

The acquisition of ectopic type I fibroblast growth factor receptor (FGFR1) is a common feature of prostate cancer (PCa), the most frequently diagnostic cancer in men. However, how ectopic FGFR1 contributes to PCa progression is not well understood. In our study we showed that ablation of FGFR1 in DU145 human PCa cells changed the cell metabolite profile. Among the changes, the choline metabolism profile was the most significantly altered by FGFR1 ablation. Detailed characterization revealed that ablation of FGFR1 altered expression of multiple choline metabolism enzymes. Among the changes of FGFR1-regulated choline metabolic enzymes, downregulation of choline kinase α (CHKA) is the most prominent changes, which phosphorylates free choline to phosphocholine. Ablation of FGFR1 blunted the activity of choline to promote cell proliferation and survival. Furthermore, depletion of CHKA compromised FGF signaling activity in DU145 cells. We also first time demonstrated that FGFR1 formed complex with CHKA, suggesting that FGFR1 regulated CHKA at the posttranslational level. Together with the previous report that ectopic FGFR1 contributes to PCa progression and metastasis, our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by dysregulating choline metabolism, and that the crosstalk between FGFR1-choline metabolism can be a potential target for managing PCa progression.

Association of Egg Consumption with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

BACKGROUND: Recent studies have reported conflicting associations between egg consumption and the risk of all-cause or cardiovascular disease (CVD) mortality, including ischemic heart disease (IHD) mortality and stroke mortality. With accumulating evidence, up-to-date evidence about the association should be synthesized. OBJECTIVES: We aimed to assess the association of the risk of all-cause and CVD mortality with egg consumption. METHODS: We searched the PubMed, Embase, and Web of Science databases through 3 November, 2021 for observational studies conducted in participants ≥18 y of age and which provided ORs, RRs, or HRs and 95% CIs for ≥3 egg consumption categories or for increased intake of egg addressing the associations of interest. A random-effects model was used to pool the reported risk estimates. Restricted cubic splines were used to examine the dose-response association. RESULTS: Twenty-four articles with 48 reports (25 for all-cause mortality, 11 for CVD mortality, 6 for IHD mortality, and 6 for stroke mortality) involving 11,890,695 participants were included. Intake of each 1-egg/d increment was associated with increased risk of all-cause mortality (RR: 1.06; 95% CI: 1.02, 1.10; P = 0.008), but the association was restricted to women, Americans, and studies with adjustments for hyperlipidemia. Egg consumption was linearly associated with CVD mortality only in participants >60 y of age, Americans, studies with follow-up duration ≥15 y, and studies with adjustments for hyperlipidemia (P ≤ 0.018). No significant association was found between egg consumption and IHD or stroke mortality (P ≥ 0.080). CONCLUSIONS: Egg consumption was linearly associated with a modestly increased risk of all-cause mortality and, in older participants, Americans, and studies with longer follow-up or adjustments for hyperlipidemia, CVD mortality. These findings suggest that it may be prudent to avoid high egg consumption.