Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study.

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One-sample Mendelian randomization (MR) and summary data-based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one-sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65-0.90; p = 0.001) and CCB use (0.83; 0.72-0.95; p = 0.007), equivalent to a 10-mm Hg reduction in systolic BP, was significantly associated with lower risk of pre-frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39-1.33; p = 0.296) or thiazides variants (0.74; 0.53-1.03; p = 0.072) on pre-frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta -0.02, p = 2.87 × 10-4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty.

Analyzing greenhouse gas emissions and influencing factors of 247 actual wastewater treatment plants in China using emission factor and operational data integrated methods (ODIM).

In response to China's policies on pollution control and carbon emission (CE) reductions, more stringent regulations have been implemented to evaluate CE in wastewater treatment facilities. In this study, we have analyzed CE from China's wastewater treatment plants (WWTPs) and influencing factor. Emission factor (EF) and operational data integrated methods (ODIM) were utilized to measure emissions, using data collected from 247 WWTPs over a 1-year period across seven regions in China. The average CE intensity was 0.45 kgCO2-eq/m3, affected by region, season, influent water quality, treatment processes, effluent discharge standards, and facilities. The scale effect was obvious only in the range of 2 × 105 m3/day. Underground WWTPs exhibited significantly higher CE compared to aboveground WWTPs. In summary, the assessment of CE in 247 actual WWTPs not only identifies emission reduction potential but also provides a scientific basis for formulating targeted emission reduction measures.

Highly efficient hydrodesulfurization driven by an in-situ reconstruction of ammonium/amine intercalated MoS2 catalysts.

Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 µmol·gcat-1·s-1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the 'intercalation-deintercalation' processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

A Multi-Interface Structure of Graphdiyne/Cobalt Oxides for Chlorine Production.

A challenge facing the chlor-alkali process is the lack of electrocatalyst with high activity and selectivity for the efficient industrial production of chlorine. Herein the authors report a new electrocatalyst that can generate multi-interface structure by in situ growth of graphdiyne on the surface of cobalt oxides (GDY/Co3O4), which shows great potential in highly selective and efficient chlorine production. This result is due to the strong electron transfer and high density charge transport between GDY and Co3O4 and the interconversion of the mixed valence states of the Co atoms itself. These intrinsic characteristics efficiently enhance the conductivity of the catalyst, facilitate the reaction kinetics, and improve the overall catalytic selectivity and activity. Besides, the protective effect of the formed GDY layer is remarkable endowing the catalyst with excellent stability. The catalyst can selectively produce chlorine in low-concentration of NaCl aqueous solution at room temperature and pressure with the highest Faraday efficiency of 80.67% and an active chlorine yield rate of 184.40 mg h-1 cm-2, as well as superior long-term stability.

Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Adherence to a healthy lifestyle including sleep and sedentary behaviors and risk of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

Spontaneous miscarriage and social support in predicting risks of depression and anxiety: a cohort study in UK Biobank.

BACKGROUND: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage. OBJECTIVE: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks. STUDY DESIGN: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety. RESULTS: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03). CONCLUSION: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support.

Major source categories of PM2.5 oxidative potential in wintertime Beijing and surroundings based on online dithiothreitol-based field measurements.

Fine particulate matter (PM2.5) causes millions of premature deaths each year worldwide. Oxidative potential (OP) has been proposed as a better metric for aerosol health effects than PM2.5 mass concentration alone. In this study, we report for the first time online measurements of PM2.5 OP in wintertime Beijing and surroundings based on a dithiothreitol (DTT) assay. These measurements were combined with co-located PM chemical composition measurements to identify the main source categories of aerosol OP. In addition, we highlight the influence of two distinct pollution events on aerosol OP (spring festival celebrations including fireworks and a severe regional dust storm). Source apportionment coupled with multilinear regression revealed that primary PM and oxygenated organic aerosol (OOA) were both important sources of OP, accounting for 41 ± 12 % and 39 ± 10 % of the OPvDTT (OP normalized by the sampled air volume), respectively. The small remainder was attributed to fireworks and dust, mainly resulting from the two distinct pollution events. During the 3.5-day spring festival period, OPvDTT spiked to 4.9 nmol min-1 m-3 with slightly more contribution from OOA (42 ± 11 %) and less from primary PM (31 ± 15 %). During the dust storm, hourly-averaged PM2.5 peaked at a very high value of 548 µg m-3 due to the dominant presence of dust-laden particles (88 % of total PM2.5). In contrast, only mildly elevated OPvDTT values (up to 1.5 nmol min-1 m-3) were observed during this dust event. This observation indicates that variations in OPvDTT cannot be fully explained using PM2.5 alone; one must also consider the chemical composition of PM2.5 when studying aerosol health effects. Our study highlights the need for continued pollution control strategies to reduce primary PM emissions, and more in-depth investigations into the source origins of OOA, to minimize the health risks associated with PM exposure in Beijing.

Enrichment methods of N-linked glycopeptides from human serum or plasma: A mini-review.

Human diseases often correlate with changes in protein glycosylation, which can be observed in serum or plasma samples. N-glycosylation, the most common form, can provide potential biomarkers for disease prognosis and diagnosis. However, glycoproteins constitute a relatively small proportion of the total proteins in human serum and plasma compared to the non-glycosylated protein albumin, which constitutes the majority. The detection of microheterogeneity and low glycan abundance presents a challenge. Mass spectrometry facilitates glycoproteomics research, yet it faces challenges due to interference from abundant plasma proteins. Therefore, methods have emerged to enrich N-glycans and N-linked glycopeptides using glycan affinity, chemical properties, stationary phase chemical coupling, bioorthogonal techniques, and other alternatives. This review focuses on N-glycans and N-glycopeptides enrichment in human serum or plasma, emphasizing methods and applications. Although not exhaustive, it aims to elucidate principles and showcase the utility and limitations of glycoproteome characterization.

Isotemporal Substitution Modeling on Sedentary Behaviors and Physical Activity With Mortality Among People With Different Diabetes Statuses: A Prospective Cohort Study From the National Health and Nutrition Examination Survey Analysis 2007-2018.

BACKGROUND: To assess the associations of replacing sedentary behavior with different types of physical activity with mortality among the US adults of varying diabetes statuses. METHODS: This prospective cohort study included 21,637 participants (mean age, 48.5 y) from the National Health and Nutrition Examination Survey 2007-2018. Physical activity including leisure-time moderate-vigorous-intensity activity (MVPA), walking/bicycling, worktime MVPA, and sedentary behavior. We conducted an isotemporal substitution analysis using Cox regression to estimate the associations between replacements and mortality risks. RESULTS: We found significant protective associations between replacing 30 minutes per day sedentary behavior with 3 types of physical activity and all-cause, cardiovascular disease (CVD) mortality risk (except worktime MVPA for CVD mortality) among total participants, with hazard ratio (HR; 95% confidence interval [CI]) ranging from 0.86 (0.77-0.95) to 0.96 (0.94-0.98). Among participants with diagnosed diabetes, replacing sedentary behavior with leisure-time MVPA was associated with a lower all-cause mortality risk (HR 0.81, 95% CI, 0.70-0.94), which was also observed in other subgroups, with HRs (95% CI) ranging from 0.87 (0.80-0.94) to 0.89 (0.81-0.99). Among those with prediabetes/undiagnosed diabetes, replacing sedentary behavior with walking/bicycling was associated with lower CVD mortality risk, and replacement to work-time MVPA was associated with lower all-cause and CVD mortality risk, with HRs (95% CI) ranging from 0.72 (0.63-0.83) to 0.96 (0.92-0.99). CONCLUSIONS: Replacing sedentary behaviors with 30 minutes per day leisure-time MVPA was associated with lower all-cause mortality, regardless of diabetes statuses. Among people with prediabetes/undiagnosed diabetes, walking/bicycling was additionally associated with lower CVD mortality, and worktime MVPA was associated with lower all-cause and CVD mortality.

Smoking timing, genetic susceptibility and the risk of incident type 2 diabetes: A cohort study from the UK Biobank.

AIM: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. MATERIALS AND METHODS: A total of 294 815 participants without diabetes from the UK Biobank, including non-smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. RESULTS: During a median follow-up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non-smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend < .001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17-1.81) for more than 2 hours, 1.51 (1.21-1.87) for 1-2 hours, 1.58 (1.34-1.85) for 30-60 minutes, 1.86 (1.57-2.21) for 5-15 minutes and 2.01 (1.60-2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52-2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P-interaction = .51). CONCLUSIONS: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D.

An Unprecedented [BO2]-Based Deep-Ultraviolet Transparent Nonlinear Optical Crystal by Superhalogen Substitution.

Solid-state structures with the superhalogen [BO2]- have thus far only been observed with a few compounds whose syntheses require high reaction temperatures and complicated procedures, while their optical properties remain almost completely unexplored. Herein, we report a facile, energy-efficient synthesis of the first [BO2]-based deep-ultraviolet (deep-UV) transparent oxide K9[B4O5(OH)4]3(CO3)(BO2)·7H2O (KBCOB). Detailed structural characterization and analysis confirm that KBCOB possesses a rare four-in-one three-dimensional quasi-honeycomb framework, with three π-conjugated anions ([BO2]-, [BO3]3-, and [CO3]2-) and one non-π-conjugated anion ([BO4]5-) in the one crystal. The evolution from the  traditional halogenated nonlinear optical (NLO) analogues to KBCOB by superhalogen [BO2]- substitution confers deep-UV transparency (< 190 nm), a large second-harmonic generation response (1.0 × KH2PO4 @ 1064 nm), and a 15-fold increase in birefringence. This study affords a new route to the facile synthesis of functional [BO2]-based oxides, paving the way for the development of next-generation high-performing deep-UV NLO materials.

Local incomplete combustion emissions define the PM2.5 oxidative potential in Northern India.

The oxidative potential (OP) of particulate matter (PM) is a major driver of PM-associated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five Indo-Gangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India.

1.55 µm wavelength band photonic crystal surface emitting laser with n-side photonic crystal and operation at up to 85 °C.

We describe the structure, fabrication, and measured performance of a 1543 nm wavelength photonic crystal surface emitting laser. An asymmetric double lattice design was used to achieve single mode lasing with side mode suppression ratios >40 dB. The photonic crystal was formed using encapsulated air holes in an n-doped InGaAsP layer with an InGaAlAs active layer then grown above it. In this way a laser with a low series resistance of 0.32 Ω capable of pulsed output powers of 171 mW at 25 °C and 40 mW at 85 °C was demonstrated.

The EAT-Lancet Diet Index, Plasma Proteins, and Risk of Heart Failure in a Population-Based Cohort.

BACKGROUND: The landmark EAT-Lancet Commission proposed that a planetary health diet is comprised mainly of plant-based foods. However, studies examining whether this diet is associated with heart failure (HF) are currently lacking. In addition, the potential proteomics mechanism on the association between diet and HF warrants further elucidation. OBJECTIVES: This study aims to both examine the association between the EAT-Lancet diet index and risk of HF and identify plasma proteins underlying such an association. METHODS: This prospective cohort study included 23,260 participants. HF cases during the follow-up were identified through the Swedish national register. An EAT-Lancet diet index (score range: 0-42) was created to assess adherence to the EAT-Lancet reference diet. In a subcohort (n = 4,742), fasting plasma proteins were quantified. RESULTS: During a median follow-up of 25.0 years, 1,768 incident HF cases were documented. After adjusting for sociodemographic, lifestyle, diabetes, hypertension, use of lipid-lowering drugs, and body mass index, the HR per 3-point increase of the EAT-Lancet diet index was 0.93 (95% CI: 0.88-0.97). This association was robust in several sensitivity analyses. Among the included 136 plasma proteins, a total of 8 proteins (AM, GDF15, IL6, TIM, CTSD, CCL20, FS, and FUR) were both inversely associated with the EAT-Lancet diet index and positively associated with risk of HF; the overall proteomic score mediated 9.4% (95% CI: 2.2%-32.1%) of the association. CONCLUSIONS: Higher adherence to the EAT-Lancet diet was associated with a lower risk of HF. The identified eight plasma proteins provide information on potential pathways mediating such an association.

Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease.

BACKGROUND: Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). METHODS: In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. RESULTS: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. CONCLUSIONS: Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial.

BACKGROUND: Distinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. OBJECTIVES: We investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates. METHODS: This study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations. RESULTS: At baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to ß (standard error) -3.3 (1.3), -3.4 (1.3), or -3.8 (1.3) mg/dL, respectively; PFDR < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was ß -4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (PFDR =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet. CONCLUSIONS: Decreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk. This trial was registered at clinicaltrials.gov as NCT00072995.

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort.

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in LS BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65 yr.

This study investigated the association between white matter hyperintensities (WMH) and bone health, focusing on BMD, incident fractures and falls. We included 26 410 participants from the UK Biobank and found that a greater WMH volume was associated with BMD in an L-shaped dose­response manner, especially in women and those under 65 yr. Additionally, per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. These findings emphasize the significance of considering brain health when evaluating bone health.

Prognostic model revealing pyroptosis-related signatures in oral squamous cell carcinoma based on bioinformatics analysis.

One of the most common oral carcinomas is oral squamous cell carcinoma (OSCC), bringing a heavy burden to global health. Although progresses have been made in the intervention of OSCC, 5 years survival of patients suffering from OSCC is poor like before regarding to the high invasiveness of OSCC, which causes metastasis and recurrence of the tumor. The relationship between pyroptosis and OSCC remains to be further investigated as pyroptosis in carcinomas has gained much attention. Herein, the key pyroptosis-related genes were identified according to The Cancer Genome Atlas (TCGA) dataset. Additionally, a prognostic model was constructed based upon three key genes (CTLA4, CD5, and IL12RB2) through least absolute shrinkage and selection operator (LASSO) analyses, as well as univariate and multivariate COX regression in OSCC. It was discovered that the high expression of these three genes was associated with the low-risk group. We also identified LAIR2 as a hub gene, whose expression negatively correlated with the risk score and the different immune cell infiltration. Finally, we proved that these three genes were independent prognostic factors linked to overall survival (OS), and reliable consequences could be predicted by this model. Our study revealed the relationship between pyroptosis and OSCC, providing insights into new treatment targets for preventing and treating OSCC.