Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

Genetic analyses identify brain imaging-derived phenotypes associated with the risk of amyotrophic lateral sclerosis.

Brain imaging-derived phenotypes have been suggested to be associated with amyotrophic lateral sclerosis in observational studies, but whether these associations are causal remains unclear. We aimed to assess the potential bidirectional causal associations between imaging-derived phenotypes and amyotrophic lateral sclerosis using bidirectional 2-sample Mendelian randomization analyses. Summary statistics for 469 imaging-derived phenotypes (33,224 individuals) and amyotrophic lateral sclerosis (20,806 cases and 59,804 controls) were obtained from 2 large-scale genome-wide association studies of European ancestry. We used the inverse-variance weighted Mendelian randomization method in the main analysis to assess the bidirectional associations between imaging-derived phenotypes and amyotrophic lateral sclerosis, followed by several sensitivity analyses for robustness validation. In the forward Mendelian randomization analyses, we found that genetically determined high orientation dispersion index in the right cerebral peduncle was associated with the increased risk of amyotrophic lateral sclerosis (odds ratio = 1.30, 95% confidence interval = 1.16-1.45, P = 2.26 × 10-6). In addition, the reverse Mendelian randomization analysis indicated that amyotrophic lateral sclerosis had no effect on 469 imaging-derived phenotypes. Mendelian randomization-Egger regression analysis showed no directional pleiotropy for the association between high orientation dispersion index in the right cerebral peduncle and amyotrophic lateral sclerosis, and sensitivity analyses with different Mendelian randomization models further confirmed these findings. The present systematic bidirectional Mendelian randomization analysis showed that high orientation dispersion index in the right cerebral peduncle might be the potential causal mediator of amyotrophic lateral sclerosis, which may provide predictive guidance for the prevention of amyotrophic lateral sclerosis. Further studies are warranted to replicate our findings and clarify the underlying mechanisms.

Genetic analyses identify brain imaging-derived phenotypes associated with the risk of intracerebral hemorrhage.

Previous observational studies have reported associations between brain imaging-derived phenotypes (IDPs) and intracerebral hemorrhage (ICH), but the causality between them remains uncertain. We aimed to investigate the potential causal relationship between IDPs and ICH by a two-sample Mendelian randomization (MR) study. We selected genetic instruments for 363 IDPs from a genome-wide association study (GWASs) based on the UK Biobank (n = 33,224). Summary-level data on ICH was derived from a European-descent GWAS with 1,545 cases and 1,481 controls. Inverse variance weighted MR method was applied in the main analysis to investigate the associations between IDPs and ICH. Reverse MR analyses were performed for significant IDPs to examine the reverse causation for the identified associations. Among the 363 IDPs, isotropic or free water volume fraction (ISOVF) in the anterior limb of the left internal capsule was identified to be associated with the risk of ICH (OR per 1-SD increase, 4.62 [95% CI, 2.18-9.81], P = 6.63 × 10-5). In addition, the reverse MR analysis indicated that ICH had no effect on ISOVF in the anterior limb of the left internal capsule (beta, 0.010 [95% CI, -0.010-0.030], P = 0.33). MR-Egger regression analysis showed no directional pleiotropy for the association between ISOVF and ICH, and sensitivity analyses with different MR models further confirmed these findings. ISOVF in the anterior limb of the left internal capsule might be a potential causal mediator of ICH, which may provide predictive guidance for the prevention of ICH. Further studies are warranted to replicate our findings and clarify the underlying mechanisms.

Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study.

BACKGROUND: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. METHODS: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. RESULTS: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. CONCLUSIONS: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.

Physical activity and sleep pattern in relation to incident Parkinson's disease: a cohort study.

BACKGROUND: How physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson's disease (PD) remain unknown. OBJECTIVE: To prospectively investigate the joint associations of PA and sleep pattern with risk of PD. METHODS: Included were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (< 600 MET-mins/week), medium (600 to < 3000 MET-mins/week) and high (≥ 3000 MET-mins/week) according to the instructions of the UK Biobank. Healthy sleep traits (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were scored from 0 to 5 and were categorized into "ideal sleep pattern" (≥ 3 sleep scores) and "poor sleep pattern" (0-2 sleep scores). Hazard ratios (HRs) and 95% confidence intervals (CIs) of PD were estimated by Cox proportional hazards models. RESULTS: During a median of 11.8 years of follow-up, 1,966 PD events were identified. The PD risk was lower in participants with high PA (HR = 0.73; 95% CI: 0.64, 0.84), compared to those with low PA; and participants with ideal sleep pattern also had a lower risk of PD (HR = 0.78; 95% CI: 0.69, 0.87), compared to those with poor sleep pattern. When jointly investigating the combined effect, participants with both high PA and ideal sleep pattern had the lowest risk of incident PD (HR = 0.55; 95% CI: 0.44, 0.69), compared to those with low PA and poor sleep pattern; notably, participants with high PA but poor sleep pattern also gained benefit on PD risk reduction (HR = 0.74; 95% CI: 0.55, 0.99). CONCLUSIONS: Both high PA and ideal sleep pattern were independently associated with lower risk of developing PD, and those with both high PA level and ideal sleep pattern had the lowest risk. Our results suggest that improving PA levels and sleep quality may be promising intervention targets for the prevention of PD.

Association of phthalate exposure with all-cause mortality across renal function status: The U.S. National Health and Nutrition Examination Survey, 2005-2018.

BACKGROUND: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear. METHODS: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status. RESULTS: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44). CONCLUSIONS: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population.

A Vision/Inertial Navigation/Global Navigation Satellite Integrated System for Relative and Absolute Localization in Land Vehicles.

This paper presents an enhanced ground vehicle localization method designed to address the challenges associated with state estimation for autonomous vehicles operating in diverse environments. The focus is specifically on the precise localization of position and orientation in both local and global coordinate systems. The proposed approach integrates local estimates generated by existing visual-inertial odometry (VIO) methods into global position information obtained from the Global Navigation Satellite System (GNSS). This integration is achieved through optimizing fusion in a pose graph, ensuring precise local estimation and drift-free global position estimation. Considering the inherent complexities in autonomous driving scenarios, such as the potential failures of a visual-inertial navigation system (VINS) and restrictions on GNSS signals in urban canyons, leading to disruptions in localization outcomes, we introduce an adaptive fusion mechanism. This mechanism allows seamless switching between three modes: utilizing only VINS, using only GNSS, and normal fusion. The effectiveness of the proposed algorithm is demonstrated through rigorous testing in the Carla simulation environment and challenging UrbanNav scenarios. The evaluation includes both qualitative and quantitative analyses, revealing that the method exhibits robustness and accuracy.

RBS and ABS Coordinated Control Strategy Based on Explicit Model Predictive Control.

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

Intrinsic RNA Targeting Triggers Indiscriminate DNase Activity of CRISPR-Cas12a.

The CRISPR-Cas12a system has emerged as a powerful tool for next-generation nucleic acid-based molecular diagnostics. However, it has long been believed to be effective only on DNA targets. Here, we investigate the intrinsic RNA-enabled trans-cleavage activity of AsCas12a and LbCas12a and discover that they can be directly activated by full-size RNA targets, although LbCas12a exhibits weaker trans-cleavage activity than AsCas12a on both single-stranded DNA and RNA substrates. Remarkably, we find that the RNA-activated Cas12a possesses higher specificity in recognizing mutated target sequences compared to DNA activation. Based on these findings, we develop the "Universal Nuclease for Identification of Virus Empowered by RNA-Sensing" (UNIVERSE) assay for nucleic acid testing. We incorporate a T7 transcription step into this assay, thereby eliminating the requirement for a protospacer adjacent motif (PAM) sequence in the target. Additionally, we successfully detect multiple PAM-less targets in HIV clinical samples that are undetectable by the conventional Cas12a assay based on double-stranded DNA activation, demonstrating unrestricted target selection with the UNIVERSE assay. We further validate the clinical utility of the UNIVERSE assay by testing both HIV RNA and HPV 16 DNA in clinical samples. We envision that the intrinsic RNA targeting capability may bring a paradigm shift in Cas12a-based nucleic acid detection and further enhance the understanding of CRISPR-Cas biochemistry.

Intelligent Vehicle Decision-Making and Trajectory Planning Method Based on Deep Reinforcement Learning in the Frenet Space.

The complexity inherent in navigating intricate traffic environments poses substantial hurdles for intelligent driving technology. The continual progress in mapping and sensor technologies has equipped vehicles with the capability to intricately perceive their exact position and the intricate interplay among surrounding traffic elements. Building upon this foundation, this paper introduces a deep reinforcement learning method to solve the decision-making and trajectory planning problem of intelligent vehicles. The method employs a deep learning framework for feature extraction, utilizing a grid map generated from a blend of static environmental markers such as road centerlines and lane demarcations, in addition to dynamic environmental cues including vehicle positions across varied lanes, all harmonized within the Frenet coordinate system. The grid map serves as the input for the state space, and the input for the action space comprises a vector encompassing lane change timing, velocity, and vertical displacement at the lane change endpoint. To optimize the action strategy, a reinforcement learning approach is employed. The feasibility, stability, and efficiency of the proposed method are substantiated via experiments conducted in the CARLA simulator across diverse driving scenarios, and the proposed method can increase the average success rate of lane change by 6.8% and 13.1% compared with the traditional planning control algorithm and the simple reinforcement learning method.

Query-Informed Multi-Agent Motion Prediction.

In a dynamic environment, autonomous driving vehicles require accurate decision-making and trajectory planning. To achieve this, autonomous vehicles need to understand their surrounding environment and predict the behavior and future trajectories of other traffic participants. In recent years, vectorization methods have dominated the field of motion prediction due to their ability to capture complex interactions in traffic scenes. However, existing research using vectorization methods for scene encoding often overlooks important physical information about vehicles, such as speed and heading angle, relying solely on displacement to represent the physical attributes of agents. This approach is insufficient for accurate trajectory prediction models. Additionally, agents' future trajectories can be diverse, such as proceeding straight or making left or right turns at intersections. Therefore, the output of trajectory prediction models should be multimodal to account for these variations. Existing research has used multiple regression heads to output future trajectories and confidence, but the results have been suboptimal. To address these issues, we propose QINET, a method for accurate multimodal trajectory prediction for all agents in a scene. In the scene encoding part, we enhance the feature attributes of agent vehicles to better represent the physical information of agents in the scene. Our scene representation also possesses rotational and spatial invariance. In the decoder part, we use cross-attention and induce the generation of multimodal future trajectories by employing a self-learned query matrix. Experimental results demonstrate that QINET achieves state-of-the-art performance on the Argoverse motion prediction benchmark and is capable of fast multimodal trajectory prediction for multiple agents.

Can major public health emergencies increase the participation of commercial insurance? Evidence from China.

Background: Public health emergencies have a lasting impact on a country's economic and social development. However, commercial insurance can disperse these negative consequences and reduce risk losses. Method: Based on the Chinese Household Tracking Survey and Peking University Digital Inclusive Finance Index, this study employed a difference-in-differences model to test the impact of the COVID-19 outbreak on commercial insurance participation and the impact mechanism. Results: The analysis showed that the outbreak of COVID-19 improved residents' risk perception, risk preference and digital finance and promoted their participation in commercial insurance, commercial endowment insurance, and commercial medical insurance. Conclusion: Major public health emergencies can increase commercial insurance participation, but the promotional effect of commercial insurance on rural and low-income individuals is relatively limited. To tap into potential customers, financial institutions should focus on vulnerable societal groups. This study supplements the relevant literature on the impact of major public health emergencies on commercial insurance participation.

Association between oral contraceptives and cervical cancer: A retrospective case-control study based on the National Health and Nutrition Examination Survey.

Background: Cervical cancer is the fourth most common cancer among females globally, with a high incidence and high mortality among females in developing countries. This retrospective case-control study aimed to investigate the association between oral contraceptives and cervical cancer, on which insufficient evidence still exists. Material and Methods: To examine the association between oral contraceptives and cervical cancer based on 7,496 females aged over 20 years from the National Health and Nutrition Examination Survey, multivariable logistic regression conducted from 1999 to 2016 was used. Results: Contraceptive use was positively associated with cervical cancer risk. In model 1 (unadjusted), a 195% increased risk of cervical cancer was observed among those who used oral contraceptives (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.39-3.98, p = 0.002) compared to those who did not. In addition, the ORs for the exposed population were 1.74 (95% CI = 1.05-3.08, p = 0.041) and 1.93 (95% CI = 1.16-3.44, p = 0.017) in model 2 (adjusted for age, race, and body mass index [BMI]) and model 3 (adjusted for education level, ratio of family income to poverty, drinking status, smoking status, number of pregnancies, age at first sex, number of sexual partners, and whether to receive the human papillomavirus (HPV) vaccine in addition to model 2), respectively. Furthermore, subgroup analyses stratified by age, smoking status, BMI, age at first sex, number of sexual partners, and whether to receive the HPV vaccine also revealed that oral contraceptives were significantly associated with cervical cancer. Conclusion: This study demonstrated that oral contraceptive use increased the risk of cervical cancer. In addition, the higher risk, including individuals older than 45 years, having a high BMI (≥30 kg/m2), being current smokers, and having more than five sexual partners, may contribute to the development of cervical cancer.

Solute carrier family 35 member A2 regulates mitophagy through the PI3K/AKT/mTOR axis, promoting the proliferation, migration, and invasion of osteosarcoma cells.

The treatment of osteosarcoma patients exhibits individual variability, underscoring the critical importance of targeted therapy. Although (Solute carrier family 35 member A2) SLC35A2's role in the progression of various cancers has been extensively investigated, its specific implications in osteosarcoma remain unexplored. Leveraging data from the (The Cancer Genome Atlas) TCGA and (Genotype-Tissue Expression) GTEx databases, we have discerned that SLC35A2 is notably upregulated in osteosarcoma and correlates with the prognosis of osteosarcoma patients. Consequently, it becomes imperative to delve into the role of SLC35A2 in the context of osteosarcoma. Our research substantiates that SLC35A2 exerts a notable influence on mitochondrial autophagy in osteosarcoma, thereby exerting cascading effects on the proliferation, migration, invasion, and apoptosis of osteosarcoma cells. Mechanistically, SLC35A2 orchestrates mitochondrial autophagy via the PI3K/AKT/mTOR signaling pathway. Moreover, we have conducted rigorous animal experiments to further corroborate the repercussions of SLC35A2 on osteosarcoma growth. In summation, our study elucidates that SLC35A2's modulation of mitochondrial autophagy through the PI3K/AKT/mTOR signaling pathway constitutes a pivotal factor in the malignant progression of osteosarcoma, unveiling promising therapeutic targets for patients grappling with this condition.

The Suitable Population for Opportunistic Low Bone Mineral Density Screening Using Computed Tomography.

Objective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD). Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD. Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups. Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.

An Ultrathin, Fast-Response, Large-Scale Liquid-Crystal-Facilitated Multi-Functional Reconfigurable Metasurface for Comprehensive Wavefront Modulation.

The rapid advancement of prevailing communication/sensing technologies necessitates cost-effective millimeter-wave arrays equipped with a massive number of phase-shifting cells to perform complicated beamforming tasks. Conventional approaches employing semiconductor switch/varactor components or tunable materials encounter obstacles such as quantization loss, high cost, high complexity, and limited adaptability for realizing large-scale arrays. Here, a low-cost, ultrathin, fast-response, and large-scale solution relying on metasurface concepts combined together with liquid crystal (LC) materials requiring a layer thickness of only 5 µm is reported. Rather than immersing resonant structures in LCs, a joint material-circuit-based strategy is devised, via integrating deep-subwavelength-thick LCs into slow-wave structures, to achieve constitutive metacells with continuous phase shifting and stable reflectivity. An LC-facilitated reconfigurable metasurface sub-system containing more than 2300 metacells is realized with its unprecedented comprehensive wavefront manipulation capacity validated through various beamforming functions, including beam focusing/steering, reconfigurable vortex beams, and tunable holograms, demonstrating a milli-second-level function-switching speed. The proposed methodology offers a paradigm shift for modulating electromagnetic waves in a non-resonating broadband fashion with fast-response and low-cost properties by exploiting functionalized LC-enabled metasurfaces. Moreover, this extremely agile metasurface-enabled antenna technology will facilitate a transformative impact on communication/sensing systems and empower new possibilities for wavefront engineering and diffractive wave calculation/inference.

Microvascular disease, modifiable risk factor profiles and incident arrhythmias in type 2 diabetes.

BACKGROUND: To assess the roles of diabetic microvascular disease and modifiable risk factors and their combination in the development of arrhythmias. METHODS: We included participants with type 2 diabetes (T2D) who were free of arrhythmias during recruitment in the UK Biobank study. The associations of microvascular disease states (defined by the presence of retinopathy, peripheral neuropathy or chronic kidney disease), four modifiable arrhythmic risk factors (body mass index, smoking, systolic blood pressure and glycosylated haemoglobin) and their joint associations with incident arrhythmias were examined. RESULTS: Among the 25 632 participants with T2D, 1705 (20.1%) of the 8482 with microvascular disease and 2017 (11.8%) of the 17 150 without microvascular disease developed arrhythmias during a median follow-up of 12.3 years. Having any of the three microvascular diseases was associated with a 48% increase in the hazard of developing arrhythmias. Incorporating microvascular disease states into a model alongside 11 traditional risk factors significantly enhanced arrhythmia prediction. Furthermore, individuals with microvascular disease who had optimal levels of zero to one, two, three or four arrhythmic risk factors showed an HR of 2.05 (95% CI 1.85, 2.27), 1.67 (95% CI 1.53, 1.83), 1.35 (95% CI 1.22, 1.50) and 0.91 (95% CI 0.73, 1.13), respectively, compared with those without microvascular disease. CONCLUSIONS: Although microvascular disease, a non-traditional risk factor, was associated with incident arrhythmias in individuals with T2D, having optimal levels of risk factors may mitigate this risk.

Complete genome sequence of Kushneria phosphatilytica YCWA18T reveals the P-solubilizing activity of the genus Kushneria.

Kushneria phosphatilytica YCWA18T (= CGMCC 1.9149T = NCCB 100306T) was isolated from sediment collected in a saltern on the eastern coast of Yellow Sea in China. The genome was sequenced and comprised of one circular chromosome with the size of 3,624,619 bp and DNA G + C content of 59.13%. A total of 3267 protein-coding genes, 64 tRNA genes and 12 rRNA genes were obtained. Genomic annotation indicated that the genome of K. phosphatilytica YCWA18T had 34 genes involved in phosphorus (P) solubilization/metabolism, e.g., gdh, pqq, phoA, phoD and phoX, which products can convert insoluble P-containing compounds to more bio-available dissolved inorganic P. Comparative genomic analysis of Kushneria strains revealed that gdh, pqq, phoA, phoD and phoX were widely distributed in these strains, indicating the genus Kushneria may play an important role in the P cycle. Additionally, a multitude of salt tolerance genes were detected in the genome of K. phosphatilytica YCWA18T. This study and the genome sequence data will be available for further research and will provide insights into potential biotechnological and agricultural applications of Kushneria strains.

Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota.

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.

Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study.

CONTEXT: The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated. OBJECTIVE: To investigate the role of MVD and CVHMs in the development of CHD among T2DM. DESIGN: We included 19 664 participants with T2DM from the UK Biobank who had CVHM data and were free of CHD during recruitment. CVHMs were defined based on 5 behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and 3 biological (glycemic control, hyperlipidemia, and hypertension) factors. MVD was defined as the presence of retinopathy, peripheral neuropathy, or chronic kidney disease. Hazard ratio (HR) and 95% CI of CHD were estimated by multivariable Cox regression models. RESULTS: There were 3252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥ 2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each unfavorable CVHM was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥ 2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR = 4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs. CONCLUSION: Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such association may be amplified by unfavorable CVHMs.