Bioaccumulation of Atmospherically Deposited Cadmium in Soybean: Three-Year Field Experiment Combined with Cadmium Isotopes.

Atmospheric deposition plays a significant role in introducing cadmium (Cd) into agroecological systems; however, accurately determining its accumulation in crops through foliar and root uptake presents challenges. This study investigated the bioaccumulation of atmospherically deposited Cd in soybean using a three-year fully factorial atmospheric exposure experiment incorporating Cd isotope analysis. Results shown that atmospheric deposition accounted for 1-13% of soil Cd pools, yet contributed 11-72% of Cd to soybean tissues during the growing seasons. Over the course of soil exposure to atmospheric deposition ranging from 1 to 3 years, no notable variations were observed in Cd concentrations in soil solutions and soybean tissues, nor in isotope ratios. Newly deposited Cd was a major source in soybean plants, and the bioavailability of deposited Cd rapidly aged in soils. Atmospheric Cd enriched in lighter isotopes induced negative isotope shifts in soybean plants. By employing an optimized isotope mixing model in conjunction with a mass balance approach, foliar Cd uptake contributed 13-51%, 16-45%, and 21-56% to stem, leaf, and seed, respectively. This study highlights substantial contribution of foliar uptake of atmospheric deposition to Cd levels in soybean and controlling foliar uptake as a potential strategy in agroecological systems experiencing high atmospheric Cd deposition.

Systemic inflammatory response to daily exposure to microcystin-LR and the underlying gut microbial mechanisms.

Cyanobacterial toxins have raised global concerns due to potential chronic disease implications from daily drinking water exposure, which remain largely unknown despite extensive research on their acute effects. To understand the mechanisms underlying microcystin-LR (MC-LR)-induced inflammation-associated diseases. Mice were exposed to MC-LR for one year at concentrations comparable to human environmental exposure levels. Comprehensive pathological observation and multi-omics approaches based on 16S rRNA gene sequencing, untargeted metabolomics, transcriptomics and proteomics were conducted across various organs. Daily exposure to MC-LR induced intestinal microbial dysbiosis and colitis-like changes. It also caused systemic chronic inflammation marked by elevated serum levels of inflammatory cytokines, inflammation-associated pathological changes, and identification of infection-related genes/proteins within the gut-brain-spleen-liver axis. Furthermore, multi-omics analysis across organs suggested that Muribaculaceae may promote a systemic infection-inflammatory response, relying on kynurenine metabolites signaling in peripheral tissues. In contrast, Lachnospiraceae may act an opposing role, dependent on intestinal indole derivatives via the neuroimmunomodulation pathway. A fecal microbiota transplantation experiment confirmed that alterations in Muribaculaceae and Lachnospiraceae resulting from exposure to MC-LR triggered the local and systemic chronic inflammation in mice. This study light on the potential strategies employed by gut microbial community in regulating MC-induced inflammation-associated chronic diseases under repeated exposure through drinking water.

Fluorine-Tuned Carbon-Based Nickel Single-Atom Catalysts for Scalable and Highly Efficient CO2 Electrocatalytic Reduction.

Electrocatalytic CO2 reduction is garnering significant interest due to its potential applications in mitigating CO2 and producing fuel. However, the scaling up of related catalysis is still hindered by several challenges, including the cost of the catalytic materials, low selectivity, small current densities to maintain desirable selectivity. In this study, Fluorine (F) atoms were introduced into an N-doped carbon-supported single nickel (Ni) atom catalyst via facile polymer-assisted pyrolysis. This method not only maintains the high atom utilization efficiency of Ni in a cost-effective and sustainable manner but also effectively manipulates the electronic structure of the active Ni-N4 site through F doping. The catalyst has also been further optimized by controlling the F states, including convalent and semi-ionic states, by adjusting the fluorine sources involved. Consequently, this catalyst with unique structure exhibited comparable electrocatalytic performance for CO2-to-CO conversion, achieving a Faradaic efficiency (FE) of over 99% across a wide potential range and an exceptional CO evolution rate of 9.5 × 104 h-1 at -1.16 V vs reversible hydrogen electrode (RHE). It also delivered a practical current of 400 mA cm-2 while maintaining more than 95% CO FE. Experimental analysis combined with density functional theory (DFT) calculations have also shown that F-doping modifies the electron configuration at the central Ni-N4 sites. This modification lowers the energy barrier for CO2 activation, thereby facilitating the production of the crucial *COOH intermediate.

Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma.

Objective: CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated. Methods: Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and in vitro experiments were then performed. Results: DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro. Conclusions: Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.

Magnetically Enhanced Oxygen Evolution Reaction in Mild Alkaline Electrolytes by Building Catalysts on Magnetic Frame.

Under large current densities, the excessive hydroxide ion (OH) consumption hampers alkaline water splitting involving the oxygen evolution reaction (OER). High OH concentration (≈30 wt.%) is often used to enhance the catalytic activity of OER, but it also leads to higher corrosion in practical systems. To achieve higher catalytic activity in low OH concentration, catalysts on magnetic frame (CMF) are built to utilize the local magnetic convection induced from the host frame's magnetic field distributions. This way, a higher reaction rate can be achieved in relatively lower OH concentrations. A CMF model system with catalytically active CoFeOx nanograins grown on the magnetic Ni foam is demonstrated. The OER current of CoFeOx@NF receives ≈90% enhancement under 400 mT (900 mA cm-2 at 1.65 V) compared to that in zero field, and exhibits remarkable durability over 120 h. As a demonstration, the water-splitting performance sees a maximum 45% magnetic enhancement under 400 mT in 1 m KOH (700 mA cm-2 at 2.4 V), equivalent to the concentration enhancement of the same electrode in a more corrosive 2 m KOH electrolyte. Therefore, the catalyst-on-magnetic-frame strategy can make efficient use of the catalysts and achieve higher catalytic activity in low OH concentration by harvesting local magnetic convection.

A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

BACKGROUND: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC. OBJECTIVE: The aim was to identify the probable novel causative gene in an autosomal recessive inherited PFBC family. METHODS: We performed a comprehensive genetic study on a consanguineous Chinese family with 3 siblings diagnosed with PFBC. We evaluated the effect of the variant in a probable novel causative gene on the protein level using Western blot, immunofluorescence, and coimmunoprecipitation. Possible downstream pathogenic mechanisms were further explored in gene knockout (KO) cell lines and animal models. RESULTS: We identified a PFBC co-segregated homozygous variant of c.460_461del (p.D154Lfs*113) in NAA60. Functional assays showed that this variant disrupts NAA60 protein localization to Golgi and accelerated protein degradation. The mutant NAA60 protein alters its interaction with the PFBC-related proteins PiT2 and XPR1, affecting intracellular phosphate homeostasis. Further mass spectrometry analysis in NAA60 KO cell lines revealed decreased expression of multiple brain calcification-associated proteins, including reduced folate carrier (RFC), a folate metabolism-related protein. CONCLUSIONS: Our study replicated the identification of NAA60 as a novel causative gene for autosomal recessive PFBC, demonstrating our causative variant leads to NAA60 loss of function. The NAA60 loss of function disrupts not only PFBC-related proteins (eg, PiT2 and XPR1) but also a wide range of other brain calcification-associated membrane protein substrates (eg, RFC), and provided a novel probable pathogenic mechanism for PFBC. © 2024 International Parkinson and Movement Disorder Society.

Functional characterization, structural basis, and protein engineering of a rare flavonoid 2'-O-glycosyltransferase from Scutellaria baicalensis.

Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2'-O-glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2'-O-glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2'-O-glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2'-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2'-O-glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by pK a calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogen‒deuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7-O-glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2'-O-glycosylation (k cat/K m, 0.23 L/(s·µmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design.

Oat ß-(1 → 3, 1 → 4)-d-glucan alleviates food allergy-induced colonic injury in mice by increasing Lachnospiraceae abundance and butyrate production.

Oat ß-(1 â†’ 3, 1 â†’ 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.

Enhancing Energy Storage Performance of 0.85Bi0.5Na0.5TiO3-0.15LaFeO3 Lead-Free Ferroelectric Ceramics via Buried Sintering.

Bismuth sodium titanate (Bi0.5Na0.5TiO3, BNT) ceramics are expected to replace traditional lead-based materials because of their excellent ferroelectric and piezoelectric characteristics, and they are widely used in the industrial, military, and medical fields. However, BNT ceramics have a low breakdown field strength, which leads to unsatisfactory energy storage performance. In this work, 0.85Bi0.5Na0.5TiO3-0.15LaFeO3 ceramics are prepared by the traditional high-temperature solid-phase reaction method, and their energy storage performance is greatly enhanced by improving the process of buried sintering. The results show that the buried sintering method can inhibit the formation of oxygen vacancy, reduce the volatilization of Bi2O3, and greatly improve the breakdown field strength of the ceramics so that the energy storage performance can be significantly enhanced. The breakdown field strength increases from 210 kV/cm to 310 kV/cm, and the energy storage density increases from 1.759 J/cm3 to 4.923 J/cm3. In addition, the energy storage density and energy storage efficiency of these ceramics have good frequency stability and temperature stability. In this study, the excellent energy storage performance of the ceramics prepared by the buried sintering method provides an effective idea for the design of lead-free ferroelectric ceramics with high energy storage performance and greatly expands its application field.

Effect of Dietary Composite Probiotic Supplementation on the Microbiota of Different Oral Sites in Cats.

Probiotics demonstrated effectiveness in modulating oral microbiota and improving oral health in humans and rodents. However, its effects and applications on the oral microbiota of cats remain underexplored. Twelve healthy cats were randomly assigned to a control group (CON) and a composite probiotic group (CPG) for a 42-day trial. The CPG diet included additional supplementation of Bifidobacterium animalis subsp. lactis HN019, Lactobacillus acidophilus NCFM, and Lactobacillus casei LC-11, each at approximately 1 × 1010 CFU/kg. On days 0 and 42, microbial samples were collected from the gingiva, tooth surfaces, and tongue of all cats for 16S rRNA gene sequencing. Bacteroidetes, Firmicutes, and Proteobacteria were the dominant phyla across all oral sites. The CPG treatment enriched seven genera, such as Moraxella, Actinomyces, and Frederiksenia in the gingiva. Meanwhile, Bergeyella and Streptococcus were enriched on the tooth surfaces, while Bergeyella, Flavobacterium, and Luteimonas were enriched on the tongue. Furthermore, the composite probiotic effectively suppressed eight genera, such as Bacteroides, Desulfovibrio, and Filifactor in the gingiva of CPG cats, as well as Helcococcus, Lentimicrobium, and Campylobacter on tooth surfaces, and Porphyromonas, Treponema, and Fusibacter on the tongue. These findings suggest that the composite probiotic used in this study modulates the feline oral microbiota by supporting beneficial or commensal bacteria and inhibiting oral pathogens, demonstrating potential to improve oral health in cats.

Spatial-temporal dynamic evolution of lewy body dementia by metabolic PET imaging.

PURPOSE: Lewy body dementia (LBD) is a neurodegenerative disease with high heterogeneity and complex pathogenesis. Our study aimed to use disease progression modeling to uncover spatial-temporal dynamic evolution of LBD in vivo, and to explore differential profiles of clinical features, glucose metabolism, and dopaminergic function among different evolution-related subtypes. METHODS: A total of 123 participants (31 healthy controls and 92 LBD patients) who underwent 18F-FDG PET scans were retrospectively enrolled. 18F-FDG PET-based Subtype and Stage Inference (SuStaIn) model was established to illustrate spatial-temporal evolutionary patterns and categorize relevant subtypes. Then subtypes and stages were further related to clinical features, glucose metabolism, and dopaminergic function of LBD patients. RESULTS: This 18F-FDG PET imaging-based approach illustrated two distinct patterns of neurodegenerative evolution originating from the neocortex and basal ganglia in LBD and defined them as subtype 1 and subtype 2, respectively. There were obvious differences between subtypes. Compared with subtype 1, subtype 2 exhibited a greater proportion of male patients (P = 0.045) and positive symptoms such as visual hallucinations (P = 0.033) and fluctuating cognitions (P = 0.033). Cognitive impairment, metabolic abnormalities, dopaminergic dysfunction and progression were all more severe in subtype 2 (all P < 0.05). In addition, a strong association was observed between SuStaIn subtypes and two clinical phenotypes (Parkinson's disease dementia and dementia with Lewy bodies) (P = 0.005). CONCLUSIONS: Our findings based on 18F-FDG PET and data-driven model illustrated spatial-temporal dynamic evolution of LBD and categorized novel subtypes with different evolutionary patterns, clinical and imaging features in vivo. The evolution-related subtypes are associated with LBD clinical phenotypes, which supports the perspective of existence of distinct entities in LBD spectrum.

Partial discharge detection, diagnosis, and location technology based on a novel transient earth voltage-ultrasonic integrated sensor used for switchgear equipment.

Medium-voltage (MV) switchgear and gas insulated switchgear (GIS) are essential components of power-grid systems. Their safe operation is crucial for the electricity consumption of users. However, insulation faults often occur during the operation of MV switchgear and GIS because of pollution, humidity, heat, mechanical shock, and other factors. Partial discharge (PD) measurements are the most effective indicator to prevent insulation failure. Transient earth voltage (TEV) and ultrasonic methods are the most popular PD measurement methods for switchgear. Currently, these two methods are used widely and independently. In this study, a novel TEV-ultrasonic integrated sensor is proposed based on the independent structure of the TEV and the ultrasonic sensor. The performance parameters of the proposed sensor were tested on test platforms. PD measurement experiments were conducted in a 10 kV switchgear and 220 kV GIS to analyze the performance of the integrated sensor. The results show that the sensor can simultaneously measure the TEV and ultrasonic signals in the same location. The integrated sensor can realize effective and sensitive detection, precise location, and accurate diagnosis of PD in the MV switchgear and GIS.

Supplementation of diethyl aminoethyl hexanoate for enhancing antibiotics removal by different microalgae-based system.

With the growth of the aquaculture industry, antibiotic residues in treated wastewater have become a serious ecological threat. The effects of supplementation with diethyl aminoethyl hexanoate (DA-6) on the removal of tetracycline (TC), ciprofloxacin (CPFX), and sulfamonomethoxine (SMM) from aquaculture wastewater by different microalgae-based systems were examined and systematically analyzed. The results demonstrated that C. vulgaris -S395-2-C. rosea symbiont performed best under 0.2 mg L-1 antibiotic treatment for antibiotic removal. At 10-7 M, DA-6 significantly enhanced C. vulgaris-S395-2-C. rosea symbiont removal of CPFX and SMM at 0.20 mg L-1. The removal of TC, CPFX and SMM by this strain under optimal conditions was 99.2 ± 0.4 %, 86.3 ± 6.3 %, and 91.3 ± 5.7 %, respectively. These results suggest that DA-6 may act on microalgae-bacteria-fungi three-phase symbionts for the removal of multiple antibiotics from aquaculture wastewater.

Negative Photoconductivity Transistors for Visuomorphic Computing.

Visuomorphic computing aims to simulate and potentially surpass the human retina by mimicking biological visual perception with an artificial retina. Despite significant progress, challenges persist in perceiving complex interactive environments. Negative photoconductivity transistors (NPTs) mimic synaptic behavior by achieving adjustable positive photoconductivity (PPC) and negative photoconductivity (NPC), simulating "excitation" and "inhibition" akin to sensory cell signals. In complex interactive environments, NPTs are desired for visuomorphic computing that can achieve a better sense of information, lower power consumption, and reduce hardware complexity. In this review, it is started by introducing the development process of NPTs, while placing a strong emphasis on the device structures, working mechanisms, and key performance parameters. The common material systems employed in NPTs based on their functions are then summarized. Moreover, it is proceeded to summarize the noteworthy applications of NPTs in optoelectronic devices, including advanced multibit nonvolatile memory, optoelectronic logic gates, optical encryption, and visual perception. Finally, the challenges and prospects that lie ahead in the ongoing development of NPTs are addressed, offering valuable insights into their applications in optoelectronics and a comprehensive understanding of their significance.

Observation of 2†µm multiple annular structured vortex pulsed beams by cavity-mode tailoring.

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

Brain metastasis magnetic resonance imaging-based deep learning for predicting epidermal growth factor receptor (EGFR) mutation and subtypes in metastatic non-small cell lung cancer.

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

Targeting pericentric non-consecutive motifs for heterochromatin initiation.

Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1-3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Cobalt-Doped Bismuth Nanosheet Catalyst for Enhanced Electrochemical CO2 Reduction to Electrolyte-Free Formic Acid.

Electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) to valuable liquid fuels, such as formic acid/formate (HCOOH/HCOO-) is a promising strategy for carbon neutrality. Enhancing CO2RR activity while retaining high selectivity is critical for commercialization. To address this, we developed metal-doped bismuth (Bi) nanosheets via a facile hydrolysis method. These doped nanosheets efficiently generated high-purity HCOOH using a porous solid electrolyte (PSE) layer. Among the evaluated metal-doped Bi catalysts, Co-doped Bi demonstrated improved CO2RR performance compared to pristine Bi, achieving ~90 % HCOO- selectivity and boosted activity with a low overpotential of ~1.0 V at a current density of 200 mA cm-2. In a solid electrolyte reactor, Co-doped Bi maintained HCOOH Faradaic efficiency of ~72 % after a 100-hour operation under a current density of 100 mA cm-2, generating 0.1 M HCOOH at 3.2 V. Density functional theory (DFT) results revealed that Co-doped Bi required a lower applied potential for HCOOH generation from CO2, due to stronger binding energy to the key intermediates OCHO* compared to pure Bi. This study shows that metal doping in Bi nanosheets modifies the chemical composition, element distribution, and morphology, improving CO2RR catalytic activity performance by tuning surface adsorption affinity and reactivity.