Novel anthropometric indices are superior adiposity indexes to portend visual impairment in middle-aged and older Chinese population.

OBJECTIVE: To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population. METHODS AND ANALYSIS: Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status. RESULTS: Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values <0.05). The multivariable-adjusted OR (95% CI) of VI associated with the highest (vs lowest) quintile of WWI was 1.900 (1.407 to 2.565). CONCLUSION: WWI is a reliable alternative adiposity index that exhibits a dose-response association with the prevalence of VI in the Chinese population. The WWI-VI correlation may eliminate the obesity paradox in the ophthalmic epidemiological area and indicate the detrimental impact of changes in body composition on VI.

Direct ink writing 3D printing of low-dimensional nanomaterials for micro-supercapacitors.

Micro-supercapacitors (MSCs) have attracted significant attention for potential applications in miniaturized electronics due to their high power density, rapid charge/discharge rates, and extended lifespan. Despite the unique properties of low-dimensional nanomaterials, which hold tremendous potential for revolutionary applications, effectively integrating these attributes into MSCs presents several challenges. 3D printing is rapidly emerging as a key player in the fabrication of advanced energy storage devices. Its ability to design, prototype, and produce functional devices incorporating low-dimensional nanomaterials positions it as an influential technology. In this review, we delve into recent advancements and innovations in micro-supercapacitor manufacturing, with a specific focus on the incorporation of low-dimensional nanomaterials using direct ink writing (DIW) 3D printing techniques. We highlight the distinct advantages offered by low-dimensional nanomaterials, from quantum effects in 0D nanoparticles that result in high capacitance values to rapid electron and ion transport in 1D nanowires, as well as the extensive surface area and mechanical flexibility of 2D nanosheets. Additionally, we address the challenges encountered during the fabrication process, such as material viscosity, printing resolution, and seamless integration of active materials with current collectors. This review highlights the remarkable progress in the energy storage sector, demonstrating how the synergistic use of low-dimensional nanomaterials and 3D printing technologies not only overcomes existing limitations but also opens new avenues for the development and production of advanced micro-supercapacitors. The convergence of low-dimensional nanomaterials and DIW 3D printing heralds the advent of the next generation of energy storage devices, making a significant contribution to the field and laying the groundwork for future innovations.

Structure optimization of Cmpd-15 as negative allosteric modulators for the ß2-adrenergic receptor.

19 derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides (H1-H19) and 5 derivatives of 1-benzyl-5-arylpyrazole-3-carboxamides (J1-J5) have been designed and synthesized as potential negative allosteric modulators (NAMs) for the ß2-adrenergic receptor (ß2AR). The new pyrazole derivatives were screened on the classic G-protein dependent signaling pathway at ß2AR. The majority of 1-benzyl-3-aryl-pyrazole-5-carboxamide derivatives show more potent allosteric antagonistic activity against ß2AR than Cmpd-15, the first reported ß2AR NAM. However, the 1-benzyl-5-arylpyrazole-3-carboxamide derivatives exhibit very poor or even no allosteric antagonistic activity for ß2AR. Furthermore, the active pyrazole derivatives have relative better drug-like profiles than Cmpd-15. Taken together, we discovered a series of derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides as a novel scaffold of ß2AR NAM.

Multi-omics analysis of nitrifying sludge under carbon disulfide stress: Nitrification performance and molecular mechanisms.

Carbon disulfide (CS2) is a widely used enzyme inhibitor with cytotoxic properties, commonly employed in viscose fibers and cellophane production due to its non-polar characteristics. In industry, CS2 is often removed by aeration, however, residual CS2 may enter the wastewater treatment plants, impacting the performance of nitrifying sludge. Currently, there is a notable dearth of research on the response of nitrifying sludge to CS2-induced stress. This study delves into the alterations in the performance of nitrifying sludge under short-term and long-term CS2 stress, scrutinizes the toxic effects of CS2 on microbial cells, elucidates the succession of microbial community structure, and delineates changes in microbial metabolic products. The findings from short-term CS2 stress revealed that low concentrations of CS2 induced oxidative stress damage, which was subsequently repaired in cells. However, at concentrations of 100-200 mg/L, CS2 inhibited reactive oxygen species, superoxide dismutase, and catalase, which are associated with metabolic and antioxidant activities. The inhibition of nitrite oxidoreductase activity by high concentrations of CS2 was attributed to its impact on the enzyme's conformation. Prolonged CS2 stress resulted in an increase in the secretion of soluble extracellular polymeric substances in sludge, while CS2 was assimilated into sulfate. The analysis of sludge microbial community structure revealed a decline in the relative abundance of Rhodanobacter, which is associated with nitrification, and an increase in Sinomonas, involved in sulfur oxidation. Metabolite analysis results demonstrated that high concentrations of CS2 affect pantothenate and CoA biosynthesis, purine metabolism, and glutathione metabolism. This study elucidated the microbial response mechanism of nitrifying sludge under short-term and long-term CS2 stress. It also clarified the composition and function of microbial ecosystems, and identified key bacterial species and metabolites. It provides a basis for future research to reduce CS2 inhibition through approaches such as the addition of metal ions, the selection of efficient CS2-degrading strains, and the modification of strain metabolic pathways.

Light-Driven Access to Selenium-Substituted Thiazole-2-imine Derivatives.

The thiazole-2-imine derivatives with interesting pharmacological activities have attracted significant attention. However, previously reported synthesis strategies usually suffered from some drawbacks, such as the use of metals/additive and harsh reaction conditions. Herein, we developed a metal- and photoinitiator-free photocatalytic strategy for the synthesis of various selenium-substituted thiazole-2-imine derivatives for the first time. The reaction displayed mild reaction conditions, simple operation, a broad substrate scope (37 examples), and good to excellent yields.

Monomeric Far-red and Near-infrared Fluorescent Biliproteins of Ultrahigh Brightness.

Far-red and near-infrared fluorescent proteins have regions of maximum transmission in most tissues and can be widely used as fluorescent biomarkers. We report that fluorescent phycobiliproteins originating from the phycobilisome core subunit ApcF2 can covalently bind biliverdin, named BDFPs. To further improve BDFPs, we conducted a series of studies. Firstly, we mutated K53Q and T144A of BDFPs to increase their effective brightness up to 190 % in vivo. Secondly, by homochromatic tandem fusion of high-brightness BDFPs to achieve monomerization, which increases the effective brightness by up to 180 % in vivo, and can effectively improve the labeling effect. By combining the above two approaches, the brightness of the tandem BDFPs was much improved compared with that of the previously reported fluorescent proteins in a similar spectral range. The tandem BDFPs were expressed stably while maintaining fluorescence in mammalian cells and Caenorhabditis elegans. They were also photostable and resistant to high temperature, low pH, and chemical denaturation. The tandem BDFPs advantages were proved in applications as biomarkers for imaging in super-resolution microscopy.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

Visible-Light-Promoted Cascade Coupling of 2-Isocyanonaphthalenes with Elemental Sulfur and Amines to Construct Naphtho[2,1-d]thiazol-2-Amines.

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation.

Chromosome-level reference genome and resequencing of 322 accessions reveal evolution, genomic imprint and key agronomic traits in adzuki bean.

Adzuki bean (Vigna angularis) is an important legume crop cultivated in over 30 countries worldwide. We developed a high-quality chromosome-level reference genome of adzuki bean cultivar Jingnong6 by combining PacBio Sequel long-read sequencing with short-read and Hi-C technologies. The assembled genome covers 97.8% of the adzuki bean genome with a contig N50 of approximately 16 Mb and a total of 32 738 protein-coding genes. We also generated a comprehensive genome variation map of adzuki bean by whole-genome resequencing (WGRS) of 322 diverse adzuki beans accessions including both wild and cultivated. Furthermore, we have conducted comparative genomics and a genome-wide association study (GWAS) on key agricultural traits to investigate the evolution and domestication. GWAS identified several candidate genes, including VaCycA3;1, VaHB15, VaANR1 and VaBm, that exhibited significant associations with domestication traits. Furthermore, we conducted functional analyses on the roles of VaANR1 and VaBm in regulating seed coat colour. We provided evidence for the highest genetic diversity of wild adzuki (Vigna angularis var. nipponensis) in China with the presence of the most original wild adzuki bean, and the occurrence of domestication process facilitating transition from wild to cultigen. The present study elucidates the genetic basis of adzuki bean domestication traits and provides crucial genomic resources to support future breeding efforts in adzuki bean.

Electroactive properties of EABs in response to long-term exposure to polystyrene microplastics/nanoplastics and the underlying adaptive mechanisms.

Given widespread presence of polystyrene (PS) microplastics/nanoplastics (MPs/NPs), the electroactive responses and adaptation mechanisms of electroactive biofilms (EABs) exposed long-term to PS-containing aquatic environments remain unclear. Therefore, this study investigated the impacts of PS MPs/NPs on electroactivity of EABs. Results found that EABs exhibited delayed formation upon initially exposure but displayed an increased maximum current density (Imax) after subsequent exposure for up to 55 days. Notably, EABs exposure to NH2PS NPs (EAB-NH2PSNPs) demonstrated a 50% higher Imax than the control, along with a 17.84% increase in viability and a 58.10% increase in biomass. The cytochrome c (c-Cyts) content in EAB-NH2PSNPs rose by 178.35%, benefiting the extracellular electron transfer (EET) of EABs. Moreover, bacterial community assembly indicated the relative abundance of electroactive bacteria increased to 87.56% in EAB-NH2PSNPs. The adaptability mechanisms of EABs under prolonged exposure to PS MPs/NPs predominantly operate by adjusting viability, EET, and bacterial community assembly, which were further confirmed a positive correlation with Imax through structural equation model. These findings provide deeper insights into long-term effects and mechanisms of MPs/NPs on the electroactive properties of EABs and even functional microorganisms in aquatic ecosystems.

Interactive Association Between Gut Microbiota and Thyroid Cancer.

CONTEXT: The association between the gut microbiota and thyroid cancer remains controversial. OBJECTIVE: We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer. METHODS: We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings. RESULTS: Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR. DISCUSSIONS: These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.

Roles of gut microbiota in atrial fibrillation: insights from Mendelian randomization analysis and genetic data from over 430,000 cohort study participants.

BACKGROUND: Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood. OBJECTIVES: To explore the causal relationships between the gut microbiota and AF using Mendelian randomization (MR) analysis. METHODS: Summary statistics were from genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) (the Dutch Microbiome Project) and two large meta-GWASs of AF. The significant results were validated in FinnGen cohort and over 430,000 UK Biobank participants. Mediation MR analyses were conducted for AF risk factors, including type 2 diabetes, coronary artery disease (CAD), body mass index (BMI), blood lipids, blood pressure, and obstructive sleep apnea, to explore the potential mediation effect of these risk factors in between the gut microbiota and AF. RESULTS: Two microbial taxa causally associated with AF: species Eubacterium ramulus (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12, P = 0.0001, false discovery rate (FDR) adjusted p-value = 0.023) and genus Holdemania (OR 1.15, 95% CI 1.07-1.25, P = 0.0004, FDR adjusted p-value = 0.042). Genus Holdemania was associated with incident AF risk in the UK Biobank. The proportion of mediation effect of species Eubacterium ramulus via CAD was 8.05% (95% CI 1.73% - 14.95%, P = 0.008), while the proportion of genus Holdemania on AF via BMI was 12.01% (95% CI 5.17% - 19.39%, P = 0.0005). CONCLUSIONS: This study provided genetic evidence to support a potential causal mechanism between gut microbiota and AF and suggested the mediation role of AF risk factors.

Effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems with two filling modes: Performance and toxic response mechanism.

To investigate the effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems, two individual reactors with the layered filling (L-SCPAD) and mixed filling (M-SCPAD) systems were established via sulfur and calcined pyrite. Effluent NO3--N concentration of the L-SCPAD and M-SCPAD systems was first increased to 6.44, 0.93 mg/L under 0.5 mg/L IBU exposure and gradually decreased to 1.66 mg/L, 0 mg/L under 4.0 mg/L IBU exposure, indicating that NO3--N removal performance of the M-SCPAD system was better than that of the L-SCPAD system. The variation of extracellular polymeric substances (EPS) characteristics demonstrated that more EPS was secreted in the M-SCPAD system compared to the L-SCPAD system, which contributed to forming a more stable biofilm structure and protecting microorganisms against the toxicity of IBU in the M-SCPAD system. Moreover, the increased electron transfer impedance and decreased cytochrome c implied that IBU inhibited the electron transfer efficiency of the L-SCPAD and M-SCPAD systems. The decreased adenosine triphosphate (ATP) and electron transfer system activity (ETSA) content showed that IBU inhibited metabolic activity, but the M-SCPAD system exhibited higher metabolic activity compared to the L-SCPAD system. In addition, the analysis of the bacterial community indicated a more stable abundance of nitrogen removal function bacteria (Bacillus) in the M-SCPAD system compared to the L-SCPAD system, which was conducive to maintaining a stable denitrification performance. The toxic response mechanism based on the biogeobattery effect was proposed in the SCPAD systems under IBU exposure. This study provided an important reference for the long-term toxic effect of IBU on the SCPAD systems.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study.

BACKGROUND AND PURPOSE: We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). METHODS: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. RESULTS: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. CONCLUSION: The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Multifaceted synergistic facilitation mechanism of conductive polymers in promoting selenite bioreduction and biological detoxification.

Here, polypyrrole (PPY) was first used to the bioreduction of toxic selenite, while the acceleration effect and mechanism were explored. Experiment results suggested that PPY could enhance the selenite bioreduction from 0.42 to 1.04 mg/(L·h). The tests of electrochemical analysis and cytochrome c (cyt-c) content confirmed that PPY promoted the intracellular/intracellular electron transfer of Shewanella oneidensis·MR-1 in selenite bioreduction process. The enhancement of metabolic activity by PPY contributed to biological detoxification, which was manifested in the increased extracellular polymeric substances (EPS), adenosine triphosphate (ATP), electron transfer system activity (ETSA), membrane permeability and enzyme activity. Transcriptome analysis of DEGs, KEGG pathway enrichment and GO functional classification verified that the environmental adaptability of Shewanella oneidensis·MR-1 was enhanced with the addition of PPY. The transmission electron microscopy (TEM) images indicated that PPY promoted the biosynthesis of selenium nanoparticles (SeNPs), which was beneficial to reduce cell damage. Combined with the above results, a multifaceted synergistic facilitation mechanism based on "conductive cross-linking network" was elaborated from electron transfer, microbial metabolism and environmental adaptability. This study shed light the effect of conductive polymers (CPs) on selenite bioreduction and provided new insights into the bioremediation of toxic pollutants.

A novel sulfur autotrophic denitrification in-situ coupled sequencing batch reactor system to treat low carbon to nitrogen ratio municipal wastewater: Performance, niche equilibrium and pollutant removal mechanisms.

A novel integrated sulfur fixed-film activated sludge in SBR system (IS0FAS-SBR) was proposed to treat the low C/N ratio municipal wastewater. The effluent total inorganic nitrogen (TIN) and PO43--P decreased from 17 mg/L and 3.5 mg/L to 8.5 mg/L and 0.5 mg/L, and higher nitrogen removal efficiency was contributed by the autotrophic denitrification. Microbial response characteristics showed that catalase (CAT), reduced nicotinamide adenine dinucleotide (NADH) and extracellular polymeric substance (EPS) alleviated the oxidative stress of sulfur carrier to maintain cell activity, while metabolic activity analysis indicated that the electron transfer rate was enhanced to improve mixotrophic denitrification efficiency. Meanwhile, the increased key enzyme activities further facilitated nitrogen removal and sulfur oxidation process. Additionally, the microbial community, functional proteins and genes revealed a niche equilibrium of C, N, S metabolic bacteria. Sulfur autotrophic in-situ coupled SBR system enlarged a promising strategy for treatment of low C/N ratio municipal wastewater.

Mechanistic insights into the response of electroactive biofilms to Cd2+ shock: bacterial viability and electron transfer behavior at the cellular and community levels.

Electroactive biofilms (EABs) play a crucial role in environmental bioremediation due to their excellent extracellular electron transfer (EET) capabilities. However, Cd2+ can have toxic effects on the electrochemical performance of EABs, and the comprehensive inhibition mechanism of EABs in response to Cd2+ shock remains elusive. This study indicated that Cd2+ shock significantly reduced biomass and increased oxidative stress in EABs at the cellular level. The bacterial viability of EABs in phase III under 0.5 mM Cd2+ shock (EABCd2+-III0.5) decreased by 16.31% compared to EABCK-III. Moreover, intracellular NADH, c-Cyts, and the abundance of electroactive species were essential indicators to evaluate EET behavior of EABs. In EABCd2+-III0.5, these indicators decreased by 26.32%, 33.40%, and 20.65%, respectively. Structural equation modeling analysis established quantitative correlations between core components and electrochemical activity at cellular and community levels. The correlation analysis revealed that the growth and electron transfer functions of EABs were predictive indicators for their electrochemical performance, with standardized path coefficients of 0.407 and 0.358, respectively. These findings enhance our understanding of EABs' response to Cd2+ shock and provide insights for improving their performance in heavy metal wastewater.

Whole Blood-based Transcriptional Risk Score for Nonobese Type 2 Diabetes Predicts Dynamic Changes in Glucose Metabolism.

CONTEXT: The performance of peripheral blood transcriptional markers in evaluating risk of type 2 diabetes (T2D) with normal body mass index (BMI) is unknown. OBJECTIVE: We developed a whole blood-based transcriptional risk score (wb-TRS) for nonobese T2D and assessed its contributions on disease risk and dynamic changes in glucose metabolism. METHODS: Using a community-based cohort with blood transcriptome data, we developed the wb-TRS in 1105 participants aged ≥40 years who maintained a normal BMI for up to 10 years, and we validated the wb-TRS in an external dataset. Potential biological significance was explored. RESULTS: The wb-TRS included 144 gene transcripts. Compared to the lowest tertile, wb-TRS in tertile 3 was associated with 8.91-fold (95% CI, 3.53-22.5) higher risk and each 1-unit increment was associated with 2.63-fold (95% CI, 1.87-3.68) higher risk of nonobese T2D. Furthermore, baseline wb-TRS significantly associated with dynamic changes in average, daytime, nighttime, and 24-hour glucose, HbA1c values, and area under the curve of glucose measured by continuous glucose monitoring over 6 months of intervention. The wb-TRS improved the prediction performance for nonobese T2D, combined with fasting glucose, triglycerides, and demographic and anthropometric parameters. Multi-contrast gene set enrichment (Mitch) analysis implicated oxidative phosphorylation, mTORC1 signaling, and cholesterol metabolism involved in nonobese T2D pathogenesis. CONCLUSION: A whole blood-based nonobese T2D-associated transcriptional risk score was validated to predict dynamic changes in glucose metabolism. These findings suggested several biological pathways involved in the pathogenesis of nonobese T2D.

Effect of ibuprofen on the sulfur autotrophic denitrification process and microbial toxic response mechanism.

The effect of ibuprofen (IBU) on the sulfur autotrophic denitrification (SAD) process and microbial toxic response mechanism were investigated. Nitrate removal performance was inhibited by high IBU concentrations (10 and 50 mg/L), and the effect of low IBU concentrations (1 mg/L) on nitrate removal performance was negligible. The low IBU concentration induced basal oxidative stress for microbial self-protection, while the high IBU concentration induced high-intensity oxidative stress to damage the microbial cell membrane structure. Electrochemical characterization showed that the low IBU concentration stimulated the electron transfer efficiency, which was inhibited at the high IBU concentration. Moreover, the variation content of nicotinamide adenine dinucleotide (NADH) and nitrate reductase showed that metabolic activity increased at low IBU concentrations and decreased at high IBU concentrations during the sulfur autotrophic nitrate reduction process. This study proposed the hormesis toxic response mechanism of the SAD process to IBU exposure.

Causal relationships between the gut microbiome, blood lipids, and heart failure: a Mendelian randomization analysis.

AIMS: Studies have linked gut microbiome and heart failure (HF). However, their causal relationships and potential mediating factors have not been well defined. To investigate the causal relationships between the gut microbiome and HF and the mediating effect of potential blood lipids by using genetics. METHODS AND RESULTS: We performed a bidirectional and mediation Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7738), blood lipids (UK Biobank, n = 115 078), and a meta-analysis of HF (115 150 cases and 1550 331 controls). We applied the inverse-variance weighted estimation method as the primary method, with several other estimators as complementary methods. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal lipids. Six microbial taxa are suggestively associated with HF causally. The most significant taxon was the species Bacteroides dorei [odds ratio = 1.059, 95% confidence interval (CI) = 1.022-1.097, P-value = 0.0017]. The MR-BMA analysis showed that apolipoprotein B (ApoB) was the most likely causal lipid for HF (the marginal inclusion probability = 0.717, P-value = 0.005). The mediation MR analysis showed that ApoB mediated the causal effects of species B. dorei on HF (proportion mediated = 10.1%, 95% CI = 0.2-21.6%, P-value = 0.031). CONCLUSION: The study suggested a causal relationship between specific gut microbial taxa and HF and that ApoB might mediate this relationship as the primary lipid determinant of HF.

We conducted a Mendelian randomization analysis to examine the causal relationships between the gut microbiome and heart failure and the mediating role of blood lipids. • Six gut microbial taxa were identified as having potentially causal effects on heart failure, with Bacteroides dorei being the most significant one. • Apolipoprotein B was found to be the primary lipid determinant of heart failure among five common lipids and mediated 10.1% of the causal effect of B. dorei on heart failure.