State-level disparities in cervical cancer prevention and impact on outcomes in the U.S.: A modeling study.

Background: Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase HPV vaccination coverage, most model-based analyses have estimated vaccine impact on the US. We estimated the impact of hypothetical changes in HPV vaccination coverage at the state level for three states with varying levels of HPV vaccination coverage and cervical cancer incidence (California, New York, Texas) using a mathematical model. Methods: We developed a new mathematical model of HPV transmission and cervical cancer tailored to state-level cancer incidence and mortality. We quantified the public health impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 and the effect on time to elimination in the three states. Results: Increasing vaccination coverage to 80% in Texas in 10 years could reduce cervical cancer incidence by 50.9% (95%-CrI: 46.6-56.1%) by 2100. In New York and California, achieving the same coverage could reduce incidence by 27.3% (95%-CrI: 23.9-31.5%) and 24.4% (95%-CrI: 20.0-30.0%), respectively. Achieving 80% coverage in 5 years will slightly increase the reduction. If 2019 vaccination coverage continues, cervical cancer elimination would be reached in the US by 2051 (95%-Crl: 2034-2064). However, the timeline by which individual states reach elimination could vary by decades. Conclusion: Achieving an HPV vaccination coverage target of 80% by 2030 will benefit states with low vaccination coverage and high cervical cancer incidence the most. Our results highlight the value of more geographically focused analyses to inform priorities.

Enhanced NOx reduction on CePO4 catalysts: Cu-loading, phosphotungstic acid, and insights from In-situ DRIFTs and DFT.

This study investigates the effects of varying Cu/Ce doping ratios on the NH3-SCR denitrification efficiency using Cu-HPW/CePO4 catalysts, where CePO4 serves as the support and copper-doped phosphotungstic acid (HPW) acts as the active phase. The NH3-SCR reaction mechanism was studied by In-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (In-situ DRIFTs) and Density Functional Theory (DFT). In-situ DRIFTs were employed to delve into the intricacies of adsorption and transformation dynamics at the surface sites of catalysts. This approach furnished a robust theoretical foundation aimed at augmenting the efficacy of low-temperature denitrification catalysts. DFT calculations were used to systematically investigate the reaction pathways, intermediates, transition states, and energy barriers over the HPW structure model to complete the NH3-SCR reaction. Empirical evidence suggests that modifying the catalysts with copper substantially enhances their denitrification efficacy and extends their operational temperature spectrum. A notable initial increase in denitrification efficiency was observed with increasing levels of copper modification, followed by a decline. Within the HPW-O15H site, the NH3-SCR reaction advances through both the E-R and L-H mechanisms, encompassing processes such as NH3 adsorption, intermediate formation and transformation, and product release.

Eudragit S100 coated iron oxide-chitosan nanocomposites for colon targeting of 5-aminosalicylic acid ameliorate ulcerative colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome.

The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2. However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier. ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1ß. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.

Elevated level of multibranched complex glycan reveals an allergic tolerance status.

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying therapy that can achieve immune tolerance in patients through long-term allergen stimulation. Glycans play crucial roles in allergic disease, but no information on changes in glycosylation related to an allergic tolerance status has been reported. METHODS: Fifty-seven patients with house dust mite (HDM) allergies were enrolled. Twenty-eight patients were not treated with AIT, 19 patients had just entered the AIT maintenance treatment phase, and 10 patients had been in the AIT maintenance phase for more than 1 year. Serum protein N-glycans were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which included linkage-specific sialylation information. RESULTS: Eighty-four N-glycans were identified in all three groups. Compared with the patients treated without AIT, the patients treated with AIT for a shorter time showed downregulated expression of high-mannose glycans and upregulated expression of α2,6 sialic acid. The patients treated with AIT in the maintenance phase for over 1 year, which was considered the start of immunological tolerance, showed downregulated expression of biantennary N-glycans and upregulated expression of multibranched and complex N-glycans. Nine N-glycans were changed between allergic and allergic-tolerant patients. CONCLUSIONS: The glycan form changed from mannose to a more complex type as treatment time increased, and multibranched complex glycans have the potential to be used as a monitoring indicator of immune tolerance. This serum N-glycome analysis provided important information for a deeper understanding of AIT treatment at the molecular level.

Coordinated control for the auricle asymmetric development by ZmIDD14 and ZmIDD15 fine-tune the high-density planting adaption in maize.

Multiple distinct specialized regions shape the architecture of maize leaves. Among them, the fringe-like and wedge-shaped auricles alter the angle between the leaf and stalk, which is a key trait in crop plant architecture. As planting density increased, a small leaf angle (LA) was typically selected to promote crop light capture efficiency and yield. In the present study, we characterized two paralogous INDETERMINATE DOMAIN (IDD) genes, ZmIDD14 and ZmIDD15, which contain the Cys2-His2 zinc finger domain and function redundantly to regulate auricle development and LA in maize. Loss-of-function mutants showed decreased LA by reducing adaxial sclerenchyma thickness and increasing the colourless cell layers. In addition, the idd14;idd15 double mutant exhibited asymmetrically smaller auricles, which might cause by a failed maintenance of symmetric expression of the key auricle size controlling gene, LIGULELESS(LG1). The transcripts of ZmIDD14 and ZmIDD15 enriched in the ligular region, where LG1 was highly expressed, and both proteins physically interacted with ZmILI1 to promote LG1 transcription. Notably, the idd14;idd15 enhanced the grain yield of hybrids under high planting densities by shaping the plant architecture with a smaller LA. These findings demonstrate the functions of ZmIDD14 and ZmIDD15 in controlling the abaxial/adaxial development of sclerenchyma in the midrib and polar development along the medial-lateral axes of auricles and provide an available tool for high-density and high-yield breeding in maize.

Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability.

Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor ß (TGFß) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFß-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.

CBX4 plays a bidirectional role in transcriptional regulation and lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Understanding the dysregulated epigenetics governing LUAD progression is pivotal for identifying therapeutic targets. CBX4, a chromobox protein, is reported to be upregulated in LUAD. This study highlights the dual impact of CBX4 on LUAD proliferation and metastasis through a series of rigorous in vitro and in vivo experiments. Further investigation into the underlying mechanism through high-throughput ChIP-seq and RNA-seq reveals that CBX4 functions in promoting LUAD proliferation via upregulating PHGDH expression and subsequent serine biosynthesis, while concurrently suppressing LUAD metastasis by inhibiting ZEB2 transcription. CBX4 facilitates PHGDH transcription through the interaction with GCN5, inducing heightened histone acetylation on the PHGDH promoter. Simultaneously, the inhibition of ZEB2 transcription involves CBX4-mediated recruitment of canonical PRC1 (cPRC1), establishing H2K119ub on the ZEB2 promoter. These findings underscore CBX4's pivotal role as a regulator of LUAD progression, emphasizing its diverse transcriptional regulatory functions contingent upon interactions with specific epigenetic partners. Understanding the nuanced interplay between CBX4 and epigenetic factors sheds light on potential therapeutic avenues in LUAD.

Towards Superior Aqueous Zinc-Ion Batteries: The Insights of Artificial Protective Interfaces.

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper the commercialization of AZIBs. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guidance to further improve the electrochemical performance of AZIBs. The failure behaviors of the Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, which are classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

FGF13 deficiency ameliorates calcium signaling abnormality in heart failure by regulating microtubule stability.

Calcium signaling abnormality in cardiomyocytes, as a key mechanism, is closely associated with developing heart failure. Fibroblast growth factor 13 (FGF13) demonstrates important regulatory roles in the heart, but its association with cardiac calcium signaling in heart failure remains unknown. This study aimed to investigate the role and mechanism of FGF13 on calcium mishandling in heart failure. Mice underwent transaortic constriction to establish a heart failure model, which showed decreased ejection fraction, fractional shortening, and contractility. FGF13 deficiency alleviated cardiac dysfunction. Heart failure reduces calcium transients in cardiomyocytes, which were alleviated by FGF13 deficiency. Meanwhile, FGF13 deficiency restored decreased Cav1.2 and Serca2α expression and activity in heart failure. Furthermore, FGF13 interacted with microtubules in the heart, and FGF13 deficiency inhibited the increase of microtubule stability during heart failure. Finally, in isoproterenol-stimulated FGF13 knockdown neonatal rat ventricular myocytes (NRVMs), wildtype FGF13 overexpression, but not FGF13 mutant, which lost the binding site of microtubules, promoted calcium transient abnormality aggravation and Cav1.2 downregulation compared with FGF13 knockdown group. Generally, FGF13 deficiency improves abnormal calcium signaling by inhibiting the increased microtubule stability in heart failure, indicating the important role of FGF13 in cardiac calcium homeostasis and providing new avenues for heart failure prevention and treatment.

Tunneling Proton Grotthuss Transfer Channels by Hydrophilic-Zincophobic Heterointerface Shielding for High-Performance Zn-MnO2 Batteries.

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

Age-specific induction of mutant p53 drives clonal hematopoiesis and acute myeloid leukemia in adult mice.

The investigation of the mechanisms behind p53 mutations in acute myeloid leukemia (AML) has been limited by the lack of suitable mouse models, which historically have resulted in lymphoma rather than leukemia. This study introduces two new AML mouse models. One model induces mutant p53 and Mdm2 haploinsufficiency in early development, showing the role of Mdm2 in myeloid-biased hematopoiesis and AML predisposition, independent of p53. The second model mimics clonal hematopoiesis by inducing mutant p53 in adult hematopoietic stem cells, demonstrating that the timing of p53 mutation determines AML vs. lymphoma development. In this context, age-related changes in hematopoietic stem cells (HSCs) collaborate with mutant p53 to predispose toward myeloid transformation rather than lymphoma development. Our study unveils new insights into the cooperative impact of HSC age, Trp53 mutations, and Mdm2 haploinsufficiency on clonal hematopoiesis and the development of myeloid malignancies.

Response of phosphorus fractions transformation and microbial community to carbon-to-phosphorus ratios during sludge composting.

Phosphorus (P) is one of the essential nutrient elements for plant growth and development. Sludge compost products can be used as an important source of soil P to solve the shortage of soil P. The difference in the initial carbon-to-phosphorus ratio (C/P) will lead to difference in the bacterial community, which would affect the biological pathway of P conversion in composting. However, few studies have been reported on adjusting the initial C/P of composting to explore P conversion. Therefore, this study investigated the response of P component transformations, bacterial community and P availability to C/P during sludge composting by adjusting initial C/P. The results showed that increasing C/P promoted the mineralization of organic P and significantly increased the content of the labile P. High C/P also increased the relative content of available P, especially when the C/P was at 45 and 60, it reached 60.51% and 60.47%. High C/P caused differences in the community structure, and improved the binding ability of microbial network modules and the competitiveness of microbial communities. Additionally, high C/P strengthened the effect of microbial communities on the transformation of P components. Finally, the study showed that C/P was the main contributor to P content variation (64.7%) and indirectly affected P component conversion by affecting the microbial community. Therefore, adjusting the C/P is crucial to improve the P utilization rate of composting products.

Uniformly elevated future heat stress in China driven by spatially heterogeneous water vapor changes.

The wet bulb temperature (Tw) has gained considerable attention as a crucial indicator of heat-related health risks. Here we report south-to-north spatially heterogeneous trends of Tw in China over 1979-2018. We find that actual water vapor pressure (Ea) changes play a dominant role in determining the different trend of Tw in southern and northern China, which is attributed to the faster warming of high-latitude regions of East Asia as a response to climate change. This warming effect regulates large-scale atmospheric features and leads to extended impacts of the South Asia high (SAH) and the western Pacific subtropical high (WPSH) over southern China and to suppressed moisture transport. Attribution analysis using climate model simulations confirms these findings. We further find that the entire eastern China, that accommodates 94% of the country's population, is likely to experience widespread and uniform elevated thermal stress the end of this century. Our findings highlight the necessity for development of adaptation measures in eastern China to avoid adverse impacts of heat stress, suggesting similar implications for other regions as well.

Photooxidation-Initiated Aqueous-Phase Formation of Organic Peroxides: Delving into Formation Mechanisms.

Formation of highly oxygenated molecules (HOMs) such as organic peroxides (ROOR, ROOH, and H2O2) is known to degrade food and organic matter. Gas-phase unimolecular autoxidation and bimolecular RO2 + HO2/RO2 reactions are prominently renowned mechanisms associated with the formation of peroxides. However, the reaction pathways and conditions favoring the generation of peroxides in the aqueous phase need to be evaluated. Here, we identified bulk aqueous-phase ROOHs in varying organic precursors, including a laboratory model compound and monoterpene oxidation products. Our results show that formation of ROOHs is suppressed at enhanced oxidant concentrations but exhibits complex trends at elevated precursor concentrations. Furthermore, we observed an exponential increase in the yield of ROOHs when UV light with longer wavelengths was used in the experiment, comparing UVA, UVB, and UVC. Water-soluble organic compounds represent a significant fraction of ambient cloud-water components (up to 500 µM). Thus, the reaction pathways facilitating the formation of HOMs (i.e., ROOHs) during the aqueous-phase oxidation of water-soluble species add to the climate and health burden of atmospheric particulate matter.

Unveiling behaviors of 8:2 fluorotelomer sulfonic acid (8:2 FTSA) in Arabidopsis thaliana: Bioaccumulation, biotransformation and molecular mechanisms of phytotoxicity.

8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.

Synergistic use of photocatalysis and convergent paired electrolysis for nickel-catalyzed arylation of cyclic alcohols.

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions.

The roles and mechanisms of histone variant H2A.Z in transcriptional regulation.

H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.

Targeting FGFR1 by ß,ß-dimethylacrylalkannin suppresses the proliferation of colorectal cancer in cellular and xenograft models.

BACKGROUND: Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. PURPOSE: This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of ß,ß-dimethylacrylalkannin (ß,ß-DMAA) as a therapeutic option to inhibit FGFR1. METHODS: In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. RESULTS: In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that ß,ß-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that ß,ß-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, ß,ß-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with ß,ß-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, ß,ß-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

Field evidence of brown carbon absorption enhancement linked to organic nitrogen formation in Indo-Gangetic Plain.

Atmospheric brown carbon (BrC), a short-lived climate forcer, absorbs solar radiation and is a substantial contributor to the warming of the Earth's atmosphere. BrC composition, its absorption properties, and their evolution are poorly represented in climate models, especially during atmospheric aqueous events such as fog and clouds. These aqueous events, especially fog, are quite prevalent during wintertime in Indo-Gangetic Plain (IGP) and involve several stages (e.g., activation, formation, and dissipation, etc.), resulting in a large variation of relative humidity (RH) in the atmosphere. The huge RH variability allowed us to examine the evolution of water-soluble brown carbon (WS-BrC) diurnally and as a function of aerosol liquid water content (ALWC) and RH in this study. We explored links between the evolution of WS-BrC mass absorption efficiency at 365 nm (MAEWS-BrC-365) and chemical characteristics, viz., low-volatility organics and water-soluble organic nitrogen (WSON) to water-soluble organic carbon (WSOC) ratio (org-N/C), in the field (at Kanpur in central IGP) for the first time worldwide. We observed that WSON formation governed enhancement in MAEWS-BrC-365 diurnally (except during the afternoon) in the IGP. During the afternoon, the WS-BrC photochemical bleaching dwarfed the absorption enhancement caused by WSON formation. Further, both MAEWS-BrC-365 and org-N/C ratio increased with a decrease in ALWC and RH in this study, signifying that evaporation of fog droplets or bulk aerosol particles accelerated the formation of nitrogen-containing organic chromophores, resulting in the enhancement of WS-BrC absorptivity. The direct radiative forcing of WS-BrC relative to that of elemental carbon (EC) was ∼19 % during wintertime in Kanpur, and âˆ¼ 40 % of this contribution was in the UV-region. These findings highlight the importance of further examining the links between the evolution of BrC absorption behavior and chemical composition in the field and incorporating it in the BrC framework of climate models to constrain the predictions.