Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses.

Fungal infection stimulates the canonical C-type lectin receptor (CLR) signaling pathway via activation of the tyrosine kinase Syk. Here we identify a crucial role for the tyrosine phosphatase SHP-2 in mediating CLR-induced activation of Syk. Ablation of the gene encoding SHP-2 (Ptpn11; called 'Shp-2' here) in dendritic cells (DCs) and macrophages impaired Syk-mediated signaling and abrogated the expression of genes encoding pro-inflammatory molecules following fungal stimulation. Mechanistically, SHP-2 operated as a scaffold, facilitating the recruitment of Syk to the CLR dectin-1 or the adaptor FcRγ, through its N-SH2 domain and a previously unrecognized carboxy-terminal immunoreceptor tyrosine-based activation motif (ITAM). We found that DC-derived SHP-2 was crucial for the induction of interleukin 1ß (IL-1ß), IL-6 and IL-23 and anti-fungal responses of the TH17 subset of helper T cells in controlling infection with Candida albicans. Together our data reveal a mechanism by which SHP-2 mediates the activation of Syk in response to fungal infection.

TMED10 mediates the trafficking of insulin-like growth factor 2 along the secretory pathway for myoblast differentiation.

The insulin-like growth factor 2 (IGF2) plays critical roles in cell proliferation, migration, differentiation, and survival. Despite its importance, the molecular mechanisms mediating the trafficking of IGF2 along the secretory pathway remain unclear. Here, we utilized a Retention Using Selective Hook system to analyze molecular mechanisms that regulate the secretion of IGF2. We found that a type I transmembrane protein, TMED10, is essential for the secretion of IGF2 and for differentiation of mouse myoblast C2C12 cells. Further analyses indicate that the residues 112-140 in IGF2 are important for the secretion of IGF2 and these residues directly interact with the GOLD domain of TMED10. We then reconstituted the release of IGF2 into COPII vesicles. This assay suggests that TMED10 mediates the packaging of IGF2 into COPII vesicles to be efficiently delivered to the Golgi. Moreover, TMED10 also mediates ER export of TGN-localized cargo receptor, sortilin, which subsequently mediates TGN export of IGF2. These analyses indicate that TMED10 is critical for IGF2 secretion by directly regulating ER export and indirectly regulating TGN export of IGF2, providing insights into trafficking of IGF2 for myoblast differentiation.

Efficient Acidic Photoelectrochemical Water Splitting Enabled by Ru Single Atoms Anchored on Hematite Photoanodes.

Photoelectrochemical (PEC) water splitting in acidic media holds promise as an efficient approach to renewable hydrogen production. However, the development of highly active and stable photoanodes under acidic conditions remains a significant challenge. Herein, we demonstrate the remarkable water oxidation performance of Ru single atom decorated hematite (Fe2O3) photoanodes, resulting in a high photocurrent of 1.42 mA cm-2 at 1.23 VRHE under acidic conditions. Comprehensive experimental and theoretical investigations shed light on the mechanisms underlying the superior activity of the Ru-decorated photoanode. The presence of single Ru atoms enhances the separation and transfer of photogenerated carriers, facilitating efficient water oxidation kinetics on the Fe2O3 surface. This is achieved by creating additional energy levels within the Fe2O3 bandgap and optimizing the free adsorption energy of intermediates. These modifications effectively lower the energy barrier of the rate-determining step for water splitting, thereby promoting efficient PEC hydrogen production.

Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.

AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.

Dynamic expression analysis of peripheral blood derived small extracellular vesicle miRNAs in sepsis progression.

Immune disorders caused by sepsis have recently drawn much attention. We sought to dynamically monitor the expression of small extracellular vesicle (sEV) miRNAs in peripheral blood during sepsis to explore these miRNAs as potential biomarkers for monitoring immune function in sepsis patients. This study included patients with sepsis. Blood samples were obtained from 10 patients on the first through 10th days, the 12th day and the 14th day since sepsis onset, resulting in 120 collected samples. Serum sEVs were extracted from peripheral venous blood, and levels of MIR497HG, miR-195, miR-497, and PD-L1 in serum sEVs were detected by qPCR, and clinical information was recorded. Our study revealed that the levels of MIR497HG, miR-195, miR-497 and PD-L1 in serum sEVs showed periodic changes; the time from peak to trough was approximately 4-5 days. The levels of sEV MIR497HG and miR-195 had a positive linear relationship with SOFA score (r values were -0.181 and -0.189; p values were 0.048 and 0.039, respectively). The recorded quantities of sEV MIR497HG, miR-195 and PD-L1 showed a substantial correlation with ARDS. ROC curve analysis revealed that sEV MIR497HG, miR-195 and miR-497 could predict the 28-day mortality of sepsis patients with an AUC of 0.66, 0.68 and 0.72, respectively. Levels of sEVs MIR497HG, miR-195, miR-497 and PD-L1 showed periodic changes with the immune status of sepsis, which provides a new exploration direction for immune function biomarkers and immunotherapy timing in sepsis patients.

Enantioselective Cyanofunctionalization of Aromatic Alkenes via Radical Anions.

Alkene radical ions constitute an integral and unique class of reactive intermediates for the synthesis of valuable compounds because they have both unpaired spins and charge. However, relatively few synthetic applications of alkene radical anions have emerged due to a dearth of generally applicable and mild radical anion generation approaches. Precise control over the chemo- and stereoselectivity in alkene radical anion-mediated processes represents another long-standing challenge due to their high reactivity. To overcome these issues, here, we develop a new redox-neutral strategy that seamlessly merges photoredox and copper catalysis to enable the controlled generation of alkene radical anions and their orthogonal enantioselective cyanofunctionalization via distonic-like species. This new strategy enables highly regio-, chemo-, and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation of alkenes without stoichiometric reductants or oxidants under visible light irradiation. This protocol provides a new blueprint for the exploration of the transformation potential of alkene radical anions.

Ir Single Atoms Boost Metal-Oxygen Covalency on Selenide-Derived NiOOH for Direct Intramolecular Oxygen Coupling.

This investigation probes the intricate interplay of catalyst dynamics and reaction pathways during the oxygen evolution reaction (OER), highlighting the significance of atomic-level and local ligand structure insights in crafting highly active electrocatalysts. Leveraging a tailored ion exchange reaction followed by electrochemical dynamic reconstruction, we engineered a novel catalytic structure featuring single Ir atoms anchored to NiOOH (Ir1@NiOOH). This novel approach involved the strategic replacement of Fe with Ir, facilitating the transition of selenide precatalysts into active (oxy)hydroxides. This elemental substitution promoted an upward shift in the O 2p band and intensified the metal-oxygen covalency, thereby altering the OER mechanism toward enhanced activity. The shift from a single-metal site mechanism (SMSM) in NiOOH to a dual-metal-site mechanism (DMSM) in Ir1@NiOOH was substantiated by in situ differential electrochemical mass spectrometry (DEMS) and supported by theoretical insights. Remarkably, the Ir1@NiOOH electrode exhibited exceptional electrocatalytic performance, achieving overpotentials as low as 142 and 308 mV at current densities of 10 and 1000 mA cm-2, respectively, setting a new benchmark for the electrocatalysis of OER.

Tolerance enhancement of Dendrobium officinale by salicylic acid family-related metabolic pathways under unfavorable temperature.

BACKGROUND: Unfavorable temperatures significantly constrain the quality formation of Dendrobium officinale, severely limiting its food demand. Salicylic acid (SA) enhances the resistance of D. officinale to stress and possesses various analogs. The impact and mechanism of the SA family on improving the quality of D. officinale under adverse temperature conditions remains unclear. RESULTS: Combined with molecular docking analysis, chlorophyll fluorescence and metabolic analysis after treatments with SA analogues or extreme temperatures are performed in this study. The results demonstrate that both heat and cold treatments impede several main parameters of chlorophyll fluorescence of D. officinale, including the ΦPSII parameter, a sensitive growth indicator. However, this inhibition is mitigated by SA or its chemically similar compounds. Comprehensive branch imaging of ΦPSII values revealed position-dependent improvement of tolerance. Molecular docking analysis using a crystal structure model of NPR4 protein reveals that the therapeutic effects of SA analogs are determined by their binding energy and the contact of certain residues. Metabolome analysis identifies 17 compounds are considered participating in the temperature-related SA signaling pathway. Moreover, several natural SA analogs such as 2-hydroxycinnamic acid, benzamide, 2-(formylamino) benzoic acid and 3-o-methylgallic acid, are further found to have high binding ability to NPR4 protein and probably enhance the tolerance of D. officinale against unfavorable temperatures through flavone and guanosine monophosphate degradation pathways. CONCLUSIONS: These results reveal that the SA family with a high binding capability of NPR4 could improve the tolerance of D. officinale upon extreme temperature challenges. This study also highlights the collaborative role of SA-related natural compounds present in D. officinale in the mechanism of temperature resistance and offers a potential way to develop protective agents for the cultivation of D. officinale.

Comprehensive genome-wide analysis of wheat xylanase inhibitor protein (XIP) genes: unveiling their role in Fusarium head blight resistance and plant immune mechanisms.

In this comprehensive genome-wide study, we identified and classified 83 Xylanase Inhibitor Protein (XIP) genes in wheat, grouped into five distinct categories, to enhance understanding of wheat's resistance to Fusarium head blight (FHB), a significant fungal threat to global wheat production. Our analysis reveals the unique distribution of XIP genes across wheat chromosomes, particularly at terminal regions, suggesting their role in the evolutionary expansion of the gene family. Several XIP genes lack signal peptides, indicating potential alternative secretion pathways that could be pivotal in plant defense against FHB. The study also uncovers the sequence homology between XIPs and chitinases, hinting at a functional diversification within the XIP gene family. Additionally, the research explores the association of XIP genes with plant immune mechanisms, particularly their linkage with plant hormone signaling pathways like abscisic acid and jasmonic acid. XIP-7A3, in particular, demonstrates a significant increase in expression upon FHB infection, highlighting its potential as a key candidate gene for enhancing wheat's resistance to this disease. This research not only enriches our understanding of the XIP gene family in wheat but also provides a foundation for future investigations into their role in developing FHB-resistant wheat cultivars. The findings offer significant implications for wheat genomics and breeding, contributing to the development of more resilient crops against fungal diseases.

Micropattern Fabricated by Acropetal Migration Controlled through Sequential Photo and Thermal Polymerization.

Bottom-up patterning technology plays a significant role in both nature and synthetic materials, owing to its inherent advantages such as ease of implementation, spontaneity, and noncontact attributes, etc. However, constrained by the uncontrollability of molecular movement, energy interaction, and stress, obtained micropatterns tend to exhibit an inevitable arched outline, resulting in the limitation of applicability. Herein, inspired by auxin's action mode in apical dominance, a versatile strategy is proposed for fabricating precision self-organizing micropatterns with impressive height based on polymerization-induced acropetal migration. The copolymer containing fluorocarbon chains (low surface energy) and tertiary amine (coinitiator) is designed to self-assemble on the surface of the photo-curing system. The selective exposure under a photomask establishes a photocuring boundary and the radicals would be generated on the surface, which is pivotal in generating a vertical concentration difference of monomer. Subsequent heating treatment activates the material continuously transfers from the unexposed area to the exposed area and is accompanied by the obviously vertical upward mass transfer, resulting in the manufacture of a rectilinear profile micropattern. This strategy significantly broadens the applicability of self-organizing patterns, offering the potential to mitigate the complexity and time-consuming limitations associated with top-down methods.

Engineering Assembly of Plasmonic Virus-Like Gold SERS Nanoprobe Guided by Intelligent Dual-Machine Nanodevice for High-Performance Analysis of Tetracycline.

Accurate detection of trace tetracyclines (TCs) in complex matrices is of great significance for food and environmental safety monitoring. However, traditional recognition and amplification tools exhibit poor specificity and sensitivity. Herein, a novel dual-machine linkage nanodevice (DMLD) is proposed for the first time to achieve high-performance analysis of TC, with a padlock aptamer component as the initiation command center, nucleic acid-encoded multispike virus-like Au nanoparticles (nMVANs) as the signal indicator, and cascade walkers circuit as the processor. The existence of spike vertices and interspike nanogaps in MVANs enables intense electromagnetic near-field focusing, allowing distinct surface-enhanced Raman scattering (SERS) activity. Moreover, through the sequential activation between multistage walker catalytic circuits, the DLMD system converts the limited TC recognition into massive engineering assemblies of SERS probes guided by DNA amplicons, resulting in synergistic enhancement of bulk plasmonic hotspot entities. The continuously guaranteed target recognition and progressively promoted signal enhancement ensure highly specific amplification analysis of TC, with a detection limit as low as 7.94 × 10-16 g mL-1. Furthermore, the reliable recoveries in real samples confirm the practicability of the proposed sensing platform, highlighting the enormous potential of intelligent nanomachines for analyzing the trace hazards in the environment and food.

Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study.

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.

Protein aggregation in plant mitochondria lacking Lon1 inhibits translation and induces unfolded protein responses.

Loss of Lon1 led to stunted plant growth and accumulation of nuclear-encoded mitochondrial proteins including Lon1 substrates. However, an in-depth label-free proteomics quantification of mitochondrial proteins in lon1 revealed that the majority of mitochondrial-encoded proteins decreased in abundance. Additionally, we found that lon1 mutants contained protein aggregates in the mitochondrial that were enriched in metabolic enzymes, ribosomal subunits and PPR-containing proteins of the translation apparatus. These mutants exhibited reduced general mitochondrial translation as well as deficiencies in RNA splicing and editing. These findings support the role of Lon1 in maintaining a functional translational apparatus for mitochondrial-encoded gene translation. Transcriptome analysis of lon1 revealed a mitochondrial unfolded protein response reminiscent of the mitochondrial retrograde signalling dependent on the transcription factor ANAC017. Notably, lon1 mutants exhibited transiently elevated ethylene production, and the shortened hypocotyl observed in lon1 mutants during skotomorphogenesis was partially alleviated by ethylene inhibitors. Furthermore, the short root phenotype was partially ameliorated by introducing a mutation in the ethylene receptor ETR1. Interestingly, the upregulation of only a select few target genes was linked to ETR1-mediated ethylene signalling. Together this provides multiple steps in the link between loss of Lon1 and signalling responses to restore mitochondrial protein homoeostasis in plants.

Modulating secondary growth of perovskite grains through residual solvent evaporation.

Over the past decade, perovskite solar cells (PSCs) have attracted enormous attention due to their high performance. One key to fabricating high-quality perovskite films lies in controlling the volatilization rate of residual solvents during the annealing process. This study systematically investigates how different protective substrates affect the volatilization rate of residual solvent in perovskite films. By adjusting the direction and rate of evaporation, the supersaturation time of the solution was precisely controlled, leading to effective recrystallization of the grains. Concurrently, the annealing time was optimized to enhance film quality further. This optimization aimed to increase crystallinity, reduce defects, and thereby minimize non-radiative recombination centers. Implementing these methodologies, particularly the use of filter paper as a protective substrate during a 2-minute annealing process, significantly improved the fill factor (FF) and open-circuit voltage (VOC) of the PSCs. This led to a remarkable 5.26% improvement in power conversion efficiency (PCE) compared to control devices. The strategies employed in this work demonstrate significant potential in improving PSC film quality. This approach not only advances our understanding of film formation dynamics but also provides a practical guideline for future PSC fabrication.

Local Excitation of Kagome Spin Ice Magnetism Seen by Scanning Tunneling Microscopy.

The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.

Programming cell-surface signaling by phase-separation-controlled compartmentalization.

The landscape of cell-surface signaling is formidably complex. Robust tools capable of manipulating the spatiotemporal distribution of cell-surface proteins (CSPs) for dissecting signaling are in high demand. Some CSPs are regulated via multivalency-driven liquid-liquid phase separation (LLPS). Employing the robustness and versatility of LLPS, we decided to engineer LLPS-based tools for precisely manipulating CSPs. We generated membrane-tethering LLPS systems by fusing multivalent modular phase-separation scaffold pairs with CSP binders. Phase separation of the scaffold pairs, concomitant compartmentalization of CSPs on membranes, and cluster-dependent signaling outputs of CSPs require membrane recruitment of one or both scaffolds. We also engineered orthogonal phase-separation systems to segregate CSPs into mutually exclusive compartments. The engineered phase-separation systems can robustly cluster individual CSPs, co-cluster two or more CSPs, or segregate different CSPs into distinct compartments on cell surfaces. These tools will enable the dissection of complicated cell-signaling landscapes with high precision.

Application potential of senolytics in clinical treatment.

Of the factors studied in individual ageing, the accumulation of senescent cells has been considered as an essential cause of organ degeneration to eventually initiate age-related diseases. Cellular senescence is attributed to the accumulation of damage for an inducement in the activation of cell cycle inhibitory pathways, resulting the cell permanently withdraw from the cell proliferation cycle. Further, senescent cells will activate the inflammatory factor secretion pathway to promote the development of various age-related diseases. Senolytics, a small molecule compound, can delay disease development and extend mammalian lifespan. The evidence from multiple trials shows that the targeted killing of senescent cells has a significant clinical application for the treatment of age-related diseases. In addition, senolytics are also significant for the development of ageing research in solid organ transplantation, which can fully develop the potential of elderly organs and reduce the age gap between demand and supply. We conclude that the main characteristics of cellular senescence, the anti-ageing drug senolytics in the treatment of chronic diseases and organ transplantation, and the latest clinical progress of related researches in order to provide a theoretical basis for the prevention and treatment of ageing and related diseases.

ExpoNano: A Strategy Based on Hyper-Cross-Linked Polymers Achieves Urinary Exposome Assessment for Biomonitoring.

Urinary analysis of exogenous and endogenous molecules constitutes an efficient, noninvasive approach to evaluate human health status. However, the exposome characterization of urinary molecules remains extremely challenging with current techniques. Herein, we develop an ExpoNano strategy based on hyper-cross-linked polymers (HCPs) to achieve ultrahigh-throughput measurement of exo/endogenous molecules in urine. The strategy includes a simple trapping-detrapping procedure (15 min) with HCPs in enzymatically treated urine, followed by mass spectrometer determination. Molecules that can be determined by ExpoNano have a wide range of molecular weight (75-837 Da) and Log Kow (octanol-water partition coefficient; -9.86 to 10.56). The HCPs can be repeatedly used five times without decreasing the trapping efficiency. Application of ExpoNano in a biomonitoring study revealed a total of 63 environmental chemicals detected in >50% of the urine pools collected from Chinese adults living in 13 cities, with a median concentration of 0.026-47 ng/mL, while nontargeted analysis detected an additional 243 exogenous molecules. Targeted and nontargeted analysis also detected 926 endogenous molecules in pooled urine. Collectively, the ExpoNano strategy demonstrates unique advantages over traditional urine analysis approaches, including a wide range of analytes, satisfactory trapping efficiency, high simplicity and reusability, and extremely reduced time demand and financial cost.

Association between Ambient Volatile Organic Compounds Exposome and Emergency Hospital Admissions for Cardiovascular Disease.

The limited research on volatile organic compounds (VOCs) has not taken into account the interactions between constituents. We used the weighted quantile sum (WQS) model and generalized linear model (GLM) to quantify the joint effects of ambient VOCs exposome and identify the substances that play key roles. For a 0 day lag, a quartile increase of WQS index for n-alkanes, iso/anti-alkanes, aromatic, halogenated aromatic hydrocarbons, halogenated saturated chain hydrocarbons, and halogenated unsaturated chain hydrocarbons were associated with 1.09% (95% CI: 0.13, 2.06%), 0.98% (95% CI: 0.22, 1.74%), 0.92% (95% CI: 0.14, 1.69%), 1.03% (95% CI: 0.14, 1.93%), 1.69% (95% CI: 0.48, 2.91%), and 1.85% (95% CI: 0.93, 2.79%) increase in cardiovascular disease (CVD) emergency hospital admissions, respectively. Independent effects of key substances on CVD-related emergency hospital admissions were also reported. In particular, an interquartile range increase in 1,1,1-trichloroethane, methylene chloride, styrene, and methylcyclohexane is associated with a greater risk of CVD-associated emergency hospital admissions [3.30% (95% CI: 1.93, 4.69%), 3.84% (95% CI: 1.21, 6.53%), 5.62% (95% CI: 1.35, 10.06%), 8.68% (95% CI: 3.74, 13.86%), respectively]. We found that even if ambient VOCs are present at a considerably low concentration, they can cause cardiovascular damage. This should prompt governments to establish and improve concentration standards for VOCs and their sources. At the same time, policies should be introduced to limit VOCs emission to protect public health.

Unequal Health Risks and Attributable Mortality Burden of Source-Specific PM2.5 in China.

Anthropogenic emissions, originating from human activities, stand as the primary contributors to PM2.5, which is recognized as a global health threat. The disease burden associated with PM2.5 has been extensively documented. However, the prevailing estimations have predominantly relied on PM2.5 exposure-response functions, neglecting the distinct risks posed by PM2.5 from various sources. China has experienced a significant reduction in the PM2.5 concentration due to stringent emission controls. With diverse sources and abundant mortality data, this situation provides a unique opportunity to estimate short-term source-specific attributable mortality. Our approach involves an integrated unequal health risk-oriented modeling in China, incorporating a source-oriented Community Multiscale Air Quality model, an adjustment and downscaling method for exposure measurement, a generalized linear model with random-effects meta-analysis, and premature mortality estimation. Adhering to the unequal health risk concept, we calculated the attributable mortality of multiple PM2.5 sources by determining the source risk-adjusted factor. In this study, we observed varying excess risks associated with multiple PM2.5 sources, with transportation-related PM2.5 exhibiting the most substantial association. An interquartile range increase (7.65 µg/m3) was linked to a 1.98% higher daily nonaccidental mortality. Residential use- and transportation-related PM2.5 emerged as the two principal sources of premature mortality. In 2018, a remarkable 53,381 avoiding deaths were estimated compared to 2013, and over 67% of these were attributed to reductions in coal-dependent sources. Notably, transportation-related PM2.5 emerged as the largest contributor to premature mortality in 2018. This study underscores the significance of a new source-oriented health risk assessment to support actions aimed at reducing air pollution. It strongly advocates for heightened attention to PM2.5 reductions in the transportation sector in China.