Regulation of TORC2 Function and Localization in Yeast.

Every eukaryotic cell contains two distinct multisubunit protein kinase complexes that each contain a TOR (target of rapamycin) protein as the catalytic subunit. These ensembles, designated TORC1 and TORC2, serve as nutrient and stress sensors, signal integrators, and regulators of cell growth and homeostasis, but they differ in their composition, localization, and function. TORC1, activated on the cytosolic surface of the vacuole (or, in mammalian cells, on the cytosolic surface of the lysosome), promotes biosynthesis and suppresses autophagy. TORC2, located primarily at the plasma membrane (PM), maintains the proper levels and bilayer distribution of all PM components (sphingolipids, glycerophospholipids, sterols, and integral membrane proteins), which are needed for the membrane expansion that accompanies cell growth and division and for combating insults to PM integrity. This review summarizes our current understanding of the assembly, structural features, subcellular distribution, and function and regulation of TORC2, obtained largely through studies conducted with Saccharomyces cerevisiae.

Endoplasmic Reticulum-Plasma Membrane Associations:Structures and Functions.

Inside eukaryotic cells, membrane contact sites (MCSs), regions where two membrane-bound organelles are apposed at less than 30 nm, generate regions of important lipid and calcium exchange. This review principally focuses on the structure and the function of MCSs between the endoplasmic reticulum (ER) and the plasma membrane (PM). Here we describe how tethering structures form and maintain these junctions and, in some instances, participate in their function. We then discuss recent insights into the mechanisms by which specific classes of proteins mediate nonvesicular lipid exchange between the ER and PM and how such phenomena, already known to be crucial for maintaining organelle identity, are also emerging as regulators of cell growth and development.

Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM2.5 components.

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.

PM2.5 exposure contributes to anxiety and depression-like behaviors via phenyl-containing compounds interfering with dopamine receptor.

As a global problem, fine particulate matter (PM2.5) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, the most important question is to clarify whether and how PM2.5 causally contributes to these mental disorders and which components are the most dangerous for crucial mitigation in a particular place. In the present study, we chronically subjected male mice to a real-world PM2.5 exposure system throughout the winter heating period in a coal combustion area and revealed that PM2.5 caused anxiety and depression-like behaviors in adults such as restricted activity, diminished exploratory interest, enhanced repetitive stereotypy, and elevated acquired immobility, through behavioral tests including open field, elevated plus maze, marble-burying, and forced swimming tests. Importantly, we found that dopamine signaling was perturbed using mRNA transcriptional profile and bioinformatics analysis, with Drd1 as a potential target. Subsequently, we developed the Drd1 expression-directed multifraction isolating and nontarget identifying framework and identified a total of 209 compounds in PM2.5 organic extracts capable of reducing Drd1 expression. Furthermore, by applying hierarchical characteristic fragment analysis and molecular docking and dynamics simulation, we clarified that phenyl-containing compounds competitively bound to DRD1 and interfered with dopamine signaling, thereby contributing to mental disorders. Taken together, this work provides experimental evidence for researchers and clinicians to identify hazardous factors in PM2.5 and prevent adverse health outcomes and for local governments and municipalities to control source emissions for diminishing specific disease burdens.

Air Pollution-Related Neurotoxicity Across the Life Span.

Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress-based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.

Fission yeast Duc1 links to ER-PM contact sites and influences PM lipid composition and cytokinetic ring anchoring.

Cytokinesis is the final stage of the cell cycle that results in the physical separation of daughter cells. To accomplish cytokinesis, many organisms build an actin- and myosin-based cytokinetic ring (CR) that is anchored to the plasma membrane (PM). Defects in CR-PM anchoring can arise when the PM lipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is depleted. In Schizosaccharomyces pombe, reduced PM PI(4,5)P2 results in a CR that cannot maintain a medial position and slides toward one cell end, resulting in two differently sized daughter cells. S. pombe PM PI(4,5)P2 is synthesized by the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, but what regulates this enzyme to maintain appropriate PM PI(4,5)P2 levels in S. pombe is not known. To identify Its3 regulators, we used proximity-based biotinylation, and the uncharacterized protein Duc1 was specifically detected. We discovered that Duc1 decorates the PM except at the cell division site and that its unique localization pattern is dictated by binding to the endoplasmic reticulum (ER)-PM contact site proteins Scs2 and Scs22. Our evidence suggests that Duc1 also binds PI(4,5)P2 and helps enrich Its3 at the lateral PM, thereby promoting PM PI(4,5)P2 synthesis and robust CR-PM anchoring.

Compartmentalized signaling in the soma: Coordination of electrical and protein kinase A signaling at neuronal ER-plasma membrane junctions.

Neuronal information processing depends on converting membrane depolarizations into compartmentalized biochemical signals that can modify neuronal activity and structure. However, our understanding of how neurons translate electrical signals into specific biochemical responses remains limited, especially in the soma where gene expression and ion channel function are crucial for neuronal activity. Here, I emphasize the importance of physically compartmentalizing action potential-triggered biochemical reactions within the soma. Emerging evidence suggests that somatic endoplasmic reticulum-plasma membrane (ER-PM) junctions are specialized organelles that coordinate electrical and biochemical signaling. The juxtaposition of ion channels and signaling proteins at a prominent subset of these sites enables compartmentalized calcium and cAMP-dependent protein kinase (PKA) signaling. I explore the hypothesis that these PKA-containing ER-PM junctions serve as critical sites for translating membrane depolarizations into PKA signals and identify key gaps in knowledge of the assembly, regulation, and neurobiological functions of this somatic signaling system.

Assessing residential PM2.5 concentrations and infiltration factors with high spatiotemporal resolution using crowdsourced sensors.

Building conditions, outdoor climate, and human behavior influence residential concentrations of fine particulate matter (PM2.5). To study PM2.5 spatiotemporal variability in residences, we acquired paired indoor and outdoor PM2.5 measurements at 3,977 residences across the United States totaling >10,000 monitor-years of time-resolved data (10-min resolution) from the PurpleAir network. Time-series analysis and statistical modeling apportioned residential PM2.5 concentrations to outdoor sources (median residential contribution = 52% of total, coefficient of variation = 69%), episodic indoor emission events such as cooking (28%, CV = 210%) and persistent indoor sources (20%, CV = 112%). Residences in the temperate marine climate zone experienced higher infiltration factors, consistent with expectations for more time with open windows in milder climates. Likewise, for all climate zones, infiltration factors were highest in summer and lowest in winter, decreasing by approximately half in most climate zones. Large outdoor-indoor temperature differences were associated with lower infiltration factors, suggesting particle losses from active filtration occurred during heating and cooling. Absolute contributions from both outdoor and indoor sources increased during wildfire events. Infiltration factors decreased during periods of high outdoor PM2.5, such as during wildfires, reducing potential exposures from outdoor-origin particles but increasing potential exposures to indoor-origin particles. Time-of-day analysis reveals that episodic emission events are most frequent during mealtimes as well as on holidays (Thanksgiving and Christmas), indicating that cooking-related activities are a strong episodic emission source of indoor PM2.5 in monitored residences.

Incident dementia and long-term exposure to constituents of fine particle air pollution: A national cohort study in the United States.

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO42-, and NH4+ for both end points (even after adjustments of other constituents), among which BC and SO42- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO42-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function.

The membrane contact site ER/PM junctions are hubs for signaling pathways, including Ca2+ signaling. Phosphatidylserine (PtdSer) mediates various physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca2+ signaling and Ca2+-dependent gene regulation are not understood. Here, we show that STIM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal lipid exchange modes and function as a rheostat that sets the junctional PtdSer/PI(4)P ratio. Targeting the ORP5 and ORP8 and their lipid transfer ORD domains to PM subdomains revealed that ORP5 sets low and ORP8 high junctional PI(4)P/PtdSer ratio that controls STIM1-STIM1 and STIM1-Orai1 interaction and the activity of the SERCA pump to determine the pattern of receptor-evoked Ca2+ oscillations, and consequently translocation of NFAT to the nucleus. Significantly, targeting the ORP5 and ORP8 ORDs to the STIM1 ER subdomain reversed their function. Notably, changing PI(4)P/PtdSer ratio by hydrolysis of PM or ER PtdSer with targeted PtdSer-specific PLA1a1 reproduced the ORPs function. The function of the ORPs is determined both by their differential lipid exchange modes and by privileged localization at the ER/PM subdomains. These findings reveal a role of PtdSer as a signaling lipid that controls the available PM PI(4)P, the unappreciated role of ER PtdSer in cell function, and the diversity of the ER/PM junctions. The effect of PtdSer on the junctional PI(4)P level should have multiple implications in cellular signaling and functions.

CsPM5.2, a phosphate transporter protein-like gene, promotes powdery mildew resistance in cucumber.

Powdery mildew (PM) is one of the most serious fungal diseases affecting cucumbers (Cucumis sativus L.). The mechanism of PM resistance in cucumber is intricate and remains fragmentary as it is controlled by several genes. In this study, we detected the major-effect Quantitative Trait Locus (QTL), PM5.2, involved in PM resistance by QTL mapping. Through fine mapping, the dominant PM resistance gene, CsPM5.2, was cloned and its function was confirmed by transgenic complementation and natural variation identification. In cultivar 9930, a dysfunctional CsPM5.2 mutant resulted from a single nucleotide polymorphism in the coding region and endowed susceptibility to PM. CsPM5.2 encodes a phosphate transporter-like protein PHO1; H3. The expression of CsPM5.2 is ubiquitous and induced by the PM pathogen. In cucumber, both CsPM5.2 and Cspm5.1 (Csmlo1) are required for PM resistance. Transcriptome analysis suggested that the salicylic acid (SA) pathway may play an important role in CsPM5.2-mediated PM resistance. Our findings help parse the mechanisms of PM resistance and provide strategies for breeding PM-resistant cucumber cultivars.

Localization of the tubby domain, a PI(4,5)P2 biosensor, to E-Syt3-rich endoplasmic reticulum-plasma membrane junctions.

The phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] acts as a signaling lipid at the plasma membrane (PM) with pleiotropic regulatory actions on multiple cellular processes. Signaling specificity might result from spatiotemporal compartmentalization of the lipid and from combinatorial binding of PI(4,5)P2 effector proteins to additional membrane components. Here, we analyzed the spatial distribution of tubbyCT, a paradigmatic PI(4,5)P2-binding domain, in live mammalian cells by total internal reflection fluorescence (TIRF) microscopy and molecular dynamics simulations. We found that unlike other well-characterized PI(4,5)P2 recognition domains, tubbyCT segregates into distinct domains within the PM. TubbyCT enrichment occurred at contact sites between PM and endoplasmic reticulum (ER) (i.e. at ER-PM junctions) as shown by colocalization with ER-PM markers. Localization to these sites was mediated in a combinatorial manner by binding to PI(4,5)P2 and by interaction with a cytosolic domain of extended synaptotagmin 3 (E-Syt3), but not other E-Syt isoforms. Selective localization to these structures suggests that tubbyCT is a novel selective reporter for a ER-PM junctional pool of PI(4,5)P2. Finally, we found that association with ER-PM junctions is a conserved feature of tubby-like proteins (TULPs), suggesting an as-yet-unknown function of TULPs.

The cytoplasmic tail of the mechanosensitive channel Pkd2 regulates its internalization and clustering in eisosomes.

Polycystins are a family of conserved ion channels, mutations of which lead to one of the most common human genetic disorders, namely, autosomal dominant polycystic kidney disease. Schizosacchromyces pombe possesses an essential polycystin homologue, Pkd2, which directs Ca2+ influx on the cell surface in response to membrane tension, but its structure remains unsolved. Here, we analyzed the structure-function relationship of Pkd2 based on its AlphaFold-predicted structure. Pkd2 consists of three domains, the extracellular lipid-binding domain (LBD), nine-helix transmembrane domain (TMD) and C-terminal cytoplasmic domain (CCD). Our genetic and microscopy data revealed that LBD and TMD are essential for targeting Pkd2 to the plasma membrane from the endoplasmic reticulum. In comparison, CCD ensures the polarized distribution of Pkd2 by promoting its internalization and preventing its clustering in the eisosome, a caveolae-like membrane compartment. The domains of Pkd2 and their functions are conserved in other fission yeast species. We conclude that both extracellular and cytoplasmic domains of Pkd2 are crucial for its intracellular trafficking and function. We propose that mechanosensitive channels can be desensitized through either internalization or clustering in low-tension membrane compartments.

C2-domain abscisic acid-related proteins regulate the dynamics of a plasma membrane H+-ATPase in response to alkali stress.

Arabidopsis (Arabidopsis thaliana) H+-ATPase1 (AHA1), a plasma membrane (PM)-localized H+-ATPase, plays a key role in plant alkali stress tolerance by pumping protons from the cytoplasm to the apoplast. However, its molecular dynamics are poorly understood. We report that many C2-domain ABA-related (CAR) protein family members interact with AHA1 in Arabidopsis. Single or double mutants of CAR1, CAR6, and CAR10 had no obvious phenotype of alkali stress tolerance, while their triple mutants showed significantly higher tolerance to this stress. The disruption of AHA1 largely compromised the increased alkali stress tolerance of the car1car6car10 mutant, revealing a key role of CARs in AHA1 regulation during the plant's response to a high alkali pH. Furthermore, variable angle total internal reflection fluorescence microscopy was used to observe AHA1-mGFP5 in intact Arabidopsis seedlings, revealing the presence of heterogeneous diffusion coefficients and oligomerization states in the AHA1 spots. In the aha1 complementation lines, alkali stress curtailed the residence time of AHA1 at the PM and increased the diffusion coefficient and particle velocity of AHA1. In contrast, the absence of CAR proteins decreased the restriction of the dynamic behavior of AHA1. Our results suggest that CARs play a negative role in plant alkali stress tolerance by interacting with AHA1 and provide a perspective to investigate the regulatory mechanism of PM H+-ATPase activity at the single-particle level.

The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling.

Loss of ER Ca2+ homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca2+. Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca2+ fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca2+ store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca2+ elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton.

Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE.

Stromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER) [Ca2+] ([Ca2+]ER) and cluster in ER-plasma membrane (ER-PM) junctions where they recruit and activate Orai1. While STIM1 responds when [Ca2+]ER is relatively low, STIM2 displays constitutive clustering in the junctions and is suggested to regulate basal Ca2+ entry. The cellular cues that determine STIM2 clustering under basal conditions is not known. By using gene editing to fluorescently tag endogenous STIM2, we report that endogenous STIM2 is constitutively localized in mobile and immobile clusters. The latter associate with ER-PM junctions and recruit Orai1 under basal conditions. Agonist stimulation increases immobile STIM2 clusters, which coordinate recruitment of Orai1 and STIM1 to the junctions. Extended synaptotagmin (E-Syt)2/3 are required for forming the ER-PM junctions, but are not sufficient for STIM2 clustering. Importantly, inositol 1,4,5-triphosphate receptor (IP3R) function and local [Ca2+]ER are the main drivers of immobile STIM2 clusters. Enhancing, or decreasing, IP3R function at ambient [IP3] causes corresponding increase, or attenuation, of immobile STIM2 clusters. We show that immobile STIM2 clusters denote decreases in local [Ca2+]ER mediated by IP3R that is sensed by the STIM2 N terminus. Finally, under basal conditions, ambient PIP2-PLC activity of the cell determines IP3R function, immobilization of STIM2, and basal Ca2+ entry while agonist stimulation augments these processes. Together, our findings reveal that immobilization of STIM2 clusters within ER-PM junctions, a first response to ER-Ca2+ store depletion, is facilitated by the juxtaposition of IP3R and marks a checkpoint for initiation of Ca2+ entry.

Pyrroloquinoline quinone ameliorates PM2.5-induced pulmonary fibrosis through targeting epithelial-mesenchymal transition.

Pulmonary fibrosis is a lung disorder affecting the lungs that involves the overexpressed extracellular matrix, scarring and stiffening of tissue. The repair of lung tissue after injury relies heavily on Type II alveolar epithelial cells (AEII), and repeated damage to these cells is a crucial factor in the development of pulmonary fibrosis. Studies have demonstrated that chronic exposure to PM2.5, a form of air pollution, leads to an increase in the incidence and severity of pulmonary fibrosis by stimulation of epithelial-mesenchymal transition (EMT) in lung epithelial cells. Pyrroloquinoline quinone (PQQ) is a bioactive compound found naturally that exhibits potent anti-inflammatory and anti-oxidative properties. The mechanism by which PQQ prevents pulmonary fibrosis caused by exposure to PM2.5 through EMT has not been thoroughly discussed until now. In the current study, we discovered that PQQ successfully prevented PM2.5-induced pulmonary fibrosis by targeting EMT. The results indicated that PQQ was able to inhibit the expression of type I collagen, a well-known fibrosis marker, in AEII cells subjected to long-term PM2.5 exposure. We also found the alterations of cellular structure and EMT marker expression in AEII cells with PM2.5 incubation, which were reduced by PQQ treatment. Furthermore, prolonged exposure to PM2.5 considerably reduced cell migratory ability, but PQQ treatment helped in reducing it. In vivo animal experiments indicated that PQQ could reduce EMT markers and enhance pulmonary function. Overall, these results imply that PQQ might be useful in clinical settings to prevent pulmonary fibrosis.

Increased Phospholipid Flux Bypasses Overlapping Essential Requirements for the Yeast Sac1p Phosphoinositide Phosphatase and ER-PM Membrane Contact Sites.

In budding yeast cells, much of the inner surface of the plasma membrane (PM) is covered with the endoplasmic reticulum (ER). This association is mediated by seven ER membrane proteins that confer cortical ER-PM association at membrane contact sites (MCSs). Several of these membrane "tether" proteins are known to physically interact with the phosphoinositide phosphatase Sac1p. However, it is unclear how or if these interactions are necessary for their interdependent functions. We find that SAC1 inactivation in cells lacking the homologous synaptojanin-like genes INP52 and INP53 results in a significant increase in cortical ER-PM MCSs. We show in sac1Δ, sac1tsinp52Δ inp53Δ, or Δ-super-tether (Δ-s-tether) cells lacking all seven ER-PM tethering genes that phospholipid biosynthesis is disrupted and phosphoinositide distribution is altered. Furthermore, SAC1 deletion in Δ-s-tether cells results in lethality, indicating a functional overlap between SAC1 and ER-PM tethering genes. Transcriptomic profiling indicates that SAC1 inactivation in either Δ-s-tether or inp52Δ inp53Δ cells induces an ER membrane stress response and elicits phosphoinositide-dependent changes in expression of autophagy genes. In addition, by isolating high-copy suppressors that rescue sac1Δ Δ-s-tether lethality, we find that key phospholipid biosynthesis genes bypass the overlapping function of SAC1 and ER-PM tethers and that overexpression of the phosphatidylserine/phosphatidylinositol-4-phosphate transfer protein Osh6 also provides limited suppression. Combined with lipidomic analysis and determinations of intracellular phospholipid distributions, these results suggest that Sac1p and ER phospholipid flux controls lipid distribution to drive Osh6p-dependent phosphatidylserine/phosphatidylinositol-4-phosphate counter-exchange at ER-PM MCSs.

Does ambient particulate matter 1 increase the risk of gastric cancer in the northwest of China?

Gastric cancer (GC) remains a significant health concern in Gansu province, China, with morbidity and mortality rates surpassing national averages. Despite the recognized health risks associated with ambient particulate matter with an aerodynamic diameter <1 µm (PM1), the relationship between PM1 exposure and GC incidence has not been extensively studied. Data on GC cases from 2013 to 2021 were gathered from 262 hospitals in Gansu, China. Concurrently, data on the normalized vegetation index (NDVI), gross domestic product (GDP), drinking and smoking behavioral index (DSBI), PM1, PM2.5, and PM2.5-1 were collected. Utilizing a Bayesian conditional autoregressive (CAR) combined generalized linear model (GLM) with quasi-Poisson regression, we evaluated the impact of PM1, PM2.5, PM2.5-1, NDVI, DSBI, and GDP on GC morbidity while adjusting for potential confounders. Our analysis indicated that exposure to PM1 (µg/m3) is significantly positively correlated with GC incidence in regions with an overall age-standardized incidence rate (ASIR) >40 (relative risks [RR]: 1.023, 95% confidence intervals [CI, 1.007, 1.039]), male ASIR >50 (RR: 1.014, 95% CI [1.009, 1.019]), and female ASIR >20 (RR: 1.010, 95% CI [1.002, 1.018]). PM2.5, PM2.5-1, DSBI, and GDP were positively correlated with GC incidence, while NDVI was negatively correlated in the study regions. Our findings provided evidence of a positive correlation between PM1 exposure and GC incidence in high-risk areas of GC within arid regions. Further research is warranted to elucidate the complex nonlinear relationships between environmental factors and GC. These insights could inform strategies for improving the control and prevention of GC in Gansu and similar regions.

The association of short-term increases in ambient PM2.5 and temperature exposures with stillbirth: racial/ethnic disparities among Medicaid recipients.

Racial/ethnic disparities in the association between short-term (eg, days, weeks), ambient fine particulate matter (PM2.5) and temperature exposures and stillbirth in the United States have been understudied. A time-stratified, case-crossover design using a distributed lag nonlinear model (0- to 6-day lag) was used to estimate stillbirth odds due to short-term increases in average daily PM2.5 and temperature exposures among 118 632 Medicaid recipients from 2000 to 2014. Disparities by maternal race/ethnicity (Black, White, Hispanic, Asian, American Indian) and zip code-level socioeconomic status (SES) were assessed. In the temperature-adjusted model, a 10 µg m-3 increase in PM2.5 concentration was marginally associated with increased stillbirth odds at lag 1 (0.68%; 95% CI, -0.04% to 1.40%) and lag 2 (0.52%; 95% CI, -0.03 to 1.06) but not lag 0-6 (2.80%; 95% CI, -0.81 to 6.45). An association between daily PM2.5 concentrations and stillbirth odds was found among Black individuals at the cumulative lag (0-6 days: 9.26% 95% CI, 3.12%-15.77%) but not among other races or ethnicities. A stronger association between PM2.5 concentrations and stillbirth odds existed among Black individuals living in zip codes with the lowest median household income (lag 0-6: 14.13%; 95% CI, 4.64%-25.79%). Short-term temperature increases were not associated with stillbirth risk among any race/ethnicity. Black Medicaid enrollees, and especially those living in lower SES areas, may be more vulnerable to stillbirth due to short-term increases in PM2.5 exposure. This article is part of a Special Collection on Environmental Epidemiology.