Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction.

We aimed to investigate the predictive value of left atrium (LA) and left ventricle (LV) longitudinal strain derived by CMR-FT early after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients with STEMI who received pPCI and completed CMR within the following week were enrolled. LA and LV longitudinal strain parameters were derived from cine CMR by FT; conventional CMR indexes were also performed. The primary endpoint was the occurrence of major cardiovascular adverse events (MACE), defined as a composite of death, reinfarction, and congestive heart failure (HF). 276 participants (median age, 57 years, IQR, 48-66 years; 85% men) were included in this study. CMR was usually completed on the 5 (IQR,4-7) days after pPCI. During a median follow-up of 16 months, MACE occurred in 35 (12.7%) participants. Multivariable Cox regression analysis showed that LA conduit strain (HR 0.91, 95%CI: 0.84, 0.98, p = 0.013) and LV global longitudinal strain (HR 1.17, 95%CI: 1.03, 1.34, p = 0.016) remained independently associated with MACE. Participants with impaired LA conduit strain (≤ 12.8%) and LV global longitudinal strain (> -13.1%) had a higher risk of MACE than those with preserved. Longitudinal strain of LA and LV could provide independent prognostic information in STEMI patients, and comprehensive assessment of Left atrial and ventricular longitudinal strain significantly improved the prognosis.

Functional Test of a Naturally Occurred Tumor Modifier Gene Provides Insights to Melanoma Development.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus , is used to study hybrid dysfunction and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids. Melanoma development is due to hybrid inheritance of an oncogene, xmrk , and loss of a co-evolved tumor modifier. It was recently found that adgre5 , a G protein-coupled receptor involved in cell adhesion, is a tumor regulator gene in naturally hybridizing Xiphophorus species X. birchmanni and X. malinche . We hypothesized that one of the two parental alleles of adgre5 is involved in regulation of cell proliferation, migration and melanomagenesis. Accordingly, we assessed the function of adgre5 alleles from each parental species of the melanoma-bearing hybrids using in vitro cell proliferation and migration assays. In addition, we expressed each adgre5 allele with the xmrk oncogene in transgenic medaka. We found that cells transfected with the X. birchmanni adgre5 exhibited decreased proliferation and migration compared to those with the X. malinche allele. Moreover, X. birchmanni allele of adgre5 completely inhibited melanoma development in xmrk transgenic medaka, while X. malinche adgre5 expression did not exhibit melanoma suppressive activity in medaka. These findings showed that adgre5 is a natural melanoma suppressor and provide new insight in melanoma etiology.

Association between cardiac magnetic resonance ventricular strain and left ventricular thrombus in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Myocardial strain can analyze early myocardial dysfunction after myocardial infarction (MI). However, the correlation between left ventricular (LV) strain (including regional and global strain) obtained by cardiac magnetic resonance (CMR) imaging and left ventricular thrombus (LVT) after ST-segment elevation myocardial infarction (STEMI) is unclear. METHODS: The retrospective clinical observation study included patients with LVT (n = 20) and non-LVT (n = 195) who underwent CMR within two weeks after STEMI. CMR images were analyzed using CVI 42 (Circle Cardiovascular Imaging, Canada) to obtain LV strain values. Logistic regression analysis identified risk factors for LVT among baseline characteristics, CMR ventricular strain, and left ventricular ejection fraction (LVEF). Considering potential correlations between strains, the ability of LV strain to identify LVT was evaluated using 9 distinct models. Receiver operating characteristic curves were generated with GraphPad Prism, and the area under the curve (AUC) of LVEF, apical longitudinal strain (LS), and circumferential strain (CS) was calculated to determine their capacity to distinguish LVT. RESULTS: Among 215 patients, 9.3% developed LVT, with a 14.5% incidence in those with anterior MI. Univariate regression indicated associations of LAD infarct-related artery, lower NT-proBNP, lower LVEF, and reduced global, midventricular, and apical strain with LVT. Further multivariable regression analysis showed that apical LS, LVEF and NT-proBNP were still independently related to LVT (Apical LS: OR = 1.14, 95%CI (1.01, 1.30), P = 0.042; LVEF: OR = 0.91, 95%CI (0.85, 0.97), P = 0.005; NT-proBNP: OR = 2.35, 95%CI (1.04, 5.31) ). CONCLUSION: Reduced apical LS on CMR is independently associated with LVT after STEMI.

ELM2-SANT Domain-Containing Scaffolding Protein 1 Regulates Differentiation and Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells.

BACKGROUND: ELMSAN1 (ELM2-SANT domain-containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human-induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. METHODS AND RESULTS: We generated ELMSAN1-deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac-specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1-deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1-null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z-line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac-specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. CONCLUSIONS: In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.

Associations between renal function, hippocampal volume, and cognitive impairment in 544 outpatients.

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

Moiré superlattices in twisted two-dimensional halide perovskites.

Moiré superlattices have emerged as a new platform for studying strongly correlated quantum phenomena, but these systems have been largely limited to van der Waals layer two-dimensional materials. Here we introduce moiré superlattices leveraging ultrathin, ligand-free halide perovskites, facilitated by ionic interactions. Square moiré superlattices with varying periodic lengths are clearly visualized through high-resolution transmission electron microscopy. Twist-angle-dependent transient photoluminescence microscopy and electrical characterizations indicate the emergence of localized bright excitons and trapped charge carriers near a twist angle of ~10°. The localized excitons are accompanied by enhanced exciton emission, attributed to an increased oscillator strength by a theoretically predicted flat band. This research showcases the promise of two-dimensional perovskites as unique room-temperature moiré materials.

Room-temperature spin injection across a chiral perovskite/III-V interface.

Spin accumulation in semiconductor structures at room temperature and without magnetic fields is key to enable a broader range of optoelectronic functionality1. Current efforts are limited owing to inherent inefficiencies associated with spin injection across semiconductor interfaces2. Here we demonstrate spin injection across chiral halide perovskite/III-V interfaces achieving spin accumulation in a standard semiconductor III-V (AlxGa1-x)0.5In0.5P multiple quantum well light-emitting diode. The spin accumulation in the multiple quantum well is detected through emission of circularly polarized light with a degree of polarization of up to 15 ± 4%. The chiral perovskite/III-V interface was characterized with X-ray photoelectron spectroscopy, cross-sectional scanning Kelvin probe force microscopy and cross-sectional transmission electron microscopy imaging, showing a clean semiconductor/semiconductor interface at which the Fermi level can equilibrate. These findings demonstrate that chiral perovskite semiconductors can transform well-developed semiconductor platforms into ones that can also control spin.

Release of ATP in the Lung Evoked by Inhalation of Irritant Gases in Rats.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl2), sulfur dioxide (SO2), and ammonia (NH3) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1) Inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl2 > SO2 > NH3. 2) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation.

Voltage-Driven Fluorine Motion for Novel Organic Spintronic Memristor.

Integrating tunneling magnetoresistance (TMR) effect in memristors is a long-term aspiration because it allows to realize multifunctional devices, such as multi-state memory and tunable plasticity for synaptic function. However, the reported TMR in different multiferroic tunnel junctions is limited to 100%. This work demonstrates a giant TMR of -266% in La0.6Sr0.4MnO3(LSMO)/poly(vinylidene fluoride)(PVDF)/Co memristor with thin organic barrier. Different from the ferroelectricity-based memristors, this work discovers that the voltage-driven florine (F) motion in the junction generates a huge reversible resistivity change up to 106% with nanosecond (ns) timescale. Removing F from PVDF layer suppresses the dipole field in the tunneling barrier, thereby significantly enhances the TMR. Furthermore, the TMR can be tuned by different polarizing voltage due to the strong modification of spin-polarization at the LSMO/PVDF interface upon F doping. Combining of high TMR in the organic memristor paves the way to develop high-performance multifunctional devices for storage and neuromorphic applications.

Solar-driven highly selective conversion of glycerol to dihydroxyacetone using surface atom engineered BiVO4 photoanodes.

Dihydroxyacetone is the most desired product in glycerol oxidation reaction because of its highest added value and large market demand among all possible oxidation products. However, selectively oxidative secondary hydroxyl groups of glycerol for highly efficient dihydroxyacetone production still poses a challenge. In this study, we engineer the surface of BiVO4 by introducing bismuth-rich domains and oxygen vacancies (Bi-rich BiVO4-x) to systematically modulate the surface adsorption of secondary hydroxyl groups and enhance photo-induced charge separation for photoelectrochemical glycerol oxidation into dihydroxyacetone conversion. As a result, the Bi-rich BiVO4-x increases the glycerol oxidation photocurrent density of BiVO4 from 1.42 to 4.26 mA cm-2 at 1.23 V vs. reversible hydrogen electrode under AM 1.5 G illumination, as well as the dihydroxyacetone selectivity from 54.0% to 80.3%, finally achieving a dihydroxyacetone production rate of 361.9 mmol m-2 h-1 that outperforms all reported values. The surface atom customization opens a way to regulate the solar-driven organic transformation pathway toward a carbon chain-balanced product.

Long-term statin use and risk of cancers: a target trial emulation study.

BACKGROUND AND OBJECTIVES: Controversy exists regarding potential cancer risks associated with long-term statin use. This study aimed to use real-world data to investigate the association between cancer incidence and sustained statin use over a 10-year period. METHODS: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of nested target trials on patients who met indications for statin initiation in each calendar month from January 2009 to December 2011. Statin initiators and noninitiators were matched in a 1:1 ratio to mimic the randomization of eligible person-trials at baseline. Pooled logistic regression was applied to obtain the hazard ratios for the cancer incidence of statin initiation in intention-to-treat analysis, with the adjustment of baseline confounders and the inverse probability weighting accounting for the postbaseline confounders in per-protocol analysis. RESULTS: Among 8,560,051 eligible person-trials, 119,715 noninitiators were matched to 119,715 initiators for analysis. Over the 10-year study period, the estimated hazard ratio of overall cancer incidence was 0.96 (0.87, 1.05), and the standardized 10-year risk difference was -0.4% (-1.3%, 0.4%) in the per-protocol analysis. For the cancer subtypes of interest (ie, breast cancer, colorectal cancer, hematological cancer, pancreatic cancer, prostate cancer, urothelial carcinoma, and lung cancer), the 10-year risk differences ranged from -0.3% to 0.2% in the per-protocol analysis. No observable risk change for cancer was found in all patient subgroups with regards to their sex, age (<70/≥70 years), Charlson Comorbidity Index (≤4/>4), and statin indication. CONCLUSION: Statin use has no impact on cancer incidence over a 10-year follow-up period, including all cancer subtypes of interest and patient subgroups with regards to sex, age, comorbidities, and statin indications.

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation.

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility. Significance: The Dobzhansky-Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky-Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.

From Structure to Application: The Evolutionary Trajectory of Spherical Nucleic Acids.

Since the proposal of the concept of spherical nucleic acids (SNAs) in 1996, numerous studies have focused on this topic and have achieved great advances. As a new delivery system for nucleic acids, SNAs have advantages over conventional deoxyribonucleic acid (DNA) nanostructures, including independence from transfection reagents, tolerance to nucleases, and lower immune reactions. The flexible structure of SNAs proves that various inorganic or organic materials can be used as the core, and different types of nucleic acids can be conjugated to realize diverse functions and achieve surprising and exciting outcomes. The special DNA nanostructures have been employed for immunomodulation, gene regulation, drug delivery, biosensing, and bioimaging. Despite the lack of rational design strategies, potential cytotoxicity, and structural defects of this technology, various successful examples demonstrate the bright and convincing future of SNAs in fields such as new materials, clinical practice, and pharmacy.

[Effect of Low-density Polyethylene Microplastics on Natural Attenuation of Oxygenated Polycyclic Aromatic Hydrocarbons in Soil].

The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.

Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis.

Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.

High Blood Pressure in Children Aged 3 to 12 Years Old With Overweight or Obesity.

Objective: (1) To describe the prevalence of high blood pressure (BP) and the association with BMI in young children with overweight/obesity; (2) to evaluate the accuracy of a single high BP to diagnose sustained hypertension over three visits. Methods: We used pre-intervention data from the Improving Pediatric Obesity Practice Using Prompts (iPOP-UP) trial. We included children aged 3-12 years with BMI ≥85th percentile at well-visits in 2019-2021 at 84 primary care practices in 3 US health systems in the Northeast, Midwest, and South. BP percentiles were calculated from the first visit with BP recorded during the study period. Hypertensive-range BP was defined by the 2017 American Academy of Pediatrics guideline. We tested the association between BMI classification and hypertensive BP using multivariable logistic regression. Results: Of 78,280 children with BMI ≥85th percentile, 76,214 (97%) had BP recorded during the study period (mean 7.4 years, 48% female, 53% with overweight, and 13% with severe obesity). The prevalence of elevated or hypertensive BP was 31%, including 27% in children with overweight and 33%, 39%, and 49% with class I, II, and III obesity, respectively. Higher obesity severity was associated with higher odds of hypertensive BP in the multivariable model. Stage 2 hypertensive BP at the initial visit had specificity of 99.1% (95% confidence interval 98.9-99.3) for detecting sustained hypertension over ≥3 visits. Conclusions: High BP is common in 3- to 12-year-olds with overweight/obesity, with higher obesity severity associated with greater hypertension. Children with overweight/obesity and stage 2 BP are likely to have sustained hypertension and should be prioritized for evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT05627011.

Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma (PRP).

BACKGROUND: Androgenic alopecia (AGA) is the most common type of hair loss in men, and there are many studies on the treatment of hair loss by platelet-rich plasma (PRP). The human scalp contains a huge microbiome, but its role in the process of hair loss remains unclear, and the relationship between PRP and the microbiome needs further study. Therefore, the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition. METHODS: We performed PRP treatment on 14 patients with AGA, observed their clinical efficacy, and collected scalp swab samples before and after treatment. The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification. RESULTS: The results showed that PRP was effective in the treatment of AGA patients, and the hair growth increased significantly. The results of relative abundance analysis of microbiota showed that after treatment, g_Cutibacterium increased and g_Staphylococcus decreased, which played a stable role in scalp microbiota. In addition, g_Lawsonella decreased, indicating that the scalp oil production decreased after treatment. CONCLUSIONS: The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

Identifying vagal bronchopulmonary afferents mediating cough response to inhaled sulfur dioxide in mice.

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1-2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1-3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2.NEW & NOTEWORTHY This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide.