SCPL acyltransferases catalyze the metabolism of chlorogenic acid during purple coneflower seed germination.

The metabolism of massively accumulated chlorogenic acid is crucial for the successful germination of purple coneflower (Echinacea purpurea (L.) Menoch). A serine carboxypeptidase-like (SCPL) acyltransferase (chicoric acid synthase, CAS) utilizes chlorogenic acid to produce chicoric acid during germination. However, it seems that the generation of chicoric acid lags behind the decrease in chlorogenic acid, suggesting an earlier route of chlorogenic acid metabolism. We discovered another chlorogenic acid metabolic product, 3,5-dicaffeoylquinic acid, which is produced before chicoric acid, filling the lag phase. Then, we identified two additional typical clade IA SCPL acyltransferases, named chlorogenic acid condensing enzymes (CCEs), that catalyze the biosynthesis of 3,5-dicaffeoylquinic acid from chlorogenic acid with different kinetic characteristics. Chlorogenic acid inhibits radicle elongation in a dose-dependent manner, explaining the potential biological role of SCPL acyltransferases-mediated continuous chlorogenic acid metabolism during germination. Both CCE1 and CCE2 are highly conserved among Echinacea species, supporting the observed metabolism of chlorogenic acid to 3,5-dicaffeoylquinic acid in two Echinacea species without chicoric acid accumulation. The discovery of SCPL acyltransferase involved in the biosynthesis of 3,5-dicaffeoylquinic acid suggests convergent evolution. Our research clarifies the metabolism strategy of chlorogenic acid in Echinacea species and provides more insight into plant metabolism.

Oxfendazole Induces Apoptosis in Ovarian Cancer Cells by Activating JNK/MAPK Pathway and Inducing Reactive Oxygen Species Generation.

Ovarian cancer (OC) is one of the most common and high mortality type of cancer among women worldwide. The majority of patients with OC respond to chemotherapy initially; however, most of them become resistant to chemotherapy and results in a high level of treatment failure in OC. Therefore, novel agents for the treatment of OC are urgently required. Benzimidazole anthelmintics might have the promising efficacy for cancer therapy as their selectively binding activity to ß-tubulin. Recent study has shown that one of the benzimidazole anthelmintics oxfendazole inhibited cell growth of non-small cell lung cancer cells, revealing its anti-cancer activity; however, the pharmacological action and detailed mechanism underlying the effects of oxfendazole on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of oxfendazole on OC cells. Our results demonstrated that oxfendazole significantly decreased the viability of OC cells. Oxfendazole inhibited the proliferation, induced G2/M phase arrest and apoptotic cell death in A2780 cells. The c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway was activated and reactive oxygen species (ROS) generation was increased in OC cells treated with oxfendazole; oxfendazole-induced apoptosis was notably abrogated when co-treated with JNK inhibitor SP600125 and ROS scavenger N-acetyl-L-cysteine (NAC), indicating that JNK/MAPK pathway activation and ROS accumulation was associated with the oxfendazole-induced apoptosis of OC cells. Moreover, oxfendazole could also induce the proliferation inhibition and apoptosis of cisplatin resistant cells. Collectively, these results revealed that oxfendazole may serve as a potential therapeutic agent for the treatment of OC.

Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.

The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) and 5-(9H-carbazol-2-yl) benzene-1,2,3-triol (6m) showed the most potent inhibitory activities against methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus faecalis with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 µg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (6e), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (6g), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant Acinetobacter baumannii. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, N-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.

Chinese nurses' perceptions on toxic leadership behaviours of nurse managers: A qualitative study.

AIM: The aim of this study is to explore the perceptions of Chinese registered nurses on toxic leadership behaviours of nurse managers and to determine its type, cause and response measures. BACKGROUND: The nurse manager is the front-line leader of the nurses who provide services directly to patients. Previous evidence suggests that toxic leadership behaviours of nurse managers do exist and it is necessary to understand the specifics of it. METHODS: We used phenomenological research methods to conduct semi-structured in-depth interviews among 12 nurses at a tertiary hospital in Wuhan over the period from January to March 2022. And the data were analysed using Colaizzi seven-step analysis method. RESULTS: Four themes were discovered: (a) nurses' perceptions of toxic leadership behaviours; (b) toxic leadership behaviours of nurse managers; (c) reasons for toxic leadership behaviours of nurse managers and (d) measures for toxic leadership behaviours of nurse managers. CONCLUSION: Chinese nurses are exposed to the toxic leadership of nurse managers for multiple reasons and respond differently. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nursing managers identify which behaviours are harmful to the nurse that require special attention in developing strategies to buffer against nurse managers' toxic leadership.

Biotransformation of rutin to isoquercitrin using recombinant α-L-rhamnosidase from Bifidobacterium breve.

OBJECTIVES: To biotransform rutin into isoquercitrin. RESULTS: A α-L-rhamnosidase from Bifidobacterium breve was produced by using Escherichia coli BL21 for biotransformation of rutin to isoquercitrin. The enzyme was purified by Ni(2+)-NTA chromatography to yield a soluble protein with a specific activity of 56 U protein mg(-1). The maximum enzyme activities were at pH 6.5, 55 °C, 20 mM rutin, and 1.2 U enzyme ml(-1). Under optimal conditions, the half-life of the enzyme was 96 h. The K m and V max values were 2.2 mM, 56.4 µmol mg(-1) min(-1) and 2.1 mM, 57.5 µmol mg(-1) min(-1) using pNP-Rha and rutin as substrates, respectively. The kinetic behavior indicated that the recombinant α-L-rhamnosidase has good catalytic performance for producing isoquercitrin. 20 mM rutin was biotransformed into 18.25 and 19.87 mM isoquercitrin after 60 and 240 min. CONCLUSION: The specific biotransformation of rutin to isoquercitrin using recombinant α-L-rhamnosidase from B. breve is a feasible method for use in industrial processes.

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis.

14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen-glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.

Association of Placental Tissue Metabolite Levels with Gestational Diabetes Mellitus: a Metabolomics Study.

The purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring.

Deep Learning Features and Metabolic Tumor Volume Based on PET/CT to Construct Risk Stratification in Non-small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: To build a risk stratification by incorporating PET/CT-based deep learning features and whole-body metabolic tumor volume (MTVwb), which was to make predictions about overall survival (OS) and progression-free survival (PFS) for those with non-small cell lung cancer (NSCLC) as a complement to the TNM staging. MATERIALS AND METHODS: The study enrolled 590 patients with NSCLC (413 for training and 177 for testing). Features were extracted by employing a convolutional neural network. The combined risk stratification (CRS) was constructed by the selected features and MTVwb, which were contrasted and integrated with TNM staging. In the testing set, those were verified. RESULTS: Multivariate analysis revealed that CRS was an independent predictor of OS and PFS. C-indexes of the CRS demonstrated statistically significant increases in comparison to TNM staging, excepting predicting OS in the testing set (for OS, C-index=0.71 vs. 0.691 in the training set and 0.73 vs. 0.736 in the testing set; for PFS, C-index=0.702 vs. 0.686 in the training set and 0.732 vs. 0.71 in the testing set). The nomogram that combined CRS with TNM staging demonstrated the most superior model performance in the training and testing sets (C-index=0.741 and 0.771). CONCLUSION: The addition of CRS improves TNM staging's predictive power and shows potential as a useful tool to support physicians in making treatment decisions.

An insect sclerotization-inspired antifouling armor on biomedical devices combats thrombosis and embedding.

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices. Herein, we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications. By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization, we develop a facile one-step method to crosslink bovine serum albumin (BSA) with oxidized hydrocaffeic acid (HCA), resulting in a stable and universal BSA@HCA armor. Furthermore, the surface of the BSA@HCA armor, enriched with carboxyl groups, supports the secondary grafting of polyethylene glycol (PEG), further enhancing both its antifouling performance and durability. The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins, platelets, and vascular cells in vitro. In ex vivo blood circulation experiment, the armored surface reduces thrombus formation by 95 %. Moreover, the antifouling armor retained over 60 % of its fouling resistance after 28 days of immersion in PBS. Overall, our armor engineering strategy presents a promising solution for enhancing the antifouling properties and clinical performance of temporary interventional medical devices.

Active Micro-Nano-Collaborative Bioelectronic Device for Advanced Electrophysiological Recording.

The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience. In recent years, active micro/nano-bioelectronic devices have undergone significant advancements, thereby facilitating the study of electrophysiology. The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale. In this paper, we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electro-excitable cells, focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals. Looking forward to the possibilities, challenges, and wide prospects of active micro-nano-devices, we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.

Revitalizing Ancient Mitochondria with Nano-Strategies: Mitochondria-Remedying Nanodrugs Concentrate on Disease Control.

Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad of vital functions across diverse cellular processes. Dysfunctions within mitochondria serve as catalysts for various diseases, prompting widespread cellular demise. Mounting research on remedying damaged mitochondria indicates that mitochondria constitute a valuable target for therapeutic intervention against diseases. But the less clinical practice and lower recovery rate imply the limitation of traditional drugs, which need a further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution and high efficacy by capitalizing on excellent nanomaterials and targeting drug delivery. Mitochondria-remedying nanodrugs have achieved ideal therapeutic effects. This review elucidates the significance of mitochondria in various cells and organs, while also compiling mortality data for related diseases. Correspondingly, nanodrug-mediate therapeutic strategies and applicable mitochondria-remedying nanodrugs in disease are detailed, with a full understanding of the roles of mitochondria dysfunction and the advantages of nanodrugs. In addition, the future challenges and directions are widely discussed. In conclusion, this review provides comprehensive insights into the design and development of mitochondria-remedying nanodrugs, aiming to help scientists who desire to extend their research fields and engage in this interdisciplinary subject.

Single-Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging.

Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, the aging-related cellular and molecular changes in human ovaries that occur during these reproductive years have not been elucidated. Here, single-cell RNA sequencing (scRNA-seq) of human ovaries is performed from different childbearing ages and reveals that the activation of the pyroptosis pathway increased with age, mainly in macrophages. The enrichment of pyroptotic macrophages leads to a switch from a tissue-resident macrophage (TRM)-involve immunoregulatory microenvironment in young ovaries to a pyroptotic monocyte-derived macrophage (MDM)-involved proinflammatory microenvironment in middle-aged ovaries. This remolded ovarian immuno-microenvironment further promotes stromal cell senescence and accelerated reproductive decline. This hypothesis is validated in a series of cell and animal experiments using GSDMD-KO mice. In conclusion, the work expands the current understanding of the ovarian aging process by illustrating a pyroptotic macrophage-involved immune mechanism, which has important implications for the development of novel strategies to delay senescence and promote reproductive health.

[Research progress in pathogenesis of IBD: the role of gut flora].

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the intestine. Both the etiology and the pathogenesis of IBD remain unclear. In recent years, the role of gut flora in IBD has become one of the most concerned issues. International metagenomic projects targeting the gut microbiota greatly promote the exploration of the role of gut flora in IBD. What are the characteristics of gut flora in IBD? How does it interact with host susceptibility? This review will discuss the enteric dysbacteriosis in IBD and show the interaction between gut flora, especially the dominant gut flora, and host susceptibility in IBD.

Pyroptosis orchestrates immune responses in endometriosis.

Endometriosis is a refractory and recurrent gynecological condition which affects about 10 % of reproductive-age women. The dysfunctional immune system is a well-established element in disease pathogenesis. Pyroptosis, a novel form of inflammatory cell death, has been revealed to be strongly connected with immune responses in tumors. Nevertheless, its relationship with microenvironment characteristics and clinical features in endometriosis is unclear. Here, we performed bioinformatics analysis on published data in humans and revealed a significant but neglected role of pyroptosis in endometriosis. Samples with higher PyrScores were generally accompanied with more aggressive disease features, such as EMT, angiogenesis and immune disorders. We further confirmed in animal models that pyroptosis exacerbated immune dysfunction by recruiting activated immune cell including macrophages, DC, neutrophils, CD8+ Tcm and Tregs with unregulated CCL2, CCL3, CXCL2 and CXCL3. Collectively, pyroptosis is a distinctive feature of endometriosis. Our work provides insights into further studies targeting pyroptosis for molecular typing and individualized precise therapy.

Influence of delayed blastulation and expansion grade on clinical outcomes of high-quality blastocyst transfer: an analysis of 1751 frozen-thawed cycles.

The aim of the study was to compare retrospectively the extent of blastulation timing (Day 5 or later) and expansion grade to predict the ability of blastocysts to give rise to a pregnancy. Blastocysts frozen on day 5 with a lower expansion grade (group D5) or day 6 with a higher expansion grade (group D6) were included. A single embryo was thawed and transferred on day 5 after ovulation or progesterone supplementation. Differences in patient baseline characteristics, endometrial preparation and pregnancy outcomes between groups were stratified by patient age and anti-Müllerian hormone (AMH) levels. Logistic regression was used to analyse the results. A total of 617 blastocysts in group D5 and 1134 blastocysts in group D6 were assessed. Stratified analyses showed higher biochemical pregnancy, clinical pregnancy and live birth rates for patients aged less than 30 years old, and higher ongoing pregnancy rate for patients with AMH ≥ 1.1 ng/ml. For patients aged less than 30 years old, the biochemical pregnancy, clinical pregnancy and live birth rates in group D5 were higher than those in group D6.

High-performance and -efficiency cardiomyocyte-based potential biosensor for temporal-specific detection of ion channel marine toxins.

Paralytic shellfish toxins (e.g., saxitoxin, STX; gonyautoxin-2, GTX-2) and tetrodotoxin (TTX) are highly toxic and widely distributed ion channel marine toxins which specifically block the voltage-dependent sodium channels (VDSCs), causing great harm to human health. It is urgent to exploit new detection methods with high specificity and high efficiency. Here, a portable high-throughput cardiomyocyte-based potential biosensor was established with cardiomyocytes, a 16-well microelectrodes (MEs) sensor and a robust 32-channel recording system, which presented high-quality and high-consistency extracellular field potential (EFP) signals in each well with a long duration of 80 h. The feature parameters, including firing rate (FR), spike amplitude (SA), spike slope (SS), spike duration (SD) and field potential duration (FPD), were extracted from EFP to quantitatively assess the toxic effects of these ion channel toxins. Importantly, the biosensor showed temporal specificity and parametric selectivity under toxin treatments, and FR, SS and SD were the optimal parameters to STX, TTX and GTX-2, respectively. This biosensor can rapidly detect 0.29 ng/mL STX, 0.30 ng/mL TTX and 0.16 ng/mL GTX-2 within 5 min, 10 min and 15 min, respectively. Thus, our novel multi-well cardiomyocyte-based biosensor will be a promising tool for high-effective detection of ion channel toxins.

Pre-harvest Nitrogen Limitation and Continuous Lighting Improve the Quality and Flavor of Lettuce (Lactuca sativa L.) under Hydroponic Conditions in Greenhouse.

Short-term nitrogen limitation and continuous lighting (red/blue = 3:1) were applied individually and in combination to butterhead and red oak leaf lettuce for 1, 2, or 3 days before harvest to assess their effects on improving the nutritional value and sweet taste and reducing nitrate content and bitterness of lettuce. The results suggested that a 3-day nitrogen limitation combined with continuous lighting reduced the lettuce content of nitrate and sesquiterpene lactones and improved the quantities of soluble sugar, soluble protein, anthocyanins, and phenolic compounds without reducing the fresh weight of lettuce. In addition, in vitro simulated digestion results suggested that the 3-day nitrogen limitation combined with continuous lighting significantly improved the sweetness and reduced the bitterness of lettuce compared to the control. In conclusion, nitrogen limitation combined with continuous lighting for 3 days before harvest effectively enhanced the quality and taste of lettuce, showing great potential for its use in hydroponic lettuce production.

A smart tablet-phone-based system using dynamic light modulation for highly sensitive colorimetric biosensing.

Facile, efficient, and inexpensive biosensing systems are in high demand for biomedical test. In recent years, numerous smartphone-based biosensing systems have been developed to match demand for biomedical test in source-limited environment. However, application of these smartphone-based biosensing systems was limited because of performance gap between the smartphone-based systems and commercial plate readers. In this study, we have developed a smart tablet-phone-based colorimetric plate reader (STPCPR) with intelligent and dynamic light modulation for broad-range colorimetric assays. The STPCPR allows controllable modulation of exciting light in three different color channels that is lack in conventional smartphone-based system. Using optimized exciting modulation, the STPCPR shows higher sensitivities, lower detection limits, and broader detection ranges in test of pigments, proteins, and cells when compared to conventional plate readers and smartphone-based system. Therefore, the developed STPCPR can serve as an ideal next-generation smartphone-based biosensing system for point-of-care colorimetric test in diverse biomedical applications in source-limited environment.

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney.

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and high mortality rate of AKI, the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot. Although existing evidence fully demonstrates that reactive oxygen and nitrogen species (RONS) burst at the AKI site is a major contributor to AKI progression, the heterogeneity, complexity, and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects. Recently, nanodrugs with intrinsic kidney targeting through the control of size, shape, and surface properties have opened exciting prospects for the treatment of AKI. Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments. In this review, we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy. First, we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI: hypoxia, harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI. Subsequently, we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI: nano-RONS-sacrificial agents, antioxidant nanozymes, and nanocarriers for antioxidants and anti-inflammatory drugs. These nanodrugs have demonstrated excellent therapeutic effects, such as greatly reducing oxidative stress damage, restoring renal function, and low side effects. Finally, we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.

Effects of Ambient O3 on Respiratory Mortality, Especially the Combined Effects of PM2.5 and O3.

BACKGROUND: In China, the increasing concentration of ozone (O3) has emerged as a significant air pollution issue, leading to adverse effects on public health, particularly the respiratory system. Despite the progress made in managing air pollution in China, it is crucial to address the problem of environmental O3 pollution at present. METHODS: The connection between O3 exposure and respiratory mortality in Shenyang, China, from 2014 to 2018 was analyzed by a time-series generalized additive regression model (GAM) with quasi-Poisson regression. Additionally, the potential combined effects of fine particulate matter (PM2.5) and O3 were investigated using the synergy index (SI). RESULTS: Our findings indicate that each 10 µg/m3 increase in O3 at lag 2 days was associated with a maximum relative risk (RR) of 1.0150 (95% CI: 1.0098-1.0202) for respiratory mortality in the total population. For individuals aged ≥55 years, unmarried individuals, those engaged in indoor occupations, and those with low educational attainment, each 10 µg/m3 increase in O3 at lag 07 days was linked to RR values of 1.0301 (95% CI: 1.0187-1.0417), 1.0437 (95% CI: 1.0266-1.0610), 1.0317 (95% CI: 1.0186-1.0450), and 1.0346 (95% CI: 1.0222-1.0471), respectively. Importantly, we discovered a synergistic effect of PM2.5 and O3, resulting in an SI of 2.372 on the occurrence of respiratory mortality. CONCLUSIONS: This study confirmed a positive association between O3 exposure and respiratory mortality. Furthermore, it highlighted the interaction between O3 and PM2.5 in exacerbating respiratory deaths.