Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients.

OBJECTIVE: The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood. METHODS: Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP. RESULTS: Patients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4+ T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs. CONCLUSION: We profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.

Mediation effect of self-efficacy on the relationship between perceived social support and resilience in caregivers of patients with first-stroke in China: a cross-sectional survey.

BACKGROUND: Self-efficacy, perceived social support, and resilience in caregivers of first-stroke patients are closely related, while the interaction mechanism remains unclear. This research explores the mediation effect of self-efficacy in the relationship between perceived social support and resilience in caregivers of first-stroke patients in China. METHODS: Convenience sampling was designed and used to recruit participants from the General Hospital of Northern Theater in Shenyang, Liaoning Province, China, from February to October 2022, in which 207 self-reported participants completed the Connor-Davidson Resilience Scale (CD-RISC), Multidimensional Scale of Perceived Social Support (MSPSS) and General Self Efficacy Scale (GSES). In addition, the mediation effect of self-efficacy between perceived social support and resilience was determined by the PROCESS macro for SPSS. RESULT: Among the 207 caregivers of patients with first-stroke, the mean CD-RISC, MSPPS and GSES scores were (72.17 ± 11.28), (71.17 ± 8.99), and (29.64 ± 5.03) respectively. Caregivers' self-efficacy was positively correlated with perceived social support (r = 0.439, p < 0.01) and resilience (r = 0.730, p < 0.01). Self-efficacy served a mediation function partially between perceived social support and resilience, whose effect accounted for 52.90% of the total. CONCLUSION: Both simple and mediation roles of perceived social support and self-efficacy are established in the relationship of resilience among caregivers of first-stroke patients. Positive social support and self-efficacy are two important targets for future interventional studies, and interventions on them may synergistically improve resilience. Hence, the nurses and community workers should correctly evaluate social support and self-efficacy, confirm the health education requirements, and implement counseling intervention to protect and improve the health of first-stroke patients and their families.

Managing urban development could halve nitrogen pollution in China.

Halving nitrogen pollution is crucial for achieving Sustainable Development Goals (SDGs). However, how to reduce nitrogen pollution from multiple sources remains challenging. Here we show that reactive nitrogen (Nr) pollution could be roughly halved by managed urban development in China by 2050, with NH3, NOx and N2O atmospheric emissions declining by 44%, 30% and 33%, respectively, and Nr to water bodies by 53%. While rural-urban migration increases point-source nitrogen emissions in metropolitan areas, it promotes large-scale farming, reducing rural sewage and agricultural non-point-source pollution, potentially improving national air and water quality. An investment of approximately US$ 61 billion in waste treatment, land consolidation, and livestock relocation yields an overall benefit of US$ 245 billion. This underscores the feasibility and cost-effectiveness of halving Nr pollution through urbanization, contributing significantly to SDG1 (No poverty), SDG2 (Zero hunger), SDG6 (Clean water), SDG12 (Responsible consumption and production), SDG14 (Climate Action), and so on.

Prediction of recurrence-related factors for patients with early-stage cervical cancer following radical hysterectomy and adjuvant radiotherapy.

OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.

Study on Low Thermal-Conductivity of PVDF@SiAG/PET Membranes for Direct Contact Membrane Distillation Application.

In order to enhance the separation performance and reduce the heat loss of transmembrane for membrane distillation, the thermal efficiency and hydrophobicity of the membrane distillation need to be simultaneously enhanced. In this work, a polyvinylidene difluoride/polyethylene glycol terephthalate (PVDF/PET) hydrophobic/hydrophilic membrane has been prepared by non-solvent phase induction method. Nanosized silica aerogel (SiAG) with high porosity has been added to the composite membranes. The modifying effects and operating conditions on permeate flux and thermal efficiency in direct contact membrane distillation (DCMD) are investigated. Furthermore, the latent heat of vaporization and the heat transfer across the membranes have been compared for SiAG addition, which indicates that the composite PVDF@SiAG/PET membranes demonstrate a great potential for distillation-separation application due to their high heat efficiency.

Network pharmacology-based study on the mechanism of ShenKang injection in diabetic kidney disease through Keap1/Nrf2/Ho-1 signaling pathway.

OBJECTIVE: To study the effect of ShenKang Injection (SKI) on the kidneys of DKD rats and its effect on oxidative stress mediated by the Keap1/Nrf2/Ho-1 signaling pathway through network pharmacology and in vivo and in vitro experiments. METHODS: SKI drug targets were screened by TCMSP, DKD targets were screened by GenGards, OMIM, Drugbank, TTD, and Disgenet databases, and the two intersected for PPI network analysis and target prediction was performed by GO and KEGG. A total of 40 SD rats were randomly divided into 10 in the control group and 30 in the model group. After the model group was fed 8 W with high-sugar and high-fat diets, a DKD model was constructed by one-time intraperitoneal injection of streptozotocin (35 mg/kg). According to the weight, the model animals were randomly divided into three groups: 8 for model validation group, 8 for Irbesartan (25 mg/kg daily) group, and 8 for SKI group (5 ml/kg). Gavaged deionized water was given to the control group and the model validation group equally. The general conditions of the rats were observed, their body weights measured and their urine volumes recorded for 24 h. After the intervention of 16 W, serum was collected to detect Urea, Scr, blood lipids, and oxidative stress and lipid peroxidation indicators; Transmission electron microscopy, HE and Mallory staining were used to observe the pathological morphology of renal tissue. Immunohistochemistry and RT-PCR were used to detect the expression of Keap1, Nrf2, Ho-1, Gpx4 proteins and mRNA in rat kidney tissues. HK-2 cells were cultured in vitro and divided into: the control group, AGEs (200 µg/ml) group and AGEs + SKI group. The cell activity of the groups was detected using CCK-8 after 48 h of cell culture, and ROS were detected using fluorescent probes. Gpx4 expression was detected by immunofluorescence, while Keap1, Nrf2, Ho-1, and Gpx4 were detected by Western Blot. RESULTS: Network pharmacological analysis predicted that SKI may delay DKD kidney injury by affecting redox-related signaling pathways and mitigating AGEs-induced oxidative stress. In the animal experiment, compared with the model validation group, the general state of rats in the SKI group was improved, and 24-hour urine protein levels were significantly reduced, and the Scr in the serum was reduced. A decreasing trend was seen in Urea, and TC, TG, and LDL levels significantly decreased and the levels of ROS, LPO and MDA were significantly lowered. Pathological staining showed that renal interstitial fibrosis was significantly improved, and electron microscopy showed that foot process effacement was alleviated. Immunohistochemistry and RT-PCR showed decreased expression of Keap1 protein and mRNA in kidney tissues of the SKI group. Additionally, Nrf2, Ho-1, and Gpx4 proteins and mRNA were expressed significantly. In the cell experiment, after 48 h treatment with AGEs, ROS in HK-2 cells increased significantly and cell activity decreased significantly, while cell activity in AGEs + SKI group increased significantly and ROS decreased. The expression of Keap1 protein in HK-2 cells in the AGEs + SKI group decreased, while the expression of Nrf2, Ho-1 and Gpx4 proteins increased significantly. CONCLUSION: SKI can protect kidney function in DKD rats, delay DKD progression, inhibit AGEs-induced oxidative stress damage in HK-2 cells, and the mechanism of SKI to improve DKD may be achieved by activating the Keap1/Nrf2/Ho-1 signal transduction pathway.

ER Ca2+ overload activates the IRE1α signaling and promotes cell survival.

BACKGROUND: Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear. RESULTS: Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells. CONCLUSIONS: Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death.

Targeting crosstalk of STAT3 between tumor-associated M2 macrophages and Tregs in colorectal cancer.

A comprehensive analysis of the molecular mechanism underlying colorectal tumor evaluated the development of colorectal cancer (CRC) and proposed targeting small molecular inhibitors. Nonetheless, the adoptive resistance of these therapies remains a challenge with respect to achieving an effective clinical response. Thus, identifying the molecular mechanisms guiding CRC growth is essential. The results of The Cancer Genome Atlas (TCGA) dataset analysis demonstrated a critical role of signal transducer and activator of transcription 3 (STAT3) pathway in tumor immune suppression via modulation of the recruitment of Treg cells and M2 type tumor-associated macrophages. The in vivo experiments elucidate that targeting STAT3 pathways markedly reduce the proportions of TAMs and Tregs by inhibiting tumor progression. These findings revealed crosstalk between Treg cells and M2 macrophages, proving a potential therapeutic strategy for CRC therapy. Combinatorial treatment with STAT3 inhibitor and programmed death 1 (PD-1) antibody therapy effectively prevents CRC tumor growth in a mouse model with high anti-tumor immunity. In summary, targeting STAT3 disrupts the interaction between Treg cells and M2 macrophages and improves the anti-tumor response in CRC, thereby offering a promising strategy to treat patients with CRC.

Potential inhibitory effects of compounds ZK-PI-5 and ZK-PI-9 on trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith).

Introduction: Spodoptera frugiperda is an omnivorous agricultural pest which is great dangerous for grain output. Methods: In order to investigate the effects of potential trehalase inhibitors, ZK-PI-5 and ZK-PI-9, on the growth and development of S. frugiperda, and to identify new avenues for S. frugiperda control, we measured the content of the trehalose, glucose, glycogen and chitin, enzyme activity, and gene expression levels in trehalose and chitin metabolism of S. frugiperda. Besides, their growth and development were also observed. Results: The results showed that ZK-PI-9 significantly reduced trehalase activity and ZK-PI-5 significantly reduced membraned-bound trehalase activity. Moreover, ZK-PI-5 inhibited the expression of SfTRE2, SfCHS2, and SfCHT, thus affecting the chitin metabolism. In addition, the mortality of S. frugiperda in pupal stage and eclosion stage increased significantly after treatment with ZK-PI-5 and ZK-PI-9, which affected their development stage and caused death phenotype (abnormal pupation and difficulty in breaking pupa). Discussion: These results have provided a theoretical basis for the application of trehalase inhibitors in the control of agricultural pests to promote future global grain yield.

Climate change unequally affects nitrogen use and losses in global croplands.

Maintaining food production while reducing agricultural nitrogen pollution is a grand challenge under global climate change. Yet, the response of global agricultural nitrogen uses and losses to climate change on the temporal and spatial scales has not been fully characterized. Here, using historical data for 1961-2018 from over 150 countries, we show that global warming leads to small temporal but substantial spatial impacts on cropland nitrogen use and losses. Yield and nitrogen use efficiency increase in 29% and 56% of countries, respectively, whereas they reduce in the remaining countries compared with the situation without global warming in 2018. Precipitation and farm size changes would further intensify the spatial variations of nitrogen use and losses globally, but managing farm size could increase the global cropland nitrogen use efficiency to over 70% by 2100. Our results reveal the importance of reducing global inequalities of agricultural nitrogen use and losses to sustain global agriculture production and reduce agricultural pollution.

Cost-effective mitigation of nitrogen pollution from global croplands.

Cropland is a main source of global nitrogen pollution1,2. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers3. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (1012 g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.

Ca2+ homeostasis maintained by TMCO1 underlies corpus callosum development via ERK signaling.

Transmembrane of coiled-coil domains 1 (TMCO1) plays an important role in maintaining homeostasis of calcium (Ca2+) stores in the endoplasmic reticulum (ER). TMCO1-defect syndrome shares multiple features with human cerebro-facio-thoracic (CFT) dysplasia, including abnormal corpus callosum (CC). Here, we report that TMCO1 is required for the normal development of CC through sustaining Ca2+ homeostasis. Tmco1-/- mice exhibit severe agenesis of CC with stalled white matter fiber bundles failing to pass across the midline. Mechanistically, the excessive Ca2+ signals caused by TMCO1 deficiency result in upregulation of FGFs and over-activation of ERK, leading to an excess of glial cell migration and overpopulated midline glia cells in the indusium griseum which secretes Slit2 to repulse extension of the neural fiber bundles before crossing the midline. Supportingly, using the clinical MEK inhibitors to attenuate the over-activated FGF/ERK signaling can significantly improve the CC formation in Tmco1-/- brains. Our findings not only unravel the underlying mechanism of abnormal CC in TMCO1 defect syndrome, but also offer an attractive prevention strategy to relieve the related agenesis of CC in patients.

A Study on Nurse Manager Competency Model of Tertiary General Hospitals in China.

(1) Background: The nurse manager competency model is widely used in hospitals in the management of nursing human resources. This study aimed to construct a scientific and practical model of nurse manager competency, which can be used as a tool by hospitals to select nurse managers. (2) Methods: The nurses' competency indicators were first collected through a literature review and behavioral event interview, and the preliminary screening of competency elements was based on the Delphi method. Then, questionnaires and statistical analyses were used to determine the elements of the model. The reliability was determined using Cronbach's alpha. Factor analysis was used to delineate the dimensions of the model. (3) Results: The results of the factor analysis show that the 22 competency elements were grouped into the four dimensions of leadership and management ability, personal traits, professional quality, and professional ability. The Cronbach's alpha coefficients of the four dimensions ranged from 0.745 to 0.885, which indicated a high level of reliability. The result of the factor analysis indicated a high structural validity and fitting effect. (4) Conclusions: Our study indicates that the nurse manager competency model of tertiary general hospitals is an instrument with fair reliability and validity that fully reflects the characteristics of nurses in Chinese public hospitals.

Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in Drosophila.

Background: Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive. Purpose: To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion. Methods: We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the RasV12/lgl -/- -induced Drosophila tumour model to carry out experimental verification. Results: XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the RasV12/lgl -/- model. Finally, the mRNA level of the transcription complex AP-1 component c-FOS was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model. Conclusion: The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.

Effects of a smartphone application named "Shared Decision Making Assistant" for informed patients with primary liver cancer in decision-making in China: a quasi-experimental study.

BACKGROUND: It is well known that decision aids can promote patients' participation in decision-making, increase patients' decision preparation and reduce decision conflict. The goal of this study is to explore the effects of a "Shared Decision Making Assistant" smartphone application on the decision-making of informed patients with Primary Liver Cancer (PLC) in China. METHODS: In this quasi-experimental study , 180 PLC patients who knew their real diagnoses in the Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China, from April to December 2020 were randomly assigned to a control group and an intervention group. Patients in the intervention group had an access to the "Shared Decision Making Assistant" application in decision-making, which included primary liver cancer treatment knowledge, decision aids path, continuing nursing care video clips, latest information browsing and interactive platforms. The study used decision conflict scores to evaluate the primary outcome, and the data of decision preparation, decision self-efficacy, decision satisfaction and regret, and knowledge of PLC treatment for secondary outcomes. Then, the data were entered into the SPSS 22.0 software and were analyzed by descriptive statistics, Chi-square, independent t-test, paired t-test, and Mann-Whitney tests. RESULTS: Informed PLC patients in the intervention group ("SDM Assistant" group) had significantly lower decision conflict scores than those in the control group. ("SDM Assistant" group: 16.89 ± 8.80 vs. control group: 26.75 ± 9.79, P < 0.05). Meanwhile, the decision preparation score (80.73 ± 8.16), decision self-efficacy score (87.75 ± 6.87), decision satisfaction score (25.68 ± 2.10) and knowledge of PLC treatment score (14.52 ± 1.91) of the intervention group were significantly higher than those of the control group patients (P < 0.05) at the end of the study. However, the scores of "regret of decision making" between the two groups had no statistical significance after 3 months (P > 0.05). CONCLUSIONS: Access to the "Shared Decision Making Assistant" enhanced the PLC patients' performance and improved their quality of decision making in the areas of decision conflict, decision preparation, decision self-efficacy, knowledge of PLC treatment and satisfaction. Therefore, we recommend promoting and updating the "Shared Decision Making Assistant" in clinical employment and future studies.

Benefit finding: understanding the impact and public health factors among COVID-19 patients in China.

BACKGROUND: This study aimed to determine the level of benefit finding among COVID-19 patients in a hospital in mainland China, and to identify its associated impact and public health factors. METHODS: Using a cross-sectional design, a total of 288 COVID-19 patients were recruited in Huoshenshan Hospital in Wuhan, China to complete a survey on benefit finding. The level of benefit finding evaluated by the Benefit Finding Scale (BFS), mental resilience evaluated by the Connor-Davidson Resilience Scale (CD-RISC), social support evaluated by the Multidimensional Scale of Perceived Social Support (MSPSS), medical coping modes evaluated by the Medical Coping Modes Questionnaire (MCMQ), and general information was collected by self-designed questionnaires. T-test and chi-square test were used for single-factor analyses. For multiple factor analyses, multivariate regression analyses were performed. RESULT: The mean BFS score of 288 participants was 61.26±10.25. Multivariate regression analysis showed that the factors associated with the level of benefit finding among COVID-19 patients in China included education level, having experienced major event, social support, optimism, confrontive coping and resigned coping mode. CONCLUSIONS: In general, the patients with COVID-19 in this study had a middle level of benefit finding. Health professionals should take measures to identify the influencing factors on the quality of the life and take targeted intervention measures.

Integrated livestock sector nitrogen pollution abatement measures could generate net benefits for human and ecosystem health in China.

Nearly one quarter of global meat production occurs in China, but a lack of detailed spatial livestock production data hinders ongoing pollution mitigation strategies. Here we generate high-resolution maps of livestock systems in China using over 480,000 farm surveys from 2007 to 2017, finding that China produced more livestock protein with fewer animals and less total pollution impact through better breeding, feeding and manure management in large-scale livestock farms. Hotspots of production can be observed across the North China Plain, Northeastern China and the Sichuan Basin. The Clean Water Act reduced manure nutrient losses to water by one third, but with limited changes to methane and ammonia emissions. Integrated production and consumption abatement measures costing approximately US$6 billion could further reduce livestock pollution by 2050, realizing benefits of up to US$30 billion due to avoided human health and ecosystem costs.

Abating ammonia is more cost-effective than nitrogen oxides for mitigating PM2.5 air pollution.

Fine particulate matter (PM2.5, particles with a mass median aerodynamic diameter of less than 2.5 micrometers) in the atmosphere is associated with severe negative impacts on human health, and the gases sulfur dioxide, nitrogen oxides, and ammonia are the main PM2.5 precursors. However, their contribution to global health impacts has not yet been analyzed. Here, we show that nitrogen accounted for 39% of global PM2.5 exposure in 2013, increasing from 30% in 1990 with rising reactive nitrogen emissions and successful controls on sulfur dioxide. Nitrogen emissions to air caused an estimated 23.3 million years of life lost in 2013, corresponding to an annual welfare loss of 420 billion United States dollars for premature death. The marginal abatement cost of ammonia emission is only 10% that of nitrogen oxides emission globally, highlighting the priority for ammonia reduction.