Development of a coupled model to simulate and assess arsenic contamination and impact factors in the Jinsha River Basin, China.

With the increasing severity of arsenic (As) pollution, quantifying the environmental behavior of pollutant based on numerical model has become an important approach to determine the potential impacts and finalize the precise control strategies. Taking the industrial-intensive Jinsha River Basin as typical area, a two-dimensional hydrodynamic water quality model coupled with Soil and Water Assessment Tool (SWAT) model was developed to accurately simulate the watershed-scale distribution and transport of As in the terrestrial and aquatic environment at high spatial and temporal resolution. The effects of hydro-climate change, hydropower station construction and non-point source emissions on As were quantified based on the coupled model. The result indicated that higher As concentration areas mainly centralized in urban districts and concentration slowly decreased from upstream to downstream. Due to the enhanced rainfall, the As concentration was significantly higher during the rainy season than the dry season. Hydro-climate change and the construction of hydropower station not only affected the dissolved As concentration, but also affected the adsorption and desorption of As in sediment. Furthermore, As concentration increased with the input of non-point source pollution, with the maximum increase about 30%, resulting that non-point sources contributed important pollutant impacts to waterways. The coupled model used in pollutant behavior analysis is general with high potential application to predict and mitigate water pollution.

Exposure of individuals aged 18-44 years to personal care products in Beijing, China: Exposure profiles, possible influencing factors, and risk assessment.

Personal care products (PCPs) are a class of emerging pollutants that have attracted public concern owing to their harmful effects on humans and the environment. Biomonitoring data is valuable for insight the levels of PCPs in the human body and can be crucial for identifying potential health hazards. To gain a better understanding of timely exposure profiles and health risk of reproductive-age population to PCPs, we determined six parabens, six benzophenone-type ultraviolet filters, and three disinfectants in 256 urine samples collected from young adults aged 18-44 years in Beijing, China. The urinary levels of benzophenone-3 (BP-3) and 4-hydroxybenzophenone (4-OHBP) were significantly higher in summer compared to winter, suggesting these compounds have different seasonal usage patterns. Moreover, the total concentration of 15 PCPs in female was 430 ng/mL, approximately two times higher than that in male. P­chloro-m-xylenol (PCMX), as a new type of antibacterial agent, has the greatest level among all target analytes, indicating the increasingly use of this antibacterial alternative recently. Five potential influencing factors that lead to the elevated exposure level of PCPs were identified. Over 19% of the target population had a high hazard index value (greater than 1) which was attributed to exposure to propyl paraben (PrP), benzophenone-1 (BP-1), BP-3 and PCMX, indicating that PCPs may pose a relatively high exposure risk at environmental levels that should be a cause for concern.

Fabrication of Flame-Retardant Ammonium Polyphosphate Modified Phytic Acid-Based Rigid Polyurethane Foam with Enhanced Mechanical Properties.

Ammonium polyphosphate (APP) and self-made nickel phytate (PANi) were used as modified materials to prepare green biomass rigid polyurethane foam (RPUF). The flame retardancy, thermal stability, smoke toxicity and mechanical properties of the modified RPUF were investigated by limiting oxygen index (LOI), a cone calorimetry (CONE) test, thermogravimetric analysis and a compression test. The results showed that the RPUF with 10 wt% APP (PANi/APP10) had the highest LOI of 26.5%. Its peak heat release rate (PHRR) and total heat release (THR) were reduced by 29.64% and 24.05% compared with PANi/APP0 without APP. And its smoke production rate (SPR) and total smoke release (TSR) decreased by 33.14% and 19.88%, respectively. Compared with pure RPUF, the compressive strength of PANi/APP10 was increased by 50%, mainly because APP itself was an ultra-fine powder, which was better compatible with the matrix and improved the hardness of the material. The results showed that the synergistic effect of the gas phase and the condensed phase mechanism could effectively improve the flame-retardant effect. The current research results provided a new strategy for the preparation of green and low-toxicity RPUF.

Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.

Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.

A bibliometric analysis and visualization of normal pressure hydrocephalus.

Background: Normal pressure hydrocephalus (NPH) has drawn an increasing amount of attention over the last 20 years. At present, there is a shortage of intuitive analysis on the trends in development, key contributors, and research hotspots topics in the NPH field. This study aims to analyze the evolution of NPH research, evaluate publications both qualitatively and quantitatively, and summarize the current research hotspots. Methods: A bibliometric analysis was conducted on data retrieved from the Web of Science Core Collection (WoSCC) database between 2003 and 2023. Quantitative assessments were conducted using bibliometric analysis tools such as VOSviewer and CiteSpace software. Results: A total of 2,248 articles published between 2003 and 2023 were retrieved. During this period, the number of publications steadily increased. The United States was the largest contributor. The University of Gothenburg led among institutions conducting relevant research. Eide P. K. was the most prolific author. The Journal of Neurosurgery is the leading journal on NPH. According to the analysis of the co-occurrence of keywords and co-cited references, the primary research directions identified were pathophysiology, precise diagnosis, and individualized treatment. Recent research hotspots have mainly focused on epidemiology, the glymphatic system, and CSF biomarkers. Conclusion: The comprehensive bibliometric analysis of NPH offers insights into the main research directions, highlights key countries, contributors, and journals, and identifies significant research hotspots. This information serves as a valuable reference for scholars to further study NPH.

Detecting biomarkers by dynamic nuclear polarization enhanced magnetic resonance.

Hyperpolarization stands out as a technique capable of significantly enhancing the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Dynamic nuclear polarization (DNP), among various hyperpolarization methods, has gained prominence for its efficacy in real-time monitoring of metabolism and physiology. By administering a hyperpolarized substrate through dissolution DNP (dDNP), the biodistribution and metabolic changes of the DNP agent can be visualized spatiotemporally. This approach proves to be a distinctive and invaluable tool for non-invasively studying cellular metabolism in vivo, particularly in animal models. Biomarkers play a pivotal role in influencing the growth and metastasis of tumor cells by closely interacting with them, and accordingly detecting pathological alterations of these biomarkers is crucial for disease diagnosis and therapy. In recent years, a range of hyperpolarized DNP molecular bioresponsive agents utilizing various nuclei, such as 13C, 15N, 31P, 89Y, etc., have been developed. In this context, we explore how these magnetic resonance signals of nuclear spins enhanced by DNP respond to biomarkers, including pH, metal ions, enzymes, or redox processes. This review aims to offer insights into the design principles of responsive DNP agents, target selection, and the mechanisms of action for imaging. Such discussions aim to propel the future development and application of DNP-based biomedical imaging agents.

A double-sided coating paper antibacterial indicator card based on polyvinyl alcohol/sodium carboxymethyl cellulose-anthocyanins and chitosan-halloysite nanotubes loaded essential oil to monitor fish freshness.

This study developed a multifunctional paper-based freshness antibacterial indicator card by dual-sided coating on conventional filter paper. The indicator coating was composed of anthocyanins from purple cabbage, and polyvinyl alcohol and sodium carboxymethyl cellulose as substrates while the antibacterial coating contained halloysite nanotubes for loaded thyme essential oil and chitosan. FT-IR, XRD, and SEM analyses revealed that the components were well-mixed, and the paper was tightly bound to the coatings through hydrogen bonds. Additionally, the coating effectively filled the porous fiber gaps in the paper, significantly enhancing the mechanical properties of the paper. The tensile strength of the coated paper was enhanced from 14.28 MPa to a range of 42.25-47.71 MPa, and the bending resistance was increased from 0.35 N·mm to a range of 1.72-1.99 N·mm compared to the uncoated paper. The addition of anthocyanins provided excellent sensitivity to pH and ammonia for the indicator card. Furthermore, the coating including halloysite nanotubes for loaded thyme essential oil exhibited antimicrobial resistance against Escherichia coli and Staphylococcus aureus. When used on fresh carp, the antibacterial indicator card not only indicated the freshness of the carp but also extended the best before date of the fish meat by 1-2 days. The indicator exhibited the most pronounced color transformation and optimal freshness indication performance when the mass fraction of anthocyanins was 2 %.

LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T cells.

BACKGROUND: The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms. METHODS: Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4+ T cell differentiation, proliferation, and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species, and ATP production measurements. The intracellular mechanism of LPG 18:0 in Tregs was investigated using small molecule inhibitors. RESULTS: The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG18:0 impaired naïve CD4+ T cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation. CONCLUSIONS: This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD+/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.

Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes.

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[n.1.1]alkanes (usually n ≤ 3), their utilization in the synthesis of bicyclo[4.1.1]octane derivatives (BCOs) is still underdeveloped. Here, a palladium-catalyzed formal (4 + 3) reaction of BCBs with 1,4-O/C dipole precursors for the synthesis of oxa-BCOs is described. Unlike previous catalytic polar (3 + X) cycloadditions of BCBs, which are typically achieved through the activation of BCB substrates, the current reaction represents a novel strategy for realizing the cycloaddition of BCBs through the activation of the "X" cycloaddition partner. Moreover, the obtained functionalized oxa-BCOs products can be readily modified through various synthetic transformations.

Airway bacterial microbiome signatures correlate with occupational pneumoconiosis progression.

Recent evidence has pinpointed a key role of the microbiome in human respiratory health and disease. However, significant knowledge gaps still exist regarding the connection between bacterial communities and adverse effects caused by particulate matters (PMs). Here, we characterized the bacterial microbiome along different airway sites in occupational pneumoconiosis (OP) patients. The sequencing data revealed that OP patients exhibited distinct dysbiosis in the composition and function of the respiratory microbiota. To different extents, there was an overall increase in the colonization of microbiota, such as Streptococcus, implying a possible intrusion pathway provided by exogenous PMs. Compared to those of healthy subjects, unhealthy living habits (i.e., smoking) had a greater impact on microbiome changes in OP patients. Importantly, the associations between the bacterial community and disease indicators indicated that specific bacterial species, including Prevotella, Actinobacillus, and Leptotrichia, might be surrogate markers of OP disease progression. Collectively, our results highlighted the potential participation of the bacterial microbiota in the pathogenesis of respiratory diseases and helped in the discovery of microbiome-based diagnostics for PM-induced disorders.

Region-selective and site-specific glycation of influenza proteins surrounding the viral envelope membrane.

Analysis of protein modifications is critical for quality control of therapeutic biologics. However, the identification and quantification of naturally occurring glycation of membrane proteins by mass spectrometry remain technically challenging. We used highly sensitive LC MS/MS analyses combined with multiple enzyme digestions to determine low abundance early-stage lysine glycation products of influenza vaccines derived from embryonated chicken eggs and cultured cells. Straightforward sequencing was enhanced by MS/MS fragmentation of small peptides. As a result, we determined a widespread distribution of lysine modifications attributed by the region-selectivity and site-specificity of glycation toward influenza matrix 1, hemagglutinin and neuraminidase. Topological analysis provides insights into the site-specific lysine glycation, localizing in the distinct structural regions of proteins surrounding the viral envelope membrane. Our finding highlights the proteome-wide discovery of lysine glycation of influenza membrane proteins and potential effects on the structural assembly, stability, receptor binding and enzyme activity, demonstrating that the impacts of accumulated glycation on the quality of products can be directly monitored by mass spectrometry-based structural proteomics analyses.

Discovery of FO-4-15, a novel 1,2,4-oxadiazole derivative, ameliorates cognitive impairments in 3×Tg mice by activating the mGluR1/CaMKIIα pathway.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

Sirt1 m6A modification-evoked Leydig cell senescence promotes Cd-induced testosterone decline.

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased ß-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.

Atmospheric observation and emission estimation of HFC-125 and HFC-32 in China from four representative cities.

HFC-125 and HFC-32 are fluorinated greenhouse gases of great concern due to their high GWPs and increasing background atmospheric concentrations. Long-term atmospheric observations of HFC-125 and HFC-32 were carried out in four representative cities of China (Beijing, Guangzhou, Hangzhou, and Lanzhou) from January 2012 to October 2019. Overall, the annual mean atmospheric concentrations of HFC-125 and HFC-32 both showed increasing trends, with average rates of 4.8 ppt yr-1 and 7.9 ppt yr-1. The average concentrations of HFC-125 and HFC-32 in urban areas were significantly higher than those in suburban areas. Significant differences in atmospheric concentrations of the two HFCs were observed among the four cities. HFC-125 and HFC-32 emissions were estimated accordingly, averaging 6.2 Gg yr-1 (23.6 Mt. CO2-eq) and 5.7 Gg yr-1 (4.3 Mt. CO2-eq) during 2012 and 2019 and growing at rates of 0.8 Gg yr-1 (3.1 Mt. CO2-eq) and 0.8 Gg yr-1 (0.6 Mt. CO2-eq), respectively, with an increasing contribution to global radiative forcing. The bottom-up inventories of HFC-125 and HFC-32 in the four cities increased annually from 2012 to 2019, with the highest emissions in Beijing, while the top-down emissions fluctuated during the research period. SYNOPSIS: The atmospheric concentrations of HFC-125 and HFC-32 were measured from 2012 to 2019 in four representative cities of China. Both HFC emissions at national and city levels were estimated using observation-based and inventory methods.

Enhanced ammonia nitration by Bio-Electrochemical systems with constructed wetlands.

The insufficient abundance of electron acceptors for ammonia during electron transfer in constructed wetlands (CWs) results in low nitrification rates. This study developed a green, low-carbon CWs enhanced by a bio-electrochemical systems (BESs-CWs) to achieve efficient ammonia (NH4+-N) removal. Electrode enhancement significantly promoted NH4+-N removal. Compared with traditional CWs, the average removal efficiency of NH4+-N in the BESs-CWs increased from 62.9 % to 90.6 %. The intermittent voltage driven by the photovoltaic power system caused minimal plant stress. However, electrode enhancement significantly affected microbial communities involved in short-path nitrification and denitrification within the biofilm. Specifically, the removal rate of NH4+-N by BESs-CWs under electrode enhancement was increased by 27.7 % compared to traditional CWs, enhancing the electron output of NH4+-N in the BESs-CWs. This system provides a method of ammonia nitration for CWs under poor electron acceptor conditions.

Authentication and validation of key genes in the treatment of atopic dermatitis with Runfuzhiyang powder: combined RNA-seq, bioinformatics analysis, and experimental research.

Background: Atopic dermatitis (AD) is inflammatory disease. So far, therapeutic mechanism of Runfuzhiyang powder on AD remains to be studied. This study aimed to mine key biomarkers to explore potential molecular mechanism for AD incidence and Runfuzhiyang powder treatment. Methods: The control group, AD group, treat group (AD mice treated with Runfuzhiyang powder were utilized for studying. Differentially expressed AD-related genes were acquired by intersecting of key module genes related to control group, AD group and treatment group which were screened by WGCNA and AD-related differentially expressed genes (DEGs). KEGG and GO analyses were further carried out. Next, LASSO regression analysis was utilized to screen feature genes. The ROC curves were applied to validate the diagnostic ability of feature genes to obtain AD-related biomarkers. Then protein-protein interaction (PPI) network, immune infiltration analysis and single-gene gene set enrichment analysis (GSEA) were presented. Finally, TF-mRNA-lncRNA and drug-gene networks of biomarkers were constructed. Results: 4 AD-related biomarkers (Ddit4, Sbf2, Senp8 and Zfp777) were identified in AD groups compared with control group and treat group by LASSO regression analysis. The ROC curves revealed that four biomarkers had good distinguishing ability between AD group and control group, as well as AD group and treatment group. Next, GSEA revealed that pathways of E2F targets, KRAS signaling up and inflammatory response were associated with 4 biomarkers. Then, we found that Ddit4, Sbf2 and Zfp777 were significantly positively correlated with M0 Macrophage, and were significantly negatively relevant to Resting NK. Senp8 was the opposite. Finally, a TF-mRNA-lncRNA network including 200 nodes and 592 edges was generated, and 20 drugs targeting SENP8 were predicted. Conclusion: 4 AD-related and Runfuzhiyang powder treatment-related biomarkers (Ddit4, Sbf2, Senp8 and Zfp777) were identified, which could provide a new idea for targeted treatment and diagnosis of AD.

Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to alleviate ulcerative colitis.

Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.

Association of carbon monoxide poisoning with cardiovascular disease risk: A systematic review and meta-analysis.

Objective: This study aims to provide an updated overview of the relationship between carbon monoxide poisoning (COP) and cardiovascular disease. Methods: A systematic literature search was conducted in PubMed, Embase, Cochrane, and Web of Science databases up to September 2023. The association between COP patients and cardiovascular adverse events was examined and summarized. The outcomes included arrhythmia, coronary heart disease, heart failure, myocardial infarction, major adverse cardiovascular events (MACE), carboxyhaemoglobin percent (COHB%), Pondus Hydrogenii (PH) electrocardiography (ECG) parameters. Results: Eight eligible articles, involving a total of 251,971 patients, were included for evidence synthesis. The analysis revealed a heightened incidence of MACE in patients with COP. Additionally, COP exhibited an impact on specific ECG parameters. The incidence of MACE after COP was found to be similar in Korean and Chinese populations, and there was no significant effect of gender or underlying diseases on MACE incidence following COP. The incidence of MACE after COP did not differ significantly in individuals aged 50 years and older. Conclusions: Considering the observed heterogeneity and potential biases in the selected studies, emergency physicians should be aware of the increased likelihood of cardiovascular events in patients diagnosed with COP.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.