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Bacterial biofilm-related infections have become a significant global concern in public health and economy. Extracellular DNA (eDNA) is regarded as one of the key elements of extracellular polymeric substances (EPS) in bacterial biofilm, providing robust support to maintain the stability of bacterial biofilms for fighting against environmental stresses (such as antibiotics, reactive oxygen species (ROS), and hyperthermia). In this study, ternary AuAgCu hydrogels nanozyme with porous network structures were utilized for the immobilization of DNase (AuAgCu@DNase hydrogels) to realize enhanced biofilm decomposition and antibacterial therapy of MRSA. The prepared AuAgCu@DNase hydrogels can efficiently hydrolyze eDNA in biofilms so that the generated ROS and hyperthermia by laser irradiation can permeate into the interior of the biofilm to achieve deep sterilization. The typical interface interactions between AuAgCu hydrogels and DNase and the excellent photothermal-boost peroxidase-like performances of AuAgCu hydrogels take responsibility for the enhanced antibacterial activity. In the MRSA-infected wounds model, the in vivo antibacterial results revealed that the AuAgCu@DNase hydrogels possess excellent drug-resistant bacteria-killing performance with superb biocompatibility. Meanwhile, the pathological analysis of collagen deposition and fibroblast proliferation of wounds demonstrate highly satisfactory wound healing. This work offers an innovative path for developing nanozyme-enzyme antibacterial composites against drug-resistant bacteria and their biofilms.
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Arsenic contamination in environmental water sources poses a significant threat to human health, necessitating the development of sensitive and accessible detection methods. This study presents a multidimensional optimization of a bacterial biosensor for the susceptible and deoxyviolacein (DV)-based visual detection of arsenic. The research involved screening six different arsenic resistance (ars) operons and optimizing the genetic circuit to minimize background noise. Introducing an arsenic-specific transport channel enhanced the sensor's sensitivity to 1 nM with a quantitative range from 0.036 to 1.171 µM. The pigment-based biosensor offers a simple colorimetric approach for arsenic detection without complex instrumentation. The preferred biosensor demonstrated characteristics of anti-chelating agent interference, consistently quantified As(III) concentrations ranging from 0.036 to 1.171 µM covering the World Health Organization (WHO) drinking water limit. Innovatively, it effectively detects arsenic in seawater within a linear regression range of 0.071 to 1.125 µM. The biosensor's selectivity for arsenic was confirmed, with minimal cross-response to group 15 metals. Our naked-eye biosensor offers a novel approach for the rapid, on-site detection of arsenic in various water sources. Its simplicity, cost-effectiveness, and versatility make it a valuable tool for environmental monitoring and public health initiatives.
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Arsénico , Técnicas Biosensibles , Contaminantes Químicos del Agua , Arsénico/análisis , Técnicas Biosensibles/métodos , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos , Colorimetría/métodos , Agua de Mar/análisis , Agua de Mar/químicaRESUMEN
Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.
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BACKGROUND: Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. METHODS: Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. RESULTS: A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein-Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test < 0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test < 0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| > 0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| > 0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples. CONCLUSION: We have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. Through the method of bioinformatics, we finally obtained 10 hub genes in As and MS, and selected 3 of the most significant genes (CX3CR1, IL32, TLR5) for blood PCR verification. This may be helpful to provide new research ideas for the diagnosis and treatment of AS complicated with MS.
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Aterosclerosis , Bases de Datos Genéticas , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Síndrome Metabólico , Mapas de Interacción de Proteínas , Humanos , Síndrome Metabólico/genética , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/inmunología , Aterosclerosis/genética , Aterosclerosis/inmunología , Aterosclerosis/diagnóstico , Aterosclerosis/sangre , Transcriptoma , Masculino , Valor Predictivo de las Pruebas , Marcadores Genéticos , Reproducibilidad de los Resultados , Predisposición Genética a la Enfermedad , Biología Computacional , Persona de Mediana Edad , Femenino , Regulación de la Expresión GénicaRESUMEN
Macrophages are plastic and play a key role in the maintenance of tissue homeostasis. In cancer progression, macrophages also take part in all processes, from initiation to progression, to final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies do not target macrophages, resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme with phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophages (M2) to M1-like macrophages (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting the capability of killing tumor-associated macrophages and antitumor effects in vivo. Furthermore, pre-coating the surface of LNO with a myeloid cell membrane significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme LNO can specifically induce macrophage autophagy, which improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.
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INTRODUCTION: Care workers play a fundamental role in delivering care services in long-term care institutions. Burnout has been found to have a negative impact on care recipients and organisations providing care. Little is known about the key factors associated with care workers' burnout. This systematic review aims to explore the prevalence, severity and correlates of burnout among care workers before and during COVID-19 pandemic. METHODS AND ANALYSIS: A five-stage framework outlined by Whittemore and Knafl will be used. The following databases will be used to identify relevant literature, including Medline (PubMed), EMBASE, Cochrane library, PsycINFO, CINAHL, Scopus and Web of Science. RevMan will be used to assist the meta-analysis. Heterogeneity of the included studies will be tested using the I 2 test. ETHICS AND DISSEMINATION: No ethics approval is required as this study only involves secondary data analysis. The findings will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42024499178.
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Agotamiento Profesional , COVID-19 , Cuidados a Largo Plazo , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Agotamiento Profesional/epidemiología , COVID-19/epidemiología , COVID-19/psicología , Personal de Salud/psicología , SARS-CoV-2 , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.
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Sofocos , Menopausia , Humanos , Femenino , Menopausia/fisiología , Prevalencia , Persona de Mediana Edad , Sofocos/epidemiología , Salud Global/estadística & datos numéricosRESUMEN
BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.
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Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR-insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.
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Cisteína-Endopeptidasas Gingipaínas , Resistencia a la Insulina , Porphyromonas gingivalis , Receptor de Insulina , Porphyromonas gingivalis/metabolismo , Receptor de Insulina/metabolismo , Animales , Ratones , Cisteína-Endopeptidasas Gingipaínas/metabolismo , Humanos , Masculino , Adhesinas Bacterianas/metabolismo , Cisteína Endopeptidasas/metabolismo , Proteolisis , Femenino , Adipocitos/metabolismo , Periodontitis/microbiología , Técnicas de CocultivoRESUMEN
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing threat leading to substantial disease burden globally. Poor sleep and physical inactivity are common in modern societies and independently associated with MAFLD, however, their joint effects on MAFLD remains unclear. METHODS: This population-based cross-sectional study was conducted in Xinjiang Uygur Autonomous Region, China, between July 2019 and September 2021. Self-reported sleep behaviors and physical activity (PA) were assessed using validated questionnaires. The primary outcome was radiological diagnosis of MAFLD. RESULTS: Of the 10 089 participants aged 47.0 (9.1) years (51.6% men), 3854 (38.2%) individuals had MAFLD. Poor sleep quality and physical inactivity were independently and jointly associated with an increased prevalence of MAFLD, independent of traditional risk factors (P < 0.05). Compared to subjects with guideline-recommended moderate-to-vigorous PA (MVPA) and good sleep quality, individuals with no recommended MVPA and poor sleep had the highest possibility of MAFLD (odds ratio = 2.36, 95% confidence interval: 1.81 - 3.08). Enhancing sleep quality substantially attenuated MAFLD prevalence regardless of the volume of PA, whereas, engaging in PA well above current guidelines did not adequately counteract the adverse impacts of poor sleep on MAFLD. CONCLUSIONS: Public health awareness and strategies concurrently targeting both sleep quality and PA should be encouraged to curb the climbing prevalence of MAFLD.
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Ejercicio Físico , Calidad del Sueño , Humanos , Estudios Transversales , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Ejercicio Físico/fisiología , Adulto , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de Riesgo , PrevalenciaRESUMEN
The CO preferential oxidation reaction (CO-PROX) is an effective strategy to remove residual poisonous CO in proton exchange membrane fuel cells, in which oxygen vacancies play a critical role in CO adsorption and activation. Herein, a series of CuO/CeO2 catalysts derived from Ce-MOFs precursors were synthesized using different organic ligands via the hydrothermal method and the CO-PROX performance was investigated. The CuO/CeO2-135 catalyst derived from homophthalic tricarboxylic acid (1,3,5-H3BTC) exhibited superior catalytic performance with 100 % CO conversion at a relatively low temperature (T100% = 100 °C), with a wide reaction temperature range and excellent stability. The superior catalytic properties were attributed to the structural improvements provided by the 1,3,5-H3BTC precursors and the promotional effects of oxygen vacancies. Additionally, in-situ Raman spectroscopy was performed to verify the dynamic roles of oxygen vacancies for CO adsorption and activation, while in-situ DRIFTS analysis revealed key intermediates in the CO-PROX reaction, shedding light on the mechanistic aspects of the catalytic process. This work not only demonstrates insights into the effective CuO/CeO2 catalysts for CO preferential oxidation, but also provides a feasible way to synthesize MOF-derived catalysts.
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Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Receptores CXCR3 , Células T Auxiliares Foliculares , Linfocitos T Reguladores , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Células B de Memoria/inmunología , Receptores CXCR3/metabolismo , Receptores CXCR3/inmunología , Células T Auxiliares Foliculares/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
OBJECTIVES: This study aimed to explore the involvement of phosphoenolpyruvate carboxykinase 2 (PCK2) in gefitinib-resistant non-small cell lung cancer (NSCLC) cells and assess its feasibility as a therapeutic target against gefitinib resistance. METHODS: Gefitinib-resistant cell lines, PC9GR and HCC827GR, were generated through progressive exposure of parental cells to escalating concentrations of gefitinib. Transcriptomic analysis encompassed the treatment of PC9 and PC9GR cells with gefitinib or vehicle, followed by RNA extraction, sequencing, and subsequent bioinformatic analysis. Cell viability was determined via CCK-8 assay, while clonogenic assays assessed colony formation. Apoptosis was detected utilizing the Annexin V-FITC/7AAD kit. Iron ion concentrations were quantified using FerroOrange. mRNA analysis was conducted through quantitative RT-PCR. Western blotting was employed for protein analysis. H&E and immunohistochemical staining were performed on tumor tissue sections. RESULTS: The results revealed that depletion or inhibition of PCK2 significantly enhanced gefitinib's efficacy in inducing cell growth arrest, apoptosis, and ferroptosis in resistant NSCLC. Moreover, PCK2 knockdown led to the downregulation of key ferroptosis-related proteins, GPX4 and SLC7A11, while upregulating ASCL4. Conversely, overexpression of PCK2 in gefitinib-sensitive cells rendered resistance to gefitinib. In vivo experiments using a gefitinib-resistant xenograft model demonstrated that PCK2 silencing not only reduced tumor growth but also considerably increased the anti-tumor effect of gefitinib. CONCLUSIONS: In conclusion, our study presents compelling evidence indicating that PCK2 plays a pivotal role in gefitinib resistance in NSCLC. The modulation of ferroptosis-related proteins and the involvement of Akt activation further elucidate the mechanisms underlying this resistance. Consequently, PCK2 emerges as a promising therapeutic target for overcoming gefitinib resistance in NSCLC, offering a new avenue for the development of more effective treatment strategies.
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Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Ferroptosis , Gefitinib , Neoplasias Pulmonares , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Gefitinib/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Animales , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Antineoplásicos/farmacología , Ratones , Ratones Desnudos , Apoptosis/efectos de los fármacosRESUMEN
Background: Serum ferritin (SF) is clinically found to be elevated in many disease conditions, and our research examines serum ferritin in patients with acute kidney injury (AKI) and its implication on the risk of short-term mortality in AKI. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database. Adult patients with AKI who had serum ferritin tested on the first day of ICU admission were included. The primary outcome was 28-day mortality. Kaplan-Meier survival curves and Cox proportional hazards models were used to test the relationship between SF and clinical outcomes. Subgroup analyses based on the Cox model were further conducted. Results: Kaplan-Meier survival curves showed that a higher SF value was significantly associated with an enhanced risk of 28-day mortality, 90-day mortality, ICU mortality and hospital mortality (log-rank test: p < 0.001 for all clinical outcomes). In multivariate Cox regression analysis, high level of SF with mortality was significantly positive in all four outcome events (all p < 0.001). This result remains robust after adjusting for all variables. Subgroup analysis of SF with 28-day mortality based on Cox model-4 showed that high level of SF was associated with high risk of 28-day mortality in patients regardless of the presence or absence of sepsis (p for interaction = 0.730). Positive correlations of SF and 28-day mortality were confirmed in all other subgroups (p for interaction>0.05). Conclusion: High level of SF is an independent prognostic predictor of 28-day mortality in patients with AKI.
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Purpose: Metabolic Syndrome (MS) greatly increases the risk of heart disease and Heart Failure(HF). Insulin Resistance (IR) is considered to be the key to the pathophysiology of MS. The purpose of this study was to evaluate the predictive effect of different alternative indicators of IR on adverse cardiovascular events in patients with MS complicated with HF. Methods: Patients with HF who were diagnosed with MS in the heart center of the first affiliated Hospital of Xinjiang Medical University were selected continuously. The baseline data of the patients in the group were compared. The diagnostic value of alternative indexes of IR was evaluated by the working characteristic curve of subjects. The relationship between different alternative indicators of IR and survival rate was evaluated by survival curve. COX regression was used to analyze the effects of different alternative indicators of IR on the risk of end-point events. Results: The levels of TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR were significantly increased in patients with Major Adverse Cardiovascular Events (MACEs). Among the five alternative indexes of IR, METS-IR had the highest AUC (0.691, 95% CI:0.657-0.752, P < 0.001) in predicting MACEs. No matter which alternative index of IR was used, the survival rate of MACEs in High group was significantly decreased. TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR can independently predict the occurrence of MACEs events, even if some confounding factors are adjusted. Conclusion: Our study shows that alternative indicators of IR, especially METS-IR, are independently associated with adverse cardiovascular events in patients with MS and HF.
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Autophagy is a highly conserved eukaryotic pathway and plays a crucial role in cell survival under stress conditions. Here, we applied a full-length transcriptome approach to study an Arabidopsis autophagy mutant (atg5-1) subjected to nitrogen-starvation, using Oxford Nanopore Technologies. A total of 39,033 transcripts were identified, including 11,356 new transcripts. In addition, alternative splicing (AS) events and lncRNAs were also detected between Col-0 (WT) and atg5-1. Differentially expressed transcript enrichment showed that autophagy upregulates the expression of many stress-responsive genes and inhibits the transcription of photosynthesis-associated genes. The qRT-PCR results showed that the expression patterns of photosynthesis-related genes in the atg5-1 differed under the conditions of nitrogen starvation and carbon starvation. Under nitrogen starvation treatment, many genes related to photosynthesis also exhibited AS. Chlorophyll fluorescence images revealed that the Fv/Fm and ΦPSII of old atg5-1 leaves were significantly reduced after nitrogen starvation treatment, but the Y(NPQ) indices were significantly increased compared to those of the WT plants. The results of qRT-PCR suggest that autophagy appears to be involved in the degradation of genes related to photodamage repair in PSII. Taken together, the full-length transcriptiome sequencing provide new insights into how new transcripts, lncRNAs and alternative splicing (AS) are involved in plant autophagy through full-length transcriptome sequencing and suggest a new potential link between autophagy and photosynthesis.
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Empalme Alternativo , Arabidopsis , Autofagia , Regulación de la Expresión Génica de las Plantas , Nitrógeno , Fotosíntesis , Transcriptoma , Arabidopsis/genética , Arabidopsis/metabolismo , Autofagia/genética , Fotosíntesis/genética , Nitrógeno/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Perfilación de la Expresión Génica , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismoRESUMEN
BACKGROUND: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD). The study aim to identify the association of RC and the discordance between RC and lipoprotein cholesterol (LDL-C) with CVD. METHODS: Data was obtained from the Kailuan study. RC was calculated as the non high-density lipoprotein cholesterol minus LDL-C. Discordant RC and LDL-C were defined by percentile difference and clinical cutoff points. Cox proportional hazard models were used to explore the association of RC and the discordance between RC and LDL-C with CVD. RESULTS: Total of 96,769 participants were inclued, with the median age of 51.61 years, 79.56% of male. There was a significant association between RC levels and the risk of CVD, with an HR of 1.10 (95% CI, 1.08-1.13) in the continuous analysis. The discordantly high RC group had a significant increase in CVD, MI, and stroke risk, with HRs of 1.18 (95%CI, 1.10-1.26), 1.23 (1.06-1.43), and 1.15 (1.07-1.24), respectively. Compared to the group with low LDL-C and low RC, the group with low LDL-C and high RC had significantly higher incidences of CVD (HR, 1.33 [95% CI, 1.26-1.40]), MI (HR, 1.59 [95% CI, 1.41-1.80]), and stroke (HR, 1.28 [95% CI, 1.20-1.35]). CONCLUSIONS: Elevated levels of RC and discordantly high RC with LDL-C both were associated with the risk of CVD, MI, and stroke. These findings demonstrate the clinical significance of identifying residual risk related to RC.
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Objective: This study aims to assess the combined predictive value of C-reactive protein (CRP) and albumin (ALB) for major adverse cardiovascular events (MACE) post-percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: We analyzed data from continuously enrolled AMI patients who underwent emergency PCI at the First Affiliated Hospital of Xinjiang Medical University over six years, employing logistic regression to derive a predictive equation for in-hospital mortality and out-of-hospital MACE events. Primary endpoints: In-hospital death and out-of-hospital major adverse cardiovascular events. The patients were followed up for 1, 3, 6, and 12 months after discharge. The average follow-up time was 41 months. Results: Among the 601 patients studied, we observed 16 in-hospital deaths and 131 out-of-hospital MACE events. Multivariate logistic regression analysis showed that the independent predictors of out-of-hospital MACE events were age (OR=1.067, 95% CI 1.013-1.124, P = .028), C-reactive protein (OR=1.012, 95% CI 1.000-1.025, P = .045) and albumin (OR=0.874, 95% CI 0.785-0.973, P = .014). Our multivariate logistic regression analysis identified age, CRP, and albumin as independent predictors, with the combined equation yielding an ROC curve area of 0.85, effectively stratifying patients into high-risk and low-risk groups. Subsequent follow-up results validated this risk stratification approach. Conclusion: The study underscores the efficacy of combining CRP and albumin levels as a predictive measure for in-hospital death and out-of-hospital MACE events in AMI patients post-PCI.
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The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Autofagia , Cadenas Ligeras de Clatrina , Inmunidad de la Planta , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/metabolismo , Cadenas Ligeras de Clatrina/metabolismo , Cadenas Ligeras de Clatrina/genética , Inmunidad de la Planta/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genéticaRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been administered as the first-line therapy for patients with EGFR mutations in LUAD, but it is almost inevitable that resistance to EGFR-TKIs therapy eventually arises. Polyphyllin I (PPI), derived from Paris polyphylla rhizomes, has been shown to have potent anti-cancer properties in a range of human cancer types including LUAD. However, the role of PPI in gefitinib resistance and the underlying mechanism remain elusive. PURPOSE: To evaluate the antitumor impacts of PPI on gefitinib resistance cells and investigate its molecular mechanism. METHODS: CCK-8, wound healing, transwell assay, and xenograft model were performed to determine the anti-cancer effects of PPI as well as its ability to overcome gefitinib resistance. Immunoblotting, co-immunoprecipitation, phospho-RTK antibody array, qRT-PCR, and immunofluorescence were utilized to explore the mechanism by which PPI overrides gefitinib resistance. RESULTS: PPI inhibited cell survival, growth, and migration/invasion in both gefitinib-sensitive (PC9) and -resistant (PC9/GR) LUAD cells (IC50 at 2.0 µM). Significantly, treatment with PPI at 1.0 µM resensitized the resistant cells to gefitinib. Moreover, cell-derived xenograft experiments revealed that the combination of PPI and gefitinib overcame gefitinib resistance. The phospho-RTK array and immunoblotting analyses showed PPI significant inhibition of the VEGFR2/p38 pathway. In addition, molecular docking suggested the interaction between PPI and HIF-1α. Mechanistically, PPI reduced the protein expression of HIF-1α in both normoxia and hypoxia conditions by triggering HIF-1α degradation. Moreover, HIF-1α protein but not mRNA level was elevated in gefitinib-resistant LUAD. We further demonstrated that PPI considerably facilitated the binding of HIF-1α to VHL. CONCLUSIONS: We present a novel discovery demonstrating that PPI effectively counteracts gefitinib resistance in LUAD by modulating the VEGF/VEGFR2/p38 pathway. Mechanistic investigations unveil that PPI facilitates the formation of the HIF-1α /VHL complex, leading to the degradation of HIF-1α and subsequent inhibition of angiogenesis. These findings uncover a previously unidentified mechanism governing HIF-1α expression in reaction to PPI, providing a promising method for therapeutic interventions targeting EGFR-TKI resistance in LUAD.