RESUMEN

In this research, the essential oils (EOs) from different parts of Ocimum gratissimum var. suave were chemically characterized and evaluated for insecticidal activity, especially against two common storage pests of Chinese herbal medicines: Tribolium castaneum and Liposcelis bostrychophila. Ocimum gratissimum is a plant with several medicinal values in traditional Chinese medicine. In the study, EOs were successfully extracted from inflorescences (OGI) and stem-leaf (OGLS) parts of O. gratissimum by steam distillation and 16 compounds were identified by gas chromatography-mass spectrometry (GC-MS), of which eugenol was the major constituent in both extracts. In fumigation toxicity tests against both pests, the EOs showed limited toxicity against T. castaneum but showed better toxicity against L. bostrychophila. Contact toxicity tests showed that OGLS had better insecticidal potential than OGI, while the insecticidal effect of eugenol sometimes exceeded that of EOs. In addition, repellency experiments showed that O. gratissimum EOs repelled the pests to varying degrees, with the effect being influenced by concentration and exposure time. The results suggest that O. gratissimum EOs could be a promising alternative to synthetic insecticides for sustainable utilization.

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The development of multicellular organisms requires coordinated changes in gene expression that are often mediated by the interaction between transcription factors (TFs) and their corresponding cis-regulatory elements (CREs). During development and differentiation, the accessibility of CREs is dynamically modulated by the epigenome. How the epigenome, CREs, and TFs together exert control over cell fate commitment remains to be fully understood. In the Arabidopsis leaf epidermis, meristemoids undergo a series of stereotyped cell divisions, then switch fate to commit to stomatal differentiation. Newly created or reanalyzed scRNA-seq and ChIP-seq data confirm that stomatal development involves distinctive phases of transcriptional regulation and that differentially regulated genes are bound by the stomatal basic helix-loop-helix (bHLH) TFs. Targets of the bHLHs often reside in repressive chromatin before activation. MNase-seq evidence further suggests that the repressive state can be overcome and remodeled upon activation by specific stomatal bHLHs. We propose that chromatin remodeling is mediated through the recruitment of a set of physical interactors that we identified through proximity labeling-the ATPase-dependent chromatin remodeling SWI/SNF complex and the histone acetyltransferase HAC1. The bHLHs and chromatin remodelers localize to overlapping genomic regions in a hierarchical order. Furthermore, plants with stage-specific knockdown of the SWI/SNF components or HAC1 fail to activate specific bHLH targets and display stomatal development defects. Together, these data converge on a model for how stomatal TFs and epigenetic machinery cooperatively regulate transcription and chromatin remodeling during progressive fate specification.

Asunto(s)

Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Ensamble y Desensamble de Cromatina , Regulación de la Expresión Génica de las Plantas , Estomas de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Estomas de Plantas/metabolismo , Estomas de Plantas/genética , Estomas de Plantas/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Diferenciación Celular/genética , Cromatina/metabolismo

RESUMEN

BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

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Objective:To observe the clinical effect of placing heterogeneous acellular dermal matrix membrane for laryngeal cavity wound healing after CO2 laser Type-Ⅴa cordectomy for glottic carcinoma. Methods:Thirty-five patients with bilateral vocal cord laryngeal cancer who underwent endoscopic CO2 laser surgery at the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University from March 2018 to December 2019 were selected and divided into 2 groups, including 18 patients in the study group and 17 patients in the control group. The control group was simply placed silicone tube stent, while in the study group, heterogeneous acellular dermal matrix membrane was coated with silicone tube stent. The postoperative laryngeal wound repair and clinical manifestations were observed and compared between the two groups. Results:Compared postoperative laryngeal wound after 6 months: no patients in the study group had granulation tissue, whereas 4 patients in the control group had granulation tissue; 3 patients in the study group developed moderate to severe tissue adhesion, while 9 patients in the control group; 10 patients in the control group developed 2nd to 4th degree laryngeal obstruction, compared with only 4 patients in the study group. Conclusion:The primary placement of ADM can reduce laryngeal granulation tissue and tissue adhesion after CO2 laser Type-Ⅴa cordectomy for laryngeal cancer, and may reduce the occurrence of postoperative laryngeal obstruction.

Asunto(s)

Dermis Acelular , Neoplasias Laríngeas , Pliegues Vocales , Cicatrización de Heridas , Humanos , Masculino , Neoplasias Laríngeas/cirugía , Femenino , Persona de Mediana Edad , Pliegues Vocales/cirugía , Láseres de Gas/uso terapéutico , Endoscopía/métodos , Anciano

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PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

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Insect infestations continually endanger stored goods, underscoring the significance of discovering eco-friendly insecticides for pest management. Essential oils (EOs) from different parts of Toddalia asiatica (leaf, fruit and branch) were extracted by hydrodistillation and analyzed by GC-MS. Carvene, p-cymene and muurolene are the principal compounds of T. asiatica leaf (TAL), T. asiatica fruit (TAF) and T. asiatica branch (TAB) EO respectively. Our work aimed to assess the contact toxicity and repellent effects of EOs on two storage pests, Tribolium castaneum and Lasioderma serricorne. All tested EOs exhibited obvious contact toxicity, especially, TAL EO against T. castaneum (33.48 µg/adult) and TAF EO against L. serricorne (16.42 µg/adult). Repellency tests revealed that TAL and TAF EOs, at a concentration of 78.63 nL/cm2, achieved nearing 100% efficiency against T. castaneum. These results suggest that EOs of T. asiatica could be used as effective botanical insecticides for managing stored-product insects.

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Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.

Asunto(s)

Colitis Ulcerosa , Colon , Microbioma Gastrointestinal , Glutamatos , Ratones Endogámicos C57BL , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Glutamatos/farmacología , Glutamatos/administración & dosificación , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Colon/inmunología , Colon/microbiología , Colon/efectos de los fármacos , Masculino , Humanos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Heces/microbiología

RESUMEN

The clear juice fermentation technique for white wines suggests that white grape seeds, rich in flavan-3-ols and proanthocyanidins, are not effectively utilized in the winemaking process. This study incorporated 'Gewürztraminer' grape seeds into 'Cabernet Sauvignon' must before cold soak to investigate how the resultant red wines' phenolic compound profiles, color, and astringency were affected. The results showed that adding seeds primarily inhibited the leaching of flavan-3-ols from both skins and seeds. A significant increase in the levels of flavan-3-ols, tannins, and phenolic acids, as well as direct and aldehyde-bridged flavan-3-ol-anthocyanin polymers, were observed in the wines with additional seeds. This led to the improvement in the wine' red hue and its resistance to SO2 bleaching. Furthermore, the wine added with seeds exhibited stronger astringency compared to those without. The findings provide a promising winemaking strategy to improve color stability and intensify the astringency of red wines through the utilization of grape seeds.

RESUMEN

OBJECTIVES: There is currently no evidence documenting the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 lung cancer (LC). The aim of this study was to investigate the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 LC. METHODS: This prospective cohort study included patients with incidental stage T1 LC who were diagnosed pathologically at the First Affiliated Hospital of Chongqing Medical University between 1st Jan 2019 and 31st Dec 2023. The follow-up time for all participants concluded on 31st Jan 2024, or upon death. All included patients were divided into non-high-risk (observation) and high-risk (control) groups based on the 2021 US preventative services task force recommendations. The primary outcomes were overall survival probability and LC-specific survival probability. The secondary outcomes were clinical characteristics, including demographic variables, histological types and TNM staging. RESULTS: We studied 1876 patients with incidental stage T1 LC. Of these, 1491 (79.48%) non-high-risk patients were included in the observation group, and the remaining 385 (20.52%) high-risk patients composed the control group. The follow-up interval was between 0 and 248 months for all participants, with a median time of 41.64 ± 23.85 months. The patients in the observation group were younger and had smaller tumors, more adenocarcinomas, and earlier disease stages than those in the control group (p ≤ 0.001). The overall survival probability (HR = 0.23, [95% CI: 0.18, 0.31], p < 0.001) and the LC-specific survival probability (HR = 0.23, [95% CI: 0.17, 0.31], p < 0.001) for the patients in the observation group were also both higher than those in the control group. The results appeared to be consistent across important subgroups. CONCLUSION: In this study, non-high-risk patients with incidental stage T1 LC were younger, had smaller tumors, had more adenocarcinomas, had a lower probability of metastasis, and had longer survival than did high-risk patients.

Asunto(s)

Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Pronóstico , Hallazgos Incidentales , Análisis de Supervivencia , Adulto , Anciano de 80 o más Años , Factores de Riesgo

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Nanocellulose, a versatile and sustainable nanomaterial derived from cellulose fibers, has attracted considerable attention in various fields due to its unique properties. Similar to dietary fibers, nanocellulose is difficult to digest in the human gastrointestinal tract. The indigestible nanocellulose is fermented by gut microbiota, producing metabolites and potentially exhibiting prebiotic activity in intestinal diseases. Additionally, nanocellulose can serve as a matrix material for probiotic protection and show promising prospects for probiotic delivery. In this review, we summarize the classification of nanocellulose, including cellulose nanocrystals (CNC), cellulose nanofibers (CNF), and bacterial nanocellulose (BNC), highlighting their distinct characteristics and applications. We discuss the metabolism-related characteristics of nanocellulose from oral ingestion to colon fermentation and introduce the prebiotic activity of nanocellulose in intestinal diseases. Furthermore, we provide an overview of commonly used nanocellulose-based encapsulation techniques, such as emulsification, extrusion, freeze drying, and spray drying, as well as the delivery systems employing nanocellulose matrix materials, including microcapsules, emulsions, and hydrogels. Finally, we discuss the challenges associated with nanocellulose metabolism, prebiotic functionality, encapsulation techniques, and delivery systems using nanocellulose matrix material for probiotics. This review will provide new insight into the application of nanocellulose in the treatment of intestinal diseases and probiotic delivery.

Asunto(s)

Celulosa , Microbioma Gastrointestinal , Nanopartículas , Probióticos , Celulosa/química , Celulosa/metabolismo , Humanos , Nanopartículas/química , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Animales , Nanofibras/química , Fermentación , Prebióticos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos

RESUMEN

BACKGROUND: Cold shock proteins (CSPs) are ubiquitous nucleic acid-binding proteins involved in growth, development, and stress response across various organisms. While extensively studied in many species, their regulatory roles in sweet cherry (Prunus avium L.) remain unclear. OBJECTIVE: To identify and analyze CSP genes (PavCSPs) in sweet cherry genome, and explore the differential responses of PavCSP1 and PavCSP3 to low temperature and salt stress. METHODS: Three methods were employed to identify and characterize CSP in sweet cherry genomes. To explore the potential functions and evolutionary relationships of sweet cherry CSP proteins, sequence alignment and phylogenetic tree incorporating genes from five species were conducted and constructed, respectively. To investigate the responses to abiotic stresses, cis-acting elements analysis and gene expression patterns to low-temperature and salt stress were examined. Moreover, transgenic yeasts overexpressing PavCSP1 or PavCSP3 were generated and their growth under stress conditions were observed. RESULTS: In this study, three CSP genes (PavCSPs) were identified and comprehensively analyzed. The quantitative real-time PCR revealed diverse expression patterns, with PavCSP1-3 demonstrating a particular activity in the upper stem and all members were responsive to low-temperature and salt stress. Further investigation demonstrated that transgenic yeasts overexpressing PavCSP1 or PavCSP3 exhibited improved growth states following high-salt and low-temperature stress. CONCLUSION: These findings elucidated the responses of PavCSP1 and PavCSP3 to salt and low-temperature stresses, laying the groundwork for further functional studies of PavCSPs in response to abiotic stresses.

Asunto(s)

Proteínas y Péptidos de Choque por Frío , Frío , Filogenia , Proteínas de Plantas , Prunus avium , Estrés Salino , Proteínas y Péptidos de Choque por Frío/genética , Proteínas y Péptidos de Choque por Frío/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Salino/genética , Prunus avium/genética , Prunus avium/metabolismo , Prunus avium/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque por Frío/genética , Genoma de Planta/genética

RESUMEN

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Asunto(s)

Biomarcadores , Diabetes Mellitus Tipo 2 , Obesidad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Índice de Masa Corporal , China/epidemiología , HDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Pueblos del Este de Asia , Obesidad/diagnóstico , Obesidad/sangre , Obesidad/epidemiología , Sobrepeso/epidemiología , Sobrepeso/sangre , Sobrepeso/diagnóstico , Sobrepeso/complicaciones , Pronóstico , Medición de Riesgo , Factores de Riesgo , Triglicéridos/sangre

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Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.

Asunto(s)

Insuficiencia Cardíaca , Miocitos Cardíacos , Nanomedicina , Nanopartículas , Animales , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/prevención & control , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Administración por Inhalación , Nanopartículas/química , Nanomedicina/métodos , Péptidos/farmacología , Péptidos/administración & dosificación , Miocardio/metabolismo , Miocardio/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , GMP Cíclico/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Modelos Animales de Enfermedad , Fosfatos de Calcio

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Thermogalvanic cells (TGCs) draw great attention in the field of heat to electricity conversion, but TGCs were only in the form of liquid or organic gel. Here, we report an all-inorganic hydrogel TGC via simply mixing and stirring two inorganic salt solutions. Benefiting from the hydrogen bonds resultant framework and endogenous Fe2+/3+ redox couple, the TGC can recurrently pulverize-gel with completely holding its initial thermogalvanic performances after even 60 cycles. As the temperature and pH coregulating Fe3+ concentration and reversible transformation between Fe3+ and Fe(OH)3, we boost thermopower and realize thermochromism. This work provides a different perspective for TGCs and offers an avenue for future hydrogel materials research.

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BACKGROUND: Hypertension development is predominantly influenced by inflammation, excessive fat deposition, and metabolic irregularities. Among these factors, liver fat accumulation is a critical metabolic disorder. However, the quantification of liver fat levels and its associated risk for hypertension incidence remain ambiguous. This project is designed to explore the association between liver fat levels and the risk of hypertension in a healthy population. METHODS: This cross-sectional study involved 4955 participants from the Health Management Center at Henan Provincial People's Hospital who were surveyed between February 2020 and February 2023. Participants were categorized into four groups based on liver fat quartiles. Subgroup analyses, restricted cubic spline regression models, and logistic regression were utilized to assess the association between liver fat levels and hypertension risk. The relationships between liver fat levels and inflammatory markers were examined using multiple linear regression models. Additionally, a mediation analysis was conducted to explore the role of inflammatory factors in the relationship between liver fat and hypertension risk. RESULTS: Participants with hypertension exhibited greater liver fat levels than did those without hypertension. An increased risk of hypertension was associated with elevated liver fat levels, even after adjusting for other covariates [Q4 vs. Q1 in model II: odds ratio (OR = 1.28), 95% confidence interval (CI) = 1.04-1.59, P  = 0.022; P for trend = 0.039]. A nonlinear relationship was observed between liver fat level and hypertension risk, with a notable increase in hypertension risk occurring at liver fat levels greater than 8.65%. Additionally, a positive correlation was found between inflammatory markers and liver fat levels. A mediation effect of 4.76% was noted, linking hypertension risk and liver fat levels through neutrophils. CONCLUSION: Liver fat levels exceeding 8.65% significantly elevated the risk of hypertension. Inflammatory factors serve as crucial mediators of the relationship between liver fat and hypertension.

Asunto(s)

Hipertensión , Humanos , Hipertensión/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , China/epidemiología , Adulto , Factores de Riesgo , Hígado/patología , Hígado Graso , Inflamación

RESUMEN

BACKGROUND: Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents' efficacy (favourable response and mortality). RESULTS: We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA. CONCLUSION: These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.

Asunto(s)

Antifúngicos , Aspergilosis , Metaanálisis en Red , Antifúngicos/uso terapéutico , Humanos , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Resultado del Tratamiento , Caspofungina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Triazoles/uso terapéutico , Anfotericina B/uso terapéutico , Voriconazol/uso terapéutico , Nitrilos , Piridinas

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At present, an in-depth knowledge of polycyclic aromatic hydrocarbons (PAHs) in the multimedia system of the urban environment remains limited. Taking the Naples metropolitan area (NMA) for instance, we simulated the cross-media transfer of PAHs using a multimedia urban model, involving air, water, soil, sediment, vegetation, and impervious film. The results indicated that the predicted PAH values in 2015 match well with their corresponding in-situ monitoring data. The PAH emission inventory and the simulated mass in various media all showed a downward trend from 2015 to 2020 due to national energy conservation policies and Corona Virus Disease 2019. The simulated mass of PAHs in the soil and sediment phases was 896.8 and 232.7 kg in 2020, respectively, contributing together to 96.7% of PAHs in the NMA. And they were identified as the greatest sinks for PAHs, and exhibited the longest retention duration, with values of PAH persistence reaching approximately 548.8 - 2,0642.3 hours. The results of transfer fluxes indicated that local emissions and atmospheric advection were the primary routes affecting the distribution of PAHs. The sensitivity analysis indicated that atmospheric advection rate was the most critical parameter for air, soil, vegetation, and film, whereas water concentration and sediment degradation rate were vital for water and sediment, respectively. This study offered valuable insights into how human activity contributes to the status and fate of PAHs in the urban environment.

RESUMEN

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

Asunto(s)

Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Humanos , Metilación , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Proteína de Replicación A/metabolismo , Proteína de Replicación A/genética , Recombinación Homóloga , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Reparación del ADN , Cromatina/metabolismo , Cromatina/genética

RESUMEN

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.

Asunto(s)

Citocinas , Inflamación , Macrófagos , Neutrófilos , Proteínas de Pez Cebra , Pez Cebra , Animales , Neutrófilos/metabolismo , Neutrófilos/inmunología , Macrófagos/metabolismo , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Citocinas/metabolismo , Mutación/genética , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2/deficiencia

RESUMEN

Objective: The predictive value of serum tumor markers (STMs) in assessing epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC), particularly those with non-stage IA, remains poorly understood. The objective of this study is to construct a predictive model comprising STMs and additional clinical characteristics, aiming to achieve precise prediction of EGFR mutations through noninvasive means. Materials and methods: We retrospectively collected 6711 NSCLC patients who underwent EGFR gene testing. Ultimately, 3221 stage IA patients and 1442 non-stage IA patients were analyzed to evaluate the potential predictive value of several clinical characteristics and STMs for EGFR mutations. Results: EGFR mutations were detected in 3866 patients (57.9 %) of all NSCLC patients. None of the STMs emerged as significant predictor for predicting EGFR mutations in stage IA patients. Patients with non-stage IA were divided into the study group (n = 1043) and validation group (n = 399). In the study group, univariate analysis revealed significant associations between EGFR mutations and the STMs (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin-19 fragment (CYFRA21-1)). The nomogram incorporating CEA, CYFRA 21-1, pathology, gender, and smoking history for predicting EGFR mutations with non-stage IA was constructed using the results of multivariate analysis. The area under the curve (AUC = 0.780) and decision curve analysis demonstrated favorable predictive performance and clinical utility of nomogram. Additionally, the Random Forest model also demonstrated the highest average C-index of 0.793 among the eight machine learning algorithms, showcasing superior predictive efficiency. Conclusion: CYFRA21-1 and CEA have been identified as crucial factors for predicting EGFR mutations in non-stage IA NSCLC patients. The nomogram and 8 machine learning models that combined STMs with other clinical factors could effectively predict the probability of EGFR mutations.