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BACKGROUND: Adherence to healthy lifestyle habits has become a mainstream approach for lessening the burden of cardiovascular disease (CVD) during initial prevention efforts. The purpose of this study was to investigate the prevalence of four healthy lifestyle habits, the associated factors, and their impact on all-cause and cardiovascular mortality among residents of Guangxi Zhuang Autonomous Region. METHODS: From 2015 to 2019, individuals between the ages of 35 and 75 from Guangxi Zhuang Autonomous Region were recruited through the ChinaHeart Million Person Project. Our study examined four healthy lifestyle habits: not smoking, no or moderate amounts of alcohol, sufficient leisure time physical activity (LTPA) and a balanced diet. RESULTS: Out of the 19,969 individuals involved, the majority, 77.3% did not smoke, while 96.7% had limited alcohol intake, 24.5% engaged in sufficient LTPA, 5.5% followed a balanced diet, and merely 1.7% adhered to all four healthy lifestyle habits. Participants who were women, older, nonfarmers, living in cities, with a high income or level of education, or had hypertension or diabetes were more likely to follow all four healthy lifestyle habits (p < 0.001). People who followed the three healthy lifestyle habits had reduced chances of death from all cause (HR 0.34[95% CI:0.15,0.76]) and cardiovascular-related death (HR 0.23 [95% CI: 0.07, 0.68]) (p < 0.01) over a median period of 3.5 years. CONCLUSIONS: In Guangxi Province, the level of adherence to healthy lifestyle habits is very minimal. Therefore, population-specific health promotion strategies are urgently needed.
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Enfermedades Cardiovasculares , Estilo de Vida Saludable , Humanos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Enfermedades Cardiovasculares/mortalidad , Adulto , Anciano , Ejercicio Físico , Causas de Muerte , Consumo de Bebidas Alcohólicas/epidemiologíaRESUMEN
BACKGROUND: The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. METHODS: Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. RESULTS: A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. CONCLUSIONS: Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.
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Quimioradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Recurrencia Local de Neoplasia , Terapia Recuperativa , Humanos , Persona de Mediana Edad , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Anciano , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Estudios Retrospectivos , Adulto , Pronóstico , Estadificación de Neoplasias , Estimación de Kaplan-MeierRESUMEN
A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda, was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4⯱â¯0.55⯵m in diameter. The octospores were oval and measured 2.3â¯×â¯1.5⯵m (fresh) and 1.96â¯×â¯1.17⯵m (fixed). The isofilar polar filament was coiled with 9-10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora, but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov.
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Introduction: Off-season upsurge of respiratory syncytial virus (RSV) infection with changed characteristics and heightened clinical severity during the post-COVID-19 era are raising serious concerns. This study aimed to develop and validate a nomogram for predicting the risk of severe acute lower respiratory tract infection (SALRTI) in children hospitalized for RSV infection during the post-COVID-19 era using machine learning techniques. Methods: A multicenter retrospective study was performed in nine tertiary hospitals in Yunnan, China, enrolling children hospitalized for RSV infection at seven of the nine participating hospitals during January-December 2023 into the development dataset. Thirty-nine variables covering demographic, clinical, and laboratory characteristics were collected. Primary screening and dimension reduction of data were performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by identification of independent risk factors for RSV-associated SALRTI using Logistic regression, thus finally establishing a predictive nomogram model. Performance of the nomogram was internally evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) based on the development dataset. External validation of our model was conducted using same methods based on two independent RSV cohorts comprising pediatric RSV inpatients from another two participating hospitals between January-March 2024. Results: The development dataset included 1102 patients, 239 (21.7%) of whom developed SALRTI; while the external validation dataset included 249 patients (142 in Lincang subset and 107 in Dali subset), 58 (23.3%) of whom were diagnosed as SALRTI. Nine variables, including age, preterm birth, underlying condition, seizures, neutrophil-lymphocyte ratio (NLR), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, and co-infection, were eventually confirmed as the independent risk factors of RSV-associated SALRTI. A predictive nomogram was established via integrating these nine predictors. In both internal and external validations, ROC curves indicated that the nomogram had satisfactory discrimination ability, calibration curves demonstrated good agreement between the nomogram-predicted and observed probabilities of outcome, and DCA showed that the nomogram possessed favorable clinical application potential. Conclusion: A novel nomogram combining several common clinical and inflammatory indicators was successfully developed to predict RSV-associated SALRTI. Good performance and clinical effectiveness of this model were confirmed by internal and external validations.
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COVID-19 , Hospitalización , Nomogramas , Infecciones por Virus Sincitial Respiratorio , SARS-CoV-2 , Humanos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Masculino , Femenino , Lactante , Estudios Retrospectivos , Preescolar , China/epidemiología , Niño , Índice de Severidad de la Enfermedad , Factores de Riesgo , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Aprendizaje Automático , Recién Nacido , Curva ROCRESUMEN
OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.
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Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein-protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.
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Diferenciación Celular , Células Madre Mesenquimatosas , Osteogénesis , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Osteogénesis/genética , Diferenciación Celular/genética , Humanos , Biomarcadores/metabolismo , Quinasas Relacionadas con NIMA/metabolismo , Quinasas Relacionadas con NIMA/genética , Mapas de Interacción de Proteínas/genética , MicroARNs/genética , MicroARNs/metabolismo , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/citología , Perfilación de la Expresión Génica , Redes Reguladoras de GenesRESUMEN
BACKGROUND: There are relatively few studies on continuing care of coronary heart disease (CHD), and its research value needs to be further clarified. AIM: To investigate the effect of continuous nursing on treatment compliance and side effect management in patients with CHD. METHODS: This is a retrospective study with patients from January 2021 to 2023. The study was divided into two groups with 30 participants in each group. Self-rating anxiety scale (SAS) and Self-rating depression scale (SDS) were used to assess patients' anxiety and depression, and medical coping questionnaire was used to assess patients' coping styles. The pelvic floor dysfunction questionnaire (PFDI-20) was used to assess the status of pelvic floor function, including bladder symptoms, intestinal symptoms, and pelvic symptoms. RESULTS: SAS score decreased from 57.33 ± 3.01before treatment to 41.33 ± 3.42 after treatment, SDS score decreased from 50.40 ± 1.45 to 39.47 ± 1.57. The decrease of these two indexes was statistically significant (P < 0.05). PFDI-20 scores decreased from the mean 16.83 ± 1.72 before treatment to 10.47 ± 1.3the mean after treatment, which was statistically significant (P < 0.05). CONCLUSION: The results of this study indicate that pioneering research in continuous care of CHD has a positive impact on improving patients' treatment compliance, reducing anxiety and depression levels, and improving coping styles and pelvic floor functional status.
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Widely-used C60 fullerene nanoparticles (C60) result in their release into the aquatic environment, which may affect the distribution and toxicity of pollutants such as arsenic (As), to aquatic organism. In this study, arsenate (As(V)) accumulation, speciation and subcellular distribution was determined in Danio rerio (zebrafish) intestine, head and muscle tissues in the presence of C60. Meanwhile we compared how single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO) and graphene (GN) nanoparticles alter the behaviors of As(V). Results showed that C60 significantly inhibited As accumulation and toxicity in D. rerio, due to a decrease in total As and monomethylarsonic acid (MMA) and As(V) species concentrations, a lower relative distribution in the metal-sensitive fraction (MSF). It was attributed that C60 may coat As(V) ion channels and consequently, affect the secretion of digestive enzymes in the gut, favoring As excretion and inhibiting As methylation. Similarly, MWCNTs reduced the species concentration of MMA and As(V) in the intestines, low GSH (glutathione) contents in the intestine. Due to the disparity of other carbon-based nanomaterial morphologies, SWCNTs, GO and GN exhibited the various effects on the toxicity of As(V). In addition, the possible pathway of arsenobetaine (AsB) biosynthesis included migration from the intestine to muscle in D. rerio, with the precursor of AsB likely to be 2-dimethylarsinylacetic acid (DMAA). The results of this study suggest that C60 is beneficial for controlling As(V) pollution and reducing the impact of As(V) biogeochemical cycles throughout the ecosystem.
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Arseniatos , Fulerenos , Nanopartículas , Contaminantes Químicos del Agua , Pez Cebra , Fulerenos/toxicidad , Animales , Arseniatos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Nanopartículas/toxicidad , Nanotubos de Carbono/toxicidad , Grafito/toxicidadRESUMEN
Green finance (GF) has emerged as a promising tool to promote low-carbon development, while knowledge is rather limited regarding the underlying mechanism. This article aims to address this void by constructing a city-level GF index covering seven dimensions and identifying the main pathways through which GF can facilitate the low-carbon development of cities. Using a balanced panel data covering 277 Chinese cities from 2010 to 2020, the results show that: (1) China's GF development exhibits an overall spatial differentiation of 'high in the east and low in the west', while the distribution of carbon intensity (CI) displays an overall spatial differentiation of 'high in the north and low in the south'; (2) GF significantly decreases CI of cities, which is robust to employing DID strategies and IV estimations; (3) The role of GF on CI varies with the level of CI whereas not with the level of GF. Specifically, the mitigating effect of GF on CI is significant in both high GF and low GF groups, but only in high CI group; and (4) GF promotes low-carbon transition of cities through mainly on adjusting industrial structure rather than stimulating technological innovation. Despite we also demonstrate green finance enhances green innovation, due to multi-factors, such technology progress it brings may not always translate into a tangible improvement in green productivity. For most developing countries including China, the future policy objective of green finance should focus on enhancing sustainable technological progress.
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Lithium hydride (LiH), a saline hydride with a hydrogen density of 12.6 wt %, is highly thermostable, which hinders its extensive application in hydrogen storage. In this study, we demonstrate a distinct photodecomposition of LiH under ambient conditions. Ultraviolet-visible (UV-vis) illumination induces hydrogen release and creates surface hydrogen vacancies on LiH. The subsequent H- migration enables hydrogen desorption and the accumulation of vacancies at the subsurface, resulting in the generation of metallic Li clusters. Rehydrogenation, on the contrary, can be charged under UV-vis illumination in 1 bar H2. Such phenomena show that the thermodynamic and kinetic limits in the re/dehydrogenation of LiH can be broken under illumination, which allows hydrogen storage over the LiH surface at temperatures â¼600 K lower than those of the corresponding thermal process. This work provides new insights into the interaction of semiconducting hydrides and photons and opens an avenue for the development and optimization of materials for hydrogen storage and related photodriven reactions.
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In this paper, we introduce the application of multiple-mode index modulation (MMIM) to filter bank multi-carrier (FBMC) for the first time in visible light communication (VLC) systems. Additionally, we propose a group-interleaved precoding (GIP) technique to enhance the performance of MM-FBMC-IM-based VLC systems. The GIP technique reduces complexity in precoding by grouping and achieves equalization of the signal-to-noise ratio (SNR) through subcarrier interleaving. Furthermore, we develop a robust low-complexity maximum likelihood (LCML) detector, which can maintain the same computational complexity as a conventional LCML detector and achieve similar performance as an ML detector. The effectiveness and superiority of the proposed MM-FBMC-IM-based VLC system with GIP are demonstrated through comprehensive validation by both simulation and experimental results.
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Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 µM and 12.12 ± 0.95 µM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.
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Antineoplásicos , Apoptosis , Proliferación Celular , Reishi , Triterpenos , Triterpenos/farmacología , Triterpenos/química , Triterpenos/síntesis química , Triterpenos/aislamiento & purificación , Reishi/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Animales , Ratones , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Femenino , Ciclo Celular/efectos de los fármacos , Estructura MolecularRESUMEN
Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.
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Cannabidiol , Cannabidiol/química , Cannabidiol/farmacología , Cannabidiol/metabolismo , Humanos , Animales , Antioxidantes/química , Antioxidantes/farmacología , Cannabis/química , Relación Estructura-Actividad , Receptores de Cannabinoides/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antidepresivos/química , Antidepresivos/farmacologíaRESUMEN
BACKGROUND: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. OBJECTIVE: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. METHODS: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. RESULTS: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90). CONCLUSIONS: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances.
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Mortalidad del Niño , Anomalías Congénitas , Humanos , China/epidemiología , Masculino , Anomalías Congénitas/mortalidad , Anomalías Congénitas/epidemiología , Femenino , Lactante , Preescolar , Recién Nacido , Mortalidad del Niño/tendencias , Vigilancia de la Población/métodos , Análisis de DatosRESUMEN
BACKGROUND: Rheumatic heart disease (RHD) is caused by inflammatory cells mistakenly attacking the heart valve due to Group A Streptococcus (GAS) infection, but it is still unclear which cells or genes are involved in the process of inflammatory cells infiltrating the valve. Inflammatory infiltration into the target tissue requires an increase in the expression of phosphorylated vascular endothelial-cadherin (p-VE-cad), p-VE-cad can increase the endothelial permeability and promote the migration of inflammatory cells across the endothelium. P-VE-cad is potentially regulated by RAS-related C3 botulinum substrate 1 (RAC1), together with phosphorylated proline-rich tyrosine kinase 2 (p-PYK2). While RAC1/p-PYK2/p-VE-cad is triggered by the activation of vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 is related to M1 macrophages adhering to the endothelium via very late antigen 4 (VLA4). Inflammatory infiltration into the valve is extremely important in the early pathogenesis of RHD. However, there is no relevant research on whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved in RHD; therefore, what we explored in this study was whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved. METHODS: We established a rat model of RHD and a cell model of M1 macrophage and endothelial cell cocultivation. Subsequently, we measured the degree of inflammatory cell infiltration, the levels of IL-6/IL-17, the degree of fibrosis (COL3/1), and the expression levels of fibrosis markers (FSP1, COL1A1 and COL3A1) in the heart valves of RHD rats. Additionally, we detected the expression of M1/M2 macrophage biomarkers in rat model and cell model, as well as the expression of M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad. We also tested the changes in endothelial permeability after coculturing M1 macrophages and endothelial cells. RESULTS: Compared to those in the control group, the levels of inflammatory cell infiltration and fibrotic factors in the heart valves of RHD rats were significantly higher; the expression of M1 macrophage biomarkers (iNOS, CD86 and TNF-α) in RHD rats was significantly higher; and significantly higher than the expression of M2 macrophage biomarkers (Arg1 and TGF-ß). And the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad in the hearts of RHD rats were significantly higher. At the cellular level, after coculturing M1 macrophages with endothelial cells, the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad were significantly higher, and the permeability of the endothelium was significantly greater due to cocultivation with M1 macrophages. CONCLUSIONS: All the results suggested that M1 macrophages and the VLA4/VCAM-1 pathway are potentially involved in the process of inflammatory infiltration in RHD.
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Macrófagos , Cardiopatía Reumática , Molécula 1 de Adhesión Celular Vascular , Animales , Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/patología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Macrófagos/metabolismo , Ratas , Integrina alfa4beta1/metabolismo , Masculino , Válvulas Cardíacas/metabolismo , Válvulas Cardíacas/patología , Transducción de Señal , Ratas Sprague-Dawley , Proteína de Unión al GTP rac1/metabolismo , Modelos Animales de Enfermedad , HumanosRESUMEN
The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.
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Amphotericin B (AmB) is a polyene-macrolide antimicrobial drug with a broad antibacterial spectrum and remarkable efficacy against deep fungal infections. It binds to ergosterol on the fungal cell membrane and alters its permeability, thereby destroying the membrane. AmB is a multicomponent antimicrobial medication that contains a wide range of impurities, rendering quality analysis extremely difficult. In the current Chinese Pharmacopoeia (Edition 2020) and European Pharmacopoeia (EP10.3), high performance liquid chromatography (HPLC) is applied to examine related substances in AmB. However, this technique presents a number of issues. For instance, the mobile phases used in the HPLC method described in both references contain nonvolatile inorganic salts, which cannot be coupled with a mass spectrometry (MS) detector. In addition, because the mobile phases used have a low pH, the component/impurities of AmB drug can easily be degraded or interconverted during the analytical process, leading to reduced analytical accuracy. Therefore, the accuracy and sensitivity of this method must be improved. In this study, a method based on on-line two-dimensional high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (2D HPLC-Q TOF/MS) was developed to analyze the impurity profile of AmB in accordance with the Chinese Pharmacopoeia (Edition 2020) and European Pharmacopoeia (EP10.3). The method combines on-line dilution and a multiple-capture HPLC system to achieve the efficient separation of AmB component/impurities. It also resolves the issue of poor solvent compatibility in 2D HPLC, increases the analytical flux, enhances the automation capability, reduces the mutual conversion of AmB and its impurities during the analytical process, and increases the detection sensitivity of the method. MS was also used to determine the structural inference of unstable components and impurities. An XBridge Shield C18 column (250 mm×4.6 mm, 3 µm) was used for first-dimensional-liquid chromatography with gradient elution using methanol-acetonitrile-4.2 g/L citric acid monohydrate solution (10â¶30â¶60, v/v/v, pH 4.7) as mobile phase A and methanol-acetonitrile-4.2 g/L citric acid monohydrate solution (12â¶68â¶20, v/v/v, pH 3.9) as mobile phase B. An Xtimate C8 column (10 mm×2.1 mm, 5 µm) was used as the trap column, and trapping and desalting were performed using 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (95â¶5, v/v). An Xtimate C8 column (250 mm×2.1 mm, 5 µm) was used for second-dimensional-liquid chromatography with gradient elution using 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (95â¶5, v/v) and 10 mmol/L ammonium formate aqueous solution containing 0.1% formic acid-acetonitrile (5â¶95, v/v) as mobile phases. The data were collected in positive-ion mode. In this study, the structures of six impurities in amphotericin B were inferred, according to the fragmentation, the MS and MS2 spectra of each impurity. The developed method can be used to quickly and sensitively analyze the impurity profile of AmB. Furthermore, the research results on impurity profiles can be applied to guide improvements in AmB production.
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Anfotericina B , Contaminación de Medicamentos , Espectrometría de Masas , Cromatografía Líquida de Alta Presión/métodos , Anfotericina B/análisis , Anfotericina B/química , Espectrometría de Masas/métodosRESUMEN
Multicellular organisms have dense affinity with the coordination of cellular activities, which severely depend on communication across diverse cell types. Cell-cell communication (CCC) is often mediated via ligand-receptor interactions (LRIs). Existing CCC inference methods are limited to known LRIs. To address this problem, we developed a comprehensive CCC analysis tool SEnSCA by integrating single cell RNA sequencing and proteome data. SEnSCA mainly contains potential LRI acquisition and CCC strength evaluation. For acquiring potential LRIs, it first extracts LRI features and reduces the feature dimension, subsequently constructs negative LRI samples through K-means clustering, finally acquires potential LRIs based on Stacking ensemble comprising support vector machine, 1D-convolutional neural networks and multi-head attention mechanism. During CCC strength evaluation, SEnSCA conducts LRI filtering and then infers CCC by combining the three-point estimation approach and single cell RNA sequencing data. SEnSCA computed better precision, recall, accuracy, F1 score, AUC and AUPR under most of conditions when predicting possible LRIs. To better illustrate the inferred CCC network, SEnSCA provided three visualization options: heatmap, bubble diagram and network diagram. Its application on human melanoma tissue demonstrated its reliability in CCC detection. In summary, SEnSCA offers a useful CCC inference tool and is freely available at https://github.com/plhhnu/SEnSCA.
Asunto(s)
Comunicación Celular , Análisis de la Célula Individual , Humanos , Ligandos , Análisis de la Célula Individual/métodos , Programas Informáticos , Biología Computacional/métodos , Algoritmos , Máquina de Vectores de Soporte , Análisis de Secuencia de ARN/métodos , Melanoma/metabolismo , Melanoma/patología , Melanoma/genética , Proteoma/metabolismo , Redes Neurales de la ComputaciónRESUMEN
Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight.