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OBJECTIVES: This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs). METHODS: The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes. RESULTS: Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts. CONCLUSIONS: Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.
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Pie Diabético , Fibroblastos , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Pie Diabético/genética , Pie Diabético/diagnóstico , Pie Diabético/patología , Humanos , Fibroblastos/metabolismo , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Biomarcadores/metabolismo , TranscriptomaRESUMEN
BACKGROUND: Norwegian scabies (NS) is a serious parasitic skin condition. Although NS is one of the causes of erythroderma, it is frequently overlooked. Therefore, it is essential to raise awareness regarding NS presenting as erythroderma. CASE SUMMARY: We present a case of NS that persisted for more than 3 years. After following nonstandard treatment, the patient's rash worsened and gradually progressed into erythroderma. Finally, NS was diagnosed by skin microscopy and pathology. CONCLUSION: When patients with pruritic dermatosis have high-risk factors such as prolonged bed rest and immunodeficiency, clinicians need to enhance their awareness of NS and ensure prompt diagnosis and treatment.
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Wilson disease (WD) is a severely autosomal genetic disorder triggered by dysregulated copper metabolism. Autophagy and apoptosis share common modulators that process cellular death. Emerging evidences suggest that Forkhead Box O1 over-expression (FoxO1-OE) aggravates abnormal autophagy and apoptosis to induce neuronal injury. However, the underlying mechanisms remain undetermined. Herein, the aim of this study was to investigate how regulating FoxO1 affects cellular autophagy and apoptosis to attenuate neuronal injury in a well-established WD cell model, the high concentration copper sulfate (CuSO4, HC)-triggered Atp7b-/- (Knockout, KO) neural stem cell (NSC) lines. The FoxO1-OE plasmid, or siRNA-FoxO1 (siFoxO1) plasmid, or empty vector plasmid was stably transfected with recombinant lentiviral vectors into HC-induced Atp7b-/- NSCs. Toxic effects of excess deposited copper on wild-type (WT), Atp7b-/- WD mouse hippocampal NSCs were tested by Cell Counting Kit-8 (CCK-8). Subsequently, the FoxO1 expression was evaluated by immunofluorescence (IF) assay, western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Meanwhile, the cell autophagy and apoptosis were evaluated by flow cytometry (FC), TUNEL staining, 2,7-dichlorofluorescein diacetate (DCFH-DA), JC-1, WB, and qRT-PCR. The current study demonstrated a strong rise in FoxO1 levels in HC-treated Atp7b-/- NSCs, accompanied with dysregulated autophagy and hyperactive apoptosis. Also, it was observed that cell viability was significantly decreased with the over-expressed FoxO1 in HC-treated Atp7b-/- WD model. As intended, silencing FoxO1 effectively inhibited abnormal autophagy in HC-treated Atp7b-/- NSCs, as depicted by a decline in LC3II/I, Beclin-1, ATG3, ATG7, ATG13, and ATG16, whereas simultaneously increasing P62. In addition, silencing FoxO1 suppressed apoptosis via diminishing oxidative stress (OS), and mitochondrial dysfunction in HC-induced Atp7b-/- NSCs. Collectively, these results clearly demonstrate the silencing FoxO1 has the neuroprotective role of suppressing aberrant cellular autophagy and apoptosis, which efficiently attenuates neuronal injury in WD.
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Studies on Oryza sativa (rice) are crucial for improving agricultural productivity and ensuring global sustenance security, especially considering the increasing drought and heat stress caused by extreme climate change. Currently, the genes and mechanisms underlying drought and heat resistance in rice are not fully understood, and the scope for enhancing the development of new strains remains considerable. To accurately identify the key genes related to drought and heat stress responses in rice, multiple datasets from the Gene Expression Omnibus (GEO) database were integrated in this study. A co-expression network was constructed using a Weighted Correlation Network Analysis (WGCNA) algorithm. We further distinguished the core network and intersected it with differentially expressed genes and multiple expression datasets for screening. Differences in gene expression levels were verified using quantitative real-time polymerase chain reaction (PCR). OsDjC53, MBF1C, BAG6, HSP23.2, and HSP21.9 were found to be associated with the heat stress response, and it is also possible that UGT83A1 and OsCPn60a1, although not directly related, are affected by drought stress. This study offers significant insights into the molecular mechanisms underlying stress responses in rice, which could promote the development of stress-tolerant rice breeds.
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Sequías , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Oryza , Oryza/genética , Oryza/metabolismo , Respuesta al Choque Térmico/genética , Redes Reguladoras de Genes/genética , Perfilación de la Expresión Génica/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de PlantasRESUMEN
The application rate of potassium fertilizer is closely related to the yield of crops. Thin-shelled Tartary buckwheat is a new variety of Tartary buckwheat with the advantages of thin shell and easy shelling. However, little is known about application rate of potassium fertilizer on the yield formation of thin-shelled Tartary buckwheat. This study aimed to clarify the effect of potassium fertilizer on the growth and yield of thin-shelled Tartary buckwheat. A field experiment to investigate the characteristics was conducted across two years using thin-shelled Tartary buckwheat (Miku 18) with four potassium fertilizer applications including 0 (no potassium fertilizer, CK), 15 (low-concentration potassium fertilizer, LK), 30 (medium-concentration potassium fertilizer, MK), and 45 kg·ha-1 (high-concentration potassium fertilizer, HK). The maximum and average grain filling rates; starch synthase activity; superoxide dismutase and peroxidase activities in leaves; root morphological indices and activities; available nitrogen, phosphorus, and organic matter content in rhizosphere soil; urease and alkaline phosphatase activities in rhizosphere soil; plant height, main stem node number, main stem branch number, leaf number; grain number per plant, grain weight per plant, and 100-grain weight increased first and then decreased with the increase in potassium fertilizer application rate and reached the maximum at MK treatment. The content of malondialdehyde was significantly lower in MK treatment than in other three treatments. The yields of thin-shelled Tartary buckwheat treated with LK, MK, and HK were 1.22, 1.37, and 1.07 times that of CK, respectively. In summary, an appropriate potassium fertilizer treatment (30kg·ha-1) can delay the senescence, promote the grain filling, and increase the grain weight and final yield of thin-shelled Tartary buckwheat. This treatment is recommended to be used in production to achieve high-yield cultivation of thin-shelled Tartary buckwheat.
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BACKGROUND: Spondyloarthritis (SpA), a chronic inflammatory disorder, predominantly impacts the sacroiliac joints and spine, significantly escalating the risk of disability. SpA's complexity, as evidenced by its diverse clinical presentations and symptoms that often mimic other diseases, presents substantial challenges in its accurate diagnosis and differentiation. This complexity becomes even more pronounced in nonspecialist health care environments due to limited resources, resulting in delayed referrals, increased misdiagnosis rates, and exacerbated disability outcomes for patients with SpA. The emergence of large language models (LLMs) in medical diagnostics introduces a revolutionary potential to overcome these diagnostic hurdles. Despite recent advancements in artificial intelligence and LLMs demonstrating effectiveness in diagnosing and treating various diseases, their application in SpA remains underdeveloped. Currently, there is a notable absence of SpA-specific LLMs and an established benchmark for assessing the performance of such models in this particular field. OBJECTIVE: Our objective is to develop a foundational medical model, creating a comprehensive evaluation benchmark tailored to the essential medical knowledge of SpA and its unique diagnostic and treatment protocols. The model, post-pretraining, will be subject to further enhancement through supervised fine-tuning. It is projected to significantly aid physicians in SpA diagnosis and treatment, especially in settings with limited access to specialized care. Furthermore, this initiative is poised to promote early and accurate SpA detection at the primary care level, thereby diminishing the risks associated with delayed or incorrect diagnoses. METHODS: A rigorous benchmark, comprising 222 meticulously formulated multiple-choice questions on SpA, will be established and developed. These questions will be extensively revised to ensure their suitability for accurately evaluating LLMs' performance in real-world diagnostic and therapeutic scenarios. Our methodology involves selecting and refining top foundational models using public data sets. The best-performing model in our benchmark will undergo further training. Subsequently, more than 80,000 real-world inpatient and outpatient cases from hospitals will enhance LLM training, incorporating techniques such as supervised fine-tuning and low-rank adaptation. We will rigorously assess the models' generated responses for accuracy and evaluate their reasoning processes using the metrics of fluency, relevance, completeness, and medical proficiency. RESULTS: Development of the model is progressing, with significant enhancements anticipated by early 2024. The benchmark, along with the results of evaluations, is expected to be released in the second quarter of 2024. CONCLUSIONS: Our trained model aims to capitalize on the capabilities of LLMs in analyzing complex clinical data, thereby enabling precise detection, diagnosis, and treatment of SpA. This innovation is anticipated to play a vital role in diminishing the disabilities arising from delayed or incorrect SpA diagnoses. By promoting this model across diverse health care settings, we anticipate a significant improvement in SpA management, culminating in enhanced patient outcomes and a reduced overall burden of the disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57001.
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Espondiloartritis , Humanos , Espondiloartritis/diagnóstico , Espondiloartritis/terapiaRESUMEN
Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.
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Atractylodes , Medicamentos Herbarios Chinos , Lactonas , Simulación del Acoplamiento Molecular , Farmacología en Red , Sesquiterpenos , Bazo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Animales , Atractylodes/química , Lactonas/química , Lactonas/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Bazo/efectos de los fármacos , Bazo/metabolismo , Rizoma/química , MasculinoRESUMEN
Prediabetes is a crucial stage for prevention and treatment of diabetes, and vitamin D (VD) has been found to be linked to the development of prediabetes and diabetes. Thus, we aimed to identify the effect of VD supplementation on glucose metabolism in prediabetic participants and mice. A 1:1 paired design of randomized, placebo-controlled trial with 1600 IU/day VD3 or placebo was administered to individuals with prediabetes, two-way repeated-measures ANCOVA was used to analyze glycolipid and inflammatory factors. A high-fat diet induced prediabetic KKay mice were utilized to evaluate the effects of VD3 with 16 weeks supplementation. Generalized estimation equation, one way ANOVA were used to analyze continuous monitoring indexes and terminal indexes, respectively. Exercise capacity, skeletal muscle pathological features and relevant proteins were examined. The clinical results showed that VD3 could improve insulin secretion and decrease inflammation. Results of KKay mice exhibited that VD3 not only ameliorate glycolipid metabolism and inflammatory indicators, but also regulated pathological changes of skeletal muscle and exercise capacity. Mechanistically, our results demonstrated that VD3 could inhibit the TLR4/NFκB and activate PI3K/AKT signaling pathway. Collectively, the study indicated that VD3 exerts its beneficial effects by inhibiting TLR4/NFκB to decrease inflammatory response, and activating PI3K/AKT signaling pathway to regulate glucose homeostasis.
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Colecalciferol , Inflamación , Músculo Esquelético , Estado Prediabético , Animales , Estado Prediabético/metabolismo , Estado Prediabético/tratamiento farmacológico , Colecalciferol/farmacología , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Ratones , Femenino , Ratones Endogámicos C57BL , Glucosa/metabolismo , Dieta Alta en Grasa/efectos adversos , Persona de Mediana Edad , Transducción de Señal/efectos de los fármacos , Adulto , Glucemia/metabolismo , Suplementos Dietéticos , FN-kappa B/metabolismoRESUMEN
Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.
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This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.
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Long non-coding RNAs (lncRNAs) are a recently discovered group of non-coding RNAs that play a crucial role in the regulation of various human diseases, especially in the study of nervous system diseases which has garnered significant attention. However, there is limited knowledge on the identification and function of lncRNAs in hepatolenticular degeneration (HLD). The objective of this study was to identify novel lncRNAs and determine their involvement in the networks associated with HLD. We conducted a comprehensive analysis of RNA sequencing (RNA-seq) data, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and computational biology to identify novel lncRNAs and explore their potential mechanisms in HLD. We identified 212 differently expressed lncRNAs, with 98 upregulated and 114 downregulated. Additionally, 32 differently expressed mRNAs were found, with 15 upregulated and 17 downregulated. We obtained a total of 1131 pairs of co-expressed lncRNAs and mRNAs by Pearson correlation test and prediction and annotation of the lncRNA-targeted miRNA-mRNA network. The differential lncRNAs identified in this study were found to be involved in various biological functions and signaling pathways. These include translational initiation, motor learning, locomotors behavior, dioxygenase activity, integral component of postsynaptic membrane, neuroactive ligand-receptor interaction, nuclear factor-kappa B (NF-κB) signaling pathway, cholinergic synapse, sphingolipid signaling pathway, and Parkinson's disease signaling pathway, as revealed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Six lncRNAs, including XR_001782921.1 (P < 0.01), XR_ 001780581.1 (P < 0.01), ENSMUST_00000207119 (P < 0.01), XR_865512.2 (P < 0.01), TCONS_00005916 (P < 0.01), and TCONS_00020683 (P < 0.01), showed significant differences in expression levels between the model group and normal group by RT-qPCR. Among these, four lncRNAs (TCONS_00020683, XR_865512.2, XR_001780581.1, and ENSMUST00000207119) displayed a high degree of conservation. This study provides a unique perspective for the pathogenesis and therapy of HLD by constructing the lncRNA-miRNA-mRNA network. This insight provides a foundation for future exploration in this field.
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Degeneración Hepatolenticular , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Encéfalo/metabolismo , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear. METHODS: The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. RESULTS: The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. CONCLUSION: In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.
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Alopecia , Interferón gamma , Humanos , Masculino , Alopecia/genética , Mastocitos , Algoritmos , Coagulación SanguíneaRESUMEN
Dimerization reactions play a critical role in various fields of research, including cell biology, biomedicine, and chemistry. In particular, the dimerization reaction of 2NO2âN2O4 has been extensively applied in pollution control and raw material preparation. Spectroscopy, as a powerful tool for investigating molecular structures and reaction kinetics, has been increasingly employed to study dimerization reactions in recent years. In this study, we successfully demonstrated the application of dual-comb spectroscopy (DCS) to analyze NO2 dimerization reactions, making the first report on the application of this technique in this context. Parallel measurements of NO2 and N2O4 fingerprints spectra with high resolution at 3000â cm-1 was performed, benefiting from the unprecedented broadband and high-precision capability of DCS. The absorption cross-sections of N2O4 from 296 to 343â K was obtained from the measured spectra, which contributes to further research on the molecular spectrum of N2O4. These results demonstrate the potential of DCS for studying the dimerization reaction mechanism.
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BACKGROUND: Higher neighbourhood greenness is associated with beneficial health outcomes, and short-term exposure to air pollution is associated with an elevated risk of stroke onset. However, little is known about their interactions. METHODS: Daily data on stroke first onset were collected from 20 counties in Shangdong Province, China, from 2013 to 2019. The enhanced vegetation index (EVI) and concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were calculated for each individual at the village or community level based on their home address to measure their neighbourhood exposure to greenness and air pollution. EVI was categorised as low or high, and a time-stratified case-crossover design was used to estimate the percent excess risk (ER%) of stroke associated with short-term exposure to air pollution. We further stratified greenness on the basis of EVI values into quartiles and introduced interaction terms between air pollutant concentrations and the median EVI values of the quartiles to assess the effect of greenness on the associations between short-term exposure and stroke. RESULTS: Individuals living in the high-greenness areas had weaker associations between total stroke risk and exposure to NO2 (low greenness: ER% = 1.765% [95% CI 1.205%-2.328%]; high greenness: ER% = 0.368% [95% CI -0.252% to 0.991%]; P = 0.001), O3 (low greenness: 0.476% [95% CI 0.246%-0.706%]; high greenness: ER% = 0.085% [95% CI -0.156% to 0.327%]; P = 0.011), and SO2 (low greenness: 0.632% [95% CI 0.138%-1.129%]; high greenness: ER% = -0.177% [95% CI -0.782% to 0.431%]; P = 0.035). CONCLUSION: Residence in areas with higher greenness was related to weaker associations between air pollution and stroke risk, suggesting that effectively planning green spaces can improve public health.
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Contaminantes Atmosféricos , Contaminación del Aire , Accidente Cerebrovascular , Humanos , Estudios Cruzados , Dióxido de Nitrógeno/análisis , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Accidente Cerebrovascular/epidemiología , China/epidemiologíaRESUMEN
PURPOSE: We aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis. METHODS: Sprague-Dawley rats were assigned to normal control (NC), diabetic model control (MC), low-dose VD3 (LVD), medium-dose VD3 (MVD), high-dose VD3 (HVD) and metformin positive control (PC) groups. Type 2 diabetes model was induced by a high-sugar, high-fat diet combined with STZ injection, and subsequently intervened with VD3 or metformin for 10 weeks. Blood glucose, body weight, food intake, water intake, urine volume, morphology, lung hydroxyproline level, immunohistochemistry, TUNEL staining, inflammatory cytokines secretion and related protein expression were analyzed. RESULTS: Diabetic rats exhibited significant impairments in fasting blood glucose, insulin resistance, body weight, food intake, water intake, and urine volume. While morphological parameters, diabetic rats exhibited severe lung fibrosis. Intriguingly, VD3 intervention reversed, at least in part, the diabetes-induced alterations. The expression of pyroptosis-related proteins was up-regulated in diabetic lungs whereas the changes were reversed by VD3. In the meanwhile, SIRT3 expression was down-regulated in diabetic lungs while VD3 up-regulated it. CONCLUSION: Fibrotic changes were observed in diabetic rat lung tissue and our study indicates that VD3 may effectively ameliorate diabetic pulmonary fibrosis via SIRT3-mediated suppression of pyroptosis.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Fibrosis Pulmonar , Sirtuina 3 , Ratas , Animales , Colecalciferol/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Sirtuina 3/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ratas Sprague-Dawley , Piroptosis , Glucemia , Apoptosis , Metformina/farmacología , Metformina/uso terapéutico , Peso CorporalRESUMEN
Background: Gandoufumu decoction (GDFMD) is a traditional Chinese medicine that has been widely used to treat Wilson's disease (WD) liver damage patients. However, its specific molecular mechanism currently remains unclear. Autophagy as a key contributor to WD liver damage has been intensely researched in the recent years. Therefore, the aim of this present study is to explore the effect of GDFMD on autophagy in WD liver damage, and the final purpose is to provide scientific evidence for GDFMD treatment in WD liver damage. Methods: The molecular mechanisms and autophagy-related pathways of GDFMD in the treatment of WD liver damage were predicted using network pharmacology. Copper assay kit was used to determine copper content in serum. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum levels of liver enzymes and oxidative stress-related indicators. Hematoxylin-eosin (HE), Masson, and Sirius red staining were used for the characterization of liver pathological changes. Transmission electron microscopy, immunofluorescence, and Western blot analyses were used to evaluate autophagy activity. The impact of the GDFMD on typical autophagy-related pathway (PI3K/Akt/mTOR pathway) molecules was also assessed via Western blot analysis. Results: GDFMD effectively attenuated serum liver enzymes, oxidative stress, autophagy, and degree of hepatic histopathological impairment and reduced serum copper content. Through network pharmacological approaches, PI3K/Akt/mTOR pathway was identified as the typical autophagy-related pathway of GDFMD in the treatment of WD liver damage. Treatment with GDFMD activated the PI3K/Akt/mTOR pathway, an effect that was able to be counteracted by LY294002, a PI3K antagonist or Rapa (rapamycin), an autophagy inducer. Conclusions: GDFMD imparted therapeutic effects on WD through autophagy suppression by acting through the PI3K/Akt/mTOR pathway.
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Degeneración Hepatolenticular , Transducción de Señal , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Degeneración Hepatolenticular/tratamiento farmacológico , Cobre/farmacología , Farmacología en Red , Serina-Treonina Quinasas TOR/metabolismo , AutofagiaRESUMEN
The aim of this study was to analyze the epidemiological characteristics and pathogen spectrum of tinea capitis in Guangxi, southern China. A multicenter prospective descriptive study was conducted in 8 hospitals across Guangxi. From January 2019 to July 2022, one hundred seventy-one (171) patients diagnosed with tinea capitis were included. Demographic data, risk factors, and fungal data were collected. If necessary, species were further identified by morphological or molecular sequencing in the central laboratory. Of the 171 cases of tinea capitis, 74.3% occurred in patients aged 2-8 years. Children with tinea capitis were mainly boys (59.6%) and were more likely than adults to have a history of animal contact (44.2% vs. 33.3%) and zoophilic dermatophyte infection (76.9% vs. 46.7%, P = 0.008). The adults were mainly female (53%) and were more likely than children to have a history of infection with anthropophilic organisms (53.3% vs. 18.9%). The causative agents of tinea capitis in Guangxi were diverse, and the most common pathogen was Microsporum canis (M. cani, n = 98, 62%), followed by Trichophyton mentagrophytes (T. mentagrophytes n = 18, 11.4%) and Trichophyton tonsurans (T. tonsurans n = 12, 7.6%). In addition, tinea capitis caused by Nannizzia incurvata (N. incurvata) and Trichophyton verrucosum (T. verrucosum) was detected in the study. Notably, the proportion of patients with kerion in the study was 41.5% (n = 71), and most of those patients were children (n = 68), especially neglected children living in the rural mountainous areas of Guangxi, where they were unable to receive timely diagnosis and appropriate treatment. In conclusion, the causative agents of tinea capitis in Guangxi, South China, are diverse, and the incidence of kerion is high, indicating that diagnosis and treatment modalities in the region remain grossly inadequate. Clinicians and policy-makers should collaborate to adopt public health strategies to control the disease.
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Tiña del Cuero Cabelludo , Niño , Masculino , Adulto , Animales , Humanos , Femenino , China/epidemiología , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/microbiología , Microsporum , Factores de Riesgo , Hospitales , Incidencia , TrichophytonRESUMEN
Optical activity (OA) spectroscopy is a powerful tool to characterize molecular chirality, explore the stereo-specific structure and study the solution-state conformation of biomolecules, which is widely utilized in the fields of molecular chirality, pharmaceutics and analytical chemistry. Due to the considerably weak effect, OA spectral analysis has high demands on measurement speed and sensitivity, especially for organic biomolecules. Moreover, gas-phase OA measurements require higher resolution to resolve Doppler-limited profiles. Here, we show the unmatched potential of dual-comb spectroscopy (DCS) in magnetic optical activity spectroscopy (MOAS) of gas-phase molecules with the resolution of hundred-MHz level and the high-speed measurement of sub-millisecond level. As a demonstration, we achieved the rapid, high-precision and high-resolution MOAS measurement of the nitrogen dioxide [Formula: see text]+[Formula: see text] band and the nitric oxide overtone band, which can be used to analyze fine structure of molecules. Besides, the preliminary demonstration of liquid-phase chiroptical activity (as weak as 10-5) has been achieved with several seconds of sampling time, which could become a routine approach enabling ultrafast dynamics analysis of chiral structural conformations.
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AIM: This study aims to explore the mind of Chinese nursing students transitioning to online education in the pandemic using health as expanding consciousness (HEC) as methodology. DESIGN: A qualitative, descriptive study based on interviews. METHODS: This qualitative study was conducted from September to November 2021 by students in the Guangzhou university of Chinese medicine. Thirteen participants were recruited using purposive sampling. A questionnaire containing two sections with demographic information, the General Self-Efficacy Scale (GSES) and the Connor-Davidson resilience scale (CD-RISC)-10 was collected to explore the health of participants. RESULTS: A total of 13 participants were enrolled in the study (69% female). Students ranged in age between 19 and 24 years and the mean age was 22 years. All students lived with their families. Five participants (38%) had a master's degree in nursing, three (23%) were in fourth year of college, four (30%) were in third year of college and one (7%) was in their second year of college respectively. More than half of the participants had high levels of mental toughness and self-efficacy. Four generic categories were identified form a unitary-transformative paradigm perspective. The respondents reported three health pattern phases: Curriculum Transformation, Curriculum adaptation and Curriculum expansion. CONCLUSION: This research backs up Newman's hypothesis, and supports the theoretical framework. HEC explains well the psychology of nursing students during the epidemic. More research is needed in the future to develop comprehensive, targeted emotional regulation therapies for nursing students.
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Estado de Conciencia , Estudiantes de Enfermería , Humanos , Femenino , Adulto Joven , Adulto , Masculino , Estudiantes de Enfermería/psicología , Proyectos de Investigación , Encuestas y Cuestionarios , CurriculumRESUMEN
Background: Conventionally, serum ceruloplasmin levels below the lower reference limit (0. 20 g/L) is considered a diagnostic cutoff point for Wilson's disease (WD). However, the lower reference limit varies with assay methodologies and the individuals in the included studies. The objective of this study was to determine the optimal cutoff value of serum ceruloplasmin levels for the diagnosis of WD in a large Chinese cohort and to identify factors associated with serum ceruloplasmin. Methods: The cutoff value of ceruloplasmin levels was developed based on a retrospective derivation cohort of 3,548 subjects (1,278 patients with WD and 2,270 controls) and was validated in a separate validation cohort of 313 subjects (203 patients with WD and 110 controls). The performance of immunoassay was tested by receiver operating characteristic curve (ROC) analysis, and differences among the groups were analyzed by using the Mann-Whitney U-test and the Kruskal-Wallis test. Results: The conventional cutoff of serum ceruloplasmin levels of <0.2 g/L had an accuracy of 81.9%, which led to a false-positive rate of 30.5%. The optimal cutoff of the serum ceruloplasmin level for separating patients with WD from other participants was 0.13 g/L, as determined by ROC analysis. This cutoff value had the highest AUC value (0.99), a sensitivity of 97.0%, and a specificity of 96.1%. Moreover, it prevented unnecessary further investigations and treatments for 492 false-positive patients. By determining the correlation between serum ceruloplasmin and phenotypes/genotypes in patients with WD, we found that the serum ceruloplasmin level was lower in early-onset patients and higher in late-onset patients. Interestingly, patients with the R778L/R919G genotype had higher serum ceruloplasmin levels than patients with other hot spot mutation combinations. Conclusion: Our work determined the optimal cutoff value of serum ceruloplasmin levels for the diagnosis of WD and identified differences in serum ceruloplasmin levels with respect to the age of symptom onset and ATP7B mutations, which may provide some valuable insights into the diagnosis and counsel of patients with WD.