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Background: In China, dementia poses a significant public health challenge, exacerbated by an ageing population and lifestyle changes. This study assesses the temporal trends and disparities in the population-attributable fractions (PAFs) of modifiable risk factors (MRFs) for new-onset dementia from 2011 to 2018. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS), covering 75,214 person-waves. We calculated PAFs for 12 MRFs identified by the Lancet Commission (including six early-to mid-life factors and six late-life factors). We also determined the individual weighted PAFs (IW-PAFs) for each risk factor. Subgroup analyses were conducted by sex, socio-economic status (SES), and geographic location. Findings: The overall PAF for dementia MRFs had a slight increase from 45.36% in 2011 to 52.46% in 2018, yet this change wasn't statistically significant. During 2011-2018, the most contributing modifiable risk was low education (average IW-PAF 11.3%), followed by depression, hypertension, smoking, and physical inactivity. Over the eight-year period, IW-PAFs for risk factors like low education, hypertension, hearing loss, smoking, and air pollution showed decreasing trends, while others increased, but none of these changes were statistically significant. Sex-specific analysis revealed higher IW-PAFs for traumatic brain injury (TBI), social isolation, and depression in women, and for alcohol and smoking in men. The decline in IW-PAF for men's hearing loss were significant. Lower-income individuals had higher overall MRF PAFs, largely due to later-life factors like depression. Early-life factors, such as TBI and low education, also contributed to SES disparities. Rural areas reported higher overall MRF PAFs, driven by factors like depression, low education, and hearing loss. The study also found that the gap in MRF PAFs across different SES groups or regions either remained constant or increased over the study period. Interpretation: The study reveals a slight but non-significant increase in dementia's MRF PAF in China, underscoring the persistent relevance of these risk factors. The findings highlight the need for targeted public health strategies, considering the demographic and regional differences, to effectively tackle and reduce dementia risk in China's diverse population. Funding: This work was supported by the PKU Young Scholarship in Global Health and Development.
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Kefir is a traditional dairy beverage, usually made from cow or goat milk fermented with kefir grains, and has many health benefits. To elucidate the fermentation patterns of animal milk kefirs during the fermentation process and find the optimal milk types, cow, camel, goat, and donkey milk were fermented with kefir grains for 0, 1, 3, 5, and 7 days. Volatile and non-volatile metabolites and microbial changes were dynamically monitored. The results showed that volatile flavor substances were massively elevated in four kefirs on days 1-3. Lipids and carbohydrates gradually decreased, while amino acids, small peptides, and tryptophan derivatives accumulated during fermentation in four kefirs. Besides, four kefirs had similar alterations in Lactobacillus and Acetobacter, while some distinctions existed in low-abundance bacteria. Association analysis of microorganisms and volatile and non-volatile metabolites also revealed the underlying fermentation mechanism. This study found that appropriately extending the fermentation time contributed to the accumulation of some functional nutrients. Furthermore, goat and donkey milk could be the better matrices for kefir fermentation.
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Equidae , Fermentación , Cabras , Kéfir , Leche , Animales , Kéfir/microbiología , Bovinos , Leche/microbiología , Leche/química , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Gusto , Camelus , Microbiología de Alimentos , Lactobacillus/metabolismo , Microbiota , Acetobacter/metabolismo , Aminoácidos/metabolismo , Aminoácidos/análisisRESUMEN
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. RESULTS AND CONCLUSION: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.
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ADN de Cadena Simple , G-Cuádruplex , Células Madre Mesenquimatosas , MicroARNs , Células Supresoras de Origen Mieloide , Animales , Células Supresoras de Origen Mieloide/metabolismo , Ratones , ADN de Cadena Simple/química , Línea Celular Tumoral , Ratones Endogámicos C57BL , Micropartículas Derivadas de Células/química , Micropartículas Derivadas de Células/metabolismo , ADN Circular/química , Humanos , Melanoma/tratamiento farmacológicoRESUMEN
Background: The radiographic classification of pulmonary nodules into benign versus malignant categories is a pivotal component of early lung cancer diagnosis. The present study aimed to investigate clinical and computed tomography (CT) clinical-radiomics nomogram for preoperative differentiation of benign and malignant pulmonary nodules. Methods: This retrospective study included 342 patients with pulmonary nodules who underwent high-resolution CT (HRCT) examination. We assigned them to a training dataset (n=239) and a validation dataset (n=103). There are 1781 tumor characteristics quantified by extracted features from the lesion segmented from patients' CT images. The features with poor reproducibility and high redundancy were removed. Then a least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation was used to further select features and build radiomics signatures. The independent predictive factors were identified by multivariate logistic regression. A radiomics nomogram was developed to predict the malignant probability. The performance and clinical utility of the clinical-radiomics nomogram was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: After dimension reduction by the LASSO algorithm and multivariate logistic regression, four radiomic features were selected, including original_shape_Sphericity, exponential_glcm_Maximum Probability, log_sigma_2_0_mm_3D_glcm_Maximum Probability, and ogarithm_firstorder_90Percentile. Multivariate logistic regression showed that carcinoembryonic antigen (CEA) [odds ratio (OR) 95% confidence interval (CI): 1.40 (1.09-1.88)], CT rad score [OR (95% CI): 2.74 (2.03-3.85)], and cytokeratin-19-fragment (CYFRA21-1) [OR (95% CI): 1.80 (1.14-2.94)] were independent influencing factors of malignant pulmonary nodule (all P<0.05). The clinical-radiomics nomogram combining CEA, CYFRA21-1 and radiomics features achieved an area of curve (AUC) of 0.85 and 0.76 in the training group and verification group for the prediction of malignant pulmonary nodules. The clinical-radiomics nomogram demonstrated excellent agreement and practicality, as evidenced by the calibration curve and DCA. Conclusions: The clinical-radiomics nomogram combined of CT-based radiomics signature, along with CYFRA21-1 and CEA, demonstrated strong predictive ability, calibration, and clinical usefulness in distinguishing between benign and malignant pulmonary nodules. The use of CT-based radiomics has the potential to assist clinicians in making informed decisions prior to biopsy or surgery while avoiding unnecessary treatment for non-cancerous lesions.
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Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6â¯J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.
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Metabolómica , Ratones Endogámicos C57BL , Patulina , Transcriptoma , Animales , Patulina/toxicidad , Ratones , Transcriptoma/efectos de los fármacos , Masculino , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Intestino Delgado/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Colon/efectos de los fármacos , Colon/patología , Intestinos/efectos de los fármacos , Intestinos/patologíaRESUMEN
BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.
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Caveolina 1 , Dieta Alta en Grasa , Células Endoteliales , Endotelio Vascular , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III , Vasodilatación , Animales , Masculino , Ratones , Aorta/enzimología , Aorta/fisiopatología , Aorta/metabolismo , Aorta/efectos de los fármacos , Aorta/patología , Caveolina 1/metabolismo , Caveolina 1/deficiencia , Caveolina 1/genética , Células Cultivadas , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/fisiopatología , Células Endoteliales/enzimología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/fisiopatología , Endotelio Vascular/metabolismo , Endotelio Vascular/enzimología , Endotelio Vascular/efectos de los fármacos , Ratones Noqueados , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/enzimología , Obesidad/fisiopatología , Obesidad/metabolismo , Transducción de Señal , Esterol Esterasa/metabolismo , Esterol Esterasa/genética , Ubiquitinación , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Culicoides is a genus of ubiquitous biting midges (Ceratopogonidae). Female midges have blood-sucking habit. They not only bite and harass humans and animals but also may be an important vector of disease transmission. Therefore, building an animal allergy model caused by Culicoides biting is very beneficial for studying its pathogenesis and exploring the therapeutic methods. MATERIAL AND METHOD: Kunming mice were used in this study to build the model and sensitised by two-step injection of midge extracts. Scratching behaviour and histological examination were used to check the immediate and delayed responses. Immunoglobulin E (IgE) and Immunoglobulin G (IgG) were detected using indirect enzyme-linked immunosorbent assay (ELISA) assay. Splenic cell proliferation and cytokine production were determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and ELISA assays. The response of cytokine gene expression to midge stimulation was analysed through quantitative real-time polymerase chain reaction (qPCR). RESULTS: Behavioural results revealed a significant increase in scratching frequency among the midge-sensitised animals (p < 0.05). Histological examination showed more inflammatory cytokine infiltration at the injection site of midge-sensitised mice comparing to the ones in the control group. The serum levels of IgE and IgG1 antibodies in the midge-sensitised group were significantly elevated (p < 0.05). After splenocytes were stimulated in vitro with midge extracts, the midge-sensitised group's splenocyte count significantly increased in comparison to the control group. The midge-sensitised group's qPCR data revealed a down-regulation of tumor necrosis factor alpha (TNF-α) expression and an increase in the expression of interleukin (IL)-4, IL-5, IL-10 and IL-13 but not in the control group (p < 0.05). CONCLUSIONS: In this study, an animal model of Culicoides-mouse sensitisation was successfully constructed using a two-step method. The mode of administration of the model was in good agreement with the natural immune pathway, and the immune response induced by the sensitisation of the model was similar to that produced by the bite of a midge.
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Ceratopogonidae , Modelos Animales de Enfermedad , Hipersensibilidad , Animales , Ceratopogonidae/fisiología , Ratones , Femenino , Hipersensibilidad/veterinaria , Hipersensibilidad/inmunología , Mordeduras y Picaduras de Insectos/veterinaria , Mordeduras y Picaduras de Insectos/inmunologíaRESUMEN
BACKGROUND: There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. OBJECTIVE: The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. METHODS: A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. RESULTS: Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. CONCLUSIONS: Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.
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Evaluación de la Discapacidad , Personas con Discapacidad , Humanos , Anciano , Técnica Delphi , Reproducibilidad de los Resultados , Personas con Discapacidad/rehabilitación , Encuestas y Cuestionarios , Actividades Cotidianas , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la SaludRESUMEN
Coridius chinensis is a traditional insect medicine in China. It is the dried whole insect of Coridius chinensis (Dallas) form the Pentatomidae family. Modern medical and pharmaceutical studies have successfully isolated and identified over 100 natural small molecular compounds from Coridius chinensis. These studies have also confirmed its various pharmacological activities, including analgesic, antioxidant, anticancer, anticoagulant, and antibacterial properties. Coridius chinensis is commonly used in traditional Chinese medicine preparations to treat impotence, hemangioma, pain and other diseases. However, more research is needed to fully explore the pharmacological effects of this herbal medicine. This paper aims to summarize both domestic and international research literature on Coridius chinensis, focusing on its main components, pharmacological activity and clinical application. The findings will provide valuable references for further research and development of Coridius chinensis as a traditional Chinese medicine resource.
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The microbiome-gut-brain axis (MGBA) plays a critical role in schizophrenia (SZ). However, the underlying mechanisms of the interactions among the gut microbiome, brain networks, and symptom severity in SZ patients remain largely unknown. Fecal samples, structural and functional magnetic resonance imaging (MRI) data, and Positive and Negative Syndrome Scale (PANSS) scores were collected from 38 SZ patients and 38 normal controls, respectively. The data of 16S rRNA gene sequencing were used to analyze the abundance of gut microbiome and the analysis of human brain networks was applied to compute the nodal properties of 90 brain regions. A total of 1,691,280 mediation models were constructed based on 261 gut bacterial, 810 nodal properties, and 4 PANSS scores in SZ patients. A strong correlation between the gut microbiome and brain networks (r = 0.89, false discovery rate (FDR) -corrected p < 0.05) was identified. Importantly, the PANSS scores were linearly correlated with both the gut microbiome (r = 0.5, FDR-corrected p < 0.05) and brain networks (r = 0.59, FDR-corrected p < 0.05). The abundance of genus Sellimonas significantly affected the PANSS negative scores of SZ patients via the betweenness centrality of white matter networks in the inferior frontal gyrus and amygdala. Moreover, 19 significant mediation models demonstrated that the nodal properties of 7 brain regions, predominately from the systems of visual, language, and control of action, showed significant mediating effects on the PANSS scores with the gut microbiome as mediators. Together, our findings indicated the tripartite relationships among the gut microbiome, brain networks, and PANSS scores and suggested their potential role in the neuropathology of SZ.
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Microbioma Gastrointestinal , Esquizofrenia , Humanos , Esquizofrenia/patología , Análisis de Mediación , ARN Ribosómico 16S , Encéfalo , Imagen por Resonancia Magnética/métodosRESUMEN
RATIONALE: Highly virulent multidrug-resistant Klebsiella pneumoniae (KP) is becoming more and more common in clinical practice, especially the rise of carbapenem-resistant KP in clinical practice, resulting in the emergence of KP liver abscess in Ningxia, China. For the prognosis of liver abscess patients, it is particularly important to identify the types of pathogens and identify antibiotics that are sensitive to the pathogens. PATIENT CONCERNS: A 73-year-old man from China presents to our hospital with abdominal pain, jaundice and fever. Patients have no obvious cause of abdominal pain, abdominal distension, and abdominal pain is persistent. Abdominal examination showed hepatomegaly, no tenderness 2 cm from the right costal margin, abdominal distension and other general examinations did not have obvious abnormalities. He had no history of hypertension and diabetes, ERCP was performed for cholangiocarcinoma 1 year before the current visit, and no significant complications occurred. DIAGNOSES: His initial diagnosis was obstructive cholangitis, and computed tomographic images and liver drainage fluid bacterial culture and genetic polymerase chain reaction tests later determined that the patient had KP liver abscess. INTERVENTIONS: Drainage by liver catheter and antibiotic treatment for 7 weeks. OUTCOMES: The patient liver abscess is basically gone. LESSION: It is particularly important to optimize the diagnosis of liver abscess pathogens for timely and effective treatment of patients.
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Infecciones por Klebsiella , Absceso Hepático , Masculino , Humanos , Anciano , Klebsiella pneumoniae , Virulencia , Absceso Hepático/microbiología , China , Dolor Abdominal , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
PURPOSE: Breast cancer is the most common cancer type worldwide, with its survivors often experiencing physical and psychosocial health problems. Wearable device use is an innovative and effective way to promote physical activity and improve health-related outcomes in breast cancer survivors; however, the current evidence is unclear. We aimed to determine the effects of wearable devices on physical activity and health-related outcomes in breast cancer survivors. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched to identify eligible studies from inception to September 2022. Additional relevant studies were obtained from the reference lists of the identified studies. Two reviewers independently screened the eligible studies, appraised the risk of bias, and extracted the data. Meta-analysis was conducted using Review Manager version 5.3. FINDINGS: Sixteen randomized controlled trials were included. Physical activity tracking and pedometer-based interventions improved moderate-intensity physical activity (standardized mean difference [SMD] = 0.32, 95% confidence interval [CI]: 0.17-0.46, p < 0.0001), moderate-to-vigorous physical activity (SMD = 0.85, 95%CI: 0.38-1.32, p = 0.0004), total physical activity (SMD = 0.51, 95%CI: 0.12-0.90, p = 0.01), quality of life (SMD = 0.17, 95%CI: 0.03-0.31, p = 0.01), physical function (SMD = 0.21, 95%CI: 0.04-0.38, p = 0.02), and mood state profiles (SMD = -0.58, 95%CI: -1.13 to 0.02, p = 0.04) in breast cancer survivors. However, the effects of low-intensity physical activity, vigorous-intensity physical activity, fatigue, anxiety, depression, and sleep quality could not be ascertained. CONCLUSIONS: Physical activity tracking and pedometer-based interventions were effective in increasing physical activity and improving health-related outcomes in breast cancer survivors. IMPLICATIONS FOR NURSING PRACTICE: This review offers availability of credible evidence supporting the potential usefulness and effectiveness of wearable physical activity trackers on physical activity and health-related outcomes in breast cancer survivors.
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Neoplasias de la Mama , Supervivientes de Cáncer , Dispositivos Electrónicos Vestibles , Humanos , Femenino , Calidad de Vida , Depresión , Ejercicio Físico , SobrevivientesRESUMEN
The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about bacteria within the HCC tumor microenvironment. Here, we showed that intratumoral Mycoplasma hyorhinis (M. hyorhinis) promoted the initiation and progression of HCC by enhancing nuclear ploidy. We quantified M. hyorhinis in clinical tissue specimens of HCC and observed that patients with high M. hyorhinis load had poor prognosis. We found that gastrointestinal M. hyorhinis can retrogradely infect the liver through the oral-duodenal-hepatopancreatic ampulla route. We further found that the increases in mononuclear polyploidy and cancer stemness resulted from mitochondrial fission caused by intracellular M. hyorhinis. Mechanistically, M. hyorhinis infection promoted the decay of mitochondrial fusion protein (MFN) 1 mRNA in an m6A-dependent manner. Our findings indicated that M. hyorhinis infection promoted pathological polyploidization and suggested that Mycoplasma clearance with antibiotics or regulating mitochondrial dynamics might have the potential for HCC therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Infecciones por Mycoplasma , Mycoplasma hyorhinis , Mycoplasma , Humanos , Mycoplasma hyorhinis/genética , Mycoplasma hyorhinis/metabolismo , Infecciones por Mycoplasma/metabolismo , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/patología , Microambiente TumoralRESUMEN
Vocoder-based speech synthesis has become a promising technique to accommodate the demands of high-quality speech analysis, manipulation, and synthesis. However, most existing works focus on how to synthesize normal human voice with high signal-to-noise ratio, neglecting individuals' pathological voice disorder in speech interaction. In this work, we propose a non-linear voice repair vocoder for pathological vowels and sentences, which takes the pathological speech as input and generates high-quality repaired speech. Our approach is specifically designed to enhance the speech quality and intelligibility for individuals with voice disorders. We employ amplitude modulated-frequency modulated (AM-FM) and Teager energy operation techniques to enhance the quality of pitch and spectral envelope. To tackle the instability and fracture problem of pitch, we present spectral tracking algorithm, which not only avoids dramatic change in the edge of voice, but also reduces the errors of half-pitch. Furthermore, we design a spectral reconstruction algorithm, which can effectively rebuild the spectral structure by energy operation to accomplish spectral envelope repair. The proposed PVR-Vocoder shows exceptional performance in pathological voice intelligibility enhancement according to various quality measures including objective indicators, subjective evaluation, and spectrum observations.
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Neurotoxicity could be induced by long exposure to manganese (Mn). The traditional Chinese medicine, Corididius chinensis (Cc) has been proven to have a certain curative effect on Mn poisoning. Therefore, network pharmacology was performed to explore potential therapeutic targets and pharmacological mechanisms of Cc. We found ingredients by building our own database through literature, (which is the first to screen traditional Chinese medicine without traditional Chinese medicine systems pharmacology database and analysis platform databases and it is applicable whenever a Chinese medicine is not found in the traditional Chinese medicine systems pharmacology database and analysis platform database) and potential targets of Mn-induced nervous system diseases from the OMIM, GeneCards, and DrugBank database were identified. A protein-protein interaction network was constructed using Cytoscape. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed for the treatment of Mn-induced nervous system disease, and molecular docking was carried out to verify the results of network pharmacology analysis. After screening disease-related genes, 12 intersecting genes overlapped between 284 target proteins of the active compound and 195 potential disease targets. The pathways of neurodegeneration_multiple diseases and Alzheimer disease pathway may be the most potential pathway of Cc treating Mn-induced nervous system diseases. CASP9 and PTGS2 in neurodegeneration_multiple diseases, NOS1, NOS2 in Alzheimer disease pathway were identified as core targets. Especially, molecule docking analysis unveil that aspongpyrazine A docking NOS2 is the most potential therapeutic drug and target, which primarily involved in the processes of oxidative stress and inflammation.
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Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Enfermedades del Sistema Nervioso , Humanos , Simulación del Acoplamiento Molecular , Manganeso , Farmacología en Red , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
BACKGROUND: Overweight and obesity have become major public health concerns worldwide. Persistent stress can activate the human hypothalamicâpituitaryâadrenal axis (HPA) and increase the intake of "self-rewarding food", thereby raising the incidence of obesity. Health care workers (HCWs) experience higher workloads and mental stress than workers in many other industries, which may put them at increased risk for overweight/obesity. However, few studies have been carried out on overweight and obesity among HCWs in China, and the overall scenario and behind-the-scenes factors of their overweight and obesity are unknown. The aim of this study is to understand the epidemic of overweight and obesity and risk factors among Chinese HCWs. METHODS: Based on a cross-sectional web survey design, 23,234 HCWs from 100 health institutions in 5 provinces/autonomous regions/municipalities across China were sampled to answer a self-administered questionnaire that was purposely developed using a multi-staged clustered random-sampling method. Chi-square test and ANOVA were performed to compare variables between two or more groups. Univariate analyses were conducted to identify the influence of self-reported persistent stress and/or recurrent anxiety/depressed mood on lifestyle behaviors. A multivariate binary logistic regression model was used to analyse the risk factors of overweight/obesity. RESULTS: Among the respondents, 34.26% were overweight, and 11.22% were obese. Most of the respondents had regular exercise habits (68.17%), had habitually stayed-up late (65.06%) and had been affected by persistent stress and/or recurrent anxiety/depressed mood (62.04%). A higher proportion of those with persistent stress and/or recurrent anxiety/depressed mood than those without habitually staying-up late (76.18%); consumed take-out food (54.92%), fried food (49.93%), snacks or desserts (50.51%); drank sugary drinks (46.57%); smoked (14.27%); and drank alcohol (23.34%). Gender (Female) (OR: 0.314, 95%CI: 0.292-0.336), age (OR: 1.742-2.334, 95%CI: 1.544-2.858), education (OR: 0.620-0.728, 95%CI: 0.445-0.973), living and working area (OR: 1.271, 95%CI: 1.192-1.355), breakfast (OR: 0.898, 95%CI: 0.839-0.960), fried food (OR: 1.133, 95%CI: 1.048-1.224), and alcohol consumption (OR: 1.111, 95%CI: 1.017-1.214) were factors for overweight/obesity. All of the aforementioned results were significant (P < 0.05). CONCLUSIONS: The overweight/obesity rate of Chinese HCWs is rather high, which might be directly associated with lifestyle behaviors. However, these behaviors fundamentally originated from persistent stress and/or recurrent anxiety/depression, mediated by lifestyle behaviors. Substantial measures should be taken for stress reduction and mental health promotion for overweight/obesity prevention and control among HCWs.
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Sistema Hipotálamo-Hipofisario , Sobrepeso , Femenino , Humanos , Sobrepeso/epidemiología , Estudios Transversales , Sistema Hipófiso-Suprarrenal , Obesidad/epidemiología , Factores de Riesgo , Estilo de VidaRESUMEN
During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.
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Pueblo Asiatico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , China , Data Warehousing , Bases de Datos Factuales , NeurocienciasRESUMEN
Glycation is a nonenzymatically catalyzed spontaneous reaction that eventually leads to the formation of advanced glycation end-products (AGEs), which can bind to the receptor for AGEs (RAGE). The consequences are oxidative damage, an inflammatory response, and aging. In this work, we synthesized echinacoside-zinc coordination polymers (ECH-Zn) by using the coordination interaction between the catechol group of ECH and zinc ions. ECH-Zn was further wrapped with hyaluronic acid/poly (ethylenimine) (HA-PEI) to obtain spherical nanoparticle polymers of HA-PEI-coated ECH-Zn (PPZn). PPZn can enhance the uptake and utilization of ECH-Zn and also have a better antiglycation effect in the skin under the effect of promoting transdermal absorption of HA-PEI. Mechanistic studies at the cellular level showed that MDM2 can interact with STAT2 to form a transcriptional complex and thus promote RAGE transcriptional activation. In vitro and in vivo studies revealed that PPZn can decrease the expression and inhibit the interaction of the MDM2/STAT2 complex. It inhibited the function of the MDM2/STAT2 complex and suppressed the transcriptional activation of RAGE, thereby exerting antiglycation effects. In conclusion, this work provides a nanomaterial and elucidated a mechanism of anti-skin glycation.
Asunto(s)
Productos Finales de Glicación Avanzada , Nanoestructuras , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Reacción de Maillard , Zinc/farmacología , Activación TranscripcionalRESUMEN
BACKGROUND: Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition. CASE PRESENTATION: A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections. CONCLUSIONS: This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.