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Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.
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Fondo de Ojo , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades de la Retina/etiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/patología , Enfermedades de la Coroides/etiología , Enfermedades de la Coroides/diagnósticoRESUMEN
Ventricular septal defect (VSD) is the most common type of congenital heart disease. HAND1 gene plays a crucial role in the development of the heart, but the role of the variants in the HAND1 gene promoter region in patients with VSD has not been explored yet. From 588 participants (300 with isolated and sporadic VSD and 288 healthy controls), DNA was extracted from blood samples. Variants at the HAND1 gene promoter region were analyzed through Sanger sequencing. Subsequently, cell functional validation was conducted through cell experiments, including dual-luciferase reporter gene analysis, electrophoretic mobility shift analysis, and bioinformatics analysis was also conducted. The promoter region of HAND1 gene had a total of 9 identified variant sites. Among them, 4 variants were exclusively found in VSD patients, and 1 variant (g.3631A>C) was newly discovered. Cell functional experiments indicated that all four variants decreased the transcriptional activity of HAND1 gene promoter with three of them reached statistical significance (p < 0.05). Subsequent analysis using JASPAR (a transcription factor binding profile database) suggests that these variants may alter the binding sites of transcription factors, potentially contributing to the formation of VSD. Our study for the first time identified variants in the promoter region of HAND1 gene in Chinese patients with isolated and sporadic VSD. These variants significantly decreased the expression of HAND1 gene, impacting transcription factor binding sites, and thereby demonstrating pathogenicity. This study offers new insights into the role of HAND1 gene promoter region, contributing to a better understanding of the genetic basis of VSD formation.
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ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 1.25-50 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.
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Medium-voltage (MV) switchgear and gas insulated switchgear (GIS) are essential components of power-grid systems. Their safe operation is crucial for the electricity consumption of users. However, insulation faults often occur during the operation of MV switchgear and GIS because of pollution, humidity, heat, mechanical shock, and other factors. Partial discharge (PD) measurements are the most effective indicator to prevent insulation failure. Transient earth voltage (TEV) and ultrasonic methods are the most popular PD measurement methods for switchgear. Currently, these two methods are used widely and independently. In this study, a novel TEV-ultrasonic integrated sensor is proposed based on the independent structure of the TEV and the ultrasonic sensor. The performance parameters of the proposed sensor were tested on test platforms. PD measurement experiments were conducted in a 10 kV switchgear and 220 kV GIS to analyze the performance of the integrated sensor. The results show that the sensor can simultaneously measure the TEV and ultrasonic signals in the same location. The integrated sensor can realize effective and sensitive detection, precise location, and accurate diagnosis of PD in the MV switchgear and GIS.
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BACKGROUND: The bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women. METHODS: The researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women. RESULTS: There were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04-0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01-0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11-1.12), P = 0.07]. CONCLUSION: Tai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis.
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Accidentes por Caídas , Densidad Ósea , Osteoporosis Posmenopáusica , Posmenopausia , Taichi Chuan , Humanos , Taichi Chuan/métodos , Accidentes por Caídas/prevención & control , Femenino , Posmenopausia/fisiología , Densidad Ósea/fisiología , Osteoporosis Posmenopáusica/prevención & control , Persona de Mediana Edad , Equilibrio Postural/fisiología , Anciano , Calcio/sangre , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population. METHODS: A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool. RESULTS: A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], -3.87 kg; 95% CI, -5.54 to -2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, -1.85 kg; 95% CI, -2.42 to -1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases. CONCLUSIONS: Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano , Femenino , Humanos , Masculino , Factores de Edad , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Resultado del TratamientoRESUMEN
Cobalt phosphide has received much attention as an efficient catalyst for electrocatalytic hydrodechlorination (EHDC). However, the active species proton hydrogen (H*) is consumed by the hydrogen evolution reaction (HER). Herein, we report a crystal regulation strategy for cobalt phosphate/graphitic nanocarbon/nickel foam (CoPO/GC/NF) catalysts applied for the EHDC of 2,4-dichlorophenoxyacetic acid (2,4-D). Characterization revealed that during the high-temperature phosphatization process, CoPO/GC/NF catalysts developed Co(PO3)2@CoP heterojunctions, enhancing charge transfer at the electrolyte-catalyst interface and water dissociation. The interaction between Co(PO3)2 and CoP induced the reconstitution of CoP into the Co-OH species, which facilitated the production of H* by accelerating the Volmer step, enhancing EHDC activity. Furthermore, Co(PO3)2 species improve the catalyst tolerance, with CoPO/GC/NF(450) maintaining over 71% yield of phenoxyacetic acid (PA) in continuous testing for up to 80 h under high-salt conditions. This work clarifies the surface transformation process of CoP/GC/NF during hydrodechlorination and demonstrates great potential for chlorophenol wastewater remediation.
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BACKGROUND: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. RESULTS: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. CONCLUSIONS: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.
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Dieta , Fragilidad , Humanos , Anciano , Femenino , Masculino , Fragilidad/epidemiología , China/epidemiología , Dieta/estadística & datos numéricos , Dieta/métodos , Estudios de Cohortes , Anciano Frágil/estadística & datos numéricos , Estudios Longitudinales , Anciano de 80 o más Años , Pueblo Asiatico/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Pueblos del Este de AsiaRESUMEN
BACKGROUND: A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. METHOD: This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan-Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. RESULTS: Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26-1.32], p < 0.001). Kaplan-Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13-1.21] for females vs. aHR 1.39 [CI:1.35-1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37-1.62]; 50-59: aHR 1.48 [CI: 1.40-1.56]; 60-69: aHR 1.30 [CI: 1.25-1.6]; 70-79: aHR 1.21 [CI: 1.17-1.26]; > 80: aHR 1.29 [CI: 1.21-1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001). CONCLUSIONS: Our cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.
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Glaucoma , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/epidemiología , Persona de Mediana Edad , Taiwán/epidemiología , Estudios Retrospectivos , Anciano , Glaucoma/epidemiología , Incidencia , Estudios de Cohortes , Factores de Riesgo , Medición de Riesgo/métodos , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales , Comorbilidad , AdultoRESUMEN
INTRODUCTION: The efficacy of myo-inositol supplementation to treat gestational diabetes remains controversial, and this meta-analysis aims to study the efficacy of myo-inositol supplementation on metabolic status for gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically searched from inception to October 2021, and we included the randomized controlled trials (RCTs) assessing the effect of myo-inositol supplementation on the outcomes of women with gestational diabetes. Gestational diabetes was diagnosed if at least one threshold of glucose concentration was exceeded and the three thresholds included 92, 180, and 153 mg/dl for 0, 1 and 2 h, respectively, after a 75-g, 2-h glucose tolerance test. RESULTS: Four RCTs and 317 patients were included in this meta-analysis. Compared with routine treatment in pregnant women with gestational diabetes, myo-inositol supplementation could lead to remarkably decreased treatment requirement with insulin (odd ratio [OR] = 0.24; 95% confidence interval [CI] = 0.11-0.52; p = .0003) and homeostasis model assessment of insulin resistance (HOMA-IR, standard mean difference [SMD]= -1.18; 95% CI= -1.50 to -0.87; p < .00001), but demonstrated no obvious impact on birth weight (SMD= -0.11; 95% CI= -0.83 to 0.61 g; p = .76), cesarean section (OR = 0.82; 95% CI = 0.46-1.47; p = .51) or the need of NICU (OR = 0.88; 95% CI = 0.03-26.57; p = .94). CONCLUSIONS: Myo-inositol supplementation is effective to decrease the need of insulin treatment and HOMA-IR for gestational diabetes.
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Diabetes Gestacional , Inositol , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/dietoterapia , Inositol/uso terapéutico , Embarazo , Femenino , Resistencia a la Insulina , Suplementos Dietéticos , Insulina/uso terapéutico , Glucemia/metabolismo , Glucemia/análisisRESUMEN
Induction of resistin-like molecule ß (Relm-ß) and mitofusin 2 (MFN2) mediated aberrant mitochondrial fission have been found to be involved in the pathogenesis of pulmonary arterial hypertension (PAH). However, the molecular mechanisms underlying Relm-ß regulation of MFN2 therefore mitochondrial fission remain unclear. This study aims to address these issues. Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. The results showed that Relm-ß promoted cells proliferation in PASMCs, this was accompanied with the upregulation of USP18, Twist1 and miR-214, and downregulation of MFN2. We found that Relm-ß increased USP18 expression which in turn raised Twist1 by suppressing its proteasome degradation. Elevation of Twist1 increased miR-214 expression and then reduced MFN2 expression and mitochondrial fragmentation leading to PASMCs proliferation. In vivo study, we confirmed that Relm-ß was elevated in MCT-induced PAH rat model, and USP18/Twist1/miR-214/MFN2 axis was altered similar as in vitro. Targeting this cascade by Relm-ß receptor inhibitor Calhex231, proteasome inhibitor MG-132, Twist1 inhibitor Harmine or miR-214 antagomiR prevented the development of pulmonary vascular remodeling and therefore PAH in MCT-treated rats. In conclusion, we demonstrate that Relm-ß promotes PASMCs proliferation and vascular remodeling by activating USP18/Twist1/miR-214 dependent MFN2 reduction and mitochondrial fission, suggesting that this signaling pathway might be a promising target for management of PAH.
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Proliferación Celular , GTP Fosfohidrolasas , MicroARNs , Mitocondrias , Ratas Sprague-Dawley , Transducción de Señal , Proteína 1 Relacionada con Twist , Ubiquitina Tiolesterasa , Animales , MicroARNs/genética , MicroARNs/metabolismo , Masculino , Ratas , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Proteína 1 Relacionada con Twist/metabolismo , Proteína 1 Relacionada con Twist/genética , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/patología , Hipertensión Arterial Pulmonar/fisiopatología , Monocrotalina/toxicidad , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , Proteínas MitocondrialesRESUMEN
Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment.
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Proliferación Celular , Citocinas , Queratinocitos , Proteína Quinasa 14 Activada por Mitógenos , Psoriasis , Factor de Transcripción STAT3 , Psoriasis/metabolismo , Psoriasis/genética , Psoriasis/patología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Queratinocitos/metabolismo , Animales , Ratones , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Proteína Quinasa 14 Activada por Mitógenos/genética , Citocinas/metabolismo , Regulación hacia Abajo , Ratones Noqueados , Interleucina-17/metabolismo , Interleucina-17/genética , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal , Humanos , ImiquimodRESUMEN
OBJECTIVES: To investigate urushiol's potential as a dentin cross-linking agent, promoting remineralization of etched dentin and preventing activation of endogenous proteases causing collagen degradation within the hybrid layer. The goal is to improve bond strength and durability at the resin-dentin interface. METHODS: Urushiol primers with varying concentrations were prepared using ethanol and dimethyl sulfoxide (DMSO) as solvents. Dentin from healthy molars underwent grinding and acid etching for 15 s, followed by a 1min application of urushiol primer. After 14 and 28 days of remineralization incubation and remineralization were used to assess by Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR), Micro-Raman spectroscopy, X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), Vickers Hardness, Scanning Electron Microscopy (SEM), and Energy X-ray dispersive spectroscopy (EDS). The overall performance of urushiol primers as dentin adhesives was observed by microtensile bond strength (µTBS) testing and nanoleakage assessment. Investigated the inhibitory properties of the urushiol primers on endogenous metalloproteinases (MMPs) utilizing in situ zymography, and the cytotoxicity of the primers was tested. RESULTS: Based on ATR-FTIR, Raman, XRD, EM-EDS and Vickers hardness analyses, the 0.7%-Ethanol group significantly enhanced dentin mineral content and improved mechanical properties the most. Pretreatment notably increased the µTBS of restorations, promoted the stability of the mixed layer, and reduced nanoleakage and MMPs activity after 28 days. SIGNIFICANCE: The urushiol primer facilitates remineralization in demineralized dentin, enhancing remineralization in etched dentin, effectively improving the bonding interface stability, with optimal performance observed at a 0.7 wt% concentration of the urushiol primer.
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Dentina , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Solventes , Resistencia a la Tracción , Remineralización Dental , Humanos , Espectroscopía Infrarroja por Transformada de Fourier , Dentina/efectos de los fármacos , Remineralización Dental/métodos , Solventes/química , Difracción de Rayos X , Recubrimientos Dentinarios/química , Espectrometría Raman , Propiedades de Superficie , Recubrimiento Dental Adhesivo/métodos , Microscopía de Fuerza Atómica , Técnicas In Vitro , Grabado Ácido Dental , Espectrometría por Rayos X , Diente Molar , Reactivos de Enlaces Cruzados/química , DurezaRESUMEN
The primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape.
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Familia de Aldehído Deshidrogenasa 1 , Glucólisis , Ratones Desnudos , Retinal-Deshidrogenasa , Escape del Tumor , Humanos , Animales , Familia de Aldehído Deshidrogenasa 1/metabolismo , Familia de Aldehído Deshidrogenasa 1/genética , Retinal-Deshidrogenasa/metabolismo , Retinal-Deshidrogenasa/genética , Ratones , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias/inmunología , Neoplasias/genética , Neoplasias/patología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Regiones Promotoras Genéticas/genética , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , Femenino , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
To explore whether digital finance can reduce agricultural carbon emissions, promote regional convergence, and foster inclusivity in rural revitalization and shared prosperity, this paper uses the provincial-level index of digital financial inclusion to analyze the impact of digital financial inclusion on the intensity of agricultural carbon emissions and the Degum Gini coefficient (D-Gini coefficient) of regional carbon emission intensity in 30 sample provinces from 2010 to 2020. It examines the mechanism of the impact of digital financial inclusion on both variables to understand the underlying factors better. The main conclusions are as follows: (1) Digital financial inclusion significantly reduces the intensity of agricultural carbon emissions and narrows the gap in carbon emission intensity between regions. (2) The unconditional quantile regression coefficients show that the negative coefficients of the digital financial inclusion index and the three-dimensional indices decrease with increasing quantiles. However, the significant effects vary significantly at different quantiles. (3) Technological progress and the government's ability to allocate financial resources play a significant mediating role, and the income gap between urban and rural areas can be further narrowed, as well as the carbon emission intensity gap between provinces. The empirical results are robust and proven by replacing the econometric analysis method, changing the core variables, and other methods.
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Agricultura , Carbono , Agricultura/economía , Agricultura/métodos , Carbono/análisis , Carbono/metabolismo , HumanosRESUMEN
AIM: This systematic review aimed to assess the psychometric properties of existing nursing informatics scales of competence and provide an evidence-based basis for selecting the most appropriate assessment instruments for specific populations. BACKGROUND: Informatics competency is one of the fundamental competencies that nurses should have. Using an informatics competency assessment instrument is an effective way to identify competency gaps and develop a professional development plan to address them. However, no systematic reviews summarizing and assessing the psychometric properties of all nursing informatics competency assessment instruments exist. DESIGN: This study systematically reviews measurement properties using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology. METHODS: Eight electronic databases (PubMed, Embase, Web of Science, CINAHL Complete, MEDLINE, PsychInfo, China National Knowledge Infrastructure and WanFang Data) were systematically searched from inception until January 10, 2024. Methodological quality was assessed using the COSMIN Risk of Bias Checklist. We used the COSMIN criteria to summarize and rate the psychometric properties. RESULTS: Twenty-seven studies reported twenty-five various versions of the instruments. Eighteen instruments assessed only one to three psychometric properties. No studies report cross-cultural effectiveness/measurement invariance and measurement error. The quality of evidence for structural validity or internal consistency for the three instruments failed to satisfy the COSMIN criteria. The SANICS-C has moderate to high-quality evidence of adequate content validity and internal consistency. In the end, the SANICS-C was an A recommendation, three instruments were C recommendations and the rest were B recommendations. CONCLUSION: The Nursing Informatics Competencies Scale for Nursing Students, SANICS-C and ICAT can be used to assess the informatics competencies of undergraduate, graduate and doctoral nursing students, respectively. The C-NICAS-FR is recommended for the assessment of nurses' informatics competence. The Self-Assessment Questionnaire for Nursing Informatics Competencies of Nursing Manager can be recommended for assessing nurse leaders' informatics competencies. Future research needs to validate these instruments' cross-cultural applicability further and comprehensively assess their psychometric properties. Along with emerging technologies, researchers should continually revisit and revise existing assessment instruments and develop instruments to assess the informatics competencies of nursing teachers.
RESUMEN
Plant-mediated interactions between herbivores play an important role in regulating the composition of herbivore community. The fall armyworm (FAW), Spodoptera frugiperda, which has become one of the most serious pests on corn in China since it invaded in 2018, has been found feeding rice in the field. However, how FAW interacts with native rice insect pests remains largely unknown. Here, we investigated the interaction between FAW and a resident herbivore, striped stem borer (SSB, Chilo suppressalis) on rice. The infestation of rice leaf sheaths (LSs) by SSB larvae systemically enhanced the level of jasmonic acid (JA), abscisic acid (ABA), and trypsin proteinase inhibitors (TPIs), reduced relative water content (RWC) in leaf blades (LBs), and suppressed the growth of FAW larvae. In contrast, because FAW larvae infested LBs and did not affect defence responses in LSs, they did not influence the performance of SSB larvae. Using different mutants, together with bioassays and chemical analysis, we revealed that SSB-induced suppression of FAW larvae growth depended on both the SSB-activated JA pathway and RWC in LBs, whereas the ABA pathway activated by SSB larvae promoted the growth of FAW larvae by impeding water loss. These results provide new insights into mechanisms underlying plant-mediated interactions between herbivores.
RESUMEN
Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested caseâcontrol study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.