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Low temperature stress poses a significant challenge to the productivity of horticultural crops. The dynamic expression of cold-responsive genes plays a crucial role in plant cold tolerance. While NAC transcription factors have been extensively studied in plant growth and development, their involvement in regulating plant cold tolerance remains poorly understood. In this study, we focused on the identification and characterisation of SlNAC3 as the most rapid and robust responsive gene in tomato under low temperature conditions. Manipulating SlNAC3 through overexpression or silencing resulted in reduced or enhanced cold tolerance, respectively. Surprisingly, we discovered a negative correlation between the expression of CBF and cold tolerance in the SlNAC3 transgenic lines. These findings suggest that SlNAC3 regulates tomato cold tolerance likely through a CBF-independent pathway. Furthermore, we conducted additional investigations to identify the molecular mechanisms underlying SINAC3-mediated cold tolerance in tomatoes. Our results revealed that SlNAC3 controls the transcription of ethylene biosynthetic genes, thereby bursting ethylene release in response to cold stress. Indeed, the silencing of these genes led to an augmentation in cold tolerance. This discovery provides valuable insights into the regulatory pathways involved in ethylene-mediated cold tolerance in tomatoes, offering potential strategies for developing innovative approaches to enhance cold stress resilience in this economically important crop species.
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Etilenos , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Solanum lycopersicum , Frío , Respuesta al Choque por Frío/fisiología , Etilenos/metabolismo , Etilenos/biosíntesis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Solanum lycopersicum/genética , Solanum lycopersicum/fisiología , Solanum lycopersicum/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
OBJECTIVES: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. METHODS: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RTâqPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAIâ2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the MannâWhitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. CONCLUSIONS: LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.
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OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.
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Lupus Eritematoso Sistémico , Receptores de Antígenos de Linfocitos T gamma-delta , Humanos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Subgrupos de Linfocitos T , FenotipoRESUMEN
Neural oscillations are electrophysiological indicators of synchronous neuronal activity in the brain. Recent work suggests aberrant patterns of neuronal activity in patients with poststroke aphasia. Yet, there is a lack of systematic explorations of neural oscillations in poststroke aphasia. Investigating changes in the dynamics of neuronal activity after stroke may be helpful to identify neural markers of aphasia and language recovery and increase the current understanding of successful language rehabilitation. This review summarizes research on neural oscillations in poststroke aphasia and evaluates their potential as biomarkers for specific linguistic processes. We searched the literature through PubMed, Web of Science, and EBSCO, and selected 31 studies that met the inclusion criteria. Our analyses focused on neural oscillation activity in each frequency band, brain connectivity, and therapy-induced changes during language recovery. Our review highlights potential neurophysiological markers; however, the literature remains confounded, casting doubt on the reliability of these findings. Future research must address these confounds to confirm the robustness of cross-study findings on neural oscillations in poststroke aphasia.
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Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.
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Frío , Cucumis sativus , Inositol , Plantones , Solanum lycopersicum , Zea mays , Inositol/metabolismo , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Zea mays/genética , Zea mays/fisiología , Plantones/crecimiento & desarrollo , Plantones/genética , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/fisiología , Cucumis sativus/crecimiento & desarrollo , Cucumis sativus/metabolismo , Cucumis sativus/genética , Cucumis sativus/fisiología , Fotosíntesis/efectos de los fármacos , Malondialdehído/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacosRESUMEN
In this research, we utilize porous tantalum, known for its outstanding elastic modulus and biological properties, as a base material in biomedical applications. The human skeletal system is rich in elements like Ca and Zn. The role of Zn is crucial for achieving a spectrum of sterilizing effects, while Ca is known to effectively enhance cell differentiation and boost cellular activity. The focus of this study is the modification of porous tantalum using a hydrothermal method to synthesize Ca2+/Zn2+-doped Ta2O5nanorods. These nanorods are subjected to extensive characterization techniques to confirm their structure and composition. Additionally, their biological performance is evaluated through a range of tests, including antibacterial assessments, MTT assays, and bacteria/cell scanning electron microscopy (SEM) analyses. The objective is to determine the most effective method of surface modification for porous tantalum, thereby laying a foundational theoretical framework for its surface enhancement.
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Antibacterianos , Calcio , Tantalio , Zinc , Tantalio/química , Antibacterianos/farmacología , Antibacterianos/química , Zinc/química , Zinc/farmacología , Calcio/química , Humanos , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Porosidad , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression. METHODS: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses. RESULTS: Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings.
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Sitobion miscanthi is a destructive wheat pest responsible for significant wheat yield losses. Pirimicarb, one of the most important representatives of N, N-dimethylcarbamate insecticides, is widely used to control wheat aphids. In present work, heterozygous S431F mutation of acetylcholinesterase 1 (AChE1) was identified and verified in three pirimicarb-resistant S. miscanthi populations (two field populations (HA and HS, >955.8-fold) and one lab-selected population (PirR, 486.1-fold)), which has not been reported in S. miscanthi yet. The molecular docking results revealed that AChE1 containing the S431F mutation of S. miscanthi (SmAChE1S431F) showed higher free binding energy to three insecticides (pirimicarb, omethoate, and methomyl) than wild-type AChE1 of S. miscanthi (SmAChE1). Enzyme kinetic and inhibition experiments showed that the recombinant SmAChE1S431F was more insensitive to pirimicarb and omethoate than the recombinant SmAChE1. Furthermore, two overexpression P450 genes (CYP6K1 and CYP6A14) associated with pirimicarb resistance of S. miscanthi were verified by RNAi. These results suggested both target alteration and enhanced metabolism contributed to high pirimicarb resistance of S. miscanthi in the field and laboratory. These findings lay a foundation for further elucidating the mechanism of pirimicarb resistance in S. miscanthi, and have important implications for the resistance management of S. miscanthi control.
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Acetilcolinesterasa , Áfidos , Carbamatos , Sistema Enzimático del Citocromo P-450 , Resistencia a los Insecticidas , Insecticidas , Mutación , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Animales , Resistencia a los Insecticidas/genética , Áfidos/genética , Áfidos/efectos de los fármacos , Insecticidas/farmacología , Carbamatos/farmacología , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Pirimidinas/farmacología , Simulación del Acoplamiento Molecular , Triticum/genética , Dimetoato/análogos & derivadosAsunto(s)
Afasia , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Afasia/etiología , Afasia/rehabilitación , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Metaanálisis como AsuntoRESUMEN
Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.
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Colorimetría , Hiperuricemia , Papel , Polímeros , Ácido Úrico , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/orina , Polímeros/química , Ácido Úrico/orina , Colorimetría/instrumentación , Dispositivos Laboratorio en un Chip , Teléfono Inteligente , Creatinina/orina , Técnicas Analíticas Microfluídicas/instrumentación , Límite de Detección , Biomarcadores/orina , Concentración de Iones de HidrógenoRESUMEN
OBJECTIVE: Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood. METHODS: Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model. RESULTS: A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-ß/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis. CONCLUSION: CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-ß/SMAD signaling, thus promoting the progression of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas , Factores de Transcripción/genética , Factor de Crecimiento Transformador betaRESUMEN
The authentication of ingredients in formulas is crucial yet challenging, particularly for constituents with comparable compositions but vastly divergent efficacy. Rehmanniae Radix and its derivatives are extensively utilized in food supplements, which contain analogous compositions but very distinct effects. Rehmanniae Radix, also a difficult-to-detect herbal ingredient, was chosen as a case to explore a novel HPTLC-QDa MS technique for the identification of herbal ingredients in commercial products. Through systematic condition optimization, including thin layer and mass spectrometry, a stable and reproducible HPTLC-QDa MS method was established, which can simultaneously detect oligosaccharides and iridoids. Rehmannia Radix and its processed products were then analyzed to screen five markers that could distinguish between raw and prepared Rehmannia Radix. An HPTLC-QDa-SIM method was further established for formula detection by using the five markers and validated using homemade prescriptions and negative controls. Finally, this method was applied to detect raw and prepared Rehmannia Radix in 12 commercial functional products and supplements.
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Medicamentos Herbarios Chinos , Rehmannia , Rehmannia/química , Cromatografía en Capa Delgada/métodos , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Raíces de Plantas/química , Suplementos Dietéticos/análisis , Espectrometría de Masas/métodos , Oligosacáridos/análisis , Oligosacáridos/química , Iridoides/análisis , Iridoides/químicaRESUMEN
Background: Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD. Methods: A prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2â h, 6â h, 12â h, 24â h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate. Results: A total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2â h, 6â h, 12â h, 24â h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups. Conclusions: In this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.
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AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.
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Enfermedad de Alzheimer , Succinatos , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Ratones Transgénicos , RNA-Seq , Proteínas Quinasas Activadas por AMP/genética , Serina-Treonina Quinasas TOR/genética , Péptidos beta-Amiloides/metabolismo , Modelos Animales de Enfermedad , Precursor de Proteína beta-Amiloide/genéticaRESUMEN
When precious nano-metals are used as environmental catalysts, it is important to tune the particle sizes and the reusability of the nano-metals for achieving their highly efficient catalytic performance at a low cost. In the present work, magnetic iron oxides (FeOx-Y) nanoparticles were pre-prepared as supports of nano-metals, where Y represented the mole percentage of Fe(III) in the total iron (Y ≥ 50 %). FeOx-Y (support), PdCl42- (Pd source) and NaBH4 (reducing agent) were added into the organic pollutant solution containing 2,2',4,4'-tetrabromodiphenyl ether (BDE47). After the NaBH4 was added, the followed reaction realized not only the rapid in-situ preparation of a Pd-loaded FeOx-Y composite catalyst (Pd-FeOx-Y), but also the ultra-fast and complete debromination of BDE47 within 30 s. Comparing the case without adding FeOx-Y, the debromination efficiency of BDE47 was much promoted in the presence of FeOx-Y. The support-induced enhancing effect on the catalytic ability of Pd nanoparticles was improved by increasing the Fe(III) content in the support, being attributed to the much more hydroxyl groups on the support surface. Considering both the catalytic and recovery abilities of Pd-FeOx-Y, Pd-FeOx-75 was the optimal choice because it could be magnetically recovered and re-used for multiple cycles with high catalytic activities. The presently developed "catalyst preparation-pollutant degradation" one-pot system could be applied to conduct complete debromination of all the PBDEs.
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OBJECTIVE: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s). METHODS: FLS were separated from synovial tissues obtained from patients with RA. Protein expression was measured by Western blot or immunohistochemistry. Gene expression was detected by quantitative RT-PCR. The EdU incorporation was used to measure cell proliferation. Migration and invasion were determined by Boyden chamber assay. RNA sequencing analysis was used to seek for the target of coptisine. The in vivo effect of coptisine was evaluated in collagen-induced arthritis (CIA) model. RESULTS: Treatment with coptisine reduced the proliferation, migration, and invasion, but not apoptosis of RA FLS. Mechanistically, we identified PSAT1, an enzyme that catalyzes serine/one-carbon/glycine biosynthesis, as a novel targeting gene of coptisine in RA FLS. PSAT1 expression was increased in FLS and synovial tissues from patients with RA compared to healthy control subjects. Coptisine treatment or PSAT1 knockdown reduced the TNF-α-induced phosphorylation of p38, ERK1/2, and JNK MAPK pathway. Interestingly, coptisine administration improved the severity of arthritis and reduced synovial PSAT1 expression in mice with CIA. CONCLUSIONS: Our data demonstrate that coptisine treatment suppresses aggressive and proliferative actions of RA FLS by targeting PSAT1 and sequential inhibition of phosphorylated p38, ERK1/2, and JNK MAPK pathway. Our findings suggest that coptisine might control FLS-mediated rheumatoid synovial proliferation and aggression, and be a novel potential agent for RA treatment.
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Artritis Reumatoide , Berberina/análogos & derivados , Sinoviocitos , Humanos , Ratones , Animales , Agresión , Movimiento Celular , Artritis Reumatoide/tratamiento farmacológico , Membrana Sinovial/patología , Proliferación Celular , Fibroblastos , Células CultivadasRESUMEN
Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients' quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.
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Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose-response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1: <4.72 g/d, Q2: ≥4.72 g/d, and <6.88 g/d, and Q3: ≥6.88 g/d). The restricted cubic spline results indicated that low-sodium salt intake decreased linearly with SBP and DBP, while low-sodium intake demonstrated a non-linear, L-shaped relationship with the risk of hypertension, with a safe range of 5.81 g to 7.66 g. The multiple linear regression analysis revealed that compared with group Q1, the DBP in group Q2 decreased by 2.843 mmHg (95%CI: -5.552, -0.133), and the SBP in group Q3 decreased by 4.997 mmHg (95%CI: -9.136, -0.858). Exploratory subgroup analyses indicated that low-sodium salt intake had a significant impact on reducing SBP in males, DBP in females, SBP in rural populations, and DBP in urban populations. The intake of low-sodium salt adheres to the principle of moderation, with 5.81-7.66 g potentially serving as a pivotal threshold.
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Presión Sanguínea , Dieta Hiposódica , Hipertensión , Cloruro de Sodio Dietético , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Femenino , Masculino , Presión Sanguínea/efectos de los fármacos , Persona de Mediana Edad , China/epidemiología , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/efectos adversos , Adulto , Pueblo Asiatico , Anciano , Factores de Riesgo , Pueblos del Este de AsiaRESUMEN
Earlier studies have revealed microRNAs (miRNAs) as potential biomarkers for neurological conditions, however, such evidence on psychiatric outcomes is limited. We utilized the Normative Aging Study (NAS) cohort to investigate the associations between extracellular miRNAs (ex-miRNA) and psychiatric symptoms among a group of older male adults, along with the targeted genes and biological pathways. We studied 569 participants with miRNA profile primarily measured in extracellular vesicles isolated from plasma, and psychiatric symptoms reported over 1996-2014 with repeated measures. Global and dimension scales of psychiatric symptoms were measured via the administration of Brief Symptom Inventory (BSI) per visit covering nine aspects of psychiatric health, such as anxiety, depression, hostility, psychoticism, etc. Ex-miRNAs were profiled using small RNA sequencing. Associations of expression of 395 ex-miRNAs (present in >70% samples) with current mental status were assessed using single-miRNA as well as Least Absolute Shrinkage and Selection Operator (LASSO)-based multi-miRNAs linear mixed effects models adjusting for key demographic and behavioral factors. Biological functions were explored using pathway analyses. We identified ex-miRNAs associated with each BSI scale. In particular, hsa-miR-320d was consistently identified for two global scales. Similar overlapping miRNAs across global and dimension scores included hsa-miR-379-3p, hsa-miR-1976, hsa-miR-151a-5p, hsa-miR-151b, hsa-miR-144-3p, etc. Top KEGG pathways for identified miRNAs included p53 signaling, Hippo signaling, FoxO signaling, protein processing in endoplasmic reticulum and several pathways related with cancer and neurological diseases. This study provided early evidence supporting the associations between extracellular miRNAs and psychiatric conditions. MiRNAs may serve as biomarkers of subclinical psychiatric illness in older adults.
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PURPOSE: To analyze the potential association between the occlusion features and the incidence of temporomandibular joint (TMJ) arthralgia in patients with partial dentures. MATERIALS AND METHODS: A total of 101 partial denture wearers were collected, 45 with unilateral TMJ arthralgia diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Binary logistic regression analysis was adopted. The TMJ asymptomatic group (n = 45) was quantified as 0, while the TMJ arthralgia group (n = 56) was quantified as 1. In total, 13 occlusion variables were analyzed: gender, age, number of prosthetic teeth, number of dentition quadrants with a prosthetic tooth, anterior or posterior prosthesis location in maxillary or mandibular dentition, occluded prosthesis pair, anterior overjet, and overbite relation. Simple and multiple binary logistic models were adopted, accordingly, for the risk impact of them on TMJ arthralgia. RESULTS: Overbite (OR = 2.238) and maxillary anterior prosthesis (OR = 0.305) were entered into the simple binary logistic model; while overbite (OR = 2.774) plus maxillary anterior prosthesis (OR = 0.347), overbite (OR = 3.425) plus unilateral maxillary posterior prosthesis (OR = 4.672), and overbite (OR = 3.476) plus overjet (OR = 0.436) and mandibular anterior prosthesis (OR = 0.177) were entered into the multivariate logistic regression model (all, P < .05). CONCLUSIONS: Partial denture wearers with a deep overbite, especially those with a unilateral maxillary posterior prosthesis, had a higher prevalence of unilateral TMJ arthralgia.