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BACKGROUND: Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated. METHODS: miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31-/-) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell. RESULTS: miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31. CONCLUSION: miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.
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Angiotensina II , Presión Sanguínea , Modelos Animales de Enfermedad , Hipertensión , Riñón , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs , Regiones Promotoras Genéticas , Linfocitos T Reguladores , Animales , MicroARNs/metabolismo , MicroARNs/genética , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/genética , Sitios de Unión , Presión Sanguínea/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/inmunología , Riñón/metabolismo , Riñón/patología , Masculino , Ratones , Regulación de la Expresión Génica , Transducción de Señal , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Antihipertensivos/farmacología , HumanosRESUMEN
High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.
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Mal de Altura , Exosomas , MicroARNs , Policitemia , Humanos , Mal de Altura/genética , Policitemia/etiología , Policitemia/genética , Altitud , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/genética , Exosomas/metabolismoRESUMEN
With the increasing volume of environmental monitoring data, extracting valuable insights from multivariate time series sensor data can facilitate comprehensive information utilization and support informed decision-making in environmental management. However, there is a dearth of comprehensive research on multivariate data analysis for process monitoring in typical polluting enterprises. In this study, an artificial neural network model based on back-propagation algorithm (BP-ANN) was developed to predict the wastewater and exhaust gas emissions using IoT data obtained from process monitoring of a typical polluting enterprise located in Taizhou, Zhejiang Province, China. The results indicate that the model constructed has a high predictive coefficient of determination (R2) with values of 0.8510, 0.9565, 0.9561, 0.9677, and 0.9061 for chemical oxygen demand (COD), potential of hydrogen (pH), electrical conductivity (EC), flue gas emission (FGE), and non-methane hydrocarbon concentration (NMHC) respectively. For the first time, the variable importance measure (VIM)-assisted BP-ANN was employed to investigate the internal and external correlations between wastewater and exhaust gas treatment, thereby enhancing the interpretability of mapping features in the BP-ANN model. The predicted errors for pH and FGE have been demonstrated to fall within the range of - 0.62 ~ 0.30 and - 0.21 ~ 0.15 m3/s, respectively, with average relative errors of 1.05% and 9.60%, which is advantageous in detecting anomalous data and forecasting pollution indicator values. Our approach successfully addresses the challenge of segregating data analysis for wastewater disposal and exhaust gas disposal in the process monitoring of polluting enterprises, while also unearthing potential variables that significantly contribute to the BP-ANN model, thereby facilitating the selection and extraction of characteristic variables.
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Monitoreo del Ambiente , Aguas Residuales , Minería de Datos , China , Conductividad Eléctrica , Emisiones de VehículosRESUMEN
OBJECTIVE: To improve the accuracy of clinical diagnosis by analyzing different contrast-enhanced ultrasound (CEUS) imagines of specific subtypes of uterine leiomyomas. METHODS: A total of 147 female patients received preoperative CEUS examination. The scanning plane of the biggest tumors for CEUS was found by common B-mode ultrasonographic scanning on pelvic cavity, then 1.5 mL SonoVue were injected into the median cubital vein. According to the CEUS images, the lesion enhanced time, enhanced level and enhanced morphology were recorded. The time-intensity curve was acquired and analyzed, meanwhile, the relevant parameters were calculated, including rise time (RT), peak intensity (PI), time to peak (TTP) and mean transit time (MTT). RESULTS: In cellular uterine leiomyoma group, the percentage of high enhancement, early enhancement was higher, equal enhancement and synchronic enhancement were lower than those in the common uterine leiomyomas group. In hysteromyoma with hyaline degeneration group, the percentage of high enhancement, early enhancement was lower, while low enhancement and delayed enhancement were higher than those in the common uterine leiomyomas group. The ratio of PI in cellular uterine leiomyoma group was the highest, but the ratios of RT, TTP and MTT were the lowest of the three benign groups. The ratio of PI in hysteromyoma with hyaline degeneration group was the lowest, while the ratios of RT and TTP was the highest among the three benign groups. CONCLUSION: Different pathological types of uterine leiomyomas have their own signal performance on CEUS. CEUS can be used to infer their pathological types and help differential diagnosis.
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Leiomioma , Neoplasias Uterinas , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Leiomioma/diagnóstico por imagen , Ultrasonografía , Neoplasias Uterinas/diagnóstico por imagenRESUMEN
A host-guest complex self-assembled through Co2+ and cucurbit[5]uril (Co@CB[5]) is used as a supramolecular catalyst on the surface of metal oxides including porous indium tin oxide (ITO) and porous BiVO4 for efficient electrochemical and photoelectrochemical water oxidation. When immobilized on ITO, Co@CB[5] exhibited a turnover frequency (TOF) of 9.9â s-1 at overpotential η=550â mV in a pHâ 9.2 borate buffer. Meanwhile, when Co@CB[5] complex was immobilized onto the surface of BiVO4 semiconductor, the assembled Co@CB[5]/BiVO4 photoanode exhibited a low onset potential of 0.15â V (vs. RHE) and a high photocurrent of 4.8â mA cm-2 at 1.23â V (vs. RHE) under 100â mW cm-2 (AMâ 1.5) light illumination. Kinetic studies confirmed that Co@CB[5] acts as a supramolecular water oxidation catalyst, and can effectively accelerate interfacial charge transfer between BiVO4 and electrolyte. Surface charge recombination of BiVO4 can be also significantly suppressed by Co@CB[5].
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Excessive erythrocytosis (EE) is a characteristic of chronic mountain sickness (CMS). Currently, the pathogenesis of CMS remains unclear. This study was intended to investigate the role of EPAS1 in the proliferation of erythroblasts in CMS. Changes of HIF-1α and EPAS1/HIF-2α in the bone marrow erythroblasts of 21 patients with CMS and 14 control subjects residing at the same altitudes were determined by RT-qPCR and western blotting. We also developed a lentiviral vector, Lv-EPAS1/sh-EPAS1, to over-express/silence EPAS1 in K562 cells. Cells cycle and proliferation were detected by flow cytometry. Transcriptome analyses were carried out on Illumina. CMS patients showed a higher expression of EPAS1/HIF-2α in the bone marrow erythroblasts than those of controls. Variations in EPAS1 expression in CMS patients were positively correlated with RBC levels, and negatively correlated with SaO2. Over-expressing of EPAS1 in K562 cells accelerated the erythroid cells cycle progression and promoted the erythroid cells proliferation-and vice versa. Transcriptome data indicated that proliferation-related DEGs were significantly enriched in EPAS1 overexpression/silencing K562 cells. Our results suggest that EPAS1 might participate in the pathogenesis of EE by regulating the proliferation of erythroblasts.
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Mal de Altura/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Eritroblastos/patología , Adulto , Mal de Altura/genética , Mal de Altura/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/análisis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Ciclo Celular , Línea Celular , Proliferación Celular , Enfermedad Crónica , Eritroblastos/citología , Eritroblastos/metabolismo , Humanos , Persona de Mediana Edad , Transcriptoma , Regulación hacia ArribaRESUMEN
The use of water as an oxygen and hydrogen source for the paired oxygenation and hydrogenation of organic substrates to produce valuable chemicals is of utmost importance as a means of establishing green chemical syntheses. Inspired by the active Ni3+ intermediates involved in electrocatalytic water oxidation by nickel-based materials, we prepared NiBx as a catalyst and used water as the oxygen source for the oxygenation of various organic compounds. NiBx was further employed as both an anode and a cathode in a paired electrosynthesis cell for the respective oxygenation and hydrogenation of organic compounds, with water as both the oxygen and hydrogen source. Conversion efficiency and selectivity of ≥99 % were observed during the oxygenation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid and the simultaneous hydrogenation of p-nitrophenol to p-aminophenol. This paired electrosynthesis cell has also been coupled to a solar cell as a stand-alone reactor in response to sunlight.
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We previously reported a novel positive feedback loop between thioredoxin-1 (Trx-1) and S100P, which promotes the invasion and metastasis of colorectal cancer (CRC). However, the underlying molecular mechanisms remain poorly understood. In this study, we examined the roles of Trx-1 and S100P in CRC epithelial-to-mesenchymal transition (EMT) and their underlying mechanisms. We observed that knockdown of Trx-1 or S100P in SW620 cells inhibited EMT, whereas overexpression of Trx-1 or S100P in SW480 cells promoted EMT. Importantly, S100A4 and the phosphorylation of AKT were identified as potential downstream targets of Trx-1 and S100P in CRC cells. Silencing S100A4 or inhibition of AKT phosphorylation eliminated S100P- or Trx-1-mediated CRC cell EMT, migration and invasion. Moreover, inhibition of AKT activity reversed S100P- or Trx-1-induced S100A4 expression. The expression of S100A4 was higher in human CRC tissues compared with their normal counterpart tissues and was significantly correlated with lymph node metastasis and poor survival. The overexpression of S100A4 protein was also positively correlated with S100P or Trx-1 protein overexpression in our cohort of CRC tissues. In addition, overexpression of S100P reversed the Trx-1 knockdown-induced inhibition of S100A4 expression, EMT and migration and invasion in SW620 cells. The data suggest that interplay between Trx-1 and S100P promoted CRC EMT as well as migration and invasion by up-regulating S100A4 through AKT activation, thus providing further potential therapeutic targets for suppressing the EMT in metastatic CRC.
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Proteínas de Unión al Calcio/genética , Neoplasias Colorrectales/genética , Proteínas de Neoplasias/genética , Proteína de Unión al Calcio S100A4/genética , Tiorredoxinas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Humanos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteína Oncogénica v-akt/genética , Fosforilación , Proteínas Proto-Oncogénicas c-aktRESUMEN
Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/genética , ARN/biosíntesis , Anciano , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , ARN/genética , ARN CircularRESUMEN
The aim of this paper is to study the participation of transforming growth factor-ß (TGF-ß) signaling pathway in mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs), via the interaction between TGF-ß and ER signaling pathways. The UL cells were prepared by primary culture and subculture methods. To validate the role of TGF-ß3 (5 ng/ml) for the viability of human uterine leiomyoma cells, CCK-8 assay was performed in each of five treatment groups including E2 group (E2 10(9) mol/l), BPA group (bisphenol A 10 µmol/l), NP group (nonylphenol 32 µmol/l), OP group (octylphenol 8 µmol/l), or control group (DMSO only). Subsequently, qRT-PCR was applied to detect mRNA expressions of ERα and c-fos, while western blot assay was used to test the expressions of p-Smad3, SnoN, and c-fos proteins in all settings mentioned above; the expressions were compared among different groups, and also in settings with and without synchronous treatment of ICI 182,780. Primarily cultured UL cells were successfully established. Compared with the control group, there were statistically significant increases in the proliferation rate of the UL cells in all EE groups or treated with TGF-ß3 only (p < 0.05). Nevertheless, a slight decrease in proliferation rate of UL was detected in coexistence with TGF-ß3 in all EE groups (p > 0.05). Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-ß3 and EEs compared to isolated EE treatment (p < 0.05). Compared with the control group, the expression of p-Smad3 and c-fos proteins significantly decreased (p < 0.05) in each of E2, BPA, NP, and OP group, and the expression of SnoN protein also significantly reduced only in BPA and NP groups (p < 0.05), followed by TGF-ß3 treatment. When adding ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group (p < 0.05), but slightly increased in E2, BPA, NP, and OP groups (p > 0.05). However, compared with the control group, the expressions of SnoN and c-fos proteins significantly decreased (p < 0.05) after adding ICI182,780. Moreover, there was a significant statistical difference in the expression of p-Smad3, SnoN, and c-fos proteins between pre- and post-treatment of ICI 182,780 in all groups (p < 0.05). The ERα signaling pathway and TGF-ß signaling pathway have different roles in the control of UL cell proliferation. The phenolic EEs can be a promoter of UL cell proliferation, which is mediated by ERα signaling pathway and its cross-talking with TGF-ß signaling pathway. Both less exposure to EEs and blockade of TGF signaling pathway are necessary strategies to prevent UL.
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Receptor alfa de Estrógeno/metabolismo , Estrógenos/química , Leiomioma/metabolismo , Fenoles/química , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Compuestos de Bencidrilo/química , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Persona de Mediana Edad , Fenol/química , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN Mensajero/metabolismo , Proteínas Smad/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta3/metabolismoRESUMEN
PURPOSE: This study explored the possible association of four single nucleotide polymorphisms (SNPs) of the three folate-related enzyme genes: MTHFR C677T and A1298C, MTR A2756G and MTRR A66G, with male infertility in the Chinese population. METHODS: The polymorphic distributions of the four SNPs (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) were investigated by the method of SNaPshot in a Chinese cohort including 296 idiopathic infertile males with azoospermia or oligozoospermia and 204 fertile males. RESULTS: We found no evidence for an association between any of these variants (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) and male infertility. CONCLUSIONS: There is no evidence for an association between male infertility and polymorphism of the three folate-related enzyme genes in the Chinese population.
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5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Ferredoxina-NADP Reductasa/genética , Infertilidad Masculina/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Azoospermia/genética , Azoospermia/patología , China , Ácido Fólico/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Infertilidad Masculina/patología , Masculino , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Cholesterol is a critical component of lipid rafts implicated in regulating multiple signal transduction. The anthrax toxin receptor 2 (ANTXR2) is a type I membrane protein acting as the second receptor for the anthrax toxin. In this study, we first investigated the association between cholesterol and ANTXR2. We provided the evidence that cholesterol depletion by methyl-beta-cyclodextrin (MßCD) promoted ANTXR2 expression in U251 neuroglioma cell, which was reversed by cholesterol supplement. MßCD-induced ANTXR2 up-regulation contributed to ERK1/2 phosphorylation, which was responsible for MT1-MMP and MMP-2 activation. Our data suggested that cellular cholesterol regulated ANTXR2-dependent activation of MMP-2 via ERK1/2 phosphorylation in neuroglioma U251 cell.
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Colesterol/metabolismo , Glioma/metabolismo , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 2 de la Matriz/metabolismo , Receptores de Péptidos/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Silenciador del Gen , Glioma/enzimología , Glioma/patología , Humanos , Fosforilación , Receptores de Péptidos/genéticaRESUMEN
In this paper, the detachment mechanism of alkane molecules from one hybrid hydrophobic and hydrophilic solid surface was studied by molecular dynamics simulation. First, some alkyl chains were linked through C-O bonds with silica surface to get one half-hydrophobic one, and the other half-hydrophilic area was still same as silica surface, thus one modified hybrid hydrophobic and hydrophilic silica surface was constructed. Second, some alkane molecules were adsorbed on the hybrid surface to get one whole hydrophobic oil layer, and the detachment mechanism of alkane molecules on the surface was discussed in aqueous solution using molecular dynamics. The simulated results showed that the key to the detachment of alkane molecules is the formation of water channel in oil layer between water phase and solid surface. In the detachment process, water molecules can penetrate oil layer to the silica surface through the strong H-bonding interaction among water molecules in water channel, and soon these molecules can form a gel layer along the silica surface by fast diffusion under the H-bonding interaction and electrostatic interaction between water molecules and silica surface. At last, the half-hydrophilic area on hybrid surface becomes hydrophilic again after the oil layer's detachment, and alkane molecules aggregate on the modified surface linked the alkyl chains. For the hybrid surface, some of alkane molecules insert into the interstice among the alkyl chains, and thus the oil drop cannot be dispatched thoroughly from the surface linked alkyl chains in aqueous solution. Our results showed that the detachment mechanism of oil from hybrid surface is different, compared with the whole pure hydrophilic surface.
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The copper complex [(bztpen)Cu](BF4)2 (bztpen=N-benzyl-N,N',N'-tris(pyridin-2-ylmethyl)ethylenediamine) displays high catalytic activity for electrochemical proton reduction in acidic aqueous solutions, with a calculated hydrogen-generation rate constant (k(obs)) of over 10000â s(-1). A turnover frequency (TOF) of 7000â h(-1) cm(-2) and a Faradaic efficiency of 96% were obtained from a controlled potential electrolysis (CPE) experiment with [(bztpen)Cu](2+) in pHâ 2.5 buffer solution at -0.90â V versus the standard hydrogen electrode (SHE) over two hours using a glassy carbon electrode. A mechanism involving two proton-coupled reduction steps was proposed for the dihydrogen generation reaction catalyzed by [(bztpen)Cu](2+).
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Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.
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Oído Interno , Fibroínas , Pérdida Auditiva , Ácido Tióctico , Animales , Cobayas , Hidrogeles/química , Ácido Tióctico/farmacología , Dexametasona , Seda/metabolismo , Oído Interno/metabolismo , Pérdida Auditiva/tratamiento farmacológico , Pérdida Auditiva/metabolismo , Fibroínas/farmacologíaRESUMEN
AIM: The purpose of this study was to understand the caregiving experiences of breast cancer family caregivers and explore the profound impacts of those experiences on their quality of life. DESIGN: A qualitative research method was used. METHODS: We extended invitations to 23 family caregivers of outpatients and inpatients receiving breast surgery and oncology treatments in Taiyuan, China, to participate in semi-structured interviews. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was employed to analyse the interview data. RESULTS: Four themes and associated categories were identified: (1) changes in family dynamics, (2) the socio-medical context, (3) interactions between family and society, (4) self-efficacy and nine subthemes and their related categories, where virtually all participants expressed future uncertainty, emotional contagion, and personal challenges, and self-efficacy had a moderating influence on the first three themes. PATIENT OR PUBLIC CONTRIBUTION: This study did not involve direct participation of patients or the public. However, their experiences and perspectives on caregiving were indirectly reflected through the insights provided by the family caregivers who participated in the interviews. Their valuable input contributed to a deeper understanding of the caregiving experience and its impact on the quality of life for Chinese breast cancer family caregivers.
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Neoplasias de la Mama , Cuidadores , Humanos , Femenino , Cuidadores/psicología , Familia/psicología , Calidad de Vida , Investigación CualitativaRESUMEN
BACKGROUND: Neointimal hyperplasia (NIH) is the pathological basis of vascular injury disease. Vascular cells are the dominant cells in the process of NIH, but the extent of heterogeneity amongst them is still unclear. METHODS: A mouse model of NIH was constructed by inducing carotid artery ligation. Single-cell sequencing was then used to analyze the transcriptional profile of vascular cells. Cluster features were determined by functional enrichment analysis, gene set scoring, pseudo-time analysis, and cell-cell communication analysis. Additionally, immunofluorescence staining was conducted on vascular tissues from fibroblast lineage-traced (PdgfraDreER-tdTomato) mice to validate the presence of Pecam1+Pdgfra+tdTomato+ cells. RESULTS: The left carotid arteries (ligation) were compared to right carotid arteries (sham) from ligation-induced NIH C57BL/6 mice. Integrative analyses revealed a high level of heterogeneity amongst vascular cells, including fourteen clusters and seven cell types. We focused on three dominant cell types: endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and fibroblasts. The major findings were: (1) four subpopulations of ECs, including ECs4, mesenchymal-like ECs (ECs1 and ECs2), and fibro-like ECs (ECs3); (2) four subpopulations of fibroblasts, including pro-inflammatory Fibs-1, Sca1+ Fibs-2, collagen-producing Fibs-3, and mesenchymal-like Fibs-4; (3) four subpopulations of vSMCs, including vSMCs-1, vSMCs-2, vSMCs-3, and vSMCs-3-derived vSMCs; (4) ECs3 express genes related to extracellular matrix (ECM) remodeling and cell migration, and fibro-like vSMCs showed strong chemokine secretion and relatively high levels of proteases; (5) fibro-like vSMCs that secrete Vegfa interact with ECs mainly through vascular endothelial growth factor receptor 2 (Vegfr2). CONCLUSIONS: This study presents the dynamic cellular landscape within NIH arteries and reveals potential relationships between several clusters, with a specific focus on ECs3 and fibro-like vSMCs. These two subpopulations may represent potential target cells for the treatment of NIH.
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Perfilación de la Expresión Génica , Hiperplasia , Ratones Endogámicos C57BL , Músculo Liso Vascular , Neointima , Análisis de la Célula Individual , Animales , Neointima/patología , Neointima/metabolismo , Neointima/genética , Análisis de la Célula Individual/métodos , Hiperplasia/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Músculo Liso Vascular/citología , Ratones , Células Endoteliales/metabolismo , Células Endoteliales/patología , Arterias Carótidas/patología , Arterias Carótidas/metabolismo , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Masculino , Fibroblastos/metabolismo , Fibroblastos/patología , Modelos Animales de Enfermedad , Análisis de Expresión Génica de una Sola CélulaRESUMEN
Large-scale hydrogen production through water splitting represents an optimal approach for storing sustainable but intermittent energy sources. However, water oxidation, a complex and sluggish reaction, poses a significant bottleneck for water splitting efficiency. The impact of outer chemical environments on the reaction kinetics of water oxidation catalytic centers remains unexplored. Herein, chemical environment impacts were integrated by featuring methylpyridinium cation group (Py+) around the classic Ru(bpy)(tpy) (bpy=2,2'-bipyridine, tpy=2,2' : 6',2''-terpyridine) water oxidation catalyst on the electrode surface via electrochemical co-polymerization. The presence of Py+ groups could significantly enhance the turnover frequencies of Ru(bpy)(tpy), surpassing the performance of typical proton acceptors such as pyridine and benzoic acid anchored around the catalyst. Mechanistic investigations reveal that the flexible internal proton acceptor anions induced by Py+ around Ru(bpy)(tpy) are more effective than conventionally anchored proton acceptors, which promoted the rate-determining proton transfer process and enhanced the rate of water nucleophilic attack during O-O bond formation. This study may provide a novel perspective on achieving efficient water oxidation systems by integrating cations into the outer chemical environments of catalytic centers.
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The abundant, active, and acidic-stable catalysts for the oxygen evolution reaction (OER) are rare to the proton exchange membrane-based water electrolysis. Mn-based materials show promise as electrocatalysts for OER in acid electrolytes. However, the relationship between the stability, activity and structure of Mn-based catalysts in acidic environments remains unclear. In this study, phase-pure MnSb2O6 was successfully prepared and investigated as a catalyst for OER in a sulfuric acid solution (pH of 2.0). A comprehensive mechanistic comparison between MnSb2O6 and Mn3O4 revealed that the rate-determining step for OER on MnSb2O6 is the direct formation of MnIV=O from MnII-H2O by the 2H+/2e- process. This process avoids the rearrangement of adjacent MnIII intermediates, leading to outstanding stability and activity.
RESUMEN
For photoelectrochemical NADH regeneration, an electrode-supported "lipid bilayer membrane" photocathode based on a p-Si semiconductor, an electron transport mediator (OBV2+), and a [Rh(Cp*)(bpy)Cl]+ catalyst was constructed by self-assembly. Mechanistic study shows that OBV2+ can enhance the charge transfer between the semiconductor and catalyst, leading to a significant improvement of the NADH photo-regeneration rate.