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1.
Angew Chem Int Ed Engl ; 62(21): e202302302, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36959698

RESUMEN

The performance of aqueous Zn ion batteries (AZIBs) is highly dependent on inner Helmholtz plane (IHP) chemistry. Notorious parasitic reactions containing hydrogen evolution reactions (HER) and Zn dendrites both originate from abundant free H2 O and random Zn deposition inside active IHP. Here, we report a universal high donor number (DN) additive pyridine (Py) with only 1 vol. % addition (Py-to-H2 O volume ratio), for regulating molecule distribution inside IHP. Density functional theory (DFT) calculations and molecular dynamics (MD) simulation verify that incorporated Py additive could tailor Zn2+ solvation sheath and exclude H2 O molecules from IHP effectively, which is in favor of preventing H2 O decomposition. Consequently, even at extreme conditions such as high depth of discharge (DOD) of 80 %, the symmetric cell based on Py additive can sustain approximately 500 h long-term stability. This efficient strategy with high DN additives furnishes a promising direction for designing novel electrolytes and promoting the practical application of AZIBs, despite inevitably introducing trace organic additives.

2.
Hum Mutat ; 43(2): 215-227, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34882887

RESUMEN

Approximately 10% of von Willebrand factor (VWF) gene variants are suspected to disrupt messenger RNA (mRNA) processing, the number of which might be underestimated due to the lack of transcript assays. In the present study, we provided a detailed strategy to evaluate the effects of nine putative splice site variants (PSSVs) of VWF on mRNA processing as well as protein properties and establish their genotype-phenotype relationships. Eight of nine PSSVs affected VWF splicing: c.322A>T, c.1534-13_1551delinsCA, and c.8116-2del caused exon skipping; c.221-2A>C, c.323+1G>T, and c.2547-13T>A resulted in the activation of cryptic splice sites; c.2684A>G led to exon skipping and activation of a cryptic splice site; c.2968-14A>G created a new splice site. The remaining c.5171-9del was likely benign. The efficiency of nonsense-mediated mRNA decay (NMD) was much higher in platelets compared to leukocytes, impairing the identification of aberrant transcripts in 4 of 8 PSSVs. The nonsense variant c.322A>T partially impaired mRNA processing, leaking a small amount of correct transcripts with c.322T (p.Arg108*), while the missense variant c.2684A>G totally disrupted normal splicing of VWF, rather than produced mutant protein with the substitution of Gln895Arg. The results of this study would certainly add novel insights into the molecular events behind von Willebrand disease.


Asunto(s)
Sitios de Empalme de ARN , Enfermedades de von Willebrand , Factor de von Willebrand , Humanos , Empalme del ARN , ARN Mensajero/genética , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genética
3.
Small ; 18(10): e2107163, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35112793

RESUMEN

Aqueous Zn-ion batteries (ZIBs) have emerged as a promising energy supply for next-generation wearable electronics, yet they are still impeded by the notorious growth of zinc dendrite and uncontrollable side reaction. While the rational design of electrolyte composition or separator decoration can effectively restrain zinc dendrite growth, synchronously regulating the interfacial electrochemical performance by tackling the physical delamination venture between electrode and electrolyte remains a major obstacle for high-performance wearable aqueous ZIB. Herein, a category of hybrid biogel electrolyte containing carrageenan and wool keratin (CWK) is put forward to regulate the interfacial electrochemistry in aqueous ZIB. Systematic electrochemical kinetics analyses and ex situ scanning electrochemical microscopy (SECM) characterizations achieve comprehensive understanding of the keratin enhanced interfacial Zn2+ redox reaction. Thanks to the keratin triggered selective ion permeability, the as-designed CWK hybrid biogel electrolyte manifests a promoted Zn2+ transference number and excellent reversibility of Zn plating/stripping and outstanding Zn utilization (average Coulombic efficiency ≈98%). More impressively, the CWK hybrid biogel electrolyte also demonstrates cathode side-reaction depression and strengthened interfacial adhesion while assembled into a quasi-solid-state flexible ZIB. This work offers a strategy to synchronously solve concurrent challenges for both of Zn anode and cathode toward realistic wearable aqueous ZIB.


Asunto(s)
Queratinas , Lana , Animales , Suministros de Energía Eléctrica , Electrólitos , Zinc
4.
Macromol Rapid Commun ; 43(23): e2200542, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35856411

RESUMEN

2D conducting polymer thin film recently has garnered numerous interests as a means of combining the molecular aggregate ordering and promoting in-plane charge transport for large-scale/flexible organic electronics. However, it remains far from satisfactory for conducting polymer chains to achieve desirable surface topography and crystallinity due to lack of control over the precursor-involved interfacial assembly. Herein, wafer-size polyaniline (PANI) and tetra-aniline thin films are developed via a controlled interfacial synthesis with customized surface morphology and crystallinity through two typical aniline precursors selective polymerization. Two crucial competing assembly mechanisms, a) direct interfacial polymerization, b) solution polymerization and subsequent interfacial assembly, are investigated to play a vital role in determining elemental chain length and aggregate architecture. The optimal PANI thin film manifests ultraflat surface topography and unambiguous crystalline domains, which also enabling fascinating ammonia sensing capability with 31.4% ppm-1 sensitivity, fast response time (88 s) with astonishing selectivity, repeatability, and recovery capability. The thus-demonstrated strategy with wafer-scale processing potential and flexible microdevice offers a promising route for large-scale manufacturing thin-film organic electronics.


Asunto(s)
Compuestos de Anilina , Polímeros , Polimerizacion , Compuestos de Anilina/química
5.
Blood ; 134(20): 1745-1754, 2019 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-31558466

RESUMEN

Combined factor V (FV) and FVIII deficiency (F5F8D) is a rare autosomal-recessive bleeding disorder caused by mutations in lectin mannose binding-1 (LMAN1) and multiple coagulation factor deficiency-2 (MCFD2). Six causative homozygous mutations (5 in LMAN1 and 1 in MCFD2) were identified in 6 patients with F5F8D. A thrombin-generation assay, triggered with tissue factor (1 pM) in F5F8D plasma, paradoxically exhibited enhanced thrombin generation compared with normal plasma. Significantly lower free tissue factor pathway inhibitor (fTFPI) was found in F5F8D patients compared with healthy controls (P < .01). Normalizing tissue factor pathway inhibitor α (TFPIα) in F5F8D plasma greatly delayed and reduced thrombin generation. Increasing FV concentrations by adding plasma FV to F5F8D plasma only caused a gradual decrease in thrombin generation, suggesting that low levels of TFPIα and FV cocontributed to the elevated thrombin generation by reducing anticoagulant effects. On the contrary, thrombin generation in F5F8D platelet-rich plasma (PRP) was significantly lower than in normal controls (P < .05); however, it was fully corrected by normalizing FVIII or after 1-deamino-8-d-arginine vasopressin (DDAVP) infusion, indicating that the hypocoagulable state of F5F8D patients is associated with low FVIII levels. In addition, plasma and platelet FV in F5F8D PRP were sufficient to support normal thrombin generation, and low TFPIα may have no effect on thrombin generation. DDAVP infusion induced a complete response in 5 F5F8D patients and a partial response in the remaining patient. Based on our findings, we suggest that DDAVP may be considered a potential substitute for FVIII concentrates, and fresh-frozen plasma (FFP) infusion may not be necessary for F5F8D patients with minor bleeding challenges.


Asunto(s)
Deficiencia del Factor V/sangre , Factor V/análisis , Hemofilia A/sangre , Hemorragia/sangre , Adulto , Deficiencia del Factor V/complicaciones , Femenino , Hemofilia A/complicaciones , Hemorragia/etiología , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Trombina/análisis , Adulto Joven
6.
Cancer Cell Int ; 21(1): 294, 2021 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-34092242

RESUMEN

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common types in the world with a high mortality rate. Despite advances in treatment strategies, the overall survival (OS) remains short. Our study aims to establish a reliable prognostic signature closely related to the survival of LUAD patients that can better predict prognosis and possibly help with individual monitoring of LUAD patients. METHODS: Raw RNA-sequencing data were obtained from Fudan University and used as a training group. Differentially expressed genes (DEGs) for the training group were screened. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate cox regression analysis were conducted to identify the candidate prognostic genes and construct the risk score model. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic power and performance of the signature. Moreover, The Cancer Genome Atlas (TCGA-LUAD) dataset was further used to validate the predictive ability of prognostic signature. RESULTS: A prognostic signature consisting of seven prognostic-related genes was constructed using the training group. The 7-gene prognostic signature significantly grouped patients in high and low-risk groups in terms of overall survival in the training cohort [hazard ratio, HR = 8.94, 95% confidence interval (95% CI)] [2.041-39.2]; P = 0.0004), and in the validation cohort (HR = 2.41, 95% CI [1.779-3.276]; P < 0.0001). Cox regression analysis (univariate and multivariate) demonstrated that the seven-gene signature is an independent prognostic biomarker for predicting the survival of LUAD patients. ROC curves revealed that the 7-gene prognostic signature achieved a good performance in training and validation groups (AUC = 0.91, AUC = 0.7 respectively) in predicting OS for LUAD patients. Furthermore, the stratified analysis of the signature showed another classification to predict the prognosis. CONCLUSION: Our study suggested a new and reliable prognostic signature that has a significant implication in predicting overall survival for LUAD patients and may help with early diagnosis and making effective clinical decisions regarding potential individual treatment.

7.
BMC Bioinformatics ; 20(1): 236, 2019 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-31077131

RESUMEN

BACKGROUND: With the widespread use of multiple amplicon-sequencing (MAS) in genetic variation detection, an efficient tool is required to remove primer sequences from short reads to ensure the reliability of downstream analysis. Although some tools are currently available, their efficiency and accuracy require improvement in trimming large scale of primers in high throughput target genome sequencing. This issue is becoming more urgent considering the potential clinical implementation of MAS for processing patient samples. We here developed pTrimmer that could handle thousands of primers simultaneously with greatly improved accuracy and performance. RESULT: pTrimmer combines the two algorithms of k-mers and Needleman-Wunsch algorithm, which ensures its accuracy even with the presence of sequencing errors. pTrimmer has an improvement of 28.59% sensitivity and 11.87% accuracy compared to the similar tools. The simulation showed pTrimmer has an ultra-high sensitivity rate of 99.96% and accuracy of 97.38% compared to cutPrimers (70.85% sensitivity rate and 58.73% accuracy). And the performance of pTrimmer is notably higher. It is about 370 times faster than cutPrimers and even 17,000 times faster than cutadapt per threads. Trimming 2158 pairs of primers from 11 million reads (Illumina PE 150 bp) takes only 37 s and no more than 100 MB of memory consumption. CONCLUSIONS: pTrimmer is designed to trim primer sequence from multiplex amplicon sequencing and target sequencing. It is highly sensitive and specific compared to other three similar tools, which could help users to get more reliable mutational information for downstream analysis.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Algoritmos , Humanos
8.
Int J Cancer ; 145(9): 2547-2557, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30919951

RESUMEN

The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell-free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer.


Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Alelos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Quimioradioterapia/métodos , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Femenino , Genoma/genética , Genómica/métodos , Humanos , Persona de Mediana Edad , Mutación/genética , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia
9.
Angew Chem Int Ed Engl ; 58(3): 811-815, 2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30417513

RESUMEN

Nanostructured-alloy-type anodes have received great interest for high-performance lithium-ion batteries (LIBs). However, these anodes experience huge volume fluctuations during repeated lithiation/delithiation and are easily pulverized and subsequently form aggregates. Herein, an efficient method to stabilize alloy-type anodes by creating defects on the surface of the metal oxide support is proposed. As a demonstration, PPy-encapsulated SnS2 nanosheets supported on defect-rich TiO2 nanotubes were produced and investigated as an anode material for LIBs. Both experimental results and theoretical calculations demonstrate that defect-rich TiO2 provides more chemical adhesions to SnS2 and discharge products, compared to defect-poor TiO2 , and then effectively stabilizes the electrode structure. As a result, the composite exhibits an unprecedented cycle stability. This work paves the way to designing durable and active nanostructured-alloy-type anodes on oxide supports.

10.
Blood Cells Mol Dis ; 73: 47-54, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30249384

RESUMEN

The development of a novel coagulation factor VIII (FVIII) expression cassette with an enhanced activity for gene therapy of hemophilia A (HA) is essential. The biological properties of several non-human FVIII sequences, such as porcine and canine, have been evaluated. Here, we compared the activity level of rat FVIII (rFVIII) and human FVIII (hFVIII) by using single-chain and dual-chain strategies in 293 T cells and the HA mice. In both in vitro and hydrodynamic injection studies, the activity of rFVIII detected by the activated partial thromboplastin time assay was higher than that of hFVIII both by single-chain (~2.96-fold and ~1.72-fold, respectively) and dual-chain (~7.69-fold and ~2.35-fold, respectively). Moreover, the dual chain exerted a potentially higher delivery efficacy compared with the single chain (~4.96-fold and ~2.99-fold, respectively). The blood loss of HA mice administrated with rFVIII was less than those with hFVIII. AAV-delivered rFVIII and hFVIII also exerted long-term therapeutic effects on HA mice and caused a transient ALT elevation. These data might help to the development of novel, optimized FVIII expression cassettes based on the amino acid difference between rFVIII and hFVIII. These data indicate that the dual-chain strategy would likely enhance the delivery efficiency of the AAV-mediated FVIII gene therapy.


Asunto(s)
Factor VIII/administración & dosificación , Terapia Genética/métodos , Hemofilia A/tratamiento farmacológico , Adenoviridae/genética , Animales , Factor VIII/genética , Vectores Genéticos , Células HEK293 , Humanos , Tiempo de Tromboplastina Parcial , Ratas , Transfección
11.
Opt Express ; 26(13): 16292-16302, 2018 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-30119462

RESUMEN

Mach-Zehnder interferometer is a common device in quantum phase estimation and the photon losses in it are an important issue for achieving a high phase accuracy. Here we thoroughly discuss the precision limit of the phase in the Mach-Zehnder interferometer with a coherent state and a superposition of coherent states as input states. By providing a general analytical expression of quantum Fisher information, the phase-matching condition and optimal initial parity are given. Especially, in the photon loss scenario, the sensitivity behaviors are analyzed and specific strategies are provided to restore the phase accuracies for symmetric and asymmetric losses.

12.
Blood Cells Mol Dis ; 58: 29-34, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27067486

RESUMEN

Congenital factor XI (FXI) deficiency is a rare bleeding disorder with unpredictable bleeding tendency. Few studies in a large cohort have been reported regarding associations between FXI activity (FXI:C) or genotypes and bleeding symptoms currently. This study characterized clinical manifestations and mutation spectrum of 57 subjects with FXI deficiency in China. Clinical data were collected and mutations were identified by direct sequencing and determined by mRNA analysis. The result revealed bleeding symptoms were only found in 12 patients (12/57, 21.1%) with severely reduced FXI:C, and prolonged bleeding post injury/surgery as well as easy bruising were the commonest bleeding manifestations presented in respective 5 cases (5/12, 41.7%). A total number of 37 mutations were identified including 19 missense mutations, 9 nonsense mutations, 6 splice site mutations and 3 small deletions. Among them, 4 missense mutations, 5 splice mutations, 3 small deletions and a nonsense mutation were newly detected. W228*, G400V, Q263* and c.1136-4delGTTG with a total frequency of 48.3% were the most four common mutations in Chinese patients. RT-PCR analysis was carried out and confirmed that both c.596-8T>A and c.1136-4delGTTG were pathogenic due to frameshift resulting in respective truncated proteins. Our findings suggested clinical manifestations had little to do with FXI:C or genotypes, which required further study. This study, the largest investigation of FXI deficiency in China revealed that the F11 mutation spectrum of Chinese population was distinct from those of other populations earlier established.


Asunto(s)
Deficiencia del Factor XI/genética , Factor XI/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Niño , Preescolar , China/epidemiología , Deficiencia del Factor XI/complicaciones , Deficiencia del Factor XI/epidemiología , Femenino , Genotipo , Hemorragia/epidemiología , Hemorragia/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , ARN Mensajero/genética , Adulto Joven
13.
Molecules ; 21(5)2016 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-27213329

RESUMEN

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3ß,7ß,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3ß,7ß,15α,25-tetrol (5) and (3ß,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2'-hydroxypalmitoyl-l-O-ß-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3ß,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds.


Asunto(s)
Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Reishi/química , Triterpenos/química , Acetilación , Antineoplásicos/uso terapéutico , División Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Humanos , Medicina Tradicional China , Estructura Molecular , Mapas de Interacción de Proteínas/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/uso terapéutico
14.
Zhongguo Zhong Yao Za Zhi ; 41(5): 806-812, 2016 Mar.
Artículo en Zh | MEDLINE | ID: mdl-28875631

RESUMEN

Salvia miltiorrhiza is one of the most common traditional Chinese medicines. It has rich resources in China. According to modern studies, phenolic acids are the main effective components in S. miltiorrhiza. These components have cardiovascular and cerebrovascular protective effect, and anti-tumor, antioxidant, anti-inflammatory, and antifibrotic activities, etc. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases and others. In this paper, the chemicals and pharmacological effects of phenolic acids from S. miltiorrhiza were summarized in the last decade. Its researches and development prospects were also analyzed for further studying and comprehensive utilization of these phenolic acids.


Asunto(s)
Alquenos/farmacología , Medicamentos Herbarios Chinos/farmacología , Polifenoles/farmacología , Salvia miltiorrhiza/química , Alquenos/química , Animales , Quimioterapia , Medicamentos Herbarios Chinos/química , Humanos , Estructura Molecular , Polifenoles/química
15.
Molecules ; 19(11): 17478-535, 2014 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-25361420

RESUMEN

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, a traditional Chinese medicine, popularly used for complementary cancer therapy. GTs are lanostane-tetracyclic triterpenes. They have been reported to possess anti-tumor, anti-inflammation, antioxidant, antimicrobial and blood fat reducing effects. To date, 316 GTs have been found and their similar chemical structures have proved difficult to elucidate. This paper compiles 316 naturally occurring triterpenes from Ganoderma based on the literature published through January 2013 along with their structures, physiological activities and 13C-NMR spectral data.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Ganoderma/química , Triterpenos/química , Triterpenos/farmacología , Animales , Humanos , Ratones , Relación Estructura-Actividad
16.
Immun Inflamm Dis ; 12(4): e1249, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38629726

RESUMEN

BACKGROUND: Sepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti-inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis-associated AKI in vitro and in vivo through lipopolysaccharide (LPS)-induced macrophages model and cecal ligation and puncture-induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization. METHODS: Enzyme-linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining. RESULTS: Deh reduced inflammation of THP-1-derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP-1-derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP-1-derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK-2) in the condition medium from DUSP3-overexpressed THP-1-derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis-induced mice. CONCLUSION: Deh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.


Asunto(s)
Lesión Renal Aguda , Diterpenos , Sepsis , Humanos , Ratones , Animales , Fosfatasa 3 de Especificidad Dual/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Sepsis/complicaciones , Sepsis/tratamiento farmacológico
17.
Thromb Res ; 236: 51-60, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387303

RESUMEN

INTRODUCTION: A novel variant involving noncanonical splicing acceptor site (c.875-5 T > G) in propeptide coding region of von Willebrand factor (VWF) was identified in a patient with type 2A von Willebrand disease (VWD), who co-inherited with a null variant (p.Tyr271*) and presented characteristic discrepancy of plasma level of VWF antigen and activity, and a selective reduction of both intermediate-molecular-weight (IMWMs) and high-molecular-weight VWF multimers (HMWMs). MATERIALS AND METHODS: VWF mRNA transcripts obtained from peripheral leukocytes and platelets of the patients were investigated to analyze the consequence of c.875-5 T > G on splicing. The impact of the variant on expression and multimer assembly was further analyzed by in vitro expression studies in AtT-20 cells. The intracellular processing of VWF mutant and the Weibel-Palade bodies (WPBs) formation was evaluated by immunofluorescence staining and electron microscopy. RESULTS: The mRNA transcript analysis revealed that c.875-5 T > G variant led to exon 8 skipping and an in-frame deletion of 41 amino acids in the D1 domain of VWF (p.Ser292_Glu333delinsLys), yielding a truncated propeptide. Consistent with the patient's laboratory manifestations, the AtT-20 cells transfected with mutant secreted less VWF, with the VWF antigen level in conditioned medium 47 % of wild-type. A slight retention in the endoplasmic reticulum was observed for the mutant. Almost complete loss of IMWMs and HMWMs in the medium and impaired WPBs formation in the cell, indicating truncated VWF propeptide lost its chaperon-like function for VWF multimerization and tubular storage. CONCLUSIONS: The VWF splicing site variant (c.875-5 T > G) causes propeptide truncation, severely compromising VWF multimer assembly and tubular storage.


Asunto(s)
Enfermedad de von Willebrand Tipo 2 , Factor de von Willebrand , Humanos , Exones/genética , Sitios de Empalme de ARN , ARN Mensajero/genética , Enfermedad de von Willebrand Tipo 2/genética , Enfermedades de von Willebrand , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismo
18.
BMJ Open ; 13(2): e068319, 2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36822803

RESUMEN

OBJECTIVE: To explore the prevalence of acute gastroenteritis (AGE) and associated factors in children and adolescents in the USA from 1999 to 2018 using nationally representative data. DESIGN: A retrospective cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (NHANES) database. PARTICIPANTS: 25 361 children and adolescents aged 6-17 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: Whether the patient suffered from AGE. RESULTS: Totally 1882 suffered from AGE. The overall monthly prevalence of AGE in children and adolescents was 7.69%. From 1999 to 2018, the prevalence of AGE in the USA had been decreasing over time. The decreasing trend was observed in all subgroups, including age, gender, body mass index (BMI), education level, poverty index and eating food at the restaurant. There were two small upticks from 2003 to 2007 and 2013 to 2015. AGE was negatively associated with male compared with female (OR=0.86, 95% CI: 0.73 to 0.99, p=0.035), Mexican American (OR=0.82, 95% CI: 0.70 to 0.97, p=0.018) and non-Hispanic Black (OR=0.80, 95% CI: 0.69 to 0.93, p=0.003) compared with non-Hispanic White. AGE was positively associated with obesity compared with underweight and normal weight (OR=1.37, 95% CI: 1.15 to 1.62, p<0.001). CONCLUSION: The monthly prevalence of AGE was 7.69% and showed a downward trend from 1999 to 2018 in the USA.


Asunto(s)
Gastroenteritis , Humanos , Masculino , Niño , Femenino , Adolescente , Estados Unidos/epidemiología , Encuestas Nutricionales , Estudios Transversales , Prevalencia , Estudios Retrospectivos , Índice de Masa Corporal , Gastroenteritis/epidemiología
19.
Heliyon ; 9(12): e22530, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38076176

RESUMEN

High-entropy alloys (HEAs) have gained significant attentions in recent years, due to their unique properties derived from the combination of multiple elements in equimolar or near-equimolar ratios. The mechanical properties of HEAs are influenced by microstructural characteristics. In this study, MnCrFeCoNi HEA ribbons were produced using a technique called melt spinning, for which the wheel speed was adjusted to control the undercooling levels. The rapid solidification process under undercooling condition resulted in refined grain sizes to micrometers in the ribbons. One notable feature was the appearance of twin boundaries, which especially accounted for approximately 7.36 % of the microstructure for the ribbons produced at a wheel speed of 10 m/s. For the ribbons with thickness of micrometer scale, the mechanical properties (ultimate tensile strength up to 2.5 GPa and hardness up to 300 MPa) were analyzed by microstructure (grain boundaries and homogeneity) and exterior factors (e.g. thickness). Overall, this study provides a new approach for tailoring the microstructures and mechanical properties of HEAs via melt spinning technique. The HEA ribbons present a novel form that could potentially broaden the scope of applications for these materials.

20.
Adv Mater ; 34(33): e2203905, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35765207

RESUMEN

Wet-spinning is a promising strategy to fabricate fiber electrodes for real commercial fiber battery applications, according to its great compatibility with large-scale fiber production. However, engineering the rheological properties of the electrochemical active materials to accommodate the viscoelasticity or liquid crystalline requirements for continuous wet-spinning remains a daunting challenge. Here, with entropy-driven volume-exclusion effects, the rheological behavior of vanadium pentoxide (V2 O5 ) nanowire dispersions is regulated through introducing 2D graphene oxide (GO) flakes in an optimal ratio. By optimizing the viscoelasticity and liquid-crystalline behavior of the spinning dope, the wet-spun hybrid fibers display controlled hierarchical orientation. The wet-spun V2 O5 /rGO hybrid fiber with the optimal 10:1 mass fraction (V2 O5 /rGO10:1 ) exhibits a highly oriented nanoblock arrangement, enabling efficient Zn-ion migration and an excellent Zn-ion storage capacity of 486.03 mAh g-1 at 0.1 A g-1 . A half-meter long quasi-solid-state fiber Zn-ion battery is assembled with a polyacrylamide gel electrolyte and biocompatible Ecoflex encapsulation. The thus-derived fiber Zn-ion battery is integrated into a wearable self-powered system, incorporating a highly efficient GaAs solar cell, which delivers a record-high overall efficiency (9.80%) for flexible solar charging systems.

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