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Substantial improvements in cycle life, rate performance, accessible voltage, and reversible capacity are required to realize the promise of Li-ion batteries in full measure. Here, we have examined insertion electrodes of the same composition (V2O5) prepared according to the same electrode specifications and comprising particles with similar dimensions and geometries that differ only in terms of their atomic connectivity and crystal structure, specifically two-dimensional (2D) layered α-V2O5 that crystallizes in an orthorhombic space group and one-dimensional (1D) tunnel-structured ζ-V2O5 crystallized in a monoclinic space group. By using particles of similar dimensions, we have disentangled the role of specific structural motifs and atomistic diffusion pathways in affecting electrochemical performance by mapping the dynamical evolution of lithiation-induced structural modifications using ex situ scanning transmission X-ray microscopy, operando synchrotron X-ray diffraction measurements, and phase-field modeling. We find the operation of sharply divergent mechanisms to accommodate increasing concentrations of Li-ions: a series of distortive phase transformations that result in puckering and expansion of interlayer spacing in layered α-V2O5, as compared with cation reordering along interstitial sites in tunnel-structured ζ-V2O5 By alleviating distortive phase transformations, the ζ-V2O5 cathode shows reduced voltage hysteresis, increased Li-ion diffusivity, alleviation of stress gradients, and improved capacity retention. The findings demonstrate that alternative lithiation mechanisms can be accessed in metastable compounds by dint of their reconfigured atomic connectivity and can unlock substantially improved electrochemical performance not accessible in the thermodynamically stable phase.
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This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone â ¡_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.
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Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Metanálise em Rede , Volume Sistólico , Humanos , Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Masculino , Feminino , Idoso , Medicamentos sem Prescrição/administração & dosagem , Pessoa de Meia-IdadeRESUMO
2D magnets can potentially revolutionize information technology, but their potential application to cooling technology and magnetocaloric effect (MCE) in a material down to the monolayer limit remain unexplored. Herein, it is revealed through multiscale calculations the existence of giant MCE and its strain tunability in monolayer magnets such as CrX3 (X = F, Cl, Br, I), CrAX (A = O, S, Se; X = F, Cl, Br, I), and Fe3 GeTe2 . The maximum adiabatic temperature change ( Δ T ad max $\Delta T_{{\rm{ad}}}^{\max }$ ), maximum isothermal magnetic entropy change, and specific cooling power in monolayer CrF3 are found as high as 11 K, 35 µJ m-2 K-1 , and 3.5 nW cm-2 under a magnetic field of 5 T, respectively. A 2% biaxial and 5% a-axis uniaxial compressive strain can remarkably increase Δ T ad max $\Delta T_{{\rm{ad}}}^{\max }$ of CrCl3 and CrOF by 230% and 37% (up to 15.3 and 6.0 K), respectively. It is found that large net magnetic moment per unit area favors improved MCE. These findings advocate the giant-MCE monolayer magnets, opening new opportunities for magnetic cooling at nanoscale.
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Lithium-ion batteries are yet to realize their full promise because of challenges in the design and construction of electrode architectures that allow for their entire interior volumes to be reversibly accessible for ion storage. Electrodes constructed from the same material and with the same specifications, which differ only in terms of dimensions and geometries of the constituent particles, can show surprising differences in polarization, stress accumulation and capacity fade. Here, using operando synchrotron X-ray diffraction and energy dispersive X-ray diffraction (EDXRD), we probe the mechanistic origins of the remarkable particle geometry-dependent modification of lithiation-induced phase transformations in V2O5 as a model phase-transforming cathode. A pronounced modulation of phase coexistence regimes is observed as a function of particle geometry. Specifically, a metastable phase is stabilized for nanometre-sized spherical V2O5 particles, to circumvent the formation of large misfit strains. Spatially resolved EDXRD measurements demonstrate that particle geometries strongly modify the tortuosity of the porous cathode architecture. Greater ion-transport limitations in electrode architectures comprising micrometre-sized platelets result in considerable lithiation heterogeneities across the thickness of the electrode. These insights establish particle geometry-dependent modification of metastable phase regimes and electrode tortuosity as key design principles for realizing the promise of intercalation cathodes.
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We report an intrinsic strain engineering, akin to thin filmlike approaches, via irreversible high-temperature plastic deformation of a tetragonal ferroelectric single-crystal BaTiO_{3}. Dislocations well-aligned along the [001] axis and associated strain fields in plane defined by the [110]/[1[over ¯]10] plane are introduced into the volume, thus nucleating only in-plane domain variants. By combining direct experimental observations and theoretical analyses, we reveal that domain instability and extrinsic degradation processes can both be mitigated during the aging and fatigue processes, and demonstrate that this requires careful strain tuning of the ratio of in-plane and out-of-plane domain variants. Our findings advance the understanding of structural defects that drive domain nucleation and instabilities in ferroic materials and are essential for mitigating device degradation.
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During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFR-expressing transitional glial cells exhibited a unique position-specific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.
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Análise de Célula Única , Medula Espinal , Humanos , Neurogênese , Neuroglia , NeurôniosRESUMO
Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas Musculares/metabolismo , Fator 2 Ativador da Transcrição/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Transdução de SinaisRESUMO
OBJECTIVE: A smartphone augmented reality (AR) application (app) was explored for clinical use in presurgical planning and lesion scalp localization. METHODS: We programmed an AR App on a smartphone. The accuracy of the AR app was tested on a 3D-printed head model, using the Euclidean distance of displacement of virtual objects. For clinical validation, 14 patients with brain tumors were included in the study. Preoperative MRI images were used to generate 3D models for AR contents. The 3D models were then transferred to the smartphone AR app. Tumor scalp localization was marked, and a surgical corridor was planned on the patient's head by viewing AR images on the smartphone screen. Standard neuronavigation was applied to evaluate the accuracy of the smartphone. Max-margin distance (MMD) and area overlap ratio (AOR) were measured to quantitatively validate the clinical accuracy of the smartphone AR technique. RESULTS: In model validation, the total mean Euclidean distance of virtual object displacement using the smartphone AR app was 4.7 ± 2.3 mm. In clinical validation, the mean duration of AR app usage was 168.5 ± 73.9 s. The total mean MMD was 6.7 ± 3.7 mm, and total mean AOR was 79%. CONCLUSIONS: The smartphone AR app provides a new way of experience to observe intracranial anatomy in situ, and it makes surgical planning more intuitive and efficient. Localization accuracy is satisfactory with lesions larger than 15 mm.
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Realidade Aumentada , Neoplasias Encefálicas , Cirurgia Assistida por Computador , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Humanos , Imageamento Tridimensional/métodos , Neuronavegação/métodos , Couro Cabeludo/diagnóstico por imagem , Couro Cabeludo/patologia , Couro Cabeludo/cirurgia , Smartphone , Cirurgia Assistida por Computador/métodosRESUMO
The bioconversion of coal at ambient conditions is a promising technology for coal processing. However, there are few examples of the optimization of processes for industrial-scale use. In this work, the optimization of process parameters affecting lignite bioconversion by an isolated fungus WF8 using an artificial neural network (ANN) combined with a genetic algorithm (GA) was carried out for modeling of humic acids (HAs) yield and parameters. Kinetic models were used to understand the release characteristics of HAs from the bioconversion of lignite. The results of the present work indicate that the optimal process parameters (OPP) are 29 °C, initial pH of 7, 180 rpm, 0.6 mmol·L-1 of CuSO4, 0.4 mmol L-1 of MnSO4, and 6.4 µmol·L-1 of veratryl alcohol (VA). The predicted experimental data obtained by ANN is similar to the actual and the significant correlation coefficient value (R2) of 0.99 indicates that ANN has good predictability. The actual yield of HAs are 5.17 mg·mL-1. During bioconversion, the fungus WF8 could loosen and attack the structure of lignite. The release of HAs produced by bioconversion of lignite under the OPP via diffusion and swelling is fit to zero-order model independent on concentration. This provides support for the industrial bioconversion of lignite.
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Carvão Mineral , Substâncias Húmicas , Carvão Mineral/análise , Difusão , Substâncias Húmicas/análise , Cinética , Redes Neurais de ComputaçãoRESUMO
Cervical cancer (CC) is a common malignancy in gynecology. Emerging evidence has demonstrated that circular RNAs (circRNAs) act as vital mediators in CC. However, the roles of circRNA ring finger protein 121 (circRNF121) in CC are largely unknown. Herein, we focused on the exact function and underlying mechanism of circRNF121 in CC development. Our results showed that circRNF121 was highly expressed in CC tissues and cells. Knockdown of circRNF121 suppressed cell growth, metastasis, epithelial-mesenchymal transition (EMT), autophagy, and wnt/ß-catenin pathway in CC cells in vitro and blocked tumor formation in vivo. For mechanism investigation, circRNF121 could affect activating transcription factor 2 (ATF2) expression by decoying miR-153-3p, thereby accelerating CC cell development. In conclusion, circRNF121 exerted the tumor-suppressive role in CC progression by altering miR-153-3p/ATF2 axis. These results suggested that circRNF121 might be a possible circ-targeted therapy for patients with CC.
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MicroRNAs , RNA Circular , Neoplasias do Colo do Útero , Via de Sinalização Wnt , beta Catenina , Fator 2 Ativador da Transcrição/genética , Fator 2 Ativador da Transcrição/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Abrus cantoniensis is a Chinese herbal medicine with efficacy in clearing heat and detoxification, as well as relieving liver pain. The whole plant, except the seeds, can be used and consumed. Flavonoids have been found in modern pharmacological studies to have important biological activities, such as anti-inflammatory, antibacterial and antioxidant properties. The antibacterial and antioxidant bioactivities of the total flavonoids of Abrus cantoniensis (ATF) have been widely reported in national and international journals, but there are fewer studies on their anti-inflammatory effects. The present study focused on the optimization of the ultrasonic extraction process of ATF by response surface methodology and the study of its anti-inflammatory effects in vitro and in vivo. The results showed that the factors that had a great impact on the ATF extraction were the material-to-liquid ratio, ultrasonic extraction cycles and ethanol concentration. The best extraction process used a material-to-liquid ratio of 1:47, ultrasonic extraction cycles of 4 times, an ethanol concentration of 50%, an ultrasonic extraction time of 40 min and an ultrasonic power of 125 W. Under these conditions, the actual extraction rate of total flavonoids was 3.68%, which was not significantly different from the predicted value of 3.71%. In an in vitro anti-inflammatory assay, ATF was found to be effective in alleviating LPS (lipopolysaccharide)-induced inflammation in mouse peritoneal macrophages. In an in vivo anti-inflammatory assay, ATF was found to have a significant inhibitory effect on xylene-induced ear swelling in mice and cotton ball granuloma in mice, and the inhibitory effect was close to that of the positive control drug dexamethasone. This may provide a theoretical basis for the further development of the medicinal value of Abrus cantoniensis.
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Abrus , Animais , Antibacterianos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Etanol , Flavonoides/farmacologia , Camundongos , Extratos Vegetais/farmacologia , UltrassomRESUMO
Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.
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Receptores ErbB/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Proteínas de Ligação ao GTP/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Traumatismos da Medula Espinal/metabolismo , Animais , Células Cultivadas , Cetuximab/farmacologia , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Flavonoides/farmacologia , Gefitinibe/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para CimaRESUMO
The notorious polysulfide shuttle effect is a crucial factor responsible for the degradation of Li-S batteries. A good way to suppress the shuttle effect is to effectively anchor dissoluble lithium polysulfides (LPSs, Li2Sn) on appropriate substrates. Previous studies have revealed that Li of Li2Sn is prone to interact with the N of N-containing materials to form Li-N bonds. In this work, by means of density functional theory (DFT) computations, we explored the possibility to form Li bonds on ten different N-containing monolayers, including BN, C2N, C2N6S3, C9N4, a covalent triazine framework (CTF), g-C3N4, p-C3N4, C3N5, S-N2S, and T-N2S, by examining the adsorption behavior of Li2Sn (n = 1, 2, 3, 4, 6, 8) on these two-dimensional (2D) anchoring materials (AMs), and investigated the performance of the formed Li bonds (if any) in inhibiting the shuttle effect. By comparing and analyzing the nitrogen content, the N-containing pore size, charge transfer, and Li bonds, we found that the N content and N-containing pore size correlate with the number of Li bonds, and the formed Li-N bonds between LPSs and AMs correspond well with the adsorption energies of the LPSs. The C9N4 and C2N6S3 monolayers were identified as promising AMs in Li-S batteries. From the view of Li bonds, this work provides guidelines for designing 2D N-containing materials as anchoring materials to reduce the shuttle effect in Li-S batteries, and thus improving the performance of Li-S batteries.
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Sympathetic stimulated-cardiac fibrosis imposes great significance on both disease progression and survival in the pathogenesis of many cardiovascular diseases. However, there are few effective therapies targeting it clinically. The cardioprotective effect of aldehyde dehydrogenase 2 (ALDH2) has been explored in many pathological conditions, whether it can exert benefit effects on chronic sympathetic stimulus-induced cardiac fibrosis remains unclear. In this study, we determined to explore the role of ALDH2 on isoproterenol (ISO)-induced cardiac fibroblasts (CF) proliferation and cardiac fibrosis. It was found that ALDH2 enzymatic activity was impaired in ISO-induced HCF proliferation and Aldh2 deficiency promoted mouse CF proliferation. Alda-1, an ALDH2 activator, exerted obvious suppressive effect on ISO-induced HCF proliferation, together with the induction of cell cycle arrest at G0/G1 phase and decreased expression of cyclin E1 and cyclin-dependent kinase 2 (CDK2). Mechanistically, the inhibitory role of Alda-1 on HCF proliferation was achieved by decreasing mitochondrial reactive oxygen species (ROS) production, which was partially reversed by rotenone, an inducer of ROS. In addition, wild-type mice treated with Alda-1 manifested with reduced fibrosis and better cardiac function after ISO pump. In summary, Alda-1 alleviates sympathetic excitation-induced cardiac fibrosis via decreasing mitochondrial ROS accumulation, highlighting ALDH2 activity as a promising drug target of cardiac fibrosis.
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Aldeído-Desidrogenase Mitocondrial/metabolismo , Cardiomiopatias/patologia , Aldeído-Desidrogenase Mitocondrial/antagonistas & inibidores , Aldeído-Desidrogenase Mitocondrial/genética , Animais , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/enzimologia , Cardiotônicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Eletrocardiografia , Fibroblastos/patologia , Fibrose , Ventrículos do Coração/patologia , Humanos , Isoproterenol/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) often involves the liver, and belongs to abnormal blood vessel disease. The etiology of Budd-Chiari syndrome (BCS) is not clear, but congenital vascular dysplasia is considered to be one of the causes. Liver cirrhosis due to hepatic hereditary hemorrhagic telangiectasia concomitant with BCS has not been reported. Here, we report a case of cirrhosis with hepatic hereditary hemorrhagic telangiectasia (HHHT) and BCS. CASE PRESENTATION: A 58-year-old woman with hepatic hereditary hemorrhagic telangiectasia showed decompensated liver cirrhosis, and abdominal imaging revealed Budd-Chiari syndrome. Disease has progressed considerably during 2.5 years after hospital discharge despite subsequent transjugular intrahepatic portosystemic shunting (TIPS). One hypothesis that might explain the coexistence of hepatic hereditary hemorrhagic telangiectasia and Budd-Chiari syndrome in this patient is ischemia and thrombosis of hepatic veins. CONCLUSIONS: Further studies are required to evaluate the relationship between HHHT and BCS. Our observations already challenged the TIPS therapeutic strategy in BCS secondary to HHHT patients.
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Síndrome de Budd-Chiari/complicações , Veias Hepáticas/anormalidades , Cirrose Hepática/etiologia , Telangiectasia Hemorrágica Hereditária/complicações , Feminino , Humanos , Fígado/irrigação sanguínea , Pessoa de Meia-IdadeRESUMO
Long noncoding RNAs (lncRNAs) have been implicated in numerous physiological and pathological processes, including cancer development and progression. However, the role and molecular mechanism of lncRNAs in resistance to chemotherapy of colorectal cancer (CRC) remain enigmatic. Here, we found that lncRNA small Cajal body-specific RNA 2 (SCARNA2) is expressed higher in CRC tissues than in adjacent normal tissues, and a robust expression of SCARNA2 is correlated with a bad prognosis of CRC patients after surgery. SCARNA2 overexpression significantly promoted chemoresistance in CRC cells, and downregulation of SCARNA2 obviously inhibited chemoresistance in vitro. SCARNA2 promotes chemotherapy resistance via competitively binding miR-342-3p to facilitate epidermal growth factor receptor (EGFR) and B-cell lymphoma 2 (BCL2) expression in CRC cells. Together, our results reveal a novel pathway that SCARNA2 regulates CRC chemoresistance through targeting miR-342-3p-EGFR/BCL2 pathway, providing a promising therapeutic target for CRC.
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Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Sequência Conservada/genética , Receptores ErbB/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Células Tumorais CultivadasRESUMO
Recently, graphene nanomaterials have attracted tremendous attention and have been utilized in various fields because of their excellent mechanical, thermal, chemical, optical properties, and good biocompatibility, especially in biomedical aspects. However, there is a concern that the unique characteristics of nanomaterials may have undesirable effects. Therefore, in this study, we sought to systematically investigate the effects of graphene quantum dots (GQDs) on the maturation of mouse oocytes and development of the offspring via in vitro and in vivo studies. In vitro, we found that the first polar body extrusion rate in the high dosage exposure groups (1.0-1.5 mg/ml) 2 decreased significantly and the failure of spindle migration and actin cap formation after GQDs exposure was observed. The underlying mechanisms might be associated with reactive oxygen species accumulation and DNA damage. Moreover, transmission electron microscope studies showed that GQDs may have been internalized into oocytes, tending to accumulate in the nucleus and severely affecting mitochondrial morphology, which included swollen and vacuolated mitochondria accompanied by cristae alteration with a lower amount of dense mitochondrial matrix. In vivo, when pregnant mice were exposed to GQDs at 8.5 days of gestation (GD, 8.5), we found that high dosage of GQD exposure (30 mg/kg) significantly affected mean fetal length; however, all the second generation of female mice grew up normal, attained sexual maturity, and gave birth to a healthy offspring after mating with a healthy male mouse. The results presented in this study are important for the future investigation of GQDs for the biomedical applications.
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Desenvolvimento Embrionário/efeitos dos fármacos , Grafite/farmacologia , Oócitos/citologia , Pontos Quânticos/química , Actinas/metabolismo , Animais , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Feto/embriologia , Masculino , Metáfase/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Oócitos/ultraestrutura , Pontos Quânticos/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/metabolismo , Difração de Raios XRESUMO
OBJECTIVE: To determine the degree of acute skin damage and the time required for the recovery of facial skin barrier function after the skin was treated with micro-needles and nanochips of various tip lengths. METHODS: For this split face comparative study, a total of 16 subjects were enrolled and randomly divided into 2 groups. In the first group, one of the facial side of each subject was treated with 0.25-mm long nanotips for a total of 6 times while the other facial side was treated with 0.25-mm traditional micro-needles with a straight blade for a total of 6 times. In the second group, one of the facial side was treated with 0.5-mm nanotips for a total of 6 times while the other facial side was treated with 0.5-mm traditional micro-needles with a straight blade for a total of 6 times. Evaluations for trans-epidermal water loss (TEWL), skin hydration and erythema were carried out at baseline, 0, 4, 8, 24, 48 and 72 hours after the treatment. RESULTS: There was no significant difference in TEWL, skin hydration and erythema between the two facial sides of the subjects in the Group one who were treated with 0.25 mm nanochips and traditional micro-needles. However, in the subjects of the Group two, the mean TEWL of the facial side treated with 0.5 mm nanochips was relatively lower than that of the 0.5 mm traditional micro-needles treated facial side at 0, 4, 8 and 24 hours after the treatment. Mean erythema of the facial side treated with 0.5-mm nanochips micro-needles was also relatively lower than that of the 0.5-mm traditional micro-needles treated facial side at 8 hours after the treatment. Rapid recovery of skin barrier function was observed within 4-8 hours after treatment with various lengths of nanochips while it took at least 48-72 hours for recovery of skin barrier function after treatment with various lengths of traditional micro-needles as measured by TEWL. CONCLUSION: The skin disruption caused by nanotips treatment recovers quicker than the traditional microneedle treatment at equal lengths.
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Técnicas Cosméticas/instrumentação , Eritema/etiologia , Agulhas , Recuperação de Função Fisiológica , Fenômenos Fisiológicos da Pele , Adulto , Técnicas Cosméticas/efeitos adversos , Face , Feminino , Humanos , Masculino , Agulhas/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Pele/química , Fatores de Tempo , Água/análise , Perda Insensível de Água , Adulto JovemRESUMO
Hepatocellular carcinoma is a complex polygenic disease. Despite the huge advances in genetic epidemiology, it still remains a challenge to unveil the genetic architecture of hepatocellular carcinoma. We, therefore, decided to meta-analytically assess the association of six non-synonymous coding variants from XRCC1, XRCC3 and XPD genes with hepatocellular carcinoma risk by pooling the results of 20 English articles. This meta-analysis was conducted according to the PRISMA statement, and data collection was independently completed in duplicate. In overall analyses, the minor alleles of four variants, Arg280His (odds ratio, 95% confidence interval, P: 1.37, 1.13-1.66, 0.001), Thr241Met (1.93, 1.17-3.20, 0.011), Asp312Asn (1.22, 1.08-1.38, 0.001) and Lys751Gln (1.42, 1.02-1.97, 0.038), were associated with the significant risk for hepatocellular carcinoma. There were low probabilities of publication bias for all variants. Subgroup analyses revealed significant association of XRCC1 gene Arg399Gln with hepatocellular carcinoma in Chinese especially from south China (odds ratio, 95% confidence interval, P: 1.57, 1.16-2.14, 0.004), in larger studies (1.48, 1.11-1.98, 0.007) and in studies with population-based controls (1.33, 1.06-1.68, 0.016). Taken together, our findings demonstrated that XPD gene Asp312Asn and XRCC1 gene Arg399Gln might be candidate susceptibility loci for hepatocellular carcinoma. Considering the ubiquity of genetic heterogeneity, further validation in a broad range of ethnic populations is warranted.
Assuntos
Carcinoma Hepatocelular/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Alelos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Methoxychlor (MXC) is used worldwide against insects and other pests. This organochlorine pesticide acts as a xenoestrogen, promotes oxidative stress, and is considered cytotoxic and genotoxic, causing abortions and stillbirths in females. Mechanistically related estrogens and oxidants affect oocyte meiosis, so we investigated the effects of MXC on mouse oocyte meiotic maturation. Our results showed that maturation rates of MXC-treated oocytes were lower than those of controls, which was due to abnormal spindle morphologies and DNA double-strand breaks, as confirmed by increased γ-H2AX foci. Our findings also suggest that MXC may affect oocyte quality by causing the accumulation of superoxide radicals and other reactive oxygen species, aberrant mitochondrial distribution, decreased mitochondrial membrane potential, and increased lipid peroxidation. Thus, exposure to MXC negatively affects oocyte meiotic maturation, primarily through impairments in cellular ROS metabolism. Mol. Reprod. Dev. 83: 768-779, 2016 © 2016 Wiley Periodicals, Inc.