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1.
ACS Appl Mater Interfaces ; 16(20): 26234-26244, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38711193

RESUMO

The huge volume expansion/contraction of silicon (Si) during the lithium (Li) insertion/extraction process, which can lead to cracking and pulverization, poses a substantial impediment to its practical implementation in lithium-ion batteries (LIBs). The development of low-strain Si-based composite materials is imperative to address the challenges associated with Si anodes. In this study, we have engineered a TiSi2 interface on the surface of Si particles via a high-temperature calcination process, followed by the introduction of an outermost carbon (C) shell, leading to the construction of a low-strain and highly stable Si@TiSi2@NC composite. The robust TiSi2 interface not only enhances electrical and ionic transport but also, more critically, significantly mitigates particle cracking by restraining the stress/strain induced by volumetric variations, thus alleviating pulverization during the lithiation/delithiation process. As a result, the as-fabricated Si@TiSi2@NC electrode exhibits a high initial reversible capacity (2172.7 mAh g-1 at 0.2 A g-1), superior rate performance (1198.4 mAh g-1 at 2.0 A g-1), and excellent long-term cycling stability (847.0 mAh g-1 after 1000 cycles at 2.0 A g-1). Upon pairing with LiNi0.6Co0.2Mn0.2O2 (NCM622), the assembled Si@TiSi2@NC||NCM622 pouch-type full cell exhibits exceptional cycling stability, retaining 90.1% of its capacity after 160 cycles at 0.5 C.

2.
Physiol Behav ; 281: 114549, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604593

RESUMO

Maternal exposure to elevated levels of steroid hormones during pregnancy is associated with the development of chronic conditions in offspring that manifest in adulthood. However, the effects of progesterone (P4) administration during early pregnancy on fetal development and subsequent offspring behavior remain poorly understood. In this study, we aimed to investigate the effects of P4 treatment during early pregnancy on the transcript abundance in the fetal brain and assess the behavioral consequences in the offspring during adolescence and adulthood. Using RNA-seq analysis, we examined the impact of P4 treatment on the fetal brain transcriptome in a dosage-dependent manner. Our results revealed differential regulation of genes involved in neurotransmitter transport, synaptic transmission, and transcriptional regulation. Specifically, we observed bidirectional regulation of transcription factors (TFs) by P4 at different doses, highlighting the critical role of these TFs in neurodevelopment. To assess behavioral outcomes, we conducted open field and elevated plus maze tests. Offspring treated with low-dose P4 (LP4) displayed increased exploratory behavior during both adolescence and adulthood. In contrast, the high-dose P4 (HP4) group exhibited impaired exploration and heightened anxiety-like behaviors compared to the control mice. Moreover, in a novel object recognition test, HP4-treated offspring demonstrated impaired object recognition memory during both developmental stages. Additionally, both LP4 and HP4 groups showed reduced social interaction in the three-chamber test. These results suggest that prenatal exposure to P4 exerts a notable influence on the expression of genes associated with neurodevelopment and may induce alterations in behavioral characteristics in progeny, highlighting the need to monitor progesterone levels during pregnancy for long-term impacts on fetal brain development and behavior.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38522713

RESUMO

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 µM), medium (5 µM), and high (10 µM), while for PRA, the corresponding concentrations were set at low (18 µM), medium (180 µM), and high (270 µM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peixe-Zebra/genética , Transcriptoma , Pravastatina/farmacologia , Pravastatina/uso terapêutico , Atorvastatina/toxicidade , Canais Iônicos
4.
BMC Public Health ; 24(1): 556, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388348

RESUMO

BACKGROUND: SARS-CoV-2 infections usually cause immune dysregulation in the human body. Studies of immunological changes resulting from coinfections with Mycobacterium tuberculosis (Mtb) or HIV are limited. METHODS: We conducted a retrospective study focusing on patients with COVID-19. A total of 550 patients infected with SARS-CoV-2 were enrolled in our study and categorized into four groups based on the presence of coinfections; 166 Delta-infected patients, among whom 103 patients had no coinfections, 52 who were coinfected with Mtb, 11 who were coinfected with HIV, and 384 Omicron-infected patients. By collecting data on epidemiologic information, laboratory findings, treatments, and clinical outcomes, we analyzed and compared clinical and immunological characteristics. RESULTS: Compared with those in the Delta group, the median white blood cell, CD4 + T-cell and B-cell counts were lower in the Mtb group and the HIV group. Except for those in the Omicron group, more than half of the patients in the three groups had abnormal chest CT findings. Among the three groups, there were no significant differences in any of the cytokines. Compared with those in the Delta group, the disease duration and LOS were longer in the Mtb group and the HIV group. For unvaccinated Delta-infected patients, in the Mtb and HIV groups, the number of B cells and CD4 + T cells was lower than that in the Delta group, with no significant difference in the LOS or disease duration. In the Mtb group, three (6%) patients presented with a disease duration greater than four months and had decreased lymphocyte and IL17A counts, possibly due to double infections in the lungs caused by SARS-CoV-2 and M. tuberculosis. CONCLUSIONS: We found that SARS-CoV-2 patients coinfected with Mtb or HIV exhibited a longer disease duration and longer LOS, with a decrease in B cells and CD4 + T cells, suggesting that these cells are related to immune function. Changes in cytokine levels suggest that coinfection with Mtb or HIV does not result in dysregulation of the immune response. Importantly, we discovered a chronic course of coinfection involving more than four months of Mtb and SARS-CoV-2 infection.


Assuntos
COVID-19 , Coinfecção , Infecções por HIV , Mycobacterium tuberculosis , Humanos , Coinfecção/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Citocinas
5.
Sci Total Environ ; 918: 170666, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38316310

RESUMO

Colloids can potentially affect the efficacy of traditional acid mine drainage (AMD) treatment methods such as precipitation and filtration. However, it is unclear how colloids affect antimony (Sb) migration in AMD, especially when natural organic matter (NOM) is present. To conduct an in-depth investigation on the formation and migration behavior of NOM, iron (Fe), Sb and NOM-Fe-Sb colloids in AMD, experiments were performed under simulated AMD conditions. The results demonstrate significant variations in the formation of NOM-Fe-Sb colloids (1-3-450 nm) as the molar ratio of carbon to iron (C/Fe) increases within acidic conditions (pH = 3). Increasing the C/Fe molar ratio from 0.1 to 1.2 resulted in a decrease in colloid formation but an increase in particulate fraction. The distribution of colloidal Sb, Sb(III), and Fe(III) within the NOM-Fe-Sb colloids decreased from 68 % to 55 %, 72 % to 57 %, and 68 % to 55 %, respectively. Their distribution in the particulate fraction increased from 28 % to 42 %, 21 % to 34 %, and 8 % to 27 %. XRD, FTIR, and SEM-EDS analyses demonstrated that NOM facilitates the formation and crystallization of Fe3O4 and FeSbO4 crystalline phases. The formation of the colloids depended on pH. Our results indicate that NOM-Fe-Sb colloids can form when the pH ≤ 4, and the proportion of colloidal Sb fraction within the NOM-Fe-Sb colloids increased from 9 % to a maximum of 73 %. Column experiments show that the concentration of NOM-Fe-Sb colloids reaches its peak and remains stable at approximately 3.5 pore volumes (PVs), facilitating the migration of Sb in the porous media. At pH ≥ 5, stable NOM-Fe-Sb colloids do not form, and the proportion of colloidal Sb fraction decreases from 7 % to 0 %. This implies that as pH increases, the electrostatic repulsion between colloidal particles weakens, resulting in a reduction in the colloidal fraction and an increase in the particulate fraction. At higher pH values (pH ≥ 5), the repulsive forces between colloidal particles nearly disappear, promoting particle aggregation. The findings of this study provide important scientific evidence for understanding the migration behavior of NOM-Fe-Sb colloids in AMD. As the pH gradually shifts from acidic to near-neutral pH during the remediation process of AMD, these results could be applied to develop new strategies for this purpose.

6.
Front Med (Lausanne) ; 10: 1161942, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324159

RESUMO

Objective: This study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA). Materials and methods: Ninety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland-Altman plots were used to evaluate the repeatability and reproducibility. Results: Ninety participants aged 6-15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61-11.11%; intermediate: COV = 7.73-14.15%; deep: COV = 14.60-32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570-0.976; intermediate plexus: ICC = 0.720-0.968; deep plexus: ICC = 0.628-0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00-6.10%; ICC = 0.856-0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01-0.21%; ICC = 0.743-0.994). Conclusion: The VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.

7.
J Environ Manage ; 323: 116216, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36137459

RESUMO

Forest losses can lead to severe damage to ecosystem services (ESs), especially in the tropics. Tropical forests are widespread in southwestern China, and they experience continual effects of human activities (e.g., rubber boom). However, forest simulations of land planning have not yet been systematically conducted. Based on a future land-use simulation model, here, the spatio-temporal characteristics of four ES (i.e., soil retention, water yield, carbon fixation, and habitat quality) were examined, and three scenarios (i.e., natural development, rubber development, and ecological protection) were designed and evaluated during 2000 for Xishuangbanna (XSBN), southwestern China. The results showed that: (1) from 2000 to 2020, the average values of the ESs declined by 449.1 t for soil retention, 13.4 mm for water yield, 0.1 for habitat quality, and 0.1 kg C/m2 for carbon fixation; (2) the four ESs, with the exception of water yield, had synergistic relationships, and trade-off appeared on the margins of these synergistic relationships; (3) compared with the scenarios of natural development and rubber development, the environmental protection scenario was found to have high efficiency for protecting nature reserves and reducing fragmentation; and (4) the intensity of land-use change will accelerate the decrease of ESs, and it is essential for nature reserves and areas of northern XSBN to improve their level of environmental protection. This work not only further enriches the ES research from the ecological environment and land-planning points of view, but it also provides different planning perspectives for ES and forest scenarios. This is useful in methodical approaches to forest sustainability.


Assuntos
Ecossistema , Borracha , China , Conservação dos Recursos Naturais/métodos , Florestas , Humanos , Solo , Água
9.
Acta Biomater ; 151: 333-345, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914692

RESUMO

Human embryonic stem cells (hESCs) and their derived products offer great promise for targeted therapies and drug screening, however, the hESC differentiation process of mature neurons is a lengthy process. To accelerate the neuron production, an acoustic stimulator producing surface acoustic waves (SAWs) is proposed and realized by clamping a flexible printed circuit board (PCB) directly onto a piezoelectric substrate. Neural differentiation of the hESCs is greatly accelerated after application of the acoustic stimulations. Acceleration mechanisms for neural differentiation have been explored by bulk RNA sequencing, quantitative polymerase chain reaction (qPCR) and immunostaining. The RNA sequencing results show changes of extracellular matrix-related and physiological activity-related gene expression in the low or medium SAW dose group and the high SAW dose group, respectively. The neural progenitor cell markers, including Pax6, Sox1, Sox2, Sox10 and Nkx2-1, are less expressed in the SAW dose groups compared with the control group by the qPCR. Other genes including Alk, Cenpf, Pcdh17, and Actn3 are also found to be regulated by the acoustic stimulation. Moreover, the immunostaining confirmed that more mature neuron marker Tuj1-positive cells, while less stem cell marker Sox2-positive cells, are presented in the SAW dose groups. These results indicate that the SAW stimulation accelerated neural differentiation process. The acoustic stimulator fabricated by using the PCB is a promising tool in regulation of stem cell differentiation process applied in cell therapy. STATEMENT OF SIGNIFICANCE: Human embryonic stem cells (hESC) are used for investigating the complex mechanisms involved in the development of specialized biological cells and organs. Different types of hESCs derived cell products can be used for cell therapy procedures aiming to regenerate functional tissues in patients who suffer from various degenerative diseases. Accelerating the hESCs' differentiation process can considerably benefit the clinical utilization of these cells. This study develops a highly effective acoustic stimulator working at ∼20 MHz to investigate what roles do acousto-mechanical stimuli play in the differentiation of hESCs. Our results show that acoustic dose alters the extracellular matrix and physiological activity-related gene expression, which indicates that the acoustic stimulation is an important tool for regulating the stem cells' differentiation processes in cell therapy.


Assuntos
Células-Tronco Embrionárias Humanas , Actinina/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias , Humanos , Neurônios/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo
10.
Bull Environ Contam Toxicol ; 109(5): 771-775, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35294977

RESUMO

The reaction mechanisms Fe(II) abiotic oxidation produce ·OH by CaCO3-induced in acid mine drainage (AMD) are well-documented, but little is known about the influence of extracellular polymeric substances (EPS) secreted by microorganisms on Fe(II) oxidation in AMD. In this study, ·OH production was experimently measured from oxygenation of simulated AMD in the presence of EPS. The cumulative ·OH increased from 56.75 to 158.70 µM within 24 h at pH 3 with the increase in EPS concentration from 0 to 12 mg/L. An appropriate pH (about 6) and EPS (6 mg/L) concentration were required for the moderate rate of Fe(II) oxidation. Besides, the yield of ·OH increased remarkably with the addition of Fe3+. In the presence of EPS, ·OH production is attributed mainly the complexation of Fe(II) with EPS, of which is rich of carboxyl and hydroxyl groups. The findings provide fundamental supplement of ·OH production from Fe(II) oxidation by microorganisms in natural AMD.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Radical Hidroxila , Radical Hidroxila/química , Ferro/química , Oxirredução , Compostos Ferrosos/química , Polímeros
11.
Water Sci Technol ; 84(3): 777-792, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388134

RESUMO

In order to assess the social factors affecting the water quality of the Zhanghe River and predict the potential impact of growth in primary, secondary, tertiary industries and population on water quality of the Zhanghe River in the next few years, a deformation derivative cumulative grey multiple convolution model (DGMC(1,N)) was applied. In order to improve the accuracy of the model, the accumulation of deformation derivatives is introduced, and the particle swarm optimization algorithm is used to solve the optimal order. The DGMC(1,N) model was compared with GM(1,2) and GM(1,1) models. The results show that the DGMC(1,N) model has the highest prediction accuracy. Finally, DGMC(1,N) model is used to predict the potential impact of growth in primary, secondary, tertiary industries and population on water quality in the Zhanghe River (using chemical oxygen demand (COD) as the water quality indicator).


Assuntos
Rios , Poluentes Químicos da Água , Algoritmos , Análise da Demanda Biológica de Oxigênio , China , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Qualidade da Água
12.
J Cancer ; 12(16): 4780-4790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234849

RESUMO

Lung adenocarcinoma (LUAD) is a lethal malignancy with metastasis, a major tumor feature that predominantly correlated with progression, but the molecules that mediated tumor metastasis remain elusive. To declare the critical regulatory genes, RNA sequencing data in LUAD patients was acquired from The Cancer Genome Atlas (TCGA) and found that ALDH3A1 was distinctly highly expressed in LUAD patients with metastasis (M1) compared with those without metastasis (M0), linked to the property of cancer stem cell and epithelial-mesenchymal transition (EMT). Besides, high ALDH3A1 expression predicted a poor prognosis. Knockdown of ALDH3A1 showed decreased proliferation, migration, and invasion in A549 cell line. Furthermore, BAG1 was regulated by ALDH3A1 through p53, enhanced cell proliferation, and predicted clinical prognosis. Our findings collectively uncovered a novel mechanism that orchestrates tumor cells' metastasis, and decreasing ALDH3A1 represented a potential therapeutic target for reprogramming metastasis.

13.
J Cell Mol Med ; 24(20): 11680-11690, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32860342

RESUMO

Lung adenocarcinoma (LUAD) is a highly malignant cancer. Although competing endogenous RNA (ceRNA)-based profiling has been investigated in patients with LUAD, it has not been specifically used to study metastasis in LUAD. We found 130 differentially expressed (DE) lncRNAs, 32 DE miRNAs and 981 DE mRNAs from patients with LUAD in The Cancer Genome Atlas (TCGA) database. We analysed the functions and pathways of 981 DE mRNAs using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Based on the target DE mRNAs and DE lncRNAs of DE miRNAs, we established an lncRNA-miRNA-mRNA ceRNA network, comprising 37 DE lncRNAs, 22 DE miRNAs and 212 DE mRNAs. Subsequently, we constructed a protein-protein interaction network of DE mRNAs in the ceRNA network. Among all, DE RNAs, 5 DE lncRNAs, 5 DE miRNAs and 45 DE mRNAs were confirmed found to be associated with clinical prognosis. Moreover, 3 DE lncRNAs, 4 DE miRNAs and 9 DE mRNAs in the ceRNA network were associated with clinical prognosis. We further screened 3 DE lncRNAs, 3 DE miRNAs and 3 DE mRNAs using clinical samples. These DE lncRNAs, DE miRNAs and DE mRNAs in ceRNA network may serve as independent biomarkers of LUAD metastasis.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Análise por Conglomerados , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genética
14.
Emerg Microbes Infect ; 9(1): 787-793, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32241244

RESUMO

On 31 December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, China, and caused the outbreak of the Coronavirus Disease 2019 (COVID-19). To date, computed tomography (CT) findings have been recommended as major evidence for the clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the imaging characteristics and changes throughout the disease course in patients with COVID-19 in order to provide some help for clinicians. Typical CT findings included bilateral ground-glass opacity, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. This review also provides a comparison between COVID-19 and other diseases that have similar CT findings. Since most patients with COVID-19 infection share typical imaging features, radiological examinations have an irreplaceable role in screening, diagnosis and monitoring treatment effects in clinical practice.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Betacoronavirus , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Técnicas de Amplificação de Ácido Nucleico , Pandemias , Radiografia Torácica , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/diagnóstico por imagem
15.
Immunology ; 160(2): 209-219, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149403

RESUMO

CD100 is an immune semaphorin constitutively expressed on T-cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T-cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8+ T-cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP-14 on mCD100 shedding for the regulation of non-cytolytic and cytolytic functions of CD8+ T-cells were also analysed in direct and indirect contact co-culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T-cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T-cells compared with the non-tumour site. Recombinant CD100 stimulation enhanced non-cytolytic and cytolytic functions of CD8+ T-cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T-cell activity. NSCLC patients had lower MMP-14 in the serum and in BALF from the tumour site. Recombinant MMP-14 mediated mCD100 shedding from CD8+ T-cell membrane, and led to promotion of CD8+ T-cell response in NSCLC patients. Overall, decreased MMP-14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung-resident CD8+ T-cell activity in NSCLC.


Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Metaloproteinase 14 da Matriz/metabolismo , Semaforinas/metabolismo , Adulto , Idoso , Antígenos CD/sangue , Líquido da Lavagem Broncoalveolar/química , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultura , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Masculino , Metaloproteinase 14 da Matriz/sangue , Pessoa de Meia-Idade , Cultura Primária de Células , Proteínas Recombinantes/metabolismo , Semaforinas/sangue , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Evasão Tumoral , Microambiente Tumoral/imunologia
16.
Cell Death Differ ; 27(2): 587-600, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31209364

RESUMO

To maintain healthy mitochondrial enzyme content and function, mitochondria possess a complex protein quality control system, which is composed of different endogenous sets of chaperones and proteases. Heat shock protein 60 (HSP60) is one of these mitochondrial molecular chaperones and has been proposed to play a pivotal role in the regulation of protein folding and the prevention of protein aggregation. However, the physiological function of HSP60 in mammalian tissues is not fully understood. Here we generated an inducible cardiac-specific HSP60 knockout mouse model, and demonstrated that HSP60 deletion in adult mouse hearts altered mitochondrial complex activity, mitochondrial membrane potential, and ROS production, and eventually led to dilated cardiomyopathy, heart failure, and lethality. Proteomic analysis was performed in purified control and mutant mitochondria before mutant hearts developed obvious cardiac abnormalities, and revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria. We also utilized an in vitro system to assess the effects of HSP60 deletion on mitochondrial protein import and protein stability after import, and found that both HSP60-dependent and HSP60-independent mitochondrial proteins could be normally imported in mutant mitochondria. However, the former underwent degradation in mutant mitochondria after import, suggesting that the protein exhibited low stability in mutant mitochondria. Interestingly, the degradation could be almost fully rescued by a non-specific LONP1 and proteasome inhibitor, MG132, in mutant mitochondria. Therefore, our results demonstrated that HSP60 plays an essential role in maintaining normal cardiac morphology and function by regulating mitochondrial protein homeostasis and mitochondrial function.


Assuntos
Chaperonina 60/metabolismo , Insuficiência Cardíaca/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Chaperonina 60/deficiência , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
17.
Cell Death Dis ; 10(10): 766, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601784

RESUMO

The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-Cre+Hspd1f/f (HSP60CKO) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60CKO yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.


Assuntos
Chaperonina 60/metabolismo , Desenvolvimento Embrionário/genética , Eritropoese/genética , Proteínas Mitocondriais/metabolismo , Saco Vitelino/citologia , Anemia/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Chaperonina 60/genética , Ciclosporina/farmacologia , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/fisiopatologia , Células Endoteliais/metabolismo , Eritrócitos/metabolismo , Eritropoese/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Células-Tronco Hematopoéticas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/genética , Camundongos , Proteínas Mitocondriais/genética , Gravidez , Canais de Ânion Dependentes de Voltagem/efeitos dos fármacos , Canais de Ânion Dependentes de Voltagem/metabolismo , Saco Vitelino/crescimento & desenvolvimento , Saco Vitelino/metabolismo , Saco Vitelino/patologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31484402

RESUMO

Facing the demands of biodiversity conservation and ecosystem service improvement, the spatial pattern optimization of nature reserves has always been a research topic of interest. However, there remains a lack of methodological guidance in the planning of nature reserves and the surrounding areas. To promote the landscape sustainability of nature reserves, we constructed ecological security patterns (ESPs) with two scenarios as a case study in Wenchuan, China. In detail, the ecological sources were identified by ecosystem service evaluation, and the resistance surface was characterized by the habitat quality. The ecological corridors were determined based on circuit theory and the minimum cumulative resistance model. The ecological sources were mainly aggregated in the protected areas, with an area of more than 1000 ha; the high-resistance values were mainly in the area with dense roads or high elevation. There were 21 corridors in the scenario of only optimizing the nature reserve, while 31 corridors were identified when considering non-nature reserves, and the landscape connectivity was enhanced accordingly. The result supported constructing the ESPs between nature and non-nature reserves in Wenchuan to further protect pandas, and a methodological contribution was made to understand the differences of ESPs between them, thus supporting a methodological formulation of sustainable landscape patterns.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Ecologia
19.
ACS Appl Mater Interfaces ; 11(19): 17313-17320, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31002223

RESUMO

Through in situ transmission electron microscopy (TEM) observation, we report the behaviors of phosphorus (P)-doped silicon nanowires (SiNWs) during electrochemical lithiation/delithiation cycling. Upon lithiation, lithium (Li) insertion causes volume expansion and formation of the crystalline Li15Si4 phase in the P-doped SiNWs. During delithiation, vacancies induced by Li extraction aggregate gradually, leading to the generation of nanopores. The as-formed nanopores can get annihilated with Li reinsertion during the following electrochemical cycle. As demonstrated by our phase-field simulations, such first-time-observed reversible nanopore formation can be attributed to the promoted lithiation/delithiation rate by the P dopant in the SiNWs. Our phase-field simulations further reveal that the delithiation-induced nanoporous structures can be controlled by tuning the electrochemical reaction rate in the SiNWs. The findings of this study shed light on the rational design of high-power performance Si-based anodes.

20.
Cell Physiol Biochem ; 47(6): 2407-2419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29991058

RESUMO

BACKGROUND/AIMS: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. METHODS: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. RESULTS: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. CONCLUSION: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Interleucinas/imunologia , Neoplasias Pulmonares/imunologia , Proteínas de Neoplasias/imunologia , Idoso , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
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