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1.
Chem Rev ; 123(24): 14119-14184, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38055201

RESUMO

Solid-state phase transformation is an intriguing phenomenon in crystalline or noncrystalline solids due to the distinct physical and chemical properties that can be obtained and modified by phase engineering. Compared to bulk solids, nanomaterials exhibit enhanced capability for phase engineering due to their small sizes and high surface-to-volume ratios, facilitating various emerging applications. To establish a comprehensive atomistic understanding of phase engineering, in situ transmission electron microscopy (TEM) techniques have emerged as powerful tools, providing unprecedented atomic-resolution imaging, multiple characterization and stimulation mechanisms, and real-time integrations with various external fields. In this Review, we present a comprehensive overview of recent advances in in situ TEM studies to characterize and modulate nanomaterials for phase transformations under different stimuli, including mechanical, thermal, electrical, environmental, optical, and magnetic factors. We briefly introduce crystalline structures and polymorphism and then summarize phase stability and phase transformation models. The advanced experimental setups of in situ techniques are outlined and the advantages of in situ TEM phase engineering are highlighted, as demonstrated via several representative examples. Besides, the distinctive properties that can be obtained from in situ phase engineering are presented. Finally, current challenges and future research opportunities, along with their potential applications, are suggested.

2.
Curr Issues Mol Biol ; 46(3): 1799-1809, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534734

RESUMO

The tumor metastasis suppressor gene CD82/KAI1 has been demonstrated to impact human trophoblast invasion and migration. Communication between trophoblasts and decidual stromal cells plays a crucial role in controlling the normal invasiveness of trophoblasts. However, whether CD82/KAI1 is involved in decidualization and what role it plays remain unclear. CD82/KAI1 demonstrates specific spatiotemporal expression patterns in stromal cells undergoing decidualization during pregnancy. This is observed in both naturally pregnant females post-implantation and pseudopregnant mice undergoing induced decidualization, as detected through in situ hybridization and immunofluorescence. CD82/KAI1 expression showed a significant time-dependent increase in cultured stromal cells after 24 and 48 h of progesterone (P4) and estrogen (E2) treatment. This was accompanied by a notable upregulation of decidualization markers, including cyclin D3 and PR. After transducing stromal cells with the adenovirus-overexpressing CD82/KAI1 for 48 h, the expression of cyclin D3 protein increased. Meanwhile, there was an attenuated expression of CD82/KAI1 due to an adenovirus siRNA knockdown, whereas cyclin D3 and PR expressions were not affected. Our findings suggest a potential role of CD82/KAI1 in regulating the process of decidualization, providing insights into stromal cell differentiation.

3.
Genome Res ; 31(4): 592-606, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33687945

RESUMO

The environment has constantly shaped plant genomes, but the genetic bases underlying how plants adapt to environmental influences remain largely unknown. We constructed a high-density genomic variation map of 263 geographically representative peach landraces and wild relatives. A combination of whole-genome selection scans and genome-wide environmental association studies (GWEAS) was performed to reveal the genomic bases of peach adaptation to diverse climates. A total of 2092 selective sweeps that underlie local adaptation to both mild and extreme climates were identified, including 339 sweeps conferring genomic pattern of adaptation to high altitudes. Using genome-wide environmental association studies (GWEAS), a total of 2755 genomic loci strongly associated with 51 specific environmental variables were detected. The molecular mechanism underlying adaptive evolution of high drought, strong UVB, cold hardiness, sugar content, flesh color, and bloom date were revealed. Finally, based on 30 yr of observation, a candidate gene associated with bloom date advance, representing peach responses to global warming, was identified. Collectively, our study provides insights into molecular bases of how environments have shaped peach genomes by natural selection and adds candidate genes for future studies on evolutionary genetics, adaptation to climate changes, and breeding.


Assuntos
Adaptação Fisiológica/genética , Mudança Climática , Genoma de Planta/genética , Genômica , Prunus persica/genética
4.
Small ; : e2403275, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934359

RESUMO

Due to the intrinsic flame-retardant, eutectic electrolytes are considered a promising candidate for sodium-metal batteries (SMBs). However, the high viscosity and ruinous side reaction with Na metal anode greatly hinder their further development. Herein, based on the Lewis acid-base theory, a new eutectic electrolyte (EE) composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI), succinonitrile (SN), and fluoroethylene carbonate (FEC) is reported. As a strong Lewis base, the ─C≡N group of SN can effectively weaken the interaction between Na+ and TFSI-, achieving the dynamic equilibrium and reducing the viscosity of EE. Moreover, the FEC additive shows a low energy level to construct thicker and denser solid electrolyte interphase (SEI) on the Na metal surface, which can effectively eliminate the side reaction between EE and Na metal anode. Therefore, EE-1:6 + 5% FEC shows high ionic conductivity (2.62 mS cm-1) and ultra-high transference number of Na+ (0.96). The Na||Na symmetric cell achieves stable Na plating/stripping for 1100 h and Na||Na3V2(PO4)3/C cell shows superior long-term cycling stability over 2000 cycles (99.1% retention) at 5 C. More importantly, the Na||NVP/C pouch cell demonstrates good cycling performance of 102.1 mAh g-1 after 135 cycles at 0.5 C with an average coulombic efficiency of 99.63%.

5.
Plant Physiol ; 193(1): 448-465, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37217835

RESUMO

Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell-cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.


Assuntos
Malus , Prunus persica , Prunus , Prunus persica/genética , Prunus persica/metabolismo , Prunus/genética , Prunus/metabolismo , Histonas/metabolismo , Estudo de Associação Genômica Ampla , Malus/genética , Regulação da Expressão Gênica de Plantas , Dormência de Plantas/genética
6.
Cancer Cell Int ; 24(1): 194, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831301

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. METHODS: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. RESULTS: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. CONCLUSION: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38546457

RESUMO

A Gram-stain-negative, aerobic, motile with flagella and rod- or ovoid-shaped bacterium, designated GG15T, was isolated from tidal flat sediment sampled in Zhoushan, Zhejiang Province. Strain GG15T grew at 20-40 °C (optimum, 30 °C), at pH 5.5-9.5 (optimum, pH 7.0-8.0) and with 1.0-10.0 % (w/v) NaCl (optimum, 1.5 %). Colony diameters ranged from 1 to 3 mm within the first week, reaching a maximum of 6-7 mm after 15 days of cultivation. Strain GG15T exhibited highest 16S rRNA gene sequence similarity to Microbulbifer taiwanensis CCM 7856T (98.1 %), with similarity to other species within the genus Microbulbifer ranging from 97.8 to 93.8 %. Similarity values to other genera were below 93.8 %. Strain GG15T exhibited positive activity for ß-glucosidase, trypsin and chymotrypsin, whereas the reference strain showed negative activity. Chemotaxonomic analyses indicated that strain GG15T contained Q-8 as the sole respiratory quinone, C16 : 0 (9.1 %), iso-C15 : 0 (30.9 %) and iso-C11 : 0 3-OH (7.2 %) as the predominant fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids, four unidentified glycolipids, one unidentified phospholipid, two unidentified aminolipids and two unidentified aminophospholipids as the main polar lipids. The genome of strain GG15T was 4 307 641 bp long, comprising 3861 protein-coding genes. The G+C content of strain GG15T was 61.5 mol% based on its genomic sequence. Strain GG15T showed low digital DNA-DNA hybridization (<70 %) and average nucleotide identity values (<95 %) with other Microbulbifer species. As a result, a novel species within the genus Microbulbifer, named Microbulbifer magnicolonia sp. nov., is proposed. The type strain is GG15T (MCCC 1K08802T=KCTC 8210T).


Assuntos
Alteromonadaceae , Ácidos Graxos , Composição de Bases , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , China
8.
J Gastroenterol Hepatol ; 39(2): 231-244, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37990622

RESUMO

Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.


Assuntos
Carcinoma Hepatocelular , Ácidos Nucleicos Livres , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Ácidos Nucleicos Livres/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos
9.
J Nanobiotechnology ; 22(1): 296, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811964

RESUMO

BACKGROUND: Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor. METHODS: A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining. RESULTS: In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model. CONCLUSION: MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.


Assuntos
Receptor 7 Toll-Like , Receptor 8 Toll-Like , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Receptor 7 Toll-Like/agonistas , Receptor 8 Toll-Like/agonistas , Camundongos , Feminino , Humanos , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Nanopartículas/química , Fatores de Transcrição/metabolismo , Camundongos Endogâmicos BALB C , Proteínas de Ciclo Celular/metabolismo , Imunoterapia/métodos , Epigênese Genética/efeitos dos fármacos , Proteínas que Contêm Bromodomínio
10.
Ecotoxicol Environ Saf ; 275: 116272, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38564870

RESUMO

This study investigated the influence of Cd (25 µM) on Zn accumulation in a hyperaccumulating (HE) and a non-hyperaccumulating (NHE) ecotype of Sedum alfredii Hance at short-term supply of replete (Zn5, 5 µM) and excess (Zn400, 400 µM) Zn. Cd inhibited Zn accumulation in both ecotypes, especially under Zn400, in organs with active metal sequestration, i.e. roots of NHE and shoots of HE. Direct biochemical Cd/Zn competition at the metal-protein interaction and changes in transporter gene expression contributed to the observed accumulation patterns in the roots. Specifically, in HE, Cd stimulated SaZIP4 and SaPCR2 under Zn5, but downregulated SaIRT1 and SaZIP4 under Zn400. However, Cd downregulated related transporter genes, except for SaNRAMP1, in NHE, irrespective of Zn. Cadmium stimulated casparian strip (CSs) development in NHE, as part of the defense response, while it had a subtle effect on the (CS) in HE. Moreover, Cd delayed the initiation of the suberin lamellae (SL) in HE, but stimulated SL deposition in NHE under both Zn5 or Zn400. Changes in suberization were mainly ascribed to suberin-biosynthesis-related genes and hormonal signaling. Altogether, Cd regulated Zn accumulation mainly via symplasmic and transmembrane transport in HE, while Cd inhibited both symplasmic and apoplasmic Zn transport in NHE.


Assuntos
Sedum , Poluentes do Solo , Zinco/metabolismo , Cádmio/metabolismo , Sedum/metabolismo , Transporte Biológico , Transporte de Íons , Raízes de Plantas/metabolismo , Poluentes do Solo/análise
11.
BMC Surg ; 24(1): 111, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622633

RESUMO

BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.


Assuntos
Proctocolectomia Restauradora , Sarcopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Sarcopenia/complicações , Sarcopenia/diagnóstico , Estudos Retrospectivos , Inteligência Artificial , Anastomose Cirúrgica/métodos , Resultado do Tratamento , Colostomia/efeitos adversos , Proctocolectomia Restauradora/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Obesidade/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
12.
BMC Med Educ ; 24(1): 321, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515120

RESUMO

BACKGROUND: Narrative Medicine (NM), a contemporary medical concept proposed in the 21st century, emphasizes the use of narrative as a literary form in medicine. This study aims to explore the understanding about NM and willingness to learn NM among medical students in our hospital. METHODS: A questionnaire survey was conducted among 130 students at Xiangya Medical College of Central South University. RESULTS: The findings revealed that a small percentage of students (3.1%) were familiar with narrative medicine and its training methods. Knowledge about the treatment skills (77.7%) and core content (55.4%) of narrative medicine was limited among the students. Despite this, a majority (63.1%) expressed a lack of interest in further understanding and learning about narrative medicine. Surprisingly, the survey indicated that students possessed a high level of narrative literacy, even without formal training in narrative medicine. Additionally, over half of the surveyed students (61.5%) believed that narrative medicine could benefit their clinical practice. CONCLUSIONS: This study serves as a preliminary basis for the future development of narrative medicine education in China. It highlights the need to prioritize medical humanities education and provide medical students with more opportunities to access information on narrative medicine. By doing so, we can strive to enhance the visibility and promote the integration of narrative medicine into medical humanities education in China.


Assuntos
Medicina Clínica , Educação Médica , Medicina Narrativa , Estudantes de Medicina , Humanos , Ciências Humanas/educação , Medicina Clínica/educação
13.
Anal Chem ; 95(31): 11641-11648, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489999

RESUMO

Reproductive hormones play vital roles in reproductive health and can be used to assess a woman's ovarian function and diagnose diseases associated with reproductive endocrine disorders. As these hormones are important biomarkers for reproductive health monitoring and diagnosis, a rapid, high-throughput, and low-invasive detection and simultaneous assessment of the levels of multiple reproductive hormones has important clinical applications. In this work, a quadruplex ultrasensitive immunoassay was developed for simultaneous assessment of 4 human reproductive hormone proteins (follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and anti-Müllerian hormone (AMH)) in a variety of human biofluid samples. This assay takes advantage of single-molecule imaging of microwell arrays and capture antibody beads as a reaction interface to construct multiplex bead array immunoassays. The analyte-bound beads can easily be parsed to individual wells and detected via fluorophores, emitting distinct wavelengths associated to the beads. As a result, this proposed quadruplex immunoassay exhibits four good 4-parameter logistic calibration curves ranging from 2.7 to 2000, 1.6 to 1200, 1.8 to 1300, and 0.3 to 220 pg/mL with limits of detection of 0.32, 0.28, 0.14, and 0.02 pg/mL for FSH, LH, PRL, and AMH, respectively. Furthermore, the developed quadruplex immunoassay was used to test clinical venous serum samples where it showed remarkable consistency with clinical test results in methodological comparison and the diagnosis of polycystic ovary syndrome. In addition, we successfully applied the ultrasensitive capability of this assay to the simultaneous testing and evaluation of four proteins in fingertip blood as well as urine samples, in which the urinary AMH level (1.42-156 pg/mL) was measured and assessed quantitatively for the first time.


Assuntos
Hormônio Luteinizante , Síndrome do Ovário Policístico , Feminino , Humanos , Hormônio Foliculoestimulante , Síndrome do Ovário Policístico/diagnóstico , Hormônio Antimülleriano , Imunoensaio
14.
J Transl Med ; 21(1): 823, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978379

RESUMO

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.


Assuntos
Cardiotoxicidade , Ferroptose , Camundongos , Animais , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Espécies Reativas de Oxigênio/metabolismo , Miócitos Cardíacos/patologia , Doxorrubicina/efeitos adversos , Mitocôndrias/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Apoptose
15.
Cancer Cell Int ; 23(1): 124, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349706

RESUMO

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. METHODS: CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan-Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We  also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. RESULTS: Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. CONCLUSIONS: In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.

16.
J Nutr ; 153(12): 3373-3381, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37923224

RESUMO

BACKGROUND: Heat stress (HS) has a harmful impact on the male reproductive system, primarily by reducing the sperm quality. The testicular microenvironment plays an important role in sperm quality. OBJECTIVES: This study aimed to explore the underlying mechanism by which HS impairs the male reproductive system through the testicular microenvironment. METHODS: Ten-week-old male mice (n = 8 mice/group) were maintained at a normal temperature (25°C, control) or subjected to HS (38°C for 2 h each day, HS) for 2 wk. The epididymides and testes were collected at week 2 to determine sperm quality, histopathology, retinol concentration, the expression of retinol metabolism-related genes, and the testicular microbiome. The testicular microbiome profiles were analyzed using biostatistics and bioinformatics; other data were analyzed using a 2-sided Student's t test. RESULTS: Compared with the control, HS reduced (P < 0.05) sperm count (42.4%) and motility (97.7%) and disrupted the integrity of the blood-testis barrier. Testicular microbial profiling analysis revealed that HS increased the abundance of the genera Asticcacaulis, Enhydrobacter, and Stenotrophomonas (P < 0.05) and decreased the abundance of the genera Enterococcus and Pleomorphomonas (P < 0.05). Notably, the abundance of Asticcacaulis spp. showed a significant negative correlation with sperm count (P < 0.001) and sperm motility (P < 0.001). Moreover, Asticcacaulis spp. correlated significantly with most blood differential metabolites, particularly retinol (P < 0.05). Compared with the control, HS increased serum retinol concentrations (25.3%) but decreased the testis retinol concentration by 23.7%. Meanwhile, HS downregulated (P < 0.05) the expression of 2 genes (STRA6 and RDH10) and a protein (RDH10) involved in retinol metabolism by 27.3%-36.6% in the testis compared with the control. CONCLUSIONS: HS reduced sperm quality, mainly because of an imbalance in the testicular microenvironment potentially caused by an increase in Asticcacaulis spp. and disturbed retinol metabolism. These findings may offer new strategies for improving male reproductive capacity under HS.


Assuntos
Testículo , Vitamina A , Masculino , Camundongos , Animais , Testículo/metabolismo , Vitamina A/metabolismo , Motilidade dos Espermatozoides , Sêmen , Espermatozoides/metabolismo , Espermatozoides/patologia , Resposta ao Choque Térmico
17.
Int J Syst Evol Microbiol ; 73(11)2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37966456

RESUMO

A Gram-stain-negative, strictly aerobic and rod- to coccoid-shaped bacterium, designated as strain M366T, was isolated from coastal sediment of Jiaoshanjiao, Zhejiang Province, PR China (121°54' E 29 °38' N). The draft genome of strain M366T was 3 225 479 bp long (with 55.6 mol% G+C content) and assembled into four contigs. The N50 value was 563 270 bp and the genomic completeness and contamination were estimated to be 99.34 and 0.05 %, respectively. Colonies of strain M366T were yellow-orange, 1 mm in diameter, round, opaque, smooth and convex after incubation on marine agar at 30 °C for 3 days. Cells were catalase-positive but oxidase-negative. Strain M366T was observed to grow at 20-40 °C (optimum, 30 °C), pH 5.5-9.0 (optimum, pH 6.5-7.0) and with 0.5-8.0 % (w/v) NaCl (optimum, 2.5 %). Strain M366T shown highest 16S rRNA gene sequence similarity of 98.1 % to Robiginitalea sediminis O458T, 95.6-95.9 % to other type strains of the genus Robiginitalea and below 93 % to other genera. The average nucleotide identity and digital DNA-DNA hybridization values between strain M366T and its closely related Robiginitalea species were 71.1-75.9 % and 17.5-19.0 %. Menaquinone-6 was the only respiratory quinone. The major fatty acids (>10 %) were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 1 (iso-C15 : 1 h and/or C13 : 0 3-OH). The main polar lipids included phosphatidylethanolamine, two unidentified phospholipid, two unidentified aminophospholipid, one unidentified glycolipid and five unidentified lipids. According to the above results, Robiginitalea aestuariiviva sp. nov. is proposed and the type strain is M366T (=KCTC 92866T=MCCC 1K04524T=CGMCC 1.61708T).


Assuntos
Ácidos Graxos , Composição de Bases , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , China
18.
Environ Sci Technol ; 57(49): 20893-20904, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38032700

RESUMO

Ferrate (Fe(VI)) is an emerging green disinfectant and has received increasing attention nowadays. This study conducted systematic analyses of Fe(VI) disinfection on six typical bacteria in different water matrices. The results showed that Fe(VI) was more effective in inactivating Gram-negative (G-) bacteria than Gram-positive (G+) bacteria, and the disinfection performance of Fe(VI) was better in a phosphate buffer than that in a borate buffer and secondary effluent. The inactivation rate constants of G- bacteria were significantly higher than those of G+ bacteria. The cell membrane damage of G- bacteria was also more severe than that of G+ bacteria after Fe(VI) treatment. The cell wall structure, especially cell wall thickness, might account for the difference of the inactivation efficiency between G- bacteria and G+ bacteria. Moreover, it is revealed that Fe(VI) primarily reacted with proteins rather than other biological molecules (i.e., phospholipids, peptidoglycan, and lipopolysaccharide). This was further evidenced by the reduction of bacterial autofluorescence due to the destruction of bacterial proteins during Fe(VI) inactivation. Overall, this study advances the understanding of Fe(VI) disinfection mechanisms and provides valuable information for the Fe(VI) application in water disinfection.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Água , Purificação da Água/métodos , Ferro/química , Poluentes Químicos da Água/análise , Bactérias , Oxirredução
19.
Environ Res ; 227: 115803, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37003546

RESUMO

Marine sediments are the world's largest known reservoir of methane. In many coastal regions, methane is trapped in sediments buried at depths ranging from centimeters to hundreds of meters below the seafloor, in the forms of gas pockets, dispersed gas bubbles and dissolved gas, also known as shallow gas (methane-dominated gas mixture). The existence of shallow gas affects the engineering geological environment and threatens the safety of artificial facilities. The escape of shallow gas from sediments into the atmosphere can even threaten ecosystem security and affect global climate change. However, until now, shallow gas has remained a mystery to the scientific community. For example, how it is generated, how it distributes and migrates in sediments, and what are the factors that influence these processes that are still unclear. In the context of increasingly intense offshore development and global warming, there is a huge gap between existing scientific understanding of shallow gas and the need to develop scientific solutions for related problems. Based on this, this paper systematically collects the information on all aspects of shallow gas mentioned above, comprehensively summarizes the current scientific understanding, and analyzes the existing shortcomings, which will provide systematic references for the research on environmental disaster prevention, engineering technology, climate change, and other fields.


Assuntos
Ecossistema , Metano , Mudança Climática , Aquecimento Global , Atmosfera , Sedimentos Geológicos
20.
Langenbecks Arch Surg ; 408(1): 9, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602593

RESUMO

OBJECTIVE: To compare the safety, weight loss, and metabolic outcomes of patients with obesity with sleeve gastrectomy (SG) or sleeve gastrectomy plus uncut jejunojejunal bypass (SG-uncut JJB). METHODS: This prospective study included patients with BMIs ≥ 32.5 kg/m2 or refractory metabolic disorders undergoing SG or SG-uncut JJB between January and December 2020 in our hospital (NCT04534504). Weight loss, metabolic outcomes, surgical results, and complaints during 1-year follow-up were compared between two groups. RESULTS: Forty-seven patients were enrolled, 26 in the SG and 21 in the SG-uncut JJB groups. A longer operative time was observed in the SG-uncut JJB than in the SG group (140 (110-180) min vs. 90 (70-180) min, P = 0.001). No significant differences were found in complications. Total weight loss (TWL%) and excess weight loss (EWL%) in both groups increased with the duration of follow-up (P = 0.001). TWL% was greater at 1 month ((11.1 ± 2.4)% vs. (8.2 ± 4.4)%, P = 0.011] and 12 months [(29.7 ± 6.9)% vs. (20.3 ± 7.2)%, P = 0.001) with SG-uncut JJB than with SG. SG-uncut JJB and SG had similar metabolic outcomes and complaints during the 1-year follow-up, but less nausea was reported with SG-uncut JJB (9.2% vs. 46.2%, P = 0.006). CONCLUSION: In short-term follow-up, SG-uncut JJB was a safe and effective bariatric surgery procedure in patients with obesity.


Assuntos
Gastrectomia , Derivação Gástrica , Obesidade , Humanos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Obesidade/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Redução de Peso
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