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1.
Adv Mater ; : e2411134, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279569

RESUMO

NiFe (oxy)hydroxides have been regarded as one of the state-of-the-art catalysts for oxygen evolution reaction (OER). Unfortunately, the sluggish hydrogen evolution reaction (HER) kinetics limit its application as bifunctional electrocatalyst for alkaline overall water splitting (OWS). Herein, a "two-pronged" strategy is proposed to construct highly active oxygen deficient Ni-Mo-Fe coordinate structures in NiFe (oxy)hydroxide (NFM-OVR/NF), which simultaneously reduces the energy barrier of Volmer and Heyrovsky steps during alkaline HER process and significantly accelerate the reaction kinetics. Consequently, NFM-OVR/NF delivers overpotentials as low as 25 and 234 mV to achieve 10 and 1000 mA cm-2 in 1.0 M KOH, respectively. Furthermore, benefiting from excellent HER and OER activity, NFM-OVR/NF exhibits a remarkable OWS activity with cell voltages of 1.44 V and 1.77 V at 10 and 1000 mA cm-2 in 1.0 M KOH, and displays ultralong-term stability for 600 h at 500 mA cm-2, while remaining durable for 300 h in an alkaline water electrolyzer in 30% KOH at 80 °C. The calculated price per gallon of gasoline equivalent for the produced H2 is $ 0.92, which is much lower than 2026 U.S. Department of Energy target ($ 2.00), demonstrating feasibility and practicability of NFM-OVR/NF for industrial applications.

2.
J Exp Bot ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39303008

RESUMO

Anthocyanins, a group of flavonoids, play diverse roles in plant growth and environmental adaptation. The biosynthesis and accumulation of anthocyanin are regulated by environmental cues, such as high light. However, the precise mechanism underlying anthocyanin biosynthesis under high light conditions remains largely unclear. Here, we report that the R3-MYB repressor MYB-LIKE 2 (MYBL2) negatively regulates high light-induced anthocyanin biosynthesis by repressing two R2R3-MYB activators, PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) and PAP2, which are core components of the MYB-bHLH-WD40 (MBW) complex. We found that MYBL2 interacts with PAP1/2 and reduces their transcriptional activation activities, thus disrupting the expression of key genes involved in anthocyanin biosynthesis, such as DIHYDROFLAVONOL 4-REDUCTASE (DFR) and TRANSPARENT TESTA 19 (TT19). Additionally, MYBL2 attenuates the transcriptional activation of PAP1 on its own expression, but not PAP2. Conversely, PAP1 collaborates with TT8, a bHLH member of the MBW complex, to activate MYBL2 transcription when excessive anthocyanins are accumulated. Taken together, our findings reveal a negative feedback regulatory module composed of MYBL2 and PAP1 that fine-tunes high light-induced anthocyanin biosynthesis through modulating MBW complex assembly.

3.
Plant Physiol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276362

RESUMO

Verticillium wilt (VW) caused by Verticillium dahliae (V. dahliae) is one of the most destructive diseases in cotton (Gossypium spp.). Histone acetylation plays critical roles in plant development and adaptive responses to biotic and abiotic stresses. However, the relevance of histone acetylation in cotton VW resistance remains largely unclear. Here, we identified Histone Deacetylase 5 (GhHDA5) from upland cotton (Gossypium hirsutum L.), as a negative regulator of VW resistance. GhHDA5 expression was responsive to V. dahliae infection. Silencing GhHDA5 in upland cotton led to improved resistance to V. dahliae, while heterologous expression of GhHDA5 in Arabidopsis (Arabidopsis thaliana) compromised V. dahliae tolerance. GhHDA5 repressed the expression of several lignin biosynthesis-related genes, such as 4-coumarate: CoA ligase gene Gh4CL3 and ferulate 5-hydroxylase gene GhF5H, through reducing the acetylation level of Histone H3 Lysine 9 and 14 (H3K9K14ac) at their promoter regions, thereby resulting in an increased deposition of lignin, especially S monomers, in the GhHDA5-silenced cotton plants. The silencing of GhF5H impaired cotton VW tolerance. Additionally, the silencing of GhHDA5 also promoted the production of reactive oxygen species (ROS), elevated the expression of several pathogenesis-related genes (PRs), and altered the content and signaling of the phytohormones salicylic acid (SA), jasmonic acid (JA) and strigolactones (SLs) after V. dahliae infection. Taken together, our findings suggest that GhHDA5 negatively regulates cotton VW resistance through modulating disease-induced lignification and the ROS- and phytohormone-mediated defense response.

4.
PLoS Pathog ; 20(9): e1012535, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39255317

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 and 2. KSHV vCyclin encoded by ORF72, is the homolog of cellular cyclinD2. KSHV vCyclin can regulate virus replication and cell proliferation by constitutively activating cellular cyclin-dependent kinase 6 (CDK6). However, the regulatory mechanism of KSHV vCyclin has not been fully elucidated. In the present study, we identified a host protein named protein arginine methyltransferase 5 (PRMT5) that interacts with KSHV vCyclin. We further demonstrated that PRMT5 is upregulated by latency-associated nuclear antigen (LANA) through transcriptional activation. Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) of PRMT5 inhibited the cell cycle progression and cell proliferation of KSHV latently infected tumor cells. Mechanistically, PRMT5 methylates vCyclin symmetrically at arginine 128 and stabilizes vCyclin in a methyltransferase activity-dependent manner. We also show that the methylation of vCyclin by PRMT5 positively regulates the phosphorylate retinoblastoma protein (pRB) pathway. Taken together, our findings reveal an important regulatory effect of PRMT5 on vCyclin that facilitates cell cycle progression and proliferation, which provides a potential therapeutic target for KSHV-associated malignancies.


Assuntos
Ciclo Celular , Proliferação de Células , Herpesvirus Humano 8 , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Humanos , Herpesvirus Humano 8/metabolismo , Herpesvirus Humano 8/fisiologia , Metilação , Antígenos Virais/metabolismo , Antígenos Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Ciclina D2/metabolismo , Células HEK293 , Replicação Viral/fisiologia , Sarcoma de Kaposi/virologia , Sarcoma de Kaposi/metabolismo , Proteínas Nucleares
5.
Viruses ; 16(5)2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38793630

RESUMO

During viral infection, the innate immune system utilizes a variety of specific intracellular sensors to detect virus-derived nucleic acids and activate a series of cellular signaling cascades that produce type I IFNs and proinflammatory cytokines and chemokines. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus that has been associated with a variety of human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Infection with KSHV activates various DNA sensors, including cGAS, STING, IFI16, and DExD/H-box helicases. Activation of these DNA sensors induces the innate immune response to antagonize the virus. To counteract this, KSHV has developed countless strategies to evade or inhibit DNA sensing and facilitate its own infection. This review summarizes the major DNA-triggered sensing signaling pathways and details the current knowledge of DNA-sensing mechanisms involved in KSHV infection, as well as how KSHV evades antiviral signaling pathways to successfully establish latent infection and undergo lytic reactivation.


Assuntos
DNA Viral , Herpesvirus Humano 8 , Imunidade Inata , Transdução de Sinais , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/fisiologia , Humanos , DNA Viral/metabolismo , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/metabolismo , Sarcoma de Kaposi/virologia , Nucleotidiltransferases/metabolismo , Interações Hospedeiro-Patógeno , Animais , Proteínas de Membrana/metabolismo , Proteínas Nucleares , Fosfoproteínas
6.
Adv Mater ; 36(28): e2401880, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38655767

RESUMO

Cost-effective transition metal chalcogenides are highly promising electrocatalysts for both alkaline and acidic hydrogen evolution reactions (HER). However, unsatisfactory HER kinetics and stability have severely hindered their applications in industrial water electrolysis. Herein, a nanoflowers-shaped W-doped cubic/orthorhombic phase-mixed CoSe2 catalyst ((c/o)-CoSe2-W) is reported. The W doping induces spontaneous phase transition from stable phase cubic CoSe2 (c-CoSe2) to metastable phase orthorhombic CoSe2, which not only enables precise regulation of the ratio of two phases but also realizes W doping at the interfaces of two phases. The (c/o)-CoSe2-W catalyst exhibits a Pt-like HER activity in both alkaline and acidic media, with record-low HER overpotentials of 29.8 mV (alkaline) and 35.9 mV (acidic) at 10 mA cm-2, respectively, surpassing the vast majority of previously reported non-precious metal electrocatalysts for both alkaline and acidic HER. The Pt-like HER activities originate from the formation of Co-Se-W active species on the c-CoSe2 side at the phase interface, which effectively modulates electron structures of active sites, not only enhancing H2O adsorption and dissociation at Co sites but also optimizing H* adsorption to ΔGH* ≈ 0 at W sites. Benefiting from the abundant phase interfaces, the catalyst also displays outstanding long-term durability in both acidic and alkaline media.

7.
J Gene Med ; 26(1): e3599, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37800684

RESUMO

Lung adenocarcinoma (LUAD), a prominent lung cancer subtype, has an underexplored relationship with PANoptosis, a recently discovered mode of tumour cell death. This study incorporated iron death, copper death, scorch death, necrotizing apoptosis and bisulfide death into a pan-death gene set (PANoptosis) and conducted single-cell analysis of scRNA-seq data from 11 LUAD samples. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Univariate COX regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen PANoptosis key genes for constructing an LUAD risk model. The model's prognostic performance was evaluated using survival curves, risk scores and validation in the Gene Expression Omnibus database. The study also explored the correlation between risk scores, tumour biological function, immunotherapy, drug sensitivity and immune infiltration. The SMS gene in the PANoptosis model was silenced in two LUAD cell lines for cellular validation. Single-cell analysis revealed eight major cell types and several PANoptosis genes significantly associated with LUAD survival. The risk model demonstrated strong prognostic performance and association with immune infiltration, suggesting PANoptosis involvement in LUAD tumour immunity. Cellular validation further supported these findings. The PANoptosis key risk genes are believed to be closely related to the tumour microenvironment and immune regulation of LUAD, potentially providing valuable insights for early diagnosis and clinical treatment, and broader applications in other tumours and complex diseases.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Microambiente Tumoral/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Aprendizado de Máquina
8.
Pharmaceutics ; 15(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37765205

RESUMO

The most common method for establishing bioequivalence (BE) is to demonstrate similarity of concentration-time profiles in the systemic circulation, as a surrogate to the site of action. However, similarity of profiles from two formulations in the systemic circulation does not imply similarity in the gastrointestinal tract (GIT) nor local BE. We have explored the concordance of BE conclusions for a set of hypothetical formulations based on budesonide concentration profiles in various segments of gut vs. those in systemic circulation using virtual trials powered by physiologically based pharmacokinetic (PBPK) models. The impact of Crohn's disease on the BE conclusions was explored by changing physiological and biological GIT attributes. Substantial 'discordance' between local and systemic outcomes of VBE was observed. Upper GIT segments were much more sensitive to formulation changes than systemic circulation, where the latter led to false conclusions for BE. The ileum and colon showed a lower frequency of discordance. In the case of Crohn's disease, a product-specific similarity factor might be needed for products such as Entocort® EC to ensure local BE. Our results are specific to budesonide, but we demonstrate potential discordances between the local gut vs. systemic BE for the first time.

9.
Medicine (Baltimore) ; 102(35): e34793, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657052

RESUMO

BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Hipertensão , Humanos , Epistaxe , Proteinúria/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
10.
J Clin Med ; 12(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37298023

RESUMO

(1) Background: At present, the efficacy and safety of thoracic radiotherapy (TRT) after chemo-immunotherapy (CT-IT) in patients with extensive-stage small-cell lung cancer (ES-SCLC) still remain unclear. The purpose of this study was to evaluate the role of TRT after CT-IT in patients with ES-SCLC. (2) Methods: From January 2020 to October 2021, patients with ES-SCLC treated with first-line anti-PD-L1 antibody plus platinum-etoposide chemotherapy were enrolled retrospectively. The survival data and adverse events data of patients treated with or without TRT after CT-IT were collected for analysis. (3) Results: A total of 118 patients with ES-SCLC treated with first-line CT-IT were retrospectively enrolled, with 45 patients with TRT and 73 patients without TRT after CT-IT. The median PFS and OS in the CT-IT + TRT group and CT-IT only group were 8.0 months versus 5.9 months (HR = 0.64, p = 0.025) and 22.7 months versus 14.7 months (HR = 0.52, p = 0.015), respectively. The median PFS and OS in all 118 patients treated with first-line CT-IT were 7.2 and 19.8 months with an ORR of 72.0%. In multivariate analyses, liver metastasis and response to CT-IT were shown to be independent prognostic factors of PFS (p < 0.05), while liver metastasis and bone metastasis were independent predictive factors of OS (p < 0.05). Although TRT was significantly associated with better PFS and OS in univariate analysis, the association of TRT and OS failed to reach statistical significance (HR = 0.564, p = 0.052) in multivariate analysis. There was no significant difference in adverse events (AEs) between two treatment groups (p = 0.58). (4) Conclusions: ES-SCLC patients treated with TRT after first-line CT-IT had prolonged PFS and OS with an acceptable safety profile. Further prospective randomized studies are necessary to explore the efficacy and safety of this treatment modality for ES-SCLC in future.

12.
Biosensors (Basel) ; 13(2)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36831994

RESUMO

Respiratory tract infections such as the ongoing coronavirus disease 2019 (COVID-19) has seriously threatened public health in the last decades. The experience of fighting against the epidemic highlights the importance of user-friendly and accessible point-of-care systems for nucleic acid (NA) detection. To realize low-cost and multiplexed point-of-care NA detection, a swing-assisted multiplexed analyzer for point-of-care respiratory tract infection testing (SMART) was proposed to detect multiple respiratory tract pathogens using visible loop-mediated isothermal amplification. By performing hand-swing movements to generate acceleration force to distribute samples into reaction chambers, the design of the SMART system was greatly simplified. By using different format of chips and integrating into a suitcase, this system can be applied to on-site multitarget and multi-sample testing. Three targets including the N and Orf genes of SARS-CoV-2 and the internal control were simultaneously analyzed (limit of detection: 2000 copies/mL for raw sample; 200 copies/mL for extracted sample). Twenty-three clinical samples with eight types of respiratory bacteria and twelve COVID-19 clinical samples were successfully detected. These results indicate that the SMART system has the potential to be further developed as a versatile tool in the diagnosis of respiratory tract infection.


Assuntos
COVID-19 , Infecções Respiratórias , Humanos , SARS-CoV-2 , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos
13.
J Immunol Res ; 2022: 8087622, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249422

RESUMO

Background: Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with bad prognosis. The association between GC and cuprotosis-related genes has not been reported. Methods: The clinical and RNA expression of patients with GC were downloaded from TCGA database. The CIBERSORT package was used to quantify the abundance of specific cell types. Using the Cox regression analysis, we conducted a prognostic nomogram model based on cuprotosis-related differential genes in GC. We evaluated the prognostic power of this model using the Kaplan-Meier (K-M) survival curve analysis, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve analysis. Results: The plasma cells, monocytes, and mast cells in GC tissue were significantly less than those in adjacent tissue (p < 0.05), while T cell CD4 memory activated macrophage M0, macrophage M1, and macrophages in GC tissue. The number of M2 was significantly more than that in the adjacent tissue (p < 0.05). Additionally, GC patients in the test group, the training group, and all the sample groups had shorter survival time with the increase of the risk factor (p < 0.05). The nomogram of GC based on cuprotosis prognosis-related genes was conducted. The AUC of the nomogram to predict 1-, 3-, and 5-year survival rate was 0.618, 0.618, and 0.625, respectively. Conclusion: A novel cuprotosis-related gene signature impacts on the prognosis of GC. Our research provides new insights and potential targets for studying the link between GC and cuprotosis point, thereby providing new insights into understanding the molecular mechanism of GC.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/metabolismo , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
14.
Xenobiotica ; 52(8): 943-956, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36222269

RESUMO

Non-specific binding in in vitro metabolism systems leads to an underestimation of the true intrinsic metabolic clearance of compounds being studied. Therefore in vitro binding needs to be accounted for when extrapolating in vitro data to predict the in vivo metabolic clearance of a compound. While techniques exist for experimentally determining the fraction of a compound unbound in in vitro metabolism systems, early in drug discovery programmes computational approaches are often used to estimate the binding in the in vitro system.Experimental fraction unbound data (n = 60) were generated in liver microsomes (fumic) from five commonly used pre-clinical species (rat, mouse, dog, minipig, monkey) and humans. Unbound fraction in incubations with mouse, rat or human hepatocytes was determined for the same 60 compounds. These data were analysed to determine the relationship between experimentally determined binding in the different matrices and across different species. In hepatocytes there was a good correlation between fraction unbound in human and rat (r2=0.86) or mouse (r2=0.82) hepatocytes. Similar correlations were observed between binding in human liver microsomes and microsomes from rat, mouse, dog, Göttingen minipig or monkey liver microsomes (r2 of >0.89, n = 51 - 52 measurements in different species). Physicochemical parameters (logP, pKa and logD) were predicted for all evaluated compounds. In addition, logP and/or logD were measured for a subset of compounds.Binding to human hepatocytes predicted using 5 different methods was compared to the measured data for a set of 59 compounds. The best methods evaluated used measured microsomal binding in human liver microsomes to predict hepatocyte binding. The collated physicochemical data were used to predict the human fumic using four different in silico models for a set of 53-60 compounds. The correlation (r2) and root mean square error between predicted and observed microsomal binding was 0.69 & 0.20, 0.47 & 0.23, 0.56 & 0.21 and 0.54 & 0.26 for the Turner-Simcyp, Austin, Hallifax-Houston and Poulin models, respectively. These analyses were extended to include measured literature values for binding in human liver microsomes for a larger set of compounds (n=697). For the larger dataset of compounds, microsomal binding was well predicted for neutral compounds (r2=0.67 - 0.70) using the Poulin, Austin, or Turner-Simcyp methods but not for acidic or basic compounds (r2<0.5) using any of the models. While the lipophilicity-based models can be used, the in vitro binding should be measured for compounds where more certainty is needed, using appropriately calibrated assays and possibly established weak, moderate, and strong binders as reference compounds to allow comparison across databases.


Assuntos
Hepatócitos , Microssomos Hepáticos , Animais , Cães , Humanos , Camundongos , Ratos , Haplorrinos , Hepatócitos/metabolismo , Taxa de Depuração Metabólica , Microssomos Hepáticos/metabolismo , Modelos Biológicos , Suínos , Porco Miniatura , Reprodutibilidade dos Testes
15.
PLoS Pathog ; 18(8): e1010744, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35914008

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus with the capacity to establish life-long latent infection. During latent infection, the viral genome persists as a circular episome that associates with cellular histones and exists as a nonintegrated minichromosome in the nucleus of infected cells. Chromatin structure and epigenetic programming are required for the proper control of viral gene expression and stable maintenance of viral DNA. However, there is still limited knowledge regarding how the host regulates the chromatin structure and maintenance of episomal DNA. Here, we found that the cellular protein structural maintenance of chromosome (SMC) complex SMC5/6 recognizes and associates with the KSHV genome to inhibit its replication. The SMC5/6 complex can bind to the KSHV genome and suppress KSHV gene transcription by condensing the viral chromatin and creating a repressive chromatin structure. Correspondingly, KSHV employs an antagonistic strategy by utilizing the viral protein RTA to degrade the SMC5/6 complex and antagonize the inhibitory effect of this complex on viral gene transcription. Interestingly, this antagonistic mechanism of RTA is evolutionarily conserved among γ-herpesviruses. Our work suggests that the SMC5/6 complex is a new host factor that restricts KSHV replication.


Assuntos
Herpesvirus Humano 8 , Proteínas Imediatamente Precoces , Infecção Latente , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/genética , Regulação Viral da Expressão Gênica , Herpesvirus Humano 8/fisiologia , Humanos , Proteínas Imediatamente Precoces/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transativadores , Ubiquitina/metabolismo , Latência Viral/genética , Replicação Viral/genética
16.
Cancer Cytopathol ; 130(12): 955-963, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35852302

RESUMO

BACKGROUND: Most human papillomavirus (HPV)-positive women recover from infections and do not develop cervical intraepithelial neoplasia (CIN) and cervical cancer. Additional triage approaches are needed to reduce unnecessary colposcopy referrals. The aim of this study is to determine the high-risk HPV prevalence in a hospital-based population and to evaluate the performance of p16/Ki-67 dual-stain test for the triage of high-risk HPV-positive women to detect precursor lesions and cervical cancer compared with the ThinPrep cytologic test (TCT). METHODS: In a hospital-based population, 100,801 women were provided with a primary HPV DNA test and only women with high-risk HPV infections were triaged using TCT and p16/Ki-67 dual-stain test. CIN2 or worse (≥CIN2) or CIN3 or worse (≥CIN3) were defined as the clinical end points. RESULTS: The p16/Ki-67 dual-stain indicated a statistically significant higher sensitivity (82.8% vs. 66.7%%), specificity (51.6% vs. 44.4%), positive predictive value (33.2% vs. 25.8%), negative predictive value (91.2% vs. 82.1%), and accuracy (58.6% vs. 49.4%) compared with TCT examination within ≥CIN2 cases. Similar patterns were observed for the ≥CIN3 end point. CONCLUSIONS: Our study demonstrated that p16/Ki-67 dual-stain test could achieve better performance compared with TCT examination for ≥CIN2 or ≥ CIN3 detection, representing a promising approach as a specific and efficient triage strategy for high-risk HPV-positive women.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Antígeno Ki-67 , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina , Corantes , Displasia do Colo do Útero/patologia , Triagem , Hospitais , Sensibilidade e Especificidade , Detecção Precoce de Câncer
17.
Entropy (Basel) ; 24(2)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35205460

RESUMO

In recent years, the pedestrian detection technology of a single 2D image has been dramatically improved. When the scene becomes very crowded, the detection performance will deteriorate seriously and cannot meet the requirements of autonomous driving perception. With the introduction of the multi-view method, the task of pedestrian detection in crowded or fuzzy scenes has been significantly improved and has become a widely used method in autonomous driving. In this paper, we construct a double-branch feature fusion structure, the first branch adopts a lightweight structure, the second branch further extracts features and gets the feature map obtained from each layer. At the same time, the receptive field is enlarged by expanding convolution. To improve the speed of the model, the keypoint is used instead of the entire object for regression without an NMS post-processing operation. Meanwhile, the whole model can be learned from end to end. Even in the presence of many people, the method can still perform better on accuracy and speed. In the standard of Wildtrack and MultiviewX dataset, the accuracy and running speed both perform better than the state-of-the-art model, which has great practical significance in the autonomous driving field.

18.
Entropy (Basel) ; 24(10)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37420346

RESUMO

In recent years, video stabilization has improved significantly in simple scenes, but is not as effective as it could be in complex scenes. In this study, we built an unsupervised video stabilization model. In order to improve the accurate distribution of key points in the full frame, a DNN-based key-point detector was introduced to generate rich key points and optimize the key points and the optical flow in the largest area of the untextured region. Furthermore, for complex scenes with moving foreground targets, we used a foreground and background separation-based approach to obtain unstable motion trajectories, which were then smoothed. For the generated frames, adaptive cropping was conducted to completely remove the black edges while maintaining the maximum detail of the original frame. The results of public benchmark tests showed that this method resulted in less visual distortion than current state-of-the-art video stabilization methods, while retaining greater detail in the original stable frames and completely removing black edges. It also outperformed current stabilization models in terms of both quantitative and operational speed.

19.
Poult Sci ; 100(7): 101137, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34111609

RESUMO

The avian leukosis virus (ALV) strain DL00766 was isolated from a farm in China. The phylogenetic analysis showed that env had the highest homology with the E subgroup reference strain, ranging from 94.5% to 94.9%, whereas gp85 had the highest homology with the B and E subgroups, which were 89.0% to 91.3% and 91.3% to 91.8%. In addition, point mutation analysis of gp85 showed that a 400 bp long fragment in gp85 of DL00766 had the highest homology with subgroup B, ranging from 90.1% to 97.5%, and only 82.7% to 83.1% with E subgroup. These results indicate, DL00766 may be an AVL subgroup E isolate with a subgroup B-like gp85 region. This is also the first finding that the E subgroup is used as a recombinant subject, and the subgroup B provides a recombinant virus of an exogenous gene.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Doenças das Aves Domésticas , Animais , Galinhas , China , Filogenia , Proteínas do Envelope Viral/genética
20.
Heart Lung Circ ; 30(2): 288-295, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32690359

RESUMO

BACKGROUND: Renal dysfunction is independently associated with increased early and late mortality after coronary artery bypass graft (CABG) surgery. Off-pump CABG (OPCABG) avoids postoperative complications from the cardiopulmonary bypass, but it is unclear how it is impacted by occult renal dysfunction (ORD). This study aimed to investigate the effects of ORD on early and late outcomes after OPCABG. METHODS: This retrospective and observational cohort study reviewed data on 1,188 patients who underwent first isolated OPCABG with normal serum creatinine (SCr) levels. According to preoperative estimated creatinine clearance (eCrCl) by the Cockcroft-Gault formula, the patients were divided into an ORD group (n=260, eCrCl <60 mL/min/1.73 m2) and a control group (n=928, eCrCl ≥60 mL/min/1.73 m2). RESULTS: The ORD patients presented with older age, higher incidence of small body surface area, hypertension, low preoperative eCrCl, cerebrovascular accident, peripheral vascular disease, New York Heart Association (NYHA) Ⅲ, and high risk score. The prevalence of hospital mortality, postoperative acute kidney injury (AKI), peak postoperative SCr, and prolonged hospital stay were greater in the ORD patients than the control patients. Multivariable logistic regression analysis showed that the ORD patients were at significantly higher risk of postoperative AKI (OR, 2.702; 95% CI, 1.994-3.662) and in-hospital mortality (OR, 2.884; 95% CI, 1.293-6.432). Multivariate Cox proportional hazard models confirmed that ORD was significantly associated with high later mortality (HR, 2.847; 95% CI, 1.262-6.425). CONCLUSIONS: Occult renal dysfunction is an independent risk factor for postoperative AKI in-hospital and later mortality in patients undergoing OPCABG with normal SCr levels.


Assuntos
Injúria Renal Aguda/etiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Taxa de Filtração Glomerular/fisiologia , Complicações Pós-Operatórias , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório
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