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1.
Cell Death Dis ; 15(4): 260, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609357

RESUMO

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Humanos , Feminino , Neoplasias da Mama/genética , Mama , Fosforilação , Regulação para Baixo , Microambiente Tumoral , Proteína A4 de Ligação a Cálcio da Família S100 , Anexinas , Fator de Transcrição STAT3
3.
Cancer Lett ; 588: 216764, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38431034

RESUMO

Immunotherapy based on PD-1/PD-L1 antagonists has been demonstrated to be efficacious in inducing tumor remission in patients with triple-negative breast cancer (TNBC). However, tumor immune evasion caused by the PD-1/PD-L1 pathway inhibits the immunotherapeutic effect of PD-1/PD-L1 inhibitors against TNBC. Therefore, identifying potential targets for blocking the PD-1/PD-L1 pathway is a compelling strategy for TNBC treatment. Here, we discovered that VGLL4 could inhibit PD-L1 transcription by suppressing STAT3 activation, thereby enhancing the efficacy of anti-PD-1 antibody immunotherapy in TNBC. Low expression of USP15, a deubiquitinating enzyme of VGLL4, was associated with reduced CD8+ T cell infiltration and poor prognosis in TNBC patients. USP15 was found to inhibit PD-L1 transcription, leading to increased CD8+ T cell infiltration and thus enhancing the efficacy of TNBC immunotherapy. Furthermore, SART3 regulated VGLL4 stability and PD-L1 transcription by influencing the nuclear translocation of USP15. In conclusion, our study provides new insights into the biological regulation of PD-L1, identifies a previously unrecognized regulator of this critical immune checkpoint, and highlights potential therapeutic targets for overcoming immune evasion in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Imunoterapia , Antígenos de Neoplasias/uso terapêutico , Proteínas de Ligação a RNA , Fatores de Transcrição/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
4.
Environ Toxicol ; 39(5): 3026-3039, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38317508

RESUMO

Long noncoding RNAs have been reported to be involved in the development of breast cancer. LINC01572 was previously reported to promote the development of various tumors. However, the potential biological function of LINC01572 in breast cancer remains largely unknown. R language was used to perform bioinformatic analysis of The Cancer Genome Atlas data. The expression level of RNAs was examined by RT-qPCR. The effect of knocking down or overexpression LINC01572 in triple-negative breast cancer (TNBC) cell lines was evaluated by detecting cell proliferation, migrant action. RNA immunoprecipitation assay and RNA pull-down assay were performed to explore the regulatory relationship between LINC01572, EIF4A3, and ß-catenin. Bioinformatics analysis identifies LINC01572 as an oncogene of breast cancer. LINC01572 is over-expressed in TNBC tissues and cell lines, correlated with poor clinical prognosis in BC patients. Cell function studies confirmed that LINC01572 facilitated the proliferation and migration of TNBC cells in both vivo and vitro. Mechanistically, ß-catenin mRNA and EIF4A3 combine spatially to form a complex, LINC01572 helps transport this complex from the nucleus to the cytoplasm, thereby facilitating the translation of ß-catenin. Our findings confirm that LINC01572 acts as a tumor promoter and may act as a biomarker in TNBC. In addition, novel molecular regulatory relationships involving LINC01572/EIF4A3/ß-catenin are critical to the development of TNBC, which led to a new understanding of the mechanisms of TNBC progression and shows a new target for precision treatment for TNBC.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias de Mama Triplo Negativas/genética , RNA Mensageiro/genética , Linhagem Celular Tumoral , RNA , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo
5.
Cell Signal ; 117: 111112, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38387687

RESUMO

Breast cancer (BC) is the most prevalent malignant tumor in women worldwide with high morbidity and mortality. NSUN2, a crucial RNA methyltransferase, plays a pivotal role in regulating the proliferation and metastasis of tumor cells. Our study demonstrated that NSUN2 is upregulated in BC tissues and cell lines, and its high expression is associated with a poor prognosis in BC patients. Knockout of NSUN2 exerted inhibitory effects on the proliferation and migration of BC cells in vitro and in vivo. Mechanistic investigations revealed that the RNA-binding protein ELAVL1 can bind to NSUN2 mRNA and increase its stability. Additionally, we identified HOST2, a long non-coding RNA, as a key player in blocking the ubiquitin-dependent proteasomal degradation of ELAVL1, thereby influencing the stability of NSUN2 mRNA. In conclusion, this study revealed for the first time that HOST2 maintains NSUN2 mRNA stability by blocking ubiquitin-dependent degradation of ELAVL1, which in turn affects BC progression. HOST2/ELAVL1/NSUN2 oncogenic cascade has the potential to be a novel therapeutic target for BC.


Assuntos
Neoplasias da Mama , Proteína Semelhante a ELAV 1 , Metiltransferases , RNA Longo não Codificante , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismo , Regulação Neoplásica da Expressão Gênica , Metiltransferases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Ubiquitinas/metabolismo
6.
Neurosci Bull ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321347

RESUMO

Synapse organizers are essential for the development, transmission, and plasticity of synapses. Acting as rare synapse suppressors, the MAM domain containing glycosylphosphatidylinositol anchor (MDGA) proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex. A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with autism. However, MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory synapses. Differentiating the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective strategy. To address this, we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal neurons. Here we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature hippocampus. Conditional deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials, vesicular glutamate transporter 1 intensity, and neuronal excitability. These effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter intensity. Functionally, evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic inputs. At a behavioral level, memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired, consistent with deficits in long-term potentiation in the CA3-CA1 pathway. Social affiliation, a behavioral analog of social deficits in autism, was similarly compromised. These results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits, thereby optimizing this network for plasticity, cognition, and social behaviors.

7.
J Cancer ; 15(4): 889-907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230219

RESUMO

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

8.
Sheng Li Xue Bao ; 75(5): 703-713, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37909141

RESUMO

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Hiper-Homocisteinemia , Humanos , Endotélio Vascular , Homocisteína/metabolismo , Hiper-Homocisteinemia/complicações , Estresse Oxidativo , Fatores de Risco
9.
Open Biol ; 13(11): 230172, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37963545

RESUMO

The halophilic zooplankton brine shrimp Artemia has been used as an experimental animal in multidisciplinary studies. However, the reproductive patterns and its regulatory mechanisms in Artemia remain unclear. In this study, the ovarian development process of parthenogenetic Artemia (A. parthenogenetica) was divided into five stages, and oogenesis or egg formation was identified in six phases. The oogenesis mode was assumed to be polytrophic. We also traced the dynamic translocation of candidate germline stem cells (cGSCs) using EdU labelling and elucidated several key cytological events in oogenesis through haematoxylin and eosin staining and fluorescence imaging. Distinguished from the ovary structure of insects and crustaceans, Artemia germarium originated from ovariole buds and are located at the base of the ovarioles. RNA-seq based on five stages of ovarian development identified 2657 upregulated genes related to reproduction by pair-to-pair comparison. Gbb, Dpp, piwi, vasa, nanos, VgA and VgR genes associated with cGSCs recognition and reproductive development were screened and verified using qPCR. Silencing of the VgR gene in A. parthenogenetica (Ap-VgR) at ovarian development Stage II led to a low level of gene expression (less than 10%) within 5 days, which resulted in variations in oogenesis-related gene expression and significantly inhibited vitellogenesis, impeded oocyte maturation, and eventually decreased the number of offspring. In conclusion, we have illustrated the patterns of ovarian development, outlined the key spatio-temporal features of oogenesis and identified the negative impacts of VgR gene knockdown on oogenesis using A. parthenogenetica as an experimental animal. The findings of this study also lay a foundation for the further study of reproductive biology of invertebrates.


Assuntos
Artemia , Oogênese , Animais , Feminino , Artemia/genética , Oogênese/genética , Ovário , Inativação Gênica , Fertilidade/genética
10.
Integr Med Res ; 12(4): 101004, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38033651

RESUMO

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

11.
Front Oncol ; 13: 1166666, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841425

RESUMO

Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA in cells mostly functioning to silence the target mRNAs. In the current study, a miRNA screening analysis identified miR-186-5p to be downregulated in human breast cancer tumors. Functional studies in vitro demonstrated that overexpression of miR-186-5p inhibited cellular proliferation and induced cell apoptosis in multiple breast cancer cell lines including MDA-MB-231, MCF-7, and BT549 cells. Transplantation of the miR-186-5p-overexpressing MDA-MB-231 cells into nude mice significantly inhibited mammary tumor growth in vivo. Sequence blast analysis predicted annexin A9 (ANXA9) as a target gene of miR-186-5p, which was validated by luciferase reporter assay, QRT-PCR analysis, and western blot. Additional gene expression analysis of clinical tumor samples indicated a negative correlation between miR-186-5p and ANXA9 in human breast cancer. Knockdown of ANXA9 mimicked the phenotype of miR-186-5p overexpression. Reintroduction of ANXA9 back rescued the miR-186-5p-induced cell apoptosis. In addition, miR-186-5p decreased the expression of Bcl-2 and increased the expression of p53, suggesting a mechanism regulating miR-186-5p-induced cellular apoptosis. In summary, our study is the first to demonstrate miR-186-5p-ANXA9 signaling in suppressing human breast cancer. It provided a potential therapeutic target in breast cancer.

12.
Medicine (Baltimore) ; 102(38): e34753, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37747014

RESUMO

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases. Gene expression profile data of GSE136701 were downloaded from the GEO database and subjected to WGCNA and DEG analysis to screen for significant modules and targets of myopia. Intersectional targets of myopia and DZP and core targets of myopia were analyzed through the String database. The GO and KEGG enrichment analyses of the interested targets were conducted. Cibersort algorithm was used for immune infiltration analysis to investigate the immunomodulatory functions of DZP on myopia. Autodock was used to dock the important targets and active constituents. Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents (Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester, and Naringenin) were identified from DZP. In pathways identified by the GO and KEGG enrichment analyses, "ATP metabolic process" and "AGE-RAGE diabetes complication signaling" pathways were closely related to the mechanisms of DZP in the treatment of myopia. Molecular docking showed that both the intersectional targets and core targets of myopia could bind stably and spontaneously with the active constituents of DZP. This study suggested that the mechanisms of DZP in the treatment of myopia were related to active constituents: Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester and Naringenin, intersectional targets: STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, and HSP90AA1, core targets of myopia: MIP and LGSN, AGE-RAGE signaling pathway, positive regulation of ATP metabolic process pathway and immunomodulatory functions.


Assuntos
Medicamentos de Ervas Chinesas , Miopia , Humanos , Trifosfato de Adenosina/metabolismo , Biologia Computacional , Simulação de Acoplamento Molecular , Miopia/tratamento farmacológico , Miopia/genética , Miopia/imunologia , Quercetina , Fatores de Transcrição , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico
13.
Epigenomics ; 15(15): 769-795, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37718931

RESUMO

Homocysteine has a wide range of biological effects. However, the specific molecular mechanism of its pathogenicity is still unclear. The diseases induced by hyperhomocysteinemia (HHcy) are called homocysteine-related diseases. Clinical treatment of HHcy is mainly through folic acid and B-complex vitamins, which are not effective in reducing the associated end point events. Epigenetics is the alteration of heritable genes caused by DNA methylation, histone modification, noncoding RNAs and chromatin remodeling without altering the DNA sequence. In recent years the role of epigenetics in homocysteine-associated diseases has been gradually discovered. This article summarizes the latest evidence on the role of epigenetics in HHcy, providing new directions for its prevention and treatment.


Assuntos
Metilação de DNA , Epigênese Genética , Humanos , Epigenômica , Montagem e Desmontagem da Cromatina , Homocisteína
14.
Appl Opt ; 62(24): 6366-6374, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706828

RESUMO

A symmetry tunable triangular waveform photonic generator based on channelized frequency synthesis is proposed and studied. The generator adopts a multichannel system architecture and harmonic amplitude control algorithm to physically isolate each subchannel. In a single subchannel, quadrature phase shift keying modulation and coherent dual-wavelength balanced detection are used to realize optical upconversion and suppress mixing interference in the process of frequency conversion. Therefore, the model has the characteristics of a high-order Fourier series fitting tunable function waveform output. The analysis results show that the Fourier series harmonic coefficients can be adjusted flexibly by the multivariable joint regulation algorithm. The relationship between the variables is analyzed and discussed. The feasibility of the scheme is verified by optical simulation; when the rms error (RMSE)≤0.03, a 20%-80% tunable symmetry triangular waveform can be obtained.

15.
Front Pediatr ; 11: 1180694, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601135

RESUMO

Background: Chinese medicine belly button application (CMBBA) has been used to treat childhood diarrhea (CD) in several randomized controlled trials (RCTs), but its effectiveness and combination strategy still need to be clarified. Therefore, we aimed to evaluate the effectiveness, safety, and the optimal combination strategy of CMBBA in treating CD. Methods: Up until January 2023, we searched for studies that met our inclusion criteria in six databases, including PubMed, the Cochrane Library, Chinese SinoMed, CNKI, VIP, and Wanfang. Heterogeneity was quantified using I2 statistics. A methodological evaluation was performed using the Cochrane Risk Bias Tool 2.0. The Confidence in Network Meta-Analysis online software was employed to evaluate evidence grading. A minimally contextualized framework was used to provide a comprehensive conclusion for the network meta-analysis. This study protocol was registered with PROSPERO. Results: We analyzed data from 33 RCTs that included 4,490 children with diarrhea. In terms of clinical effectiveness, CMBBA plus montmorillonite powder plus anti-infectives may be the most effective treatment option for children with diarrhea and concurrent infection according to a minimally contextualized framework. Either exclusive use of CMBBA or CMBBA in combination with modern medicine was beneficial in reducing the time to diarrhea disappearance (MD = -1.33 days, 95% CI: -1.59 to -1.08, Z = -10.103, p < 0.001) compared to modern medicine exclusively, and the difference was statistically significant. The combined usage of CMBBA could shorten the recovery time of dehydration by an average of 0.74 days (MD = -0.74 days, 95% CI: -1.10 to -0.37, Z = -3.931.103, p < 0.001). While some studies have reported mild allergic reactions and mild abdominal pain after CMBBA use, these symptoms can be cured in a relatively short period of time. Conclusions: The combination of CMBBA, montmorillonite powder, and anti-infectives may provide superior clinical effectiveness for children with diarrhea and concurrent infection. To treat CD, CMBBA can be used effectively and safely. However, the findings must be interpreted with cautiously due to the limited number of clinical trials and the low quality of the studies. In addition, the choice of treatment plan should also be based on the specific conditions of each patient. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022380694.

16.
IEEE Trans Image Process ; 32: 4443-4458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37527316

RESUMO

In this paper, we propose a scribble-based video colorization network with temporal aggregation called SVCNet. It can colorize monochrome videos based on different user-given color scribbles. It addresses three common issues in the scribble-based video colorization area: colorization vividness, temporal consistency, and color bleeding. To improve the colorization quality and strengthen the temporal consistency, we adopt two sequential sub-networks in SVCNet for precise colorization and temporal smoothing, respectively. The first stage includes a pyramid feature encoder to incorporate color scribbles with a grayscale frame, and a semantic feature encoder to extract semantics. The second stage finetunes the output from the first stage by aggregating the information of neighboring colorized frames (as short-range connections) and the first colorized frame (as a long-range connection). To alleviate the color bleeding artifacts, we learn video colorization and segmentation simultaneously. Furthermore, we set the majority of operations on a fixed small image resolution and use a Super-resolution Module at the tail of SVCNet to recover original sizes. It allows the SVCNet to fit different image resolutions at the inference. Finally, we evaluate the proposed SVCNet on DAVIS and Videvo benchmarks. The experimental results demonstrate that SVCNet produces both higher-quality and more temporally consistent videos than other well-known video colorization approaches. The codes and models can be found at https://github.com/zhaoyuzhi/SVCNet.

17.
Redox Biol ; 65: 102837, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37544244

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar-/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.


Assuntos
Infecções por Bunyaviridae , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Humanos , Animais , Camundongos , Espécies Reativas de Oxigênio , Infecções por Bunyaviridae/metabolismo , Antioxidantes , Glicoproteínas/metabolismo , Trombocitopenia/metabolismo , Ativação Plaquetária
18.
Biomacromolecules ; 24(8): 3647-3656, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37462907

RESUMO

A series of cellulose-graft-diblock bottlebrush copolymer elastomers (cellulose-graft-poly(n-butyl acrylate)-block-poly(methyl methacrylate) (Cell-g-PBA-b-PMMA)) with short side chains were synthesized via successive atom transfer radical polymerization (ATRP) to study the influence of varying compositions and lengths of the graft diblock side chains on microphase morphologies and properties. The microphase-separated morphologies from misaligned spheres to cylinders were observed by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS) measurements. These bottlebrush copolymer elastomers possessed thermal stability and enhanced mechanical properties because the PMMA outer block could self-assemble into hard microdomains, which served as physical cross-links. The viscoelastic responses of these bottlebrush copolymers within the linear viscoelastic (LVE) regime were carried out by the oscillatory shear rheology. The time-temperature superposition (tTs) principle was applied to construct the master curves of the dynamic moduli, and the sequential relaxation of dense bottlebrush copolymers with different PMMA hard outer block lengths was analyzed. The rheological behaviors in this work could be utilized to build up the connection of microstructures and properties for the application of these bottlebrush copolymers as high-performance thermoplastic elastomers.


Assuntos
Elastômeros , Nanoestruturas , Elastômeros/química , Celulose/química , Polimetil Metacrilato/química , Espalhamento a Baixo Ângulo , Difração de Raios X , Polímeros/química , Nanoestruturas/química , Reologia
19.
J Colloid Interface Sci ; 647: 296-305, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37262992

RESUMO

Constructing carbon electrodes with abundant heteroatoms and appropriate graphitic interlayer spacing remains a major challenge for achieving high gravimetric and volumetric potassium storage capacities with fast kinetics. Herein, we constructed 3D graphene-like N, F dual-doped carbon sheets induced by Ni template (N, F-CNS-Ni) with dense structure and rich active sites, providing a promising approach to address the facing obstacles. Highly reversible K-ion insertion/extraction is realized in the graphitic carbon structure, and K-adsorption capability is enhanced by introducing N/F heteroatoms. As a result, the N, F-CNS-Ni electrode exhibits ultrahigh gravimetric and volumetric capacities of 404.5 mA h g-1 and 281.3 mA h cm-3 at 0.05 A/g, respectively, and a superb capacity of 259.3 mA h g-1 with a capacity retention ratio of 90 % even after 600 cycles at 5 A/g. This work presents a simple Ni-based template method to prepare graphene-like carbon nanosheets with high packing density and rich heteroatoms, and offers mechanism insight for achieving superior K-ion storage.

20.
Front Public Health ; 11: 1167490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234763

RESUMO

Objective: The goal of the present study was to investigate gender differences in disability-free life expectancy (DFLE) and DFLE/LE ratio among older adults in China; portray changing trend from 2010 to 2020; and discuss the implications for public policies. Methods: Mortality data and disability rate data were derived from the Sixth China Population Census in 2010 and the Seventh China Population Census in 2020. The study assessed disability status of older adults based on self-assessment health in the above censuses. Life table and Sullivan method were used to estimate LE, DFLE, and DFLE/LE ratio by gender. Results: DFLE increased from 19.33 to 21.78 years for 60-year-old males, while from 21.94 to 24.80 years for 60-year-old females, from 2010 to 2020, respectively. DFLE/LE ratio was 96.40% for 60-year-old males and 94.86% for 60-year-old females in 2010, while DFLE/LE ratio was 96.63% for 60-year-old males and 95.44% for 60-year-old females in 2020, respectively. In terms of gender differences in DFLE/LE ratio, men aged 60 are 1.19 percentage points higher than women at the same age; men aged 70 are 1.71 percentage points higher than women; men aged 80 are 2.87 percentage points higher than women. Conclusion: From 2010 to 2020, the DFLE of China's male and female older adults increased simultaneously with the increase of LE, and the DFLE/LE ratio also increased. However, the DFLE/LE ratio of female older adults is lower than that of male at the same age, and this gender difference is narrowing over the decade but has not yet been eliminated, especially the health disadvantage of female older adults among the oldest old age group (age 80 and above) is more prominent.


Assuntos
Pessoas com Deficiência , Expectativa de Vida Saudável , Idoso de 80 Anos ou mais , Humanos , Masculino , Feminino , Idoso , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Fatores Sexuais , Expectativa de Vida , China/epidemiologia
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