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1.
J Biol Chem ; 300(2): 105610, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159847

RESUMO

Many metabolic diseases are caused by disorders of lipid homeostasis. CIDEC, a lipid droplet (LD)-associated protein, plays a critical role in controlling LD fusion and lipid storage. However, regulators of CIDEC remain largely unknown. Here, we established a homogeneous time-resolved fluorescence (HTRF)-based high-throughput screening method and identified LPXN as a positive regulatory candidate for CIDEC. LPXN and Hic-5, the members of the Paxillin family, are focal adhesion adaptor proteins that contribute to the recruitment of specific kinases and phosphatases, cofactors, and structural proteins, participating in the transduction of extracellular signals into intracellular responses. Our data showed that Hic-5 and LPXN significantly increased the protein level of CIDEC and enhanced CIDEC stability not through triacylglycerol synthesis and FAK signaling pathways. Hic-5 and LPXN reduced the ubiquitination of CIDEC and inhibited its proteasome degradation pathway. Furthermore, Hic-5 and LPXN enlarged LDs and promoted lipid storage in adipocytes. Therefore, we identified Hic-5 and LPXN as novel regulators of CIDEC. Our current findings also suggest intervention with Hic-5 and LPXN might ameliorate ectopic fat storage by enhancing the lipid storage capacity of white adipose tissues.


Assuntos
Adipócitos , Proteínas Reguladoras de Apoptose , Moléculas de Adesão Celular , Proteínas com Domínio LIM , Adipócitos/metabolismo , Gotículas Lipídicas/metabolismo , Ubiquitinação , Células HEK293 , Células HeLa , Humanos , Proteínas com Domínio LIM/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo
2.
J Cell Sci ; 136(15)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37461827

RESUMO

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.


Assuntos
Complexo de Golgi , Proteínas de Membrana , Membrana Celular/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Membrana/metabolismo , Transporte Proteico
3.
J Immunol ; 210(1): 72-81, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36426999

RESUMO

Fish possess a powerful IFN system to defend against aquatic virus infections. Nevertheless, spring viremia of carp virus (SVCV) causes large-scale mortality in common carp and significant economic losses to aquaculture. Therefore, it is necessary to investigate the strategies used by SVCV to escape the IFN response. In this study, we show that the SVCV nucleoprotein (N protein) negatively regulates cellular IFN production by degrading stimulator of IFN genes (STING) via the autophagy-lysosome-dependent pathway. First, overexpression of N protein inhibited the IFN promoter activation induced by polyinosinic-polycytidylic acid and STING. Second, the N protein associated with STING and experiments using a dominant-negative STING mutant demonstrated that the N-terminal transmembrane domains of STING were indispensable for this interaction. Then, the N protein degraded STING in a dose-dependent and autophagy-lysosome-dependent manner. Intriguingly, in the absence of STING, individual N proteins could not elicit host autophagic flow. Furthermore, the autophagy factor Beclin1 was found to interact with the N protein to attenuate N protein-mediated STING degradation after beclin1 knockdown. Finally, the N protein remarkably weakened STING-enhanced cellular antiviral responses. These findings reveal that SVCV uses the host autophagic process to achieve immune escape, thus broadening our understanding of aquatic virus pathogenesis.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Rhabdoviridae , Rhabdoviridae , Animais , Proteínas do Nucleocapsídeo , Viremia , Proteína Beclina-1 , Rhabdoviridae/fisiologia , Lisossomos , Autofagia
4.
Fish Shellfish Immunol ; 149: 109568, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636741

RESUMO

Pompano fishes have been widely farmed worldwide. As a representative commercial marine species of the Carangidae family, the golden pompano (Trachinotus blochii) has gained significant popularity in China and worldwide. However, because of rapid growth and high-density aquaculture, the golden pompano has become seriously threatened by various diseases. Cell lines are the most cost-effective resource for in vitro studies and are widely used for physiological and pathological research owing to their accessibility and convenience. In this study, we established a novel immortal cell line, GPF (Golden pompano fin cells). GPF has been passaged over 69 generations for 10 months. The morphology, adhesion and extension processes of GPF were evaluated using light and electron microscopy. GPF cells were passaged every 3 days with L-15 containing 20 % fetal bovine serum (FBS) at 1:3. The optimum conditions for GPF growth were 28 °C and a 20 % FBS concentration. DNA sequencing of 18S rRNA and mitochondrial 16S rRNA confirmed that GPF was derived from the golden pompano. Chromosomal analysis revealed that the number pattern of GPF was 48 chromosomes. Transfection experiments demonstrated that GPF could be utilized to express foreign genes. Furthermore, heavy metals (Cd, Cu, and Fe) exhibited dose-dependent cytotoxicity against GPF. After polyinosinic-polycytidylic acid (poly I:C) treatment, transcription of the retinoic acid-inducible gene I-like receptor (RLR) pathway genes, including mda5, mita, tbk1, irf3, and irf7 increased, inducing the expression of interferon (IFN) and anti-viral proteins in GPF cells. In addition, lipopolysaccharide (LPS) stimulation up-regulated the expression of inflammation-related factors, including myd88, irak1, nfκb, il1ß, il6, and cxcl10 expression. To the best of our knowledge, this is the first study on the immune response signaling pathways of the golden pompano using an established fin cell line. In this study, we describe a preliminary investigation of the GPF cell line immune response to poly I:C and LPS, and provide a more rapid and efficient experimental material for research on marine fish immunology.


Assuntos
Doenças dos Peixes , Animais , Linhagem Celular , Doenças dos Peixes/imunologia , Nadadeiras de Animais/imunologia , Poli I-C/farmacologia , Imunidade Inata , Perciformes/imunologia , Perciformes/genética , Peixes/imunologia
5.
Acta Obstet Gynecol Scand ; 103(2): 225-240, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37997035

RESUMO

INTRODUCTION: Lumbopelvic pain (LPP) is common in pregnant women and has a significant negative effect on physical and psychological health. In this study, for the first time, we conduct a meta-analysis to estimate the overall prevalence of LPP among pregnant women and clarify the reasons for the differences in the estimated results. MATERIAL AND METHODS: A systematic search of four databases (PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials) was conducted from inception until October 2022. Two reviewers conducted a methodological quality assessment. Random-effects model analysis was used to estimate the pooled prevalence and the 95% confidence interval. Chi-square tests and I2 -values were used to assess the heterogeneity. Subgroup analysis (according to the participants' continent, age, body mass index [BMI], gestational age and study risk of bias), sensitivity analysis and random-effects meta-regression were used to explore the the sources of heterogeneity. RESULTS: Of the 1661 unique citations, 38 studies (21 533 pregnant participants) were included in this systematic review and meta-analysis. The overall pooled prevalence of LPP during pregnancy was 63% (95% CI: 0.57 to 0.69), with significant heterogeneity (I2 = 99.1%, P < 0.001). The prevalence differed by participants' continents, 71% (North America), 74% (South America), 63% (Asia), 64% (Europe), 59% (Africa) and 45% (Oceania). The prevalence differed by BMI, 64% (BMI <25), 64% (25 ≤ BMI ≤ 28), and 71% (BMI >28). The prevalence differed by age, 72% (age <25 years), 58% (25 ≤ age ≤ 30 years), and 69% (age >30 years). The prevalence were the same differed by study risk of bias, 63% (both low and moderate risk of bias studies). The prevalence were similar by gestational age, 62% (second trimester) and 63% (third trimester). CONCLUSIONS: Lumbopelvic pain during pregnancy is common; about three-fifths of pregnant women experience LPP. More prevention and intervention research for lumbopelvic should be conducted in pregnant women with different clinical characteristics.


Assuntos
Complicações na Gravidez , Gestantes , Gravidez , Feminino , Humanos , Adulto , Estudos Transversais , Prevalência , Complicações na Gravidez/epidemiologia , Dor
6.
Environ Monit Assess ; 196(3): 306, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407649

RESUMO

Fractional vegetation cover (FVC) is a crucial indicator to estimate degradation and desertification for grasslands. However, traditional small-scale FVC analysis methods, such as visual estimation and point-sampling, are cumbersome and imprecise. Innovative methods like image-based FVC analysis methods, while accurate, face challenges such as complex analytical procedures and the necessary training for operations. Therefore, in this study, a combined application of ImageJ and Photoshop was employed to achieve a more effective analysis of FVC values in desertification areas. Our results showed that the FVC results obtained by combination of Photoshop and ImageJ were dependable and precise (R2 > 0.98), demonstrating equivalency to results obtained through either visual estimation or Photoshop-based methods. Furthermore, even in the face of background interference and varied shooting angles, the combination of ImageJ and Photoshop software was still able to maintain a low error rate when analyzing FVC values (average error rate = - 2.6%). In conclusion, the imaged-based combined FVC analysis method employed in our research was an effective, precise, and efficient technique for analyzing small-scale FVC, promising substantial improvement over conventional methods.


Assuntos
Monitoramento Ambiental , Processamento de Imagem Assistida por Computador , Software
7.
J Cell Mol Med ; 27(6): 788-802, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36811277

RESUMO

Pancreatic cancer (PAAD) is a highly malignant tumour characterized of high mortality and poor prognosis. Huntingtin-interacting protein 1-related (HIP1R) has been recognized as a tumour suppressor in gastric cancer, while its biological function in PAAD remains to be elucidated. In this study, we reported the downregulation of HIP1R in PAAD tissues and cell lines, and the overexpression of HIP1R suppressed the proliferation, migration and invasion of PAAD cells, while silencing HIP1R showed the opposite effects. DNA methylation analysis revealed that the promoter region of HIP1R was heavily methylated in PAAD cell lines when compared to the normal pancreatic duct epithelial cells. A DNA methylation inhibitor 5-AZA increased the expression of HIP1R in PAAD cells. 5-AZA treatment also inhibited the proliferation, migration and invasion, and induced apoptosis in PAAD cell lines, which could be attenuated by HIP1R silencing. We further demonstrated that HIP1R was negatively regulated by miR-92a-3p, which modulates the malignant phenotype of PAAD cells in vitro and the tumorigenesis in vivo. The miR-92a-3p/HIP1R axis could regulate PI3K/AKT pathway in PAAD cells. Taken together, our data suggest that targeting DNA methylation and miR-92a-3p-mediated repression of HIP1R could serve as novel therapeutic strategies for PAAD treatment.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Metilação de DNA , Fosfatidilinositol 3-Quinases/metabolismo , Movimento Celular/genética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Pancreáticas
8.
EMBO J ; 38(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30858281

RESUMO

SREBPs are master regulators of lipid homeostasis and undergo sterol-regulated export from ER to Golgi apparatus for processing and activation via COPII-coated vesicles. While COPII recognizes SREBP through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet-associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Sterol deprivation releases SCAP from Insig and enhances ER export of SREBP/SCAP by inducing SCAP-Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites, where assembling of COPII complex initiates. Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and alleviates diet-induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated ER export of SREBP and lipid homeostasis.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/fisiologia , Retículo Endoplasmático/fisiologia , Complexo de Golgi/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Esteróis/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/efeitos dos fármacos , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/fisiologia , Retículo Endoplasmático/efeitos dos fármacos , Complexo de Golgi/efeitos dos fármacos , Células HEK293 , Células Hep G2 , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Transporte Proteico , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
9.
Inorg Chem ; 62(26): 10193-10202, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37320970

RESUMO

Square-like metallamacrocyclic palladium(II) complexes [M8L4]8+ (1-7) were synthesized by reacting aromatic dipyrazole ligands (H2L1-H2L3 with pyromellitic arylimide-, 1,4,5,8-naphthalenetetracarboxylic arylimide-, and anthracene-based aromatic groups, respectively) with dipalladium corners ([(bpy)2Pd2(NO3)2](NO3)2, [(dmbpy)2Pd2(NO3)2](NO3)2, or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, and phen = 1,10-phenanthroline) in aqueous solutions via metal-directed self-assembly. Metallamacrocycles 1-7 were fully characterized by 1H and 13C nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry, and the square structure of 7·8NO3- was further confirmed via single crystal X-ray diffraction. These square-like metallamacrocycles exhibit effective performance for iodine adsorption.

10.
Fish Shellfish Immunol ; 143: 109163, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37838211

RESUMO

The golden pompano (Trachinotus blochii), a pivotal commercial marine species in China, has gained significant popularity worldwide. However, accompanied with rapid growth and high density aquaculture, golden pompano has been seriously threatened by Nervous necrosis virus (NNV), while its molecular biology research regarding the innate immune system remains unexplored, which is crucial for understanding the activation of interferon (IFN) production and antiviral responses. In this study, we aimed to identify the characterization and function of golden pompano TANK-binding kinase 1 (gpTBK1), thereby providing evidence of the conservation of this classical factor in the RLR pathway among marine fish. Initially, we found the expression of gpTBK1 upregulation in diseased golden pompano with NNV infection and we successfully cloned the full-length open reading frame (ORF) of gpTBK1, consisting of 2172 nucleotides encoding 723 amino acids, from the head kidney. Subsequent analysis of the amino acid sequence revealed homology between gpTBK1 and other fish TBK1 proteins, with conserved N-terminal Serine/Threonine protein kinases catalytic domain (S_TKc) and C-terminal coiled coil domain (CCD). Moreover, the expression pattern showed that gpTBK1 exhibited ubiquitous expression across all evaluated tissues. Furthermore, functional identification experiments indicated that gpTBK1 activated interferon promoters' activity in golden pompano and induced the expression of downstream IFN-stimulated genes (ISGs). Notably, gpTBK1 was found to co-localize and interact with gpIRF3 in the cytoplasm. Collectively, these data provide a comprehensive analysis of the characterization and functional role of gpTBK1 in promoting interferon production. This research may facilitate the further study of the innate antiviral response, particularly the anti-NNV mechanisms, in golden pompano.


Assuntos
Peixes , Imunidade Inata , Animais , Imunidade Inata/genética , Proteínas de Peixes/química , Interferons , Antivirais
11.
Proc Natl Acad Sci U S A ; 117(44): 27412-27422, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33087562

RESUMO

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.


Assuntos
Neoplasias da Mama/patologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , PPAR gama/metabolismo , Fenilacetatos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Ácidos Graxos/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Metabolismo dos Lipídeos/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Camundongos , Pessoa de Meia-Idade , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/agonistas , PPAR gama/agonistas , Cultura Primária de Células , Prognóstico , Proteólise/efeitos dos fármacos , Análise Serial de Tecidos , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/metabolismo , Ubiquitinação/efeitos dos fármacos
12.
Glia ; 70(2): 379-392, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724258

RESUMO

Myelin sheath is an important structure to maintain functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin-forming proteins to the myelin membrane, however, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by reducing total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation and suppresses STAT3 phosphorylation and activation. As a result, the transcription of the myelin-related and anti-apoptosis genes is inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate a key role DHHC5 in controlling myelinogenesis.


Assuntos
Bainha de Mielina , Oligodendroglia , Células Cultivadas , Lipoilação , Bainha de Mielina/metabolismo , Neurogênese , Oligodendroglia/metabolismo
13.
Mol Biol Evol ; 38(5): 1995-2013, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33432361

RESUMO

Evolutionary fates of duplicated genes have been widely investigated in many polyploid plants and animals, but research is scarce in recurrent polyploids. In this study, we focused on foxl2, a central player in ovary, and elaborated the functional divergence in gibel carp (Carassius gibelio), a recurrent auto-allo-hexaploid fish. First, we identified three divergent foxl2 homeologs (Cgfoxl2a-B, Cgfoxl2b-A, and Cgfoxl2b-B), each of them possessing three highly conserved alleles and revealed their biased retention/loss. Then, their abundant sexual dimorphism and biased expression were uncovered in hypothalamic-pituitary-gonadal axis. Significantly, granulosa cells and three subpopulations of thecal cells were distinguished by cellular localization of CgFoxl2a and CgFoxl2b, and the functional roles and the involved process were traced in folliculogenesis. Finally, we successfully edited multiple foxl2 homeologs and/or alleles by using CRISPR/Cas9. Cgfoxl2a-B deficiency led to ovary development arrest or complete sex reversal, whereas complete disruption of Cgfoxl2b-A and Cgfoxl2b-B resulted in the depletion of germ cells. Taken together, the detailed cellular localization and functional differences indicate that Cgfoxl2a and Cgfoxl2b have subfunctionalized and cooperated to regulate folliculogenesis and gonad differentiation, and Cgfoxl2b has evolved a new function in oogenesis. Therefore, the current study provides a typical case of homeolog/allele diversification, retention/loss, biased expression, and sub-/neofunctionalization in the evolution of duplicated genes driven by polyploidy and subsequent diploidization from the recurrent polyploid fish.


Assuntos
Evolução Molecular , Proteína Forkhead Box L2/genética , Duplicação Gênica , Carpa Dourada/genética , Poliploidia , Animais , Feminino , Proteína Forkhead Box L2/metabolismo , Carpa Dourada/crescimento & desenvolvimento , Carpa Dourada/metabolismo , Masculino , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Ovário/crescimento & desenvolvimento , Ovário/metabolismo
14.
J Neuroinflammation ; 19(1): 184, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836200

RESUMO

BACKGROUND: Reactive oxygen species (ROS) often promote acute brain injury after stroke, but their roles in the recovery phase have not been well studied. We tested the hypothesis that ROS activity mediated by NADPH oxidase 2 (NOX2) contributes to acute brain injury but promotes functional recovery during the delayed phase, which is linked with neuroinflammation, autophagy, angiogenesis, and the PI3K/Akt signaling pathway. METHODS: We used the NOX2 inhibitor apocynin to study the role of NOX2 in brain injury and functional recovery in a middle cerebral artery occlusion (MCAO) stroke mouse model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7, 10 and 14 after reperfusion. In addition, dynamic NOX2-induced ROS levels were measured by dihydroethidium (DHE) staining. Autophagy, inflammasomes, and angiogenesis were measured by immunofluorescence staining and western blotting. RNA sequencing was performed, and bioinformatics technology was used to analyze differentially expressed genes (DEGs), as well as the enrichment of biological functions and signaling pathways in ischemia penumbra at 7 days after reperfusion. Then, Akt pathway-related proteins were further evaluated by western blotting. RESULTS: Our results showed that apocynin injection attenuated infarct size and mortality 3 days after stroke but promoted mortality and blocked functional recovery from 5 to 14 days after stroke. DHE staining showed that ROS levels were increased at 3 days after reperfusion and then gradually declined in WT mice, and these levels were significantly reduced by the NOX2 inhibitor apocynin. RNA-Seq analysis indicated that apocynin activated the immune response under hypoxic conditions. The immunofluorescence and western blot results demonstrated that apocynin inhibited the NLRP3 inflammasome and promoted angiogenesis at 3 days but promoted the NLRP3 inflammasome and inhibited angiogenesis at 7 and 14 days after stroke, which was mediated by regulating autophagy activation. Furthermore, RNA-Seq and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that apocynin injection resulted in PI3K-Akt signaling pathway enrichment after 7 days of MCAO. We then used an animal model to show that apocynin decreased the protein levels of phosphorylated PI3K and Akt and NF-κB p65, confirming that the PI3K-Akt-NF-κB pathway is involved in apocynin-mediated activation of inflammation and inhibition of angiogenesis. CONCLUSIONS: NOX2-induced ROS production is a double-edged sword that exacerbates brain injury in the acute phase but promotes functional recovery. This effect appears to be achieved by inhibiting NLRP3 inflammasome activation and promoting angiogenesis via autophagy activation.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/metabolismo , Inflamassomos , Camundongos , NADPH Oxidase 2 , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo
15.
Nanotechnology ; 33(28)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35030550

RESUMO

A green method for the synthesis ofin situCu paste is developed. Cu particles are prepared through chemical reduction by selecting a special copper source, reducing agent, and solvent. Then the reaction solution is directly concentrated to obtain anin situCu paste. The synthesis of Cu particles and the preparation of Cu paste are conducted simultaneously, and the process of separation, purification, drying, storage, and re-dispersion of powder are reduced. Particles are not directly exposed to air, thus the oxidation of micro/submicron -Cu is effectively prevented, and the agglomeration of particles caused by drying and dispersion operations is simultaneously reduced. Furthermore, the proposed method has a certain universality, and different types of Cu sources can be used to preparein situpaste with different sizes and morphologies. The entire preparation process is simple, efficient, green, and the yield can reach 99.99%, which breaks through the bottleneck of the application of traditional micro/submicron-Cu materials. Copper acetate-basedin situpaste is sintered for 30 min at 260 °C and 2 MPa in a reducing atmosphere. The shear strength, resistivity, and thermal conductivity reach 55.26 MPa, 4.01 × 10-8Ω·m, and 92.75 W/(m·K), respectively, which could meet the interconnection application of power semiconductor devices.

16.
J Clin Ultrasound ; 50(1): 60-69, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34625988

RESUMO

To investigate the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) for the diagnosis of cervical lymph nodes metastasis (CLNM) of papillary thyroid carcinoma (PTC), eight available datasets of seven qualified articles before March 31, 2021 were included after a comprehensive search. Meta-analysis results showed that CEUS demonstrated acceptable diagnostic performance in the diagnosis of CLNM of PTC. Furthermore, meta-regression analysis was conducted to identify the reasons for heterogeneity and the results indicated that the criteria of CEUS for the diagnosis of CLNM in PTC need to be unified.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
17.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35457024

RESUMO

Here, we report a design strategy for constructing supramolecular organic frameworks by introducing 1H-pyrazole groups to aromatic cores as non-coplanar molecules to form diverse supramolecular assemblies through multiple 1H-pyrazole [N-H···N] hydrogen bonds as well as other weak interactions. The new supramolecular organic frameworks displayed interesting crystallization-induced emission (CIE) behavior.


Assuntos
Pirazóis , Cristalização , Ligação de Hidrogênio , Pirazóis/química
18.
Nanotechnology ; 32(50)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474405

RESUMO

In this paper, the particle size effect on the sintering behaviors of Cu particles at nanometer to micron scale is explored. The results show that micron-sized particles could form obvious sintering necks at a low temperature of 260 °C, exhibiting a shear strength as high as 64 MPa. A power relation ofx âˆ a0.8between sintering neck radius (x) and particle radius (a) is discovered, and a sintering model with a quantitative relational expression of (x/a)5 = 160γδDt/3akTis proposed by considering the surface tension driven microflow process between adjacent particles to predict the growth of sintering necks. It is concluded that the sintering process of particles at nanometer to micron scale is controlled by microflow mechanism instead of diffusion mechanism. Our proposed model provides a new theoretical basis for understanding the kinetic growth mechanism of sintering necks of metal particles.

19.
Korean J Parasitol ; 59(1): 103-108, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33684994

RESUMO

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.


Assuntos
Ácaros e Carrapatos/genética , Variação Genética/genética , Animais , China , Complexo IV da Cadeia de Transporte de Elétrons/genética , Evolução Molecular , Cazaquistão , Mitocôndrias/enzimologia , Mitocôndrias/genética , Filogenia
20.
Clin Infect Dis ; 71(16): 2132-2138, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32442265

RESUMO

PURPOSE: We aimed to further clarify the epidemiological and clinical characteristics of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. METHODS: We identified close contacts of confirmed coronavirus disease 2019 (COVID-19) cases in northeast Chongqing, China, who were confirmed by real-time reverse transcription polymerase chain reaction-positive (RT-PCR+). We stratified this cohort by normal vs abnormal findings on chest computed tomography (CT) and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors. RESULTS: Between January 2020 and March 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days, and it was 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (P < .05). Nine patients (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of time for nucleic acid to turn negative was 13 days compared with 10.4 days in those with normal chest CT scans (P < .05). CONCLUSIONS: A portion of asymptomatic individuals were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment of asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Adulto Jovem
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