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Oxaliplatin is effective against colorectal cancer (CRC), but resistance hampers treatment. We found upregulated Dickkopf-1 (DKK1, a secreted protein) in oxaliplatin-resistant (OR) CRC cell lines and DKK1 levels increased by more than 2-fold in approximately 50% of oxaliplatin-resistant CRC tumors. DKK1 activates AKT via cytoskeleton-associated protein 4 (CKAP4, a DKK1 receptor), modulating oxaliplatin responses in vitro and in vivo. The leucine zipper (LZ) domain of CKAP4 and cysteine-rich domain 1 (CRD1) of secreted DKK1 are crucial for their interaction and AKT signaling. By utilizing the LZ protein, we disrupted DKK1 signaling, enhancing oxaliplatin sensitivity in OR CRC cells and xenograft tumors. This suggests that DKK1 as a chemoresistant factor in CRC via AKT activation. Targeting DKK1 with the LZ protein offers a promising therapeutic strategy for oxaliplatin-resistant CRC with high DKK1 levels. This study sheds light on oxaliplatin resistance mechanisms and proposes an innovative intervention for managing this challenge.
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The H9N2 subtype of avian influenza virus (AIV) causes enormous economic losses and poses a significant threat to public health; the development of vaccines against avian influenza is ongoing. To study the immunogenicity of hemagglutinin (HA) protein, we constructed a recombinant pET-32a-HA plasmid, induced HA protein expression with isopropyl ß-D-1-thiogalactopyranoside (IPTG), verified it by SDS-PAGE and Western blotting, and determined the sensitivity of the recombinant protein to acid and heat. Subsequently, mice were immunized with the purified HA protein, and the immunization effect was evaluated according to the hemagglutination inhibition (HI) titer, serum IgG antibody titer, and cytokine secretion level of the mice. The results showed that the molecular weight of the HA protein was approximately 84 kDa, and the protein existed in both soluble and insoluble forms; in addition, the HA protein exhibited good acid and thermal stability, the HI antibody titer reached 6 log2-8 log2, and the IgG-binding antibody titer was 1:1,000,000. Moreover, the levels of IL-2, IL-4, and IL-5 in the immunized mouse spleen cells were significantly increased compared with those in the control group. However, the levels of IL-1ß, IL-6, IL-13, IFN-γ, IL-18, TNF-α, and GM-CSF were decreased in the immunized group. The recombinant HA protein utilized in this study exhibited good stability and exerted beneficial immune effects, providing a theoretical basis for further research on influenza vaccines.
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H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3' ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross-reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples.
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Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China's poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019-014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4.
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BACKGROUND: Hepatitis B virus (HBV) exhibits high prevalence rates within Ethiopia. The genetic diversity of HBV, marked by mixed genotype infections, may hold significant implications for the trajectory of disease and responses to treatment. Ethiopia grapples with a substantial public health challenge posed by co-infections involving HBV, hepatitis C virus (HCV), and human immunodeficiency virus 1 (HIV-1), particularly among vulnerable populations. METHODS: A comprehensive investigation into HBV, HCV, and HIV-1 co-infection was conducted. A total of 7,789 blood samples were meticulously analyzed, among which 815 exhibited HBV positivity. Among the HBV-positive samples, 630 were subjected to genotyping procedures, resulting in the identification of a prevalent trend of mixed infections characterized by HBV genotypes A/E/F (67.30%). Serological assessments were performed on 492 specimens to ascertain the presence of HCV and HIV-1 co-infections, revealing respective co-infection rates of 13.02% for HBV/HIV, 3.31% for HBV/HCV, and 2.07% for triple infection. RESULTS: The investigation revealed the intricate prevalence of co-infections in Ethiopia, notably underlining the continued transmission of viruses. The prominent occurrence of mixed HBV genotypes A/E/F suggests dynamic viral interactions and ongoing transmission pathways. These findings accentuate the necessity for targeted interventions and enhanced patient care, as co-infections carry significant clinical complexities. CONCLUSIONS: This study furnishes crucial insights into the molecular epidemiology of HBV, HCV, and HIV-1 co-infections in Ethiopia. The acquired knowledge can contribute to the advancement of strategies for clinical management and the formulation of public health interventions aimed at ameliorating the burden of viral infections within the nation.
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Coinfecção , Genótipo , Infecções por HIV , HIV-1 , Hepacivirus , Vírus da Hepatite B , Hepatite B , Hepatite C , Epidemiologia Molecular , Humanos , Etiópia/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Hepatite C/epidemiologia , Hepatite C/virologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/epidemiologia , Hepatite B/virologia , Masculino , Adulto , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , HIV-1/genética , HIV-1/classificação , HIV-1/isolamento & purificação , Adulto Jovem , Hepacivirus/genética , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Adolescente , Pessoa de Meia-Idade , Prevalência , Criança , Pré-Escolar , Idoso , Lactente , Variação GenéticaRESUMO
Avian orthoreviruses have become a global challenge to the poultry industry, causing significant economic impacts on commercial poultry. Avian reoviruses (ARVs) are resistant to heat, proteolytic enzymes, a wide range of pH values, and disinfectants, so keeping chicken farms free of ARV infections is difficult. This review focuses on the global prevalence of ARVs and associated clinical signs and symptoms. The most common signs and symptoms include tenosynovitis/arthritis, malabsorption syndrome, runting-stunting syndrome, and respiratory diseases. Moreover, this review also focused on the characterization of ARVs in genotypic clusters (I-VI) and their relation to tissue tropism or viral distribution. The prevailing strains of ARV in Africa belong to all genotypic clusters (GCs) except for GC VI, whereas all GCs are present in Asia and the Americas. In addition, all ARV strains are associated with or belong to GC I-VI in Europe. Moreover, in Oceania, only GC V and VI are prevalent. This review also showed that, regardless of the genotypic cluster, tenosynovitis/arthritis was the predominant clinical manifestation, indicating its universal occurrence across all clusters. Globally, most avian reovirus infections can be prevented by vaccination against four major strains: S1133, 1733, 2408, and 2177. Nevertheless, these vaccines may not a provide sufficient defense against field isolates. Due to the increase in the number of ARV variants, classical vaccine approaches are being developed depending on the degree of antigenic similarity between the vaccine and field strains, which determines how successful the vaccination will be. Moreover, there is a need to look more closely at the antigenic and pathogenic properties of reported ARV strains. The information acquired will aid in the selection of more effective vaccine strains in combination with biosecurity and farm management methods to prevent ARV infections.
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Genótipo , Orthoreovirus Aviário , Doenças das Aves Domésticas , Infecções por Reoviridae , Orthoreovirus Aviário/genética , Orthoreovirus Aviário/classificação , Animais , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Infecções por Reoviridae/veterinária , Infecções por Reoviridae/epidemiologia , Infecções por Reoviridae/virologia , Filogenia , Galinhas/virologia , Prevalência , Aves Domésticas/virologiaRESUMO
Fowl adenovirus serotype 4 (FAdV-4) is highly pathogenic to broilers aged 3 to 5 weeks and has caused considerable economic loss in the poultry industry worldwide. FAdV-4 is the causative agent of hydropericardium-hepatitis syndrome (HHS) or hydropericardium syndrome (HPS). The virus targets mainly the liver, and HPS symptoms are observed in infected chickens. This disease was first reported in Pakistan but has now spread worldwide, and over time, various deletions in the FAdV genome and mutations in its major structural proteins have been detected. This review provides detailed information about FAdV-4 genome organization, physiological features, epidemiology, coinfection with other viruses, and host immune suppression. Moreover, we investigated the role and functions of important structural proteins in FAdV-4 pathogenesis. Finally, the potential regulatory effects of FAdV-4 infection on ncRNAs are also discussed.
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Infecções por Adenoviridae , Aviadenovirus , Galinhas , Genoma Viral , Doenças das Aves Domésticas , Sorogrupo , Animais , Galinhas/virologia , Doenças das Aves Domésticas/virologia , Aviadenovirus/genética , Aviadenovirus/classificação , Aviadenovirus/patogenicidade , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Coinfecção/virologia , Coinfecção/veterináriaRESUMO
PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.
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Carcinoma de Células Escamosas , Quimiorradioterapia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Estudos Retrospectivos , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Adulto , Idoso , Pontuação de Propensão , Resultado do TratamentoRESUMO
Interferon-inducible transmembrane protein 3 (IFITM3) is an antiviral factor that plays an important role in the host innate immune response against viruses. Previous studies have shown that IFITM3 is upregulated in various tissues and organs after avian reovirus (ARV) infection, which suggests that IFITM3 may be involved in the antiviral response after ARV infection. In this study, the chicken IFITM3 gene was cloned and analyzed bioinformatically. Then, the role of chicken IFITM3 in ARV infection was further explored. The results showed that the molecular weight of the chicken IFITM3 protein was approximately 13 kDa. This protein was found to be localized mainly in the cytoplasm, and its protein structure contained the CD225 domain. The homology analysis and phylogenetic tree analysis showed that the IFITM3 genes of different species exhibited great variation during genetic evolution, and chicken IFITM3 shared the highest homology with that of Anas platyrhynchos and displayed relatively low homology with those of birds such as Anser cygnoides and Serinus canaria. An analysis of the distribution of chicken IFITM3 in tissues and organs revealed that the IFITM3 gene was expressed at its highest level in the intestine and in large quantities in immune organs, such as the bursa of Fabricius, thymus and spleen. Further studies showed that the overexpression of IFITM3 in chicken embryo fibroblasts (DF-1) could inhibit the replication of ARV, whereas the inhibition of IFITM3 expression in DF-1 cells promoted ARV replication. In addition, chicken IFITM3 may exert negative feedback regulatory effects on the expression of TBK1, IFN-γ and IRF1 during ARV infection, and it is speculated that IFITM3 may participate in the innate immune response after ARV infection by negatively regulating the expression of TBK1, IFN-γ and IRF1. The results of this study further enrich the understanding of the role and function of chicken IFITM3 in ARV infection and provide a theoretical basis for an in-depth understanding of the antiviral mechanism of host resistance to ARV infection.
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Interferons , Orthoreovirus Aviário , Animais , Embrião de Galinha , Interferons/genética , Galinhas , Orthoreovirus Aviário/genética , Filogenia , Antivirais , Expressão Gênica , Replicação ViralRESUMO
An enzyme-free sandwich amperometric immunosensor based on bimetallic Pt/Ag nanoparticle (Pt/AgNPs)-functionalized chitosan (Chi)-modified multiwalled carbon nanotubes (MWCNTs) as dual signal amplifiers and Chi-modified MWCNTs (MWCNTs-Chi) as substrate materials was developed for ultrasensitive detection of fowl adenovirus group I (FAdV-I). MWCNTs have a large specific surface area, and many accessible active sites were formed after modification with Chi. Hence, MWCNTs-Chi, as a substrate material for modifying glassy carbon electrodes (GCEs), could immobilize more antibodies (fowl adenovirus group I-monoclonal antibody, FAdV-I/MAb). Multiple Pt/AgNPs were attached to the surface of MWCNTs-Chi to generate MWCNTs-Chi-Pt/AgNPs with high catalytic ability for the reaction of H2O2 and modified active sites for fowl adenovirus group I-polyclonal antibody (FAdV-I/PAb) binding. Amperometric i-t measurements were employed to characterize the recognizability of FAdV-I. Under optimal conditions, and the developed immunosensor exhibited a wide linear range (100.93 EID50 mL-1 to 103.43 EID50 mL-1), a low detection limit (100.67 EID50 mL-1) and good selectivity, reproducibility and stability. This immunosensor can be used in clinical sample detection.
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Técnicas Biossensoriais , Antígenos de Grupos Sanguíneos , Nanopartículas Metálicas , Nanotubos de Carbono , Nanotubos de Carbono/química , Nanopartículas Metálicas/química , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Peróxido de Hidrogênio , Imunoensaio , Prata , Antígenos de Fungos , Anticorpos Monoclonais , Adenoviridae , Limite de Detecção , Ouro/químicaRESUMO
PURPOSE: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. RESULTS: A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. CONCLUSION: AC did not improve survival in patients with stage IIB CSCC receiving CCRT.
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Carcinoma de Células Escamosas , Neoplasias Nasofaríngeas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , China , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/patologia , Estudos RetrospectivosRESUMO
Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 µM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.
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Aspergillus , Fígado Gorduroso , Aspergillus/química , Dicroísmo Circular , Estrutura MolecularRESUMO
Avian reovirus (ARV) infection is prevalent in farmed poultry and causes viral arthritis and severe immunosuppression. The spleen plays a very important part in protecting hosts against infectious pathogens. In this research, transcriptome and translatome sequencing technology were combined to investigate the mechanisms of transcriptional and translational regulation in the spleen after ARV infection. On a genome-wide scale, ARV infection can significantly reduce the translation efficiency (TE) of splenic genes. Differentially expressed translational efficiency genes (DTEGs) were identified, including 15 upregulated DTEGs and 396 downregulated DTEGs. These DTEGs were mainly enriched in immune regulation signaling pathways, which indicates that ARV infection reduces the innate immune response in the spleen. In addition, combined analyses revealed that the innate immune response involves the effects of transcriptional and translational regulation. Moreover, we discovered the key gene IL4I1, the most significantly upregulated gene at both the transcriptional and translational levels. Further studies in DF1 cells showed that overexpression of IL4I1 could inhibit the replication of ARV, while inhibiting the expression of endogenous IL4I1 with siRNA promoted the replication of ARV. Overexpression of IL4I1 significantly downregulated the mRNA expression of IFN-ß, LGP2, TBK1 and NF-κB; however, the expression of these genes was significantly upregulated after inhibition of IL4I1, suggesting that IL4I1 may be a negative feedback effect of innate immune signaling pathways. In addition, there may be an interaction between IL4I1 and ARV σA protein, and we speculate that the IL4I1 protein plays a regulatory role by interacting with the σA protein. This study not only provides a new perspective on the regulatory mechanisms of the innate immune response after ARV infection but also enriches the knowledge of the host defense mechanisms against ARV invasion and the outcome of ARV evasion of the host's innate immune response.
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Galinhas , Orthoreovirus Aviário , Animais , Transcriptoma , Orthoreovirus Aviário/genética , Baço , Imunidade Inata , Transdução de Sinais , Perfilação da Expressão GênicaRESUMO
Background: Helicobacter pylori (Hp) infection is highly prevalent globally and is predominantly managed by antibiotics. Recently, the anti-adhesive, antioxidant, antitoxin, immunomodulatory, anti-coagulant, and anti-infective activities of fucoidan, a polysaccharide extracted from brown seaweeds, have been widely studied, and the results showed promise. Fucoidan has the potential to be utilized in Hp eradication therapy. Our present clinical study was designed to evaluate the efficiency of Lewuyou®, a fucoidan plant drink (FPD) in eradicating Hp in humans. Methods: This multi-center, clinical study was conducted between October 2020 and July 2021. Hp infection was confirmed by urea breath test (UBT). A total of 122 patients with confirmed Hp infection were enrolled; after exclusion of incomplete data, 85 eligible patients (37 males and 48 females aged 20-81 years) were included in the final analysis. FPD (50 mL per vial) was orally administered twice daily for a 4-week cycle, and 41 patients completed an 8-week cycle. Results: No adverse event (AE) was reported in all 122 participants who had consumed FPD. The Hp eradication rate and clearance rate were 77.6% (66/85) and 20.0% (17/85), respectively, after 4 weeks of FPD consumption and 80.5% (33/41) and 26.8 (11/41) , respectively, after 8 weeks of consumption. Conclusions: The 4- and 8-week protocols of FPD consumption were safe and effective at reducing Hp load on the gastric mucosa, with Hp eradicated in the majority of participants.
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Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-ß were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity.
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X-ray nanodiffraction was used to measure the thermal stress of 10 µm nanotwinned Cu bumps in Cu/SiO2 hybrid structures at -55 °C, 27 °C, 100 °C, 150 °C, and 200 °C. Bonding can be achieved without externally applied compression. The X-ray beam size is about 100 nm in diameter. The Cu bump is dominated by (111) oriented nano-twins. Before the hybrid bonding, the thermal stress in Cu bumps is compressive and remains compressive after bonding. The average stress in the bonded Cu joint at 200 °C is as large as -169.1 MPa. In addition, using the strain data measured at various temperatures, one can calculate the effective thermal expansion coefficient (CTE) for the 10 µm Cu bumps confined by the SiO2 dielectrics. This study reports a useful approach on measuring the strain and stress in oriented metal bumps confined by SiO2 dielectrics. The results also provide a deeper understanding on the mechanism of hybrid bonding without externally applied compression.
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BACKGROUND: East Asia is the most dynamic region in the world and includes three major countries: Japan, South Korea and China. Due to rapid economic growth, orthopedics research in East Asia has achieved great advances during the past 10 years. However, the current status of orthopedic research in Japan, South Korea and China is still unclear. AIM: To understand the current status of orthopedic research in Japan, South Korea, and China. METHODS: Journals listed in the ''Orthopedics'' category of Science Citation Index Expanded subject categories were included. The PubMed and Web of Knowledge electronic databases were searched to identify scientific publications from the selected journals written by researchers from Japan, South Korea and China. A systematic analysis was conducted to analyze orthopedic research articles published in the three countries based on the number of articles, study design, impact factors (IFs) and citations. Furthermore, we also ranked the top 10 countries worldwide with the highest publications in the past 10 years. Additionally, we ranked the top 10 countries with the highest number of publications in the world in the past 10 years. Statistical analyses were performed using SPSS 20.0 software (SPSS Inc., Chicago, IL, United States), and statistical results are given in Tables and Figures. The Kruskal-Wallis test and the Mann-Whitney test were used to detect differences between countries. The tendency regarding the number of articles was analyzed by curvilinear regression. A two-tailed P < 0.05 was considered significant. RESULTS: From 2012-2021, a total of 144518 articles were published in the 86 selected orthopedic journals. During this period, the number of worldwide published orthopedic articles has shown an annual increasing trend. A total of 27164 orthopedic research articles were published by Japan, South Korea and China during the past 10 years; 44.32% were from China, 32.98% were from Japan, and 22.70% were from South Korea. From 2012 to 2021, the annual number of articles markedly increased in each of the three countries. Over time, the worldwide share of articles increased substantially in South Korea (3.37% to 6.53%, P < 0.001) and China (5.29% to 9.61%, P < 0.001). However, the worldwide share of articles significantly decreased in Japan (5.22% to 3.80%, P < 0.001). The annual total IFs of articles from China were well above those of articles from Japan and South Korea (36597.69 vs 27244.48 vs 20657.83, P < 0.05). There was no significant difference among the articles in the top 10 high-IF orthopedics journals published from those three countries [South Korea (800) > China (787) > Japan (646), P > 0.05]. CONCLUSION: Over the past 10 years, China's scientific publications in orthopedic journals have shown an increasing trend. Considering the relative scale of the populations, Japan and South Korea have outpaced China with respect to quality.
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In this study, thermal and argon (Ar) plasma/wetting treatments were combined to enhance the bonding strength of polyimide (PI) films. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to analyze the changes in the PI imidization degrees. The contact angles of the PI films were also measured. The results show that the contact angles of the fully cured PI films markedly decreased from 78.54° to 26.05° after the Ar plasma treatments. X-ray photoelectron spectroscopy (XPS) analysis was also conducted on the PI surfaces. We found that the intensities of the C-OH and C-N-H bonds increased from 0% to 13% and 29% to 57%, respectively, after Ar plasma activation. Such increases in the C-OH and C-N-H intensities could be attributed to the generation of dangling bonds and the breakage of the imide ring or polymer long chains. Shear tests were also conducted to characterize the bonding strength of the PI films, which, after being treated with the appropriate parameters of temperature, plasma power, and wetting droplets, was found to be excellent at greater than 35.3 MPa.
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The GX2020-019 strain of fowl adenovirus serotype 4 (FAdV-4) was isolated from the liver of chickens with hydropericardium hepatitis syndrome in Guangxi Province, China, and was purified by plaque assay three times. Pathogenicity studies showed that GX2020-019 can cause typical FAdV-4 pathology, such as hydropericardium syndrome and liver yellowing and swelling. Four-week-old specific pathogen-free (SPF) chickens inoculated with the virus at doses of 103 median tissue culture infectious dose (TCID50), 104 TCID50, 105 TCID50, 106 TCID50, and 107 TCID50 had mortality rates of 0, 20, 60, 100, and 100%, respectively, which were lower than those of chickens inoculated with other highly pathogenic Chinese isolates, indicating that GX2020-019 is a moderately virulent strain. Persistent shedding occurred through the oral and cloacal routes for up to 35 days postinfection. The viral infection caused severe pathological damage to the liver, kidney, lung, bursa of Fabricius, thymus, and spleen. The damage to the liver and immune organs could not be fully restored 21 days after infection, which continued to affect the immune function of chickens. Whole genome analysis indicated that the strain belonged to the FAdV-C group, serotype 4, and had 99.7-100% homology with recent FAdV-4 strains isolated from China. However, the amino acid sequences encoded by ORF30 and ORF49 are identical to the sequences found in nonpathogenic strains, and none of the 32 amino acid mutation sites that appeared in other Chinese isolates were found. Our research expands understanding of the pathogenicity of FAdV-4 and provides a reference for further studies.