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1.
ACS Nano ; 18(34): 23380-23391, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39157965

RESUMO

Rapid capacity fading, interfacial instability, and thermal runaway due to oxygen loss are critical obstacles hindering the practical application and commercialization of Ni-rich cathodes (LiNi0.8Co0.1Mn0.1O2, NCM811). Herein, a Sn4+/F- codoping and LiF-coated Ni-rich cathode, denoted as NCM811-SF, is structurally fabricated that demonstrates very high cyclic and thermal stabilities. The introduction of Sn4+ regulates the local electronic structure and facilitates the conversion of the layered structure into a spinel phase; F- captures lithium impurities to form LiF coatings and forms TM-F bonds to reduce Ni/Li disordering. The compositionally complex codoping strategy reduces the internal structure strain, inhibits the Li+/Ni2+ intermixing during cycling and degradation of the nanoscale structure, and further improves the thermal stability and the crystal structure. The cathodic electrode showed a little volume shift at 2.8-4.5 V, which significantly decreased lattice flaws and fractures generated by local strain, based on detailed analyses performed using COMSOL simulations, X-ray diffraction, and scanning transmission electron microscopy. Benefiting from this, after 300 cycles, our as-prepared NCM811-SF cathode maintains 85.4% of its initial capacity at 4.5 V and has an excellent reversible capacity equal to 169 mAh·g-1 at 1 C. In addition, the NCM811-SF/graphite cell in a pouch-type complete cell retained 94.8% of its starting capacity following 500 cycles. These findings underscore the effectiveness of introducing the Sn-O and TM-F bonds in improving the durability and electrochemical efficiency of the cathode material, which makes it a good choice for high-efficiency Li-ion batteries.

2.
Methods Mol Biol ; 2837: 185-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044085

RESUMO

Covalently closed circular DNA (cccDNA) exists as a stable episomal minichromosome in the nucleus of hepatocytes and is responsible for hepatitis B virus (HBV) persistence. We recently reported a technique involving recombinant cccDNA (rcccDNA) of HBV by site-specific DNA recombination. A floxed monomeric HBV genome was engineered into a precursor plasmid (prcccDNA) which was excised via Cre/loxP-mediated DNA recombination to form a 3.3-kb rcccDNA bearing a loxP-chimeric intron. The foreign sequence was efficiently removed during RNA splicing, rendering a functionally seamless insertion. We characterized rcccDNA formation, effective viral transcription, and replication induced by rcccDNA both in vitro and in vivo. Furthermore, we closely simulated chronic hepatitis by using a replication-defective recombinant adenoviral vector to deliver rcccDNA to the transgenic mice expressing Cre recombinase, which led to prominent HBV persistence. Here, we describe a detailed protocol about how to construct and evaluate Cre/loxP-based recombinant HBV cccDNA system both in vitro and in vivo.


Assuntos
DNA Circular , DNA Viral , Vírus da Hepatite B , Integrases , Recombinação Genética , Replicação Viral , DNA Circular/genética , Vírus da Hepatite B/genética , Animais , Integrases/genética , Integrases/metabolismo , Camundongos , DNA Viral/genética , Humanos , Vetores Genéticos/genética , Camundongos Transgênicos , Plasmídeos/genética , DNA Recombinante/genética
3.
Arch Med Res ; 55(5): 103034, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38972195

RESUMO

BACKGROUND AND OBJECTIVE: Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100ß has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100ß, and functional coronary stenosis as determined by quantitative flow ratio (QFR). METHODS: Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100ß levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden. RESULTS: Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100ß>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100ß was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912-8.793, p <0.001). According to 3V-QFR, S100ß is inversely associated with total atherosclerosis burden (B = -0.002, p <0.001). CONCLUSIONS: S100ß was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP.


Assuntos
Angina Instável , Biomarcadores , Angiografia Coronária , Subunidade beta da Proteína Ligante de Cálcio S100 , Humanos , Masculino , Feminino , Angina Instável/sangue , Angina Instável/fisiopatologia , Angina Instável/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Estudos Retrospectivos , Biomarcadores/sangue , Curva ROC , Estenose Coronária/sangue , Estenose Coronária/fisiopatologia , Estenose Coronária/diagnóstico por imagem
4.
Artigo em Inglês | MEDLINE | ID: mdl-38904448

RESUMO

PURPOSE: To investigate the relationship between the abundance of CD4+ and CD8+ T cells in the tumor microenvironment and the prognosis of patients with esophageal squamous cell carcinoma, and to analyze their correlation and explore its clinical value. MATERIALS AND METHODS: In total, we enrolled 120 cases of esophageal squamous cell carcinoma diagnosed. The abundance of CD4+ and CD8+ T lymphocytes in the tissue specimens of esophageal cancer was examined by immunohistochemistry. We measured the correlation between the abundance of CD4+ and CD8+ T lymphocytes and the clinical and pathological characteristics and prognosis of esophageal squamous cell carcinoma. RESULTS: The tissue abundance of CD4+ T lymphocytes was closely related to tumor prognosis (P < 0.05). Similarly, there was a statistically significant relationship between the tissue abundance of CD8+ T lymphocytes and patients' prognosis (P < 0.05), indicating that a high abundance of CD8+ T lymphocytes predicts better prognosis in esophageal squamous cell carcinoma. Surprisingly, we found that a higher CD4+/CD8+ ratio predicted a better prognosis of esophageal squamous cell carcinoma. CONCLUSIONS: The tissue abundance of CD4+ and CD8+ T lymphocytes can serve as an important indicator for predicting the long-term survival of patients with esophageal squamous cell carcinoma. A high CD4+/CD8+ ratio may improve patients' prognosis through several pathways. The association of this ratio with clinical and pathological characteristics may explain the poor efficacy of immunotherapy in patients with esophageal cancer. These findings may help us find new targets for immunotherapy by exploring the immune microenvironment of esophageal squamous cell carcinoma.

5.
World J Clin Cases ; 12(17): 3235-3242, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898830

RESUMO

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

6.
Viruses ; 16(5)2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38793589

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces direct cytopathic effects, complicating the establishment of low-cytotoxicity cell culture models for studying its replication. We initially developed a DNA vector-based replicon system utilizing the CMV promoter to generate a recombinant viral genome bearing reporter genes. However, this system frequently resulted in drug resistance and cytotoxicity, impeding model establishment. Herein, we present a novel cell culture model with SARS-CoV-2 replication induced by Cre/LoxP-mediated DNA recombination. An engineered SARS-CoV-2 transcription unit was subcloned into a bacterial artificial chromosome (BAC) vector. To enhance biosafety, the viral spike protein gene was deleted, and the nucleocapsid gene was replaced with a reporter gene. An exogenous sequence was inserted within NSP1 as a modulatory cassette that is removable after Cre/LoxP-mediated DNA recombination and subsequent RNA splicing. Using the PiggyBac transposon strategy, the transcription unit was integrated into host cell chromatin, yielding a stable cell line capable of inducing recombinant SARS-CoV-2 RNA replication. The model exhibited sensitivity to the potential antivirals forsythoside A and verteporfin. An innovative inducible SARS-CoV-2 replicon cell model was introduced to further explore the replication and pathogenesis of the virus and facilitate screening and assessment of anti-SARS-CoV-2 therapeutics.


Assuntos
SARS-CoV-2 , Replicação Viral , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Humanos , COVID-19/virologia , Técnicas de Cultura de Células , Replicon/genética , Animais , Genoma Viral , Linhagem Celular , Cromossomos Artificiais Bacterianos/genética , Chlorocebus aethiops , Células Vero , RNA Viral/genética , RNA Viral/metabolismo , Genes Reporter , Recombinação Genética
7.
Heliyon ; 10(10): e31546, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38807894

RESUMO

Background: In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to investigate the serum exosomal miRNA expression profile of dengue-infected individuals through a community survey of dengue virus (DENV) infection. Methods: A seroprevalence study of 1253 healthy persons was first conducted to ascertain the DENV infection status in Baiyun District, Guangzhou. A total of 18 serum samples, including 6 healthy controls (HC), 6 asymptomatic DENV infections (AsymptDI), and 6 confirmed dengue fever patients (AcuteDI), were collected for exosome isolation and then sRNA sequencing. Through bioinformatics analysis, we discovered distinct serum exosomal miRNA profiles among the different groups and identified differentially expressed miRNAs (DEMs). These findings were further validated by qRT-PCR. Results: The community survey of DENV infection indicated that the DENV IgG antibody positivity rate among the population was 11.97 % in the study area, with asymptomatic infected individuals accounting for 93.06 % of the anti-DENV IgG positives. The age and Guangzhou household registration were associated with DENV IgG antibody positivity by logistic regression analysis. Distinct miRNA profiles were observed between healthy individuals and DENV infections. A total of 1854 miRNAs were identified in 18 serum exosome samples from the initial analysis of the sequencing data. Comparative analysis revealed 23 DEMs comprising 5 upregulated and 18 downregulated miRNAs in the DENV-infected group (mergedDI). In comparison to AcuteDI, 18 upregulated miRNAs were identified in AsymptDI. Moreover, functional enrichment of the predicted target genes of DEMs indicated that these miRNAs were involved in biological processes and pathways related to cell adhesion, focal adhesion, endocytosis, and ECM-receptor interaction. Eight DEMs were validated by qRT-PCR. Conclusion: The Baiyun District of Guangzhou exhibits a notable proportion of asymptomatic DENV infections as suggested in other research, highlighting the need for enhanced monitoring and screening of asymptomatic persons and the elderly. Differential miRNA expression among healthy, symptomatic and asymptomatic DENV-infected individuals suggests their potential as biomarkers for distinguishing DENV infection and offers new avenues of investigating the mechanisms underlying DENV asymptomatic infections.

8.
Adv Mater ; 36(26): e2402245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615264

RESUMO

Zinc metal is an attractive anode material for rechargeable aqueous Zn-ion batteries (ZIBs). However, the dendrite growth, water-induced parasitic reactions, and freezing problem of aqueous electrolyte at low temperatures are the major roadblocks that hinder the widely commercialization of ZIBs. Herein, tetrahydrofuran (THF) is proposed as the electrolyte additive to improve the reversibility and stability of Zn anode. Theoretical calculation and experimental results reveal that the introduction of THF into the aqueous electrolyte can optimize the solvation structure which can effectively alleviate the H2O-induced side reactions and protect the Zn anode from corrosion. Moreover, THF can act as a hydrogen bond acceptor to interact with H2O, which can greatly reduce the activity of free H2O in electrolytes and improve the low-temperature electrochemical performance of Zn anode. As a result, the Zn anodes demonstrate high cyclic stability for 2800 h at 27 °C and over 4000 h at -10 °C at 1.0 mA cm-2 /1.0 mAh cm-2. The full cell exhibits excellent cyclic stability and rate capability at 27 and -10 °C. This work is expected to provide a new approach to regulate the aqueous electrolyte and Zn anode interface chemistry for highly stable and reversible Zn anodes.

9.
Acta Biochim Biophys Sin (Shanghai) ; 56(7): 986-996, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655616

RESUMO

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Biologia Computacional , Epitopos de Linfócito T , Antígeno HLA-A2 , SARS-CoV-2 , Vacinas de DNA , Epitopos de Linfócito T/imunologia , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Animais , Vacinas de DNA/imunologia , Vacinas de DNA/genética , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/genética , Camundongos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Feminino , Camundongos Endogâmicos BALB C , Imunoinformática
10.
Sci Bull (Beijing) ; 69(16): 2580-2595, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38670853

RESUMO

Chronic hepatitis B virus (HBV) infection can lead to advanced liver pathology. Here, we establish a transgenic murine model expressing a basic core promoter (BCP)-mutated HBV genome. Unlike previous studies on the wild-type virus, the BCP-mutated HBV transgenic mice manifest chronic liver injury that culminates in cirrhosis and tumor development with age. Notably, agonistic anti-Fas treatment induces fulminant hepatitis in these mice even at a negligible dose. As the BCP mutant exhibits a striking increase in HBV core protein (HBc) expression, we posit that HBc is actively involved in hepatocellular injury. Accordingly, HBc interferes with Fis1-stimulated mitochondrial recruitment of Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15). HBc may also inhibit multiple Rab GTPase-activating proteins, including Rab7-specific TBC1D15 and TBC1D5, by binding to their conserved catalytic domain. In cells under mitochondrial stress, HBc thus perturbs mitochondrial dynamics and prevents the recycling of damaged mitochondria. Moreover, sustained HBc expression causes lysosomal consumption via Rab7 hyperactivation, which further hampers late-stage autophagy and substantially increases apoptotic cell death. Finally, we show that adenovirally expressed HBc in a mouse model is directly cytopathic and causes profound liver injury, independent of antigen-specific immune clearance. These findings reveal an unexpected cytopathic role of HBc, making it a pivotal target for HBV-associated liver disease treatment. The BCP-mutated HBV transgenic mice also provide a valuable model for understanding chronic hepatitis B progression and for the assessment of therapeutic strategies.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Camundongos Transgênicos , Proteínas rab de Ligação ao GTP , proteínas de unión al GTP Rab7 , Animais , Camundongos , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Vírus da Hepatite B/genética , Humanos , Hepatite B Crônica/patologia , Hepatite B Crônica/genética , Progressão da Doença , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Autofagia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Apoptose , Dinâmica Mitocondrial
12.
J Colloid Interface Sci ; 667: 136-146, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38636215

RESUMO

Breaking through the limitations of lithium-ion transmission is imperative for high-power rechargeable batteries. As a promising anode material for fast-charging lithium-ion batteries (LIBs), niobium pentoxide (Nb2O5) has garnered considerable research attention due to its exceptional rate performance, stable lithium storage performance and high safety attributes. Nevertheless, the limited intrinsic conductivity of Nb2O5, coupled with its structural degradation during the cycling process, imposes constraints on its viability as a commercially viable electrode material. Herein, a ruthenium (Ru) doping method is employed to regulate the oxygen defects and the interlayer spacing of the tetragonal Nb2O5 (M-Nb2O5), offering superior reaction kinetics, higher stability for lithium storage sites and more unobstructed lithium-ion transport channels. Ru-doped Nb2O5 (RNO) manifests excellent electrochemical properties, including remarkable rate capacity (166 mAh/g at 80C), reversible capacity (246.98 mAh/g at 0.5C), improved initial Coulombic efficiency (95.77 % compared to 81.44 % of the pure sample) and cycling stability (maintaining a capacity of 113.5 mAh/g at 10C for 2,000 cycles). The enhancement mechanism of Ru doping on the structural stability and ion transport kinetics in tetragonal Nb2O5 is comprehensively elucidated through diverse electrochemical analyses and in-situ techniques.

14.
Adv Healthc Mater ; 13(13): e2303619, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38340040

RESUMO

The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine-induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS-SUMO (SUMO, small ubiquitin-likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS-SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS-SUMO conjugates produce CD4+ T cell-mediated Th2-biased responses and promote humoral immunity. Importantly, LS-SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS-SUMO is a powerful biotargeting nanoplatform with high-yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.


Assuntos
Vírus Chikungunya , Zika virus , Animais , Camundongos , Vírus Chikungunya/imunologia , Zika virus/imunologia , Nanopartículas/química , Vacinas Virais/imunologia , Vacinas Virais/química , Camundongos Endogâmicos BALB C , Feminino , Febre de Chikungunya/imunologia , Febre de Chikungunya/prevenção & controle , Imunidade Humoral/efeitos dos fármacos , Anticorpos Neutralizantes/imunologia , Antígenos Virais/imunologia , Antígenos Virais/química , Nanovacinas , Complexos Multienzimáticos
16.
Angew Chem Int Ed Engl ; 63(18): e202401716, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38372050

RESUMO

High-capacity Ni-rich layered oxides are promising cathode materials for fabrication of lithium-ion batteries (LIBs) with high energy density. However, thermal runaway of LIBs with these cathodes leads to great safety concerns. In this study, single crystalline LiNi0.9Co0.05Mn0.05O2 (NCM-SC) has been prepared and a flexible optical fiber was buried inside the pouch-type LIBs with NCM-SC cathode to in situ study its real-time temperature evolution during charge/discharge process. NCM-SC exhibits an enhanced Li+ ions transportation efficiency and electrode reaction kinetics, which can effectively reduce the generation of polarization heat and mitigate the internal temperature rise of the pouch-type battery. Meanwhile, solid-electrolyte interface (SEI) film decomposition and gas accumulation are effectively alleviated, due to the enhanced thermal stability of SEI film formed on NCM-SC. Moreover, the single crystal architecture can effectively retard layered to spinal and rock-salt phase transition, mitigate the crack formation and structural collapse. Consequently, NCM-SC exhibits an excellent electrochemical performance and enhanced thermal stability.

17.
J Virol ; 98(2): e0134523, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38226815

RESUMO

Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.


Assuntos
Hepatite B Crônica , Hepatite B , Fator de Transcrição MSX1 , Animais , Humanos , Camundongos , DNA Circular , DNA Viral/genética , Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , RNA Viral , Fatores de Transcrição/genética , Replicação Viral/genética , Fator de Transcrição MSX1/metabolismo
18.
Basic Res Cardiol ; 119(1): 75-91, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38172251

RESUMO

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.


Assuntos
Antialérgicos , Estabilizadores de Mastócitos , Humanos , Neuroimunomodulação , Arritmias Cardíacas/prevenção & controle , Coração
19.
Angew Chem Int Ed Engl ; 63(10): e202318042, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38225208

RESUMO

Ni-rich layered oxides are promising lithium-ion batteries (LIBs) cathode materials for their high reversible capacity, but they suffer from fast structural degradation during cycling. Here, we report the Ce/Gd incorporated single-crystalline LiNi0.83 Co0.07 Mn0.10 O2 (SC-NCM) cathode materials with significantly enhanced cycling stability. The Gd ions are adequately incorporated in SC-NCM while Ce ions are prone to aggregate in the outer surface, resulting in the formation of a high-entropy zone in the near-surface of SC-NCM, including a Gd doped LiCeO2 (LCGO) shell and Ce/Gd dopant-concentrated layer. The high-entropy zone can effectively inhibit the oxygen evolution and prevent the formation of oxygen vacancies. Meanwhile, it leads to a greatly improved H2-H3 phase transformation reversibility and mitigated stress/strain caused by Li-ion extraction/insertion during (de)lithiation process. The synergetic effects of reduced oxygen vacancies concentration and mitigated stress/strain can effectively prevent the in-plane migration of TM ions, lattice planar gliding as well as the formation of intragranular nanocracks. Consequently, Ce/Gd incorporated SC-NCM (SC-NCM@CG2) delivers a high initial discharge specific capacity of 219.7 mAh g-1 at 0.1 C and an excellent cycling stability with a capacity retention of 90.2 % after 100 cycles at 1.0 C.

20.
BMC Surg ; 24(1): 41, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297255

RESUMO

OBJECTIVE: Sciatic scoliosis can be seen in patients with lumbar disc herniation. Percutaneous endoscopic lumbar discectomy (PELD) is a common surgical method for the treatment of lumbar disc herniation. The difference between single-segment lumbar disc herniation and double-segment lumbar disc herniation with Sciatic Scoliosis in adults after PELD needs further study. The aim of this study was to compare the imaging features of single-segment and double-segment lumbar disc herniation with Sciatic Scoliosis in adults and to further explore the clinical outcomes of functional improvement and scoliosis imaging parameters of the two groups after PELD. METHODS: Adult patients with lumbar disc herniation with sciatic scoliosis who received PELD from January 2019 to June 2022 were analyzed retrospectively. According to the number of operative segments, the patients were divided into a single-segment group and a double-segment group. Perioperative parameters were observed and compared between the two groups. The Visual Analogue Scale (VAS) score, Oswestry dysfunction index (ODI), Japanese Orthopaedic Association scores (JOA) and imaging parameters of the two groups were recorded and compared before the operation and during the follow-up. RESULTS: A total of 53 patients with single segments and 21 patients with double segments were included in this study. During the follow-up, the VAS score, ODI index and JOA score of the two groups were significantly improved as compared with those before the operation(P < 0. 05). Ninety-two point five percent of single-segment patients and 90.5% of double segment patients returned to normal scoliosis within 12 months after the operation. The operation time, number of intraoperative fluoroscopy times and the amount of intraoperative blood loss in single-segment patients were better than those in double-segment group(P < 0. 05). At the last follow-up, the AVT, CBD and SVA in the double-segment group were 5.2 ± 2.3, 5.1 ± 1.0 and 12.2 ± 3.0 mm, respectively, which were higher than those in the single-segment group (1.9 ± 0.4, 1.1 ± 1.6 and 3.9 ± 2.1 mm) (P < 0. 05). CONCLUSION: PELD is an effective treatment for single-segment and double-segment lumbar disc herniation with Sciatic scoliosis. Double-segment patients can enjoy similar clinical efficacy to single-segment patients, avoiding complications caused by decompression, fusion, and internal fixation. Scoliosis was corrected spontaneously within 12 months after operation, and the sagittal curve was significantly improved in both groups. The improvement of coronal and sagittal balance in double -segment patients may take longer.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Escoliose , Adulto , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Discotomia Percutânea/métodos , Escoliose/complicações , Escoliose/cirurgia , Endoscopia/métodos , Vértebras Lombares/cirurgia , Discotomia/métodos , Resultado do Tratamento
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