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The cytoplasm is highly compartmentalized, but the extent and consequences of subcytoplasmic mRNA localization in non-polarized cells are largely unknown. We determined mRNA enrichment in TIS granules (TGs) and the rough endoplasmic reticulum (ER) through particle sorting and isolated cytosolic mRNAs by digitonin extraction. When focusing on genes that encode non-membrane proteins, we observed that 52% have transcripts enriched in specific compartments. Compartment enrichment correlates with a combinatorial code based on mRNA length, exon length, and 3' UTR-bound RNA-binding proteins. Compartment-biased mRNAs differ in the functional classes of their encoded proteins: TG-enriched mRNAs encode low-abundance proteins with strong enrichment of transcription factors, whereas ER-enriched mRNAs encode large and highly expressed proteins. Compartment localization is an important determinant of mRNA and protein abundance, which is supported by reporter experiments showing that redirecting cytosolic mRNAs to the ER increases their protein expression. In summary, the cytoplasm is functionally compartmentalized by local translation environments.
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Retículo Endoplasmático , Proteínas , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Proteínas/metabolismo , Citosol/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transporte Proteico , Biossíntese de ProteínasRESUMO
INTRODUCTION: It is crucial to investigate the distinct proteins that contribute to the advancement of lung cancer. MATERIAL AND METHODS: We analyzed the expression levels of 92 immuno-oncology-related proteins in 96 pairs of lung adenocarcinoma tissue samples using Olink proteomics. The differentially expressed proteins (DEPs) were successively screened in tumor and paraneoplastic groups, early and intermediate-late groups by a nonparametric rank sum test, and the distribution and expression levels of DEPs were determined by volcano and heat maps, etc., and the area under the curve was calculated. RESULTS: A total of 24 DEPs were identified in comparisons between tumor and paracancerous tissues. Among them, interleukin-8 (IL8) and chemokine (C-C motif) ligand 20 (CCL20) as potential markers for distinguishing tumor tissues. Through further screening, it was found that interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) may be able to lead to tumor progression through the JaK-STAT signaling pathway, Toll-like receptor signaling pathway and PI3K/AKT signaling pathway. Interestingly, our study revealed a down-regulation of IL6 and VEGFA in tumor tissues compared to paracancerous tissues. CONCLUSIONS: IL8 + CCL20 (AUC: 0.7056) have the potential to differentiate tumor tissue from paracancerous tissue; IL6 + VEGFA (AUC: 0.7531) are important protein markers potentially responsible for tumor progression.
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Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Quimiocina CCL20 , Progressão da Doença , Interleucina-8 , Neoplasias Pulmonares , Proteômica , Fator A de Crescimento do Endotélio Vascular , Humanos , Proteômica/métodos , Biomarcadores Tumorais/metabolismo , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Quimiocina CCL20/metabolismo , Interleucina-8/metabolismo , Interleucina-6/metabolismo , Transdução de Sinais , Feminino , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: In recent decades, osteosarcoma has remained the most prevalent kind of malignant tumor. An important and crucial factor in immunotherapy is antigen processing and presentation (APP). The specific functions and pathogenic processes of APP in osteosarcoma have not, however, been studied. METHODS: Patients with osteosarcoma were divided into groups using APP-related genes. Machine learning was used to further build the APP-related score. Investigated in-depth were the prognostic relevance of the score, mutation features, immunological aspects, and pharmacological prediction performance. Investigations of the prognostic utility, immunological traits, drug prediction effectiveness and immunotherapy prediction of BNIP3 were performed in-depth. RESULTS: Investigations by cell counting kit-8, Transwell and 5-ethynyl-2-deoxyuridine (EdU) demonstrated that BNIP3 is an osteosarcoma tumor accelerator. The osteosarcoma gene BNIP3 may promote macrophage migration. The APP-related score shows potential for clinical use. CONCLUSIONS: It was anticipated that more in vitro and in vivo studies would confirm BNIP3's tumorigenic and immunogenic processes in osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Apresentação de Antígeno , Oncogenes , Osteossarcoma/genética , Osteossarcoma/terapia , Aprendizado de Máquina , Imunoterapia , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genéticaRESUMO
Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.
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Listeria monocytogenes (L. monocytogenes) is a prevalent foodborne pathogen with a remarkable capacity to form biofilms on utensil surfaces. The Listeriolysin O (LLO) exhibits hemolytic activity, which is responsible for causing human infections. In this study, we investigated the inhibitory effect and mechanism of oregano essential oil (OEO) on L. monocytogenes, evaluated the effects on its biofilm removal and hemolytic activity. The minimum inhibitory concentration (MIC) of OEO against L. monocytogenes was 0.03 % (v/v). L. monocytogenes was treated with OEO at 3/2 MIC for 30 min the bacteria was decreased below the detection limit (10 CFU/mL) in PBS and TSB (the initial bacterial load was about 6.5 log CFU/mL). The level of L. monocytogenes in minced pork co-cultured with OEO (15 MIC) about 2.5 log CFU/g lower than that in the untreated group. The inhibitory mechanisms of OEO against planktonic L. monocytogenes encompassed perturbation of cellular morphology, elevation in reactive oxygen species levels, augmentation of lipid oxidation extent, hyperpolarization of membrane potential, and reduction in intracellular ATP concentration. In addition, OEO reduced biofilm coverage on the surface of glass slides by 62.03 % compared with the untreated group. Meanwhile, OEO (1/8 MIC) treatment reduced the hemolytic activity of L. monocytogenes to 24.6 % compared with the positive control. Molecular docking suggested carvacrol and thymol might reduce the hemolytic activity of L. monocytogenes. The results of this study demonstrate that OEO exhibits inhibitory effects against L. monocytogenes, biofilms and LLO, which had potential as natural antimicrobial for the inhibition of L. monocytogenes.
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Coamorphous and cocrystal drug delivery systems provide attractive crystal engineering strategies for improving the solubilities, dissolution rates, and oral bioavailabilities of poorly water-soluble drugs. Polymeric additives have often been used to inhibit the unwanted crystallization of amorphous drugs. However, the transformation of a coamorphous phase to a cocrystal phase in the presence of polymers has not been fully elucidated. Herein, we investigated the effects of low concentrations of the polymeric excipients poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) on the growth of carbamazepine-celecoxib (CBZ-CEL) cocrystals from the corresponding coamorphous phase. PEO accelerated the growth rate of the cocrystals by increasing the molecular mobility of the coamorphous system, while PVP had the opposite effect. The coamorphous CBZ-CEL system exhibited two anomalously fast crystal growth modes: glass-to-crystal (GC) growth in the bulk and accelerated crystal growth at the free surface. These two fast growth modes both disappeared after doping with PEO (1-3% w/w) but were retained in the presence of PVP, indicating a potential correlation between the two fast crystal growth modes. We propose that the different effects of PEO and PVP on the crystal growth modes arose from weaker effects of the polymers on cocrystallization at the surface than in the bulk. This work provides a deep understanding of the mechanisms by which polymers influence the cocrystallization kinetics of a multicomponent amorphous phase and highlights the importance of polymer selection in stabilizing coamorphous systems or preparing cocrystals via solid-based methods.
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Carbamazepina , Cristalização , Polietilenoglicóis , Polímeros , Povidona , Solubilidade , Polímeros/química , Polietilenoglicóis/química , Carbamazepina/química , Povidona/química , Excipientes/química , Vidro/químicaRESUMO
Micro- and nanoparticles delivery systems have been widely studied as vaccine adjuvants to enhance immunogenicity and sustain long-term immune responses. Polygonatum sibiricum polysaccharide (PSP) has been widely studied as an immunoregulator in improving immune responses. In this study, we synthesized and characterized cationic modified calcium carbonate (CaCO3) microparticles loaded with PSP (PEI-PSP-CaCO3, CTAB-PSP-CaCO3), studied the immune responses elicited by PEI-PSP-CaCO3 and CTAB-PSP-CaCO3 carrying ovalbumin (OVA). Our results demonstrated that PEI-PSP-CaCO3 significantly enhanced the secretion of IgG and cytokines (IL-4, IL-6, IFN-γ, and TNF-α) in vaccinated mice. Additionally, PEI-PSP-CaCO3 induced the activation of dendritic cells (DCs), T cells, and germinal center (GC) B cells in draining lymph nodes (dLNs). It also enhanced lymphocyte proliferation, increased the ratio of CD4+/CD8+ T cells, and elevated the frequency of CD3+ CD69+ T cells in spleen lymphocytes. Therefore, PEI-PSP-CaCO3 microparticles induced a stronger cellular and humoral immune response and could be potentially useful as a vaccine delivery and adjuvant system.
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Carbonato de Cálcio , Células Dendríticas , Polygonatum , Polissacarídeos , Animais , Camundongos , Carbonato de Cálcio/química , Polygonatum/química , Polissacarídeos/química , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Feminino , Adjuvantes de Vacinas/química , Ovalbumina/imunologia , Ovalbumina/administração & dosagem , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Nanopartículas/químicaRESUMO
Transient receptor potential melastatin 4 (TRPM4) is considered to be a potential target for cancer and other human diseases. Herein, a series of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives were designed and synthesized as new TRPM4 inhibitors, aiming to improve cellular potency. One of the most promising compounds, 7d (ZX08903), displayed promising antiproliferative activity against prostate cancer cell lines. 7d also suppressed colony formation and the expression of androgen receptor (AR) protein in prostate cancer cells. Furthermore, 7d can concentration-dependently induce cell apoptosis in prostate cancer cells. Collectively, these findings indicated that compound 7d may serve as a promising lead compound for further anticancer drug development.
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Antineoplásicos , Neoplasias da Próstata , Canais de Cátion TRPM , Masculino , Humanos , Linhagem Celular Tumoral , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proliferação de Células , Relação Estrutura-Atividade , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura MolecularRESUMO
OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções Assintomáticas/epidemiologia , Ureia/análise , Gastroscopia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Radioisótopos de CarbonoRESUMO
Beta-cypermethrin (ß-CY) residues in food are an important threat to human health. Microorganisms can degrade ß-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of ß-CY in a food microorganism was conducted based on proteomics analysis. The ß-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of ß-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of ß-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of ß-CY, which confirmed that this enzyme was the key enzyme in the process of ß-CY degradation. This study reveals the degradation mechanism of ß-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in ß-CY residues.
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Esterases , Proteômica , Piretrinas , Piretrinas/metabolismo , Esterases/metabolismo , Esterases/genética , Alimentos Fermentados/microbiologia , Fermentação , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Drugs with anti-platelet aggregation and neuroprotection are of great significance for the treatment of ischemic stroke. A series of edaravone and 6-phenyl-4,5-dihydropyridazin-3(2H)-one hybrids were designed and synthesized. Among them, 6g showed the most effective cytoprotective effect against oxygen-glucose deprivation/reoxygenation-induced damage in BV2 cells and an excellent inhibitory effect on platelet aggregation induced by adenosine diphosphate and arachidonic acid. Additionally, 6g could prevent thrombosis caused by ferric chloride in rats and pose a lower risk of causing bleeding compared with aspirin. It provides better protection against ischemia/reperfusion injury in rats compared with edaravone and alleviates the oxidative stress related to cerebral ischemia/reperfusion by increasing the GSH and SOD levels and decreasing the MDA concentration. Finally, molecular docking results showed that 6g probably acts on PDE3â A and plays an anti-platelet aggregation effect. Overall, 6g could be a potential candidate compound for the treatment of ischemic stroke.
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Edaravone , AVC Isquêmico , Fármacos Neuroprotetores , Inibidores da Agregação Plaquetária , Agregação Plaquetária , Animais , Edaravone/farmacologia , Edaravone/química , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Ratos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/síntese química , Simulação de Acoplamento Molecular , Masculino , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Ratos Sprague-Dawley , Descoberta de Drogas , Piridazinas/farmacologia , Piridazinas/química , Estresse Oxidativo/efeitos dos fármacosRESUMO
The clinical outcomes of osteosarcoma are relatively dismal. As immunotherapy has revolutionized treatment for solid tumors, exploring novel immunotherapy-related therapeutic targets for osteosarcoma is important. In this study, we aimed to establish the connection between RNA modification and immunotherapy in osteosarcoma to identify novel therapeutic targets. An RNA modification-related signature was first developed using weight gene correlation network analysis and a machine-learning algorithm, random forest. The signature's prognostic value, drug prediction, and immune characteristics were analyzed. EIF4G2 from the signature was next identified as a critical immunotherapy determinant. EIF4G2 could also promote tumor proliferation, migration, and M2 macrophage migration by single-cell sequencing analysis and in vitro validation. Our signature and EIF4G2 are expected to provide valuable insights into the clinical management of osteosarcoma.
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BACKGROUND: Automated test assembly (ATA) represents a modern methodology that employs data science optimization on computer platforms to automatically create test form, thereby significantly improving the efficiency and accuracy of test assembly procedures. In the realm of medical education, large-scale high-stakes assessments often necessitate lengthy tests, leading to elevated costs in various dimensions (such as examinee fatigue and expenses associated with item development). This study aims to augment the design of the medical education assessments by leveraging modern ATA approaches. METHODS: To achieve the objective, a four-step process employing psychometric methodologies was used to calibrate and analyze the item pool of the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test comprising 300 multiple-choice questions (MCQ) in China. Subsequently, two modern ATA approaches were employed to determine the optimal item combination, accounting for both statistical and content requirements specified in the test blueprint. The qualities of the assembled test form, generated using modern ATA approaches, underwent meticulous evaluation. RESULTS: Through an exploration of the psychometric properties of the SCTCMU as a foundational step, the evaluation revealed commendable quality in the item properties. Furthermore, the evaluation of the quality of assembled test form using modern ATA approaches indicated the ability to ascertain the optimal test length within the predefined measurement precision. Specifically, this investigation demonstrates that the application of modern ATA approaches can substantially reduce the test length of assembled test form, while simultaneously maintaining the required statistical and content standards specified in the test blueprint. CONCLUSIONS: This study harnessed modern ATA approaches to facilitate the automatic construction of test form, thereby significantly enhancing the efficiency and precision of test assembly procedures. The utilization of modern ATA approaches offers medical educators a valuable tool to enhance the efficiency and cost-effectiveness of medical education assessment.
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Educação de Graduação em Medicina , Avaliação Educacional , Psicometria , Humanos , Avaliação Educacional/métodos , Educação de Graduação em Medicina/normas , China , Estudantes de Medicina , Competência Clínica/normasRESUMO
Shape recognition plays a significant role in the field of robot perception. In view of the low efficiency and few types of shape recognition of the fiber tactile sensor applied to flexible skin, a convolutional-neural-network-based FBG tactile sensing array shape recognition method was proposed. Firstly, a sensing array was fabricated using flexible resin and 3D printing technology. Secondly, a shape recognition system based on the tactile sensing array was constructed to collect shape data. Finally, shape classification recognition was performed using convolutional neural network, random forest, support vector machine, and k-nearest neighbor. The results indicate that the tactile sensing array exhibits good sensitivity and perception capability. The shape recognition accuracy of convolutional neural network is 96.58%, which is 6.11%, 9.44%, and 12.01% higher than that of random forest, k-nearest neighbor, and support vector machine. Its F1 is 96.95%, which is 6.3%, 8.73%, and 11.94% higher than random forest, k-nearest neighbor, and support vector machine. The research of FBG shape sensing array based on convolutional neural network provides an experimental basis for shape perception of flexible tactile sensing.
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Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.
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Autofagia , Vírus da Raiva , Proteínas com Motivo Tripartido , Replicação Viral , Animais , Humanos , Camundongos , Autofagia/genética , Linhagem Celular Tumoral , Interações Hospedeiro-Patógeno , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Raiva/virologia , Raiva/metabolismo , Vírus da Raiva/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genéticaRESUMO
The Pichia kluyveri, a proliferation commonly found in Sichuan pickles (SCPs), can accelerate the growth and reproduction of spoilage bacteria, causing off-odor development and decay. Although D-limonene, a common natural preservative, effectively restricts P. kluyveri, its inhibitory mechanism remains unclear. This study aimed to elucidate this molecular mechanism by investigating the impact on basic P. kluyveri metabolism. The findings revealed that D-limonene inhibited P. kluyveri growth and disrupted the transcription of the genes responsible for encoding the enzymes involved in cell wall and membrane synthesis, oxidative phosphorylation, glycolysis, and the tricarboxylic acid (TCA) cycle pathway. The results indicated that these events disrupted crucial metabolism such as cell wall and membrane integrity, adenosine triphosphate (ATP) synthesis, and reactive oxygen species (ROS) balance. These insights provided a comprehensive understanding of the inhibitory effect of D-limonene on the growth and reproduction of P. kluyveri while highlighting its potential application in the SCP industry.
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Limoneno , Pichia , Limoneno/farmacologia , Pichia/metabolismo , Pichia/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Silicon (Si) anode suffers from huge volume expansion which causes poor structural stability in terms of electrode material, solid electrolyte interface, and electrode, limiting its practical application in high-energy-density lithium-ion batteries. Rationally designing architectures to optimize the stress distribution of Si/carbon (Si/C) composites has been proven to be effective in enhancing their structural stability and cycling stability, but this remains a big challenge. Here, metal-organic frameworks (ZIF-67)-derived carbon nanotube-reinforced carbon framework is employed as an outer protective layer to encapsulate the inner carbon-coated Si nanoparticles (Si@C@CNTs), which features dual carbon stress-buffering to enhance the structural stability of Si/C composite and prolong their cycling lifetime. Finite element simulation proves the structural advantage of dual carbon stress-buffering through significantly relieving stress concentration when Si lithiation. The outer carbon framework also accelerates the charge transfer efficiency during charging/discharging by the improvement of lithium-ion diffusion and electron transport. As a result, the Si@C@CNTs electrode exhibits excellent long-term lifetime and good rate capability, showing a specific capacity of 680 mAh g-1 even at a high rate of 1 A g-1 after 1000 cycles. This work provides insight into the design of robust architectures for Si/C composites by stress optimization.
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Hepatitis B virus (HBV) infection and type-2 diabetes mellitus (T2DM) affect millions of individuals worldwide, whereas their interplay remains largely unclear. Here, we analyzed a large cohort of 330 HBV-infected inpatients with T2DM (so-called HBV + T2DM patients) and 330 T2DM inpatients without HBV infection (T2DM patients). Poor glycemic control was defined by glycated hemoglobin (HbA1c) ≥ 7%. Among 330 HBV + T2DM patients, 252 (76%) aged ≥ 50 years, 223 (68%) were males, 205 (62%) experienced poor glycemic control. The propensity-score matching approach was applied to match patient age, gender, comorbidities, and antidiabetic treatment between T2DM + HBV and T2DM patients. Compared with T2DM patients, HBV + T2DM patients had poorer glycemic control, longer hospitalization length, and higher alanine aminotransferase (p < 0.05). HBV + T2DM patients with HBV DNA ≥ 100 IU/mL or HBsAg ≥ 0.05 IU/mL had worse HbA1c control than T2DM patients without HBV infection (p < 0.05). HBV + T2DM patients who received no anti-HBV therapy had worse HbA1c control than HBV + T2DM patients receiving anti-HBV therapy (p < 0.05). Both insulin and anti-HBV therapy were significant factors associated with glycemic control in HBV + T2DM patients. Overall, HBV + T2DM patients exhibited poorer glycemic control than T2DM patients, but their clinical outcomes were likely improved by insulin plus anti-HBV treatment. Early management of HBV infection likely contributes to better clinical outcomes in HBV-infected patients with T2DM.
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Diabetes Mellitus Tipo 2 , Hepatite B , Masculino , Humanos , Feminino , Estudos Retrospectivos , Hemoglobinas Glicadas , Controle Glicêmico , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Insulina/uso terapêutico , Vírus da Hepatite B/genéticaRESUMO
Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of Coronavirus Disease 2019 (COVID-19). Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a 6-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large T cell receptor/B cell receptor clones, decreased diversity, abnormal class-switch recombination, and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19+ CD138+ B cells were found in COVID-19 survivors. The proportion of CD4+ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3+ CD4- T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3+ CD4- T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage.
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COVID-19 , Humanos , SARS-CoV-2 , Estudos Prospectivos , Linfócitos B , Anticorpos Antivirais , SobreviventesRESUMO
Hypervirulent Klebsiella pneumoniae (hvKp), characterized by high virulence and epidemic potential, has become a global public health challenge. Therefore, improving the identification of hvKp and enabling earlier and faster detection in the community to support subsequent effective treatment and prevention of hvKp are an urgent issue. To address these issues, a number of assays have emerged, such as String test, Galleria mellonella infection test, PCR, isothermal exponential amplification, and so on. In this paper, we have collected articles on the detection methods of hvKp and conducted a retrospective review based on two aspects: traditional detection technology and biomarker-based detection technology. We summarize the advantages and limitations of these detection methods and discuss the challenges as well as future directions, hoping to provide new insights and references for the rapid detection of hvKp in the future. The aim of this study is to focus on the research papers related to Hypervirulent Klebsiella pneumoniae involving the period from 2012 to 2022. We conducted searches using the keywords "Hypervirulent Klebsiella pneumoniae, biomarkers, detection techniques" on ScienceDirect and Google Scholar. Additionally, we also searched on PubMed, using MeSH terms associated with the keywords (such as Klebsiella pneumoniae, Klebsiella Infections, Virulence, Biomarkers, diagnosis, etc.).