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OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.
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With the continuous expansion of pixel arrays in digital microfluidics (DMF) chips, precise droplet control has emerged as a critical issue requiring detailed consideration. This paper proposes a novel capacitance-based droplet sensing system for thin-film transistor DMF. The proposed circuit features a distinctive inner and outer dual-pixel electrode structure, integrating droplet driving and sensing functionalities. Discharge occurs exclusively at the inner electrode during droplet sensing, effectively addressing droplet perturbation in existing sensing circuits. The circuit employs a novel fan-shaped structure of thin-film transistors. Simulation results show that it can provide a 48 V pixel voltage and demonstrate a sensing voltage difference of over 10 V between deionized water and silicone oil, illustrating its proficiency in droplet driving and accurate sensing. The stability of threshold voltage drift and temperature was also verified for the circuit. The design is tailored for integration into active matrix electrowetting-on-dielectric (AM-EWOD) chips, offering a novel approach to achieve precise closed-loop control of droplets.
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This study aims to enhance the durability, cost-effectiveness, and sustainability of recycled fine aggregate concrete (RFAC) subjected to the combined effects of wet-dry cycles and sulfate erosion. Dry-wet cycle tests were conducted in RFAC with different admixtures of biotite metakaolin (MK) and 15% fly ash (FA) mix (M) under 5% sulfate erosion environment. The effect of 0%, 30%, 60% and 90% recycled fine aggregate (RFA) replacement of natural fine aggregate on mass loss, cubic compressive strength, relative dynamic modulus test of RFAC, damage modeling and prediction of damage life of concrete were investigated. The results showed that the concrete cubic compressive strength and relative dynamic modulus were optimal for recycled concrete at 15% MK biotite dosing and 60% RFA substitution, and its maximum service life was accurately predicted to be about 578 cycles under 5% sulfate dry-wet cycling using Weibull function model. This study is pioneering in addressing the durability of RFAC under sulfate attack combined with wet-dry cycling, employing a novel approach of incorporating MK and FA into RFAC. The findings highlight the practical application potential for using MK and FA in RFAC to produce durable and sustainable construction materials, particularly in sulfate-exposed environments. This research addresses a critical challenge in the construction industry, providing valuable insights for developing more durable and eco-friendly construction materials and contributing to long-term sustainability goals.
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INTRODUCTION: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui. METHODOLOGY: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens. RESULTS: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found. CONCLUSIONS: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.
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Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Humanos , China/epidemiologia , Estudos Retrospectivos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antibacterianos/uso terapêutico , Resultado do Tratamento , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/genética , Adulto , Testes de Sensibilidade Microbiana , Pneumopatias/microbiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/epidemiologia , Escarro/microbiologiaRESUMO
Interfacial hydrogen transfer between metal particles and catalyst supports is a ubiquitous phenomenon in heterogeneous catalysis, and this occurrence on reducible supports has been established, yet controversies remain about how hydrogen transfer can take place on nonreducible supports, such as silica. Herein, highly dispersed Pt clusters supported on a series of porous silica materials with zeolitic or/and amorphous frameworks were prepared to interrogate the nature of hydrogen transfer and its promotional effect on H2-HDO isotope catalytic exchange. The formation of zeolitic frameworks upon these porous silica supports by hydrothermal crystallization greatly promotes the interfacial hydrogen bidirectional migration between metal clusters and supports. Benefiting from this transfer effect, the isotope exchange rate is enhanced by 10 times compared to that on the amorphous counterpart (e.g., Pt/SBA-15). In situ spectroscopic and theoretical studies suggest that the defective silanols formed within the zeolite framework serve as the reactive sites to bind HDO or H2O by hydrogen bonds. Under the electrostatic attraction interaction, the D of hydrogen-bonded HDO scrambles to the Pt site and the dissociated H on Pt simultaneously spills back to the electronegative oxygen atom of adsorbed water to attain H-D isotope exchange with an energy barrier of 0.43 eV. The reverse spillover D on Pt combines with the other H on Pt to form HD in the effluent. We anticipate that these findings are able to improve our understanding of hydrogen transfer between metal and silica supports and favor the catalyst design for the hydrogen-involving reaction.
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Digital liquid sample handling is an enabling tool for cutting-edge life-sciences research. We present here an active-matrix thin-film transistor (TFT) based digital microfluidics system, referred to as Field Programmable Droplet Array (FPDA). The system contains 256 × 256 pixels in an active area of 10.65 cm2, which can manipulate thousands of addressable liquid droplets simultaneously. By leveraging a novel TFT device and circuits design solution, we manage to programmatically manipulate droplets at single-pixel level. The minimum achievable droplet volume is around 0.5 nL, which is two orders of magnitude smaller than the smallest droplet ever reported on active-matrix digital microfluidics. The movement of droplets can be either pre-programmed or controlled in real-time. The FPDA system shows great potential of the ubiquitous thin-film electronics technology in digital liquid handling. These efforts will make it possible to create a true programmable lab-on-a-chip device to enable great advances in life science research.
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BACKGROUND/AIMS: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. METHODS: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. RESULTS: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). CONCLUSION: FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.
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Transplante de Fígado , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Fígado/patologia , Fígado/metabolismo , Adulto , Interleucinas/genética , Interleucinas/metabolismo , Transcriptoma , Piroptose , Células Matadoras Naturais/metabolismo , Sobrevivência de Enxerto , Doadores de Tecidos , Pontuação de PropensãoRESUMO
OBJECTIVE: Unilateral biportal endoscopic decompression (UBED) offers the advantages of minimal tissue damage, operational flexibility, and clear visualization, positioning it as an innovative and minimally invasive endoscopic technique. Nevertheless, the clinical evidence supporting the use of UBED in the treatment of degenerative lumbar diseases is limited and conflicting. METHODS: As of October 1, 2023, a comprehensive search was conducted across databases including Web of Science, PubMed, Embase, and the Cochrane Library to identify all published studies on minimally invasive UBED for the treatment of degenerative lumbar diseases. Data pertaining to patient demographics, fluoroscopy time, operative duration, intraoperative hemorrhage, hospitalization length, visual analog scale (VAS) score for back and leg pain, MacNab criteria, Oswestry Disability Index (ODI), and complication rates were extracted. The Newcastle-Ottawa scale was utilized to assess the quality. RESULTS: Twelve articles were included, involving 816 patients. The back VAS score (95% confidence interval [CI]: -0.09-0.07, P = 0.75), MacNab criteria (95% CI: 0.52-2.3, P = 0.82), fluoroscopy time (95% CI: -7.03 to -0.4, P = 0.08), and the incidence of complications (95% CI: 0.5-1.73, P = 0.82) were not significantly different, while the leg VAS score (95% CI: 0.01-0.18, P = 0.03), ODI score (95% CI: -1.03 to -0.09, P = 0.02), operation time (95% CI: 5.76-20.62, P = 0.0005), hospitalization length (95% CI: 0.41-2.76, P = 0.008), and intraoperative hemorrhage (95% CI: 21.92-72.44, P = 0.0003) were significantly different. CONCLUSIONS: UBED offers superiority in ODI, flexibility, and visual field clarity. Conversely, percutaneous endoscopic lumbar decompression presents advantages in terms of operation duration, blood loss, hospitalization length, and leg VAS score. These factors should be thoroughly considered when selecting a surgical approach.
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Descompressão Cirúrgica , Degeneração do Disco Intervertebral , Vértebras Lombares , Humanos , Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Degeneração do Disco Intervertebral/cirurgia , Resultado do Tratamento , Neuroendoscopia/métodos , Endoscopia/métodos , Duração da CirurgiaRESUMO
The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.
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BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.
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Transplante de Fígado , Fígado , Preservação de Órgãos , Perfusão , Humanos , Perfusão/métodos , Perfusão/instrumentação , Transplante de Fígado/métodos , Fígado/cirurgia , Fígado/patologia , Preservação de Órgãos/métodos , Preservação de Órgãos/instrumentação , Masculino , Pessoa de Meia-Idade , Feminino , Hepatopatias/patologiaRESUMO
Automated concentration gradient generation is one of the most important applications of lab-on-a-chip devices. Digital microfluidics is a unique platform that can effectively achieve digitalized gradient concentration preparation. However, the dynamic range and concentration resolution of the prepared samples heavily rely on the size and the number of effective electrodes. In this work, we report an active-matrix digital microfluidic device with polar coordinate electrode arrangement. The device contains 33 different electrode sizes, generating digital droplets of different volumes. To compare with the conventional rectangular coordinate arrangement with a similar electrode number, this work shows an approximately 19 times resolution enhancement for the achievable concentration gradient. We characterized the stability and uniformity of droplets generated by electrodes of different sizes, and the coefficient of variation of stable droplets was less than 3%. The fluorescent nanomaterial's concentration quantification and glucose concentration characterization experiments were also conducted, and the correlation coefficients for the linearities were all above 0.99.
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Glioblastoma (GBM) is the most aggressive brain tumor and is characterized by a poor prognosis and high recurrence and mortality rates. Biochanin A (BCA) exhibits promising clinical anti-tumor effects. In this study, we aimed to explore the pharmacological mechanisms by which BCA acts against GBM. Network pharmacology was employed to identify overlapping target genes between BCA and GBM. Differentially expressed genes from the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database were visualized using VolcaNose. Interactions among these overlapping genes were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Protein-protein interaction networks were constructed using Cytoscape 3.8.1. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Survival analyses for these genes were performed using the GEPIA2 database. The Chinese Glioma Genome Atlas database was used to study the correlations between key prognostic genes. Molecular docking was confirmed using the DockThor database and visualized with PyMol software. Cell viability was assessed via the CCK-8 assay, apoptosis and the cell cycle stages were examined using flow cytometry, and protein expression was detected using western blotting. In all, 63 genes were initially identified as potential targets for BCA in treating GBM. Enrichment analysis suggested that the pharmacological mechanisms of BCA primarily involved cell cycle inhibition, induction of cell apoptosis, and immune regulation. Based on these findings, AKT1, EGFR, CASP3, and MMP9 were preliminarily predicted as key prognostic target genes for BCA in GBM treatment. Furthermore, molecular docking analysis suggested stable binding of BCA to the target protein. In vitro experiments revealed the efficacy of BCA in inhibiting GBM, with an IC50 value of 98.37 ± 2.21 µM. BCA inhibited cell proliferation, induced cell apoptosis, and arrested the cell cycle of GBM cells. Furthermore, the anti-tumor effects of BCA on U251 cells were linked to the regulation of the target protein. We utilized integrated bioinformatics analyses to predict targets and confirmed through experiments that BCA possesses remarkable anti-tumor activities. We present a novel approach for multi-target treatment of GBM using BCA.
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Glioblastoma , Humanos , Prognóstico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Simulação de Acoplamento Molecular , Genisteína/farmacologiaRESUMO
INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.
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Transplante de Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Adulto , IdosoRESUMO
Two-sided coated optical lenses are important in optical applications. A film-stress-induced aberration can adversely affect the lens performance. In this paper, a mechanical method has been developed to reduce this aberration. The proposed method uses a specialized finite element method with an easy modeling process and high versatility to analyze the impact of film parameters (including stress, the thickness, and the coating range) on aberrations under different lens geometric parameters. Theoretically, by selecting the property film parameters within the range of an application's requirements can reduce the aberrations. The proposed method could reduce film-stress-induced aberrations to make the aberration compensation easier.
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Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 ß, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.
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Reabsorção Óssea , Flavonas , Osteogênese , Feminino , Humanos , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Reabsorção Óssea/metabolismo , Ovariectomia , Ligante RANK/metabolismo , Fatores de Transcrição NFATC/metabolismo , Camundongos Endogâmicos C57BL , Diferenciação CelularRESUMO
BACKGROUND AND PURPOSE: The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF-219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S-600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3-(4-([3-chloro-4-isopropoxyphenyl]amino)-3-(4-methylbenzyl)-2,6-dioxo-3,6-dihydro-1,3,5-triazin-1(2H)-yl)propanoic acid (DDTPA), exhibit both high affinity and high selectivity for hP2X3 homotrimers, compared with hP2X2/3 heterotrimers. The mechanism underlying the druggable site and its high selectivity remains unclear. EXPERIMENTAL APPROACH: To analyse mechanisms that distinguish this drug candidate from other inhibitors of the P2X3 receptors we used a combination of chimera construction, site covalent occupation, metadynamics, mutagenesis and whole-cell recording. KEY RESULTS: The high affinity and selectivity of sivopixant/DDTPA for hP2X3 receptors was determined by the tri-symmetric site located close to the upper vestibule. Substitution of only four amino acids inside the upper body domain of hP2X2 with those of hP2X3, enabled the hP2X2/3 heterotrimer to exhibit a similar level of apparent affinity for sivopixant/DDTPA as the hP2X3 homotrimer. CONCLUSION AND IMPLICATIONS: From the receptor-ligand recognition perspective, we have elucidated the molecular basis of novel RCC clinical candidates' cough-suppressing properties and reduced side effects, offering a promising approach to the discovery of novel drugs that specifically target P2X3 receptors.
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Compostos de Anilina , Benzenossulfonamidas , Carcinoma de Células Renais , Neoplasias Renais , Pirimidinas , Triazinas , Humanos , Carcinoma de Células Renais/induzido quimicamente , Piridinas/uso terapêutico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Tosse/induzido quimicamente , Receptores Purinérgicos P2X3 , Sulfonamidas , Neoplasias Renais/induzido quimicamente , Receptores Purinérgicos P2X2RESUMO
Ducks infected with duck circovirus (DuCV) show symptoms such as feather loss, growth retardation and low body weight in the flock. The virus induces immunosuppression and increases the prevalence of infection with other pathogens. However, most studies on duck circovirus were focused on coinfection, and fewer studies had been conducted on the pathogenicity of duck circovirus alone. The aim of the present study was to investigate the pathogenesis of DuCV-1 in experimentally infected specific pathogen-free ducks. In this study, we sequenced the whole genome of a strain of duck circovirus and identified the virus genotype as DuCV-1b. This strain of duck circovirus was named SDLH(OR567883). Animal pathogenicity experiments were then conducted, wherein specific pathogen-free ducks were infected by mucosal injection and abdominal injection. Infected ducks were sampled for 4 consecutive weeks after infection and showed symptoms of dwarfism. We further examined the replication of DuCV-1 in the ducks. The highest virus titers in the 2 infection groups were found in the liver and spleen, with different results for the different routes of infection. Pathological sections of duck organs were made and it was found that organs such as the liver and spleen were damaged by DuCV-1. In conclusion, our experimental results indicate that DuCV-1 can infect ducks individually and cause widespread organ damage in infected ducks.
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Infecções por Circoviridae , Circovirus , Doenças das Aves Domésticas , Animais , Virulência , Galinhas/genética , Sequência de Bases , Circovirus/genética , Infecções por Circoviridae/veterináriaRESUMO
BACKGROUND: Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit. METHODS: Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30-min warm ischemia time and 90-min cold ischemia time. The liver-kidney NMP group (n = 5) and the single-kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared. RESULTS: The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver-kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver-kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL-6, IL-8, IL-1ß, NLRP3, and GSDMD. CONCLUSIONS: Our results indicated that the expression of renal pro-inflammatory factors was reduced in the liver-kidney NMP system.
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Fígado , Preservação de Órgãos , Suínos , Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Rim/patologia , Isquemia Quente/métodosRESUMO
OBJECTIVE: To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-ß on T cell acute lymphoblastic leukemia (T-ALL) cell lines. METHODS: Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy. RESULTS: Different concentrations of FA-2-b-ß significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-ß inhibited ABCB1ãABCG2ãCTNNBãMYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-ß reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/ß-catenin inhibitor (ICG001), the process was further intensified. CONCLUSION: Agaricus Blazei Extract FA-2-b-ß inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.