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1.
Polymers (Basel) ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675072

RESUMO

The blending of polyolefins (POs), such as polyethylene (PE) and polypropylene (PP), is a growing area of research, particularly for recycling mixed polyolefin (MPO) waste through flotation sorting techniques. However, understanding the thermomechanical behavior of these recycled blends is challenging due to limitations in the existing characterization methods. This paper introduces a combined experimental and numerical method to accurately assess the complex mechanical behavior of high-density PE, PP, and their blends. We conducted detailed thermomechanical analyses using a high-speed stereo digital image correlation (DIC) system paired with an infrared camera to capture temperature variations alongside mechanical stress and strain. This approach allowed us to correct for distortions caused by necking and to derive accurate stress-strain relationships. We also applied a cutting-edge unified semi-crystalline polymer (USCP) model to simplify the analysis, focusing on the effects of strain rate and temperature, including self-heating and thermal softening phenomena. Our results, which closely match experimental observations of stress-strain behavior and temperature changes, offer new insights into the thermomechanical properties of PO blends, which are essential for advancing their practical applications in various fields.

2.
J Transl Med ; 22(1): 300, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521905

RESUMO

BACKGROUND: Crohn's disease (CD) is a disease characterized by intestinal immune dysfunction, often accompanied by metabolic abnormalities. Disturbances in lactate metabolism have been found in the intestine of patients with CD, but studies on the role of lactate and related Lactylation in the pathogenesis of CD are still unknown. METHODS: We identified the core genes associated with Lactylation by downloading and merging three CD-related datasets (GSE16879, GSE75214, and GSE112366) from the GEO database, and analyzed the functions associated with the hub genes and the correlation between their expression levels and immune infiltration through comprehensive analysis. We explored the Lactylation levels of different immune cells using single-cell data and further analyzed the differences in Lactylation levels between inflammatory and non-inflammatory sites. RESULTS: We identified six Lactylation-related hub genes that are highly associated with CD. Further analysis revealed that these six hub genes were highly correlated with the level of immune cell infiltration. To further clarify the effect of Lactylation on immune cells, we analyzed single-cell sequencing data of immune cells from inflammatory and non-inflammatory sites in CD patients and found that there were significant differences in the levels of Lactylation between different types of immune cells, and that the levels of Lactylation were significantly higher in immune cells from inflammatory sites. CONCLUSIONS: These results suggest that Lactylation-related genes and their functions are closely associated with changes in inflammatory cells in CD patients.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/genética , Bases de Dados Factuais , Ácido Láctico , Análise de Sequência de RNA
3.
EMBO Mol Med ; 16(2): 334-360, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177537

RESUMO

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Neoplasias Colorretais/genética , Microambiente Tumoral
4.
Cell Mol Immunol ; 21(1): 80-90, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38082146

RESUMO

Regulatory T (Treg) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis. However, simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways. Thus, our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis, thereby providing novel insights into the mechanisms of Treg cell homeostasis.


Assuntos
Apoptose , Linfócitos T Reguladores , Animais , Camundongos , Morte Celular , Homeostase
5.
PLoS Pathog ; 19(10): e1011662, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37788227

RESUMO

Coxsackievirus A10 (CVA10) has recently emerged as one of the major causative agents of hand, foot, and mouth disease. CVA10 may also cause a variety of complications. No approved vaccine or drug is currently available for CVA10. The residues of CVA10 critical for viral attachment, infectivity and in vivo pathogenicity have not been identified by experiment. Here, we report the identification of CVA10 residues important for binding to cellular receptor KREMEN1. We identified VP2 N142 as a key receptor-binding residue by screening of CVA10 mutants resistant to neutralization by soluble KREMEN1 protein. The receptor-binding residue N142 is exposed on the canyon rim but highly conserved in all naturally occurring CVA10 strains, which provides a counterexample to the canyon hypothesis. Residue N142 when mutated drastically reduced receptor-binding activity, resulting in decreased viral attachment and infection in cell culture. More importantly, residue N142 when mutated reduced viral replication in limb muscle and spinal cord of infected mice, leading to lower mortality and less severe clinical symptoms. Additionally, residue N142 when mutated could decrease viral binding affinity to anti-CVA10 polyclonal antibodies and a neutralizing monoclonal antibody and render CVA10 resistant to neutralization by the anti-CVA10 antibodies. Overall, our study highlights the essential role of VP2 residue N142 of CVA10 in the interactions with KREMEN1 receptor and neutralizing antibodies and viral virulence in mice, facilitating the understanding of the molecular mechanisms of CVA10 infection and immunity. Our study also provides important information for rational development of antibody-based treatment and vaccines against CVA10 infection.


Assuntos
Anticorpos Neutralizantes , Enterovirus , Animais , Camundongos , Enterovirus/genética , Virulência , Anticorpos Antivirais
6.
Chem Biol Drug Des ; 102(4): 793-804, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37455324

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a prevalent long-term disease in the world. Liquiritigenin (LQ) is protective against a variety of hepatotoxins. Herein, we report the potential mechanism of LQ on a high-fat diet (HFD) induced NAFLD. NAFLD mice model was established by HFD for 12 weeks, and LQ treatment for 1 week. Commercially available assay kits measure liver triglycerides (TG) and total cholesterol (TC) levels. Plasm TC, TG, high-density-lipoprotein (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) levels were also monitored by biochemistry. Enzyme linked immunosorbent assay (ELISA) kits were performed to analyze the pro-inflammatory factors, and intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and serum insulin were also determined. GO and KEGG pathway enrichment analysis was employed to analyze the overlapping genes of LQ targets and NAFLD development-related targets. Western blot was performed on key proteins of the enriched signaling pathway. HFD mice showed significant increases in hepatic TG and TC, and plasm TC, TG, and LDL-C in blood lipids, while HDL-C significantly decreased, and LQ treatment reversed their levels (p < 0.05). LQ also alleviated HFD-induced elevated levels of IPGTT, IPITT, and homeostasis model assessment of insulin resistance (HOMA-IR). And serum levels of the pro-inflammatory factor were also suppressed by LQ. PI3K/AKT pathway was enriched by KEGG pathway enrichment, and its key proteins p-PI3K and p-AKT were elevated after LQ treatment (p < 0.05). We found for the first time that LQ improves lipid accumulation, alleviates insulin resistance, and suppresses inflammatory responses in NAFLD mice, which might be associated with the activation of the PI3K/AKT pathway.


Assuntos
Resistência à Insulina , Insulinas , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , LDL-Colesterol/metabolismo , Fígado/metabolismo , Triglicerídeos , Dieta Hiperlipídica/efeitos adversos , Insulinas/metabolismo , Insulina/metabolismo
7.
Sci China Life Sci ; 66(10): 2329-2341, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37300753

RESUMO

Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have been reported. Its causal agent, monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, Orthopoxviridae, that also includes vaccinia virus (VACV) and others. MPV produces two distinct forms of viral particles during its replication cycles: the enveloped viron (EV) that is released via exocytosis, and the mature viron (MV) that is discharged through lysis of host cells. This study was designed to develop multi-valent mRNA vaccines against monkeypox EV and MV surface proteins, and examine their efficacy and mechanism of action. Four mRNA vaccines were produced with different combinations of surface proteins from EV (A35R and B6R), MV (A29L, E8L, H3L and M1R), or EV and MV, and were administered in Balb/c mice to assess their immunogenicity potentials. A dynamic immune response was observed as soon as seven days after initial immunization, while a strong IgG response to all immunogens was detected with ELISA after two vaccinations. The higher number of immunogens contributed to a more robust total IgG response and correlating neutralizing activity against VACV, indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection. Further, the mRNA vaccines elicited an antigen-specific CD4+ T cell response that is biased towards Th1. The mRNA vaccines with different combinations of EV and MV surface antigens protected a mouse model from a lethal dose VACV challenge, with the EV and MV antigens-combined vaccine offering the strongest protection. These findings provide insight into the protective mechanism of multi-valent mRNA vaccines against MPV, and also the foundation for further development of effective and safe mRNA vaccines for enhanced protection against monkeypox virus outbreak.


Assuntos
Mpox , Animais , Camundongos , Antígenos de Superfície , Vaccinia virus/genética , Proteínas de Membrana , Imunidade , Imunoglobulina G , Anticorpos Antivirais
8.
Heliyon ; 9(5): e16017, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37153418

RESUMO

Aim: To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization. Methods: In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups. We analyzed the relationship between the VST and demographics, clinical characteristics, medications, and vaccination histories, respectively. Results: The median duration of VST was 24 d (IQR, 20-29) of all patients. The VST of critical cases was longer than non-critical cases (27 d, IQR, 22.0-30.0 vs. 23 d, IQR 20-28, P < 0.05). Cox proportional hazards model showed that ALT (HR = 1.610, 95%CI 1.186-2.184, P = 0.002) and EO% (HR = 1.276, 95%CI 1.042-1.563, P = 0.018) were independent factors of prolonged VST in total cases; HGB (HR = 0.343, 95%CI 0.162-0.728, P = 0.005) and ALP (HR = 0.358, 95%CI 0.133-0.968, P = 0.043) were independent factors of prolonged VST in critical cases, while EO% (HR = 1.251, 95%CI 1.015-1.541, P = 0.036) was the independent factor of prolonged VST in non-critical cases. Vaccinated critical cases showed higher levels of SARS-CoV-2-IgG (1.725 S/CO, IQR 0.3975-28.7925 vs 0.07 S/CO, IQR 0.05-0.16, P < 0.001) and longer VSTs (32.5 d, IQR 20.0-35.25 vs 23 d, IQR 18.0-30.0, P = 0.011) compared with unvaccinated critical patients. Fully vaccinated non-critical cases, however, presented higher levels of SARS-CoV-2-IgG (8.09 S/CO, IQR 1.6975-55.7825 vs 0.13 S/CO IQR 0.06-0.41, P < 0.001) and shorter VSTs (21 d, IQR 19.0-28.0 vs 24 d, IQR 21.0-28.5, P = 0.013) compared with unvaccinated non-critical patients. Conclusions: Our results suggested that risk factors of prolonged VST were different between critical and non-critical COVID-19 patients. Increased level of SARS-CoV-2-IgG and vaccination did not shorten the VST and hospital stay in critical COVID-19 patients.

9.
Nano Lett ; 23(10): 4375-4383, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37159332

RESUMO

Microorganism-mediated self-assembling of living formulations holds great promise for disease therapy. Here, we constructed a prebiotic-probiotic living capsule (PPLC) by coculturing probiotics (EcN) with Gluconacetobacter xylinus (G. xylinus) in a prebiotic-containing fermentation broth. Through shaking the culture, G. xylinus secretes cellulose fibrils that can spontaneously encapsulate EcN to form microcapsules under shear forces. Additionally, the prebiotic present in the fermentation broth is incorporated into the bacterial cellulose network through van der Waals forces and hydrogen bonding. Afterward, the microcapsules were transferred to a selective LB medium, which facilitated the colonization of dense probiotic colonies within them. The in vivo study demonstrated that PPLC-containing dense colonies of EcN can antagonize intestinal pathogens and restore microbiota homeostasis by showing excellent therapeutic performance in treating enteritis mice. The in situ self-assembly of probiotics and prebiotics-based living materials provides a promising platform for the treatment of inflammatory bowel disease.


Assuntos
Doenças Inflamatórias Intestinais , Prebióticos , Animais , Camundongos , Cápsulas , Técnicas de Cocultura , Celulose
11.
Genome Biol ; 24(1): 75, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069604

RESUMO

Single-molecule detection and phasing of A-to-I RNA editing events remain an unresolved problem. Long-read and PCR-free nanopore native RNA sequencing offers a great opportunity for direct RNA editing detection. Here, we develop a neural network model, DeepEdit, that not only recognizes A-to-I editing events in single reads of Oxford Nanopore direct RNA sequencing, but also resolves the phasing of RNA editing events on transcripts. We illustrate the robustness of DeepEdit by applying it to Schizosaccharomyces pombe and Homo sapiens transcriptome data. We anticipate DeepEdit to be a powerful tool for the study of RNA editing from a new perspective.


Assuntos
Nanoporos , Humanos , Edição de RNA , RNA/genética , Análise de Sequência de RNA , Sequenciamento de Nucleotídeos em Larga Escala , Sequência de Bases
12.
In Vivo ; 37(2): 661-666, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36881067

RESUMO

BACKGROUND/AIM: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a major cause of blindness in working-age adults. Diosgenin (DG), a natural steroidal sapogenin extracted from fenugreek seeds and wild yam roots, has hypolipidemic, hypoglycemic, anticancer, and anti-inflammatory properties. Given its pharmacological effects, we speculated that DG may be a promising treatment for DR. Therefore, this study was aimed at evaluating the effectiveness of DG in preventing or slowing DR progression in a mouse model (+Leprdb/+Leprdb strain) of type 2 diabetes (T2D). MATERIALS AND METHODS: DG (5.0 mg/kg body weight) or phosphate-buffered saline (PBS) was administered to 8-week-old T2D mice via oral gavage daily for 24 weeks. Paraffin-embedded eye tissues from the mice were collected and stained with hematoxylin and eosin to evaluate retinal histopathology. Apoptosis-related proteins BCL2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 were evaluated by western blotting of mouse retinas. RESULTS: Body weight was slightly reduced in the DG-treated group; however, glucose levels were not markedly different between the DG- and PBS-treated groups. Total retinal thickness, thickness of the photoreceptor and outer nuclear layers, and loss of ganglion cells significantly improved in the retina of the DG-treated T2D mice compared with those in the PBS-treated T2D mice. Cleaved caspase-3 level significantly decreased in the retina of the DG-treated T2D mice. Conclusion: DG alleviates DR pathology and exerts a protective effect on the T2D mouse retina. The inhibitory effects of DG on DR may involve mechanisms of the anti-apoptotic pathway.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diosgenina , Sapogeninas , Animais , Camundongos , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Caspase 3 , Sapogeninas/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Peso Corporal , Diosgenina/farmacologia
13.
Polymers (Basel) ; 15(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36904505

RESUMO

The nonlinear behaviour of fibre-reinforced polymer composites (FRPC) in transverse loading is mainly induced by the constituent polymer matrix. The thermoset and thermoplastic matrices are typically rate- and temperature-dependent, complicating the dynamic material characterization process. Under dynamic compression, the microstructure of the FRPC develops local strains and local strain rates whose values can be much higher than those applied at macroscopic level. The correlation between the local (microscopic) values and the measurable (macroscopic) ones still present challenges when applying the strain rate in the range 10-3-103 s-1. This paper presents an in-house uniaxial compression test setup to provide robust stress-strain measurements applying strain rates up to 100 s-1. A semi-crystalline thermoplastic polyetheretherketone (PEEK) and a toughened thermoset epoxy PR520 are assessed and characterized. The thermomechanical response of the polymers is further modelled using an advanced glassy polymer model, naturally capturing the isothermal to adiabatic transition. A micromechanical model of a unidirectional composite undergoing dynamic compression is developed by using both validated polymers as matrices reinforced by carbon fibres (CF) using Representative Volume Element (RVE) models. These RVEs are used to analyse the correlation between the micro- and macroscopic thermomechanical response of the CF/PR520 and CF/PEEK systems investigated at intermediate to high strain rates. Both systems experience an excessive strain localization with local plastic strain about 19% when a macroscopic strain of 3.5% is applied. The comparison of using a thermoplastic and a thermoset as a matrix in composites is discussed with regard to the rate-dependence, the interface debonding and the self-heating effect.

14.
Redox Rep ; 28(1): 2158526, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36738240

RESUMO

OBJECTIVES: To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms. METHODS: One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined. RESULTS: Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2. CONCLUSIONS: Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.


Assuntos
Dexmedetomidina , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Sirtuína 3 , Animais , Masculino , Ratos , Apoptose , Dexmedetomidina/uso terapêutico , Dexmedetomidina/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Transdução de Sinais , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Superóxido Dismutase/metabolismo
15.
Front Cell Infect Microbiol ; 12: 1009894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389157

RESUMO

Objectives: To summarize the clinical characteristics of patients infected by SARS-CoV-2 omicron variant and explore the risk factors affecting the progression in a Fangcang hospital, Shanghai, China. Methods: A total of 25,207 patients were retrospectively enrolled. We described the clinical characteristics and performed univariate and multivariate logistic regression analysis to identify the risk factors for non-severe to severe COVID-19 or death. Results: According to the outcomes, there were 39 severe patients (including 1 death) and 25,168 non-severe patients enrolled in this study. Among the 25,207 cases, the median age was 45 years (IQR 33-54), and 65% patients were male. Cough (44.5%) and expectoration (38.4%) were the most two common symptoms. Hypertension (10.4%) and diabetes (3.5%) were most two common comorbidities. Most patients (81.1%) were fully vaccinated. The unvaccinated and partially vaccinated patients were 15.1% and 3.9%, respectively. The length of viral shedding time was six days (IQR 4-9) in non-severe patients. Multivariate logistic regression analysis suggested that age (OR=1.062, 95%CI 1.034-1.090, p<0.001), fever (OR=2.603, 95%CI 1.061-6.384, p=0.037), cough (OR=0.276, 95%CI 0.119-0.637, p=0.003), fatigue (OR=4.677, 95%CI 1.976-11.068, p<0.001), taste disorders (OR=14.917, 95%CI 1.884-118.095, p=0.010), and comorbidity (OR=2.134, 95%CI 1.059-4.302, p=0.034) were predictive factors for deterioration of SARS-CoV-2 omicron variant infection. Conclusions: Non-critical patients have different clinical characteristics from critical patients. Age, fever, cough, fatigue, taste disorders, and comorbidity are predictors for the deterioration of SARS-CoV-2 omicron variant infection.


Assuntos
COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , COVID-19/epidemiologia , SARS-CoV-2 , Tosse , China/epidemiologia , Fatores de Risco , Hospitais , Distúrbios do Paladar , Fadiga , Progressão da Doença
16.
Cells ; 11(20)2022 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-36291120

RESUMO

Daphnoretin extracted from the stem and roots of Wikstroemia indica (L.) C.A. Mey has been shown to possess antiviral and antitumor activities. Herein, we hypothesized that daphnoretin might induce megakaryocytic differentiation, thereby inhibiting the proliferation of cells and serving as a differentiation therapy agent for chronic myeloid leukemia (CML). Daphnoretin-treated K562 and HEL cells were examined for growth inhibition, cell morphology, and megakaryocyte-specific markers. Potential mechanisms of megakaryocytic differentiation of daphnoretin-treated K562 cells were evaluated. The results showed that daphnoretin inhibited the growth of K562 and HEL cells in a dose- and time-dependent manner. Flow cytometry analyses revealed that daphnoretin treatment slightly increased the proportion of sub-G1 and polyploid cells compared to that of dimethyl sulfoxide (DMSO)-treated control cells. Morphological examination showed that daphnoretin-treated K562 and HEL cells exhibited enlarged contours and multinucleation as megakaryocytic characteristics compared to DMSO-treated control cells. Daphnoretin treatment also dramatically enhanced the expression of megakaryocytic markers CD61 and CD41. Under optimal megakaryocytic differentiation conditions, daphnoretin increased the phosphorylation of STAT3 but not STAT5. In summary, daphnoretin inhibited cell growth and induced megakaryocytic differentiation in K562 and HEL cells. The efficacy of daphnoretin in vivo and in patients with CML may need further investigations for validation.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Dimetil Sulfóxido/farmacologia , Diferenciação Celular , Leucemia Mieloide/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Antivirais/farmacologia
17.
Anal Chim Acta ; 1233: 340513, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36283772

RESUMO

Digital nucleic acid amplification techniques are powerful and attractive approaches for providing sensitive and absolute quantification in biology. Among these, digital loop-mediated isothermal amplification (dLAMP) shows the potential for field detection, since its robustness and independence from thermal cycling. The key of dLAMP is to generate a large number of individual droplets or microwells. However, an auxiliary precision pump is always required for sample digitalization. In addition, current systems for droplet dLAMP usually need to transfer the droplets after digitalization or amplification. Herein, we developed and evaluated a pump-free microfluidic chip for duplex droplet dLAMP (TriD-LAMP) detection. This chip was designed based on step emulsification and contains a droplet generation zone and a droplet storage zone. Droplets are formed through the step due to the difference in Laplace pressure. There are 64 parallel nozzles that could generate tens of thousands of uniform droplets manually (variation <5%). The storage zone for droplets collection was previously filled with oil containing fluorosurfactant that keeps the droplets from fusing and evaporation during the amplification. Therefore, this custom chip is able to perform all stages of the dLAMP process without transferring droplets. Combined with the optimized fluorescent probe method, the chip achieves accurate quantification of the E. coli DNA down to 19.8 copies/µL. As a proof of concept, the simultaneous quantification of two targets was successfully realized on this custom chip. Conclusively, this integrated, pump-free TriD-LAMP chip can provide a promising tool for multiple targets detection in clinical diagnostics and point-of-care applications.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Microfluídica/métodos , Escherichia coli/genética , Corantes Fluorescentes , Técnicas de Amplificação de Ácido Nucleico/métodos , DNA , Técnicas Analíticas Microfluídicas/métodos
18.
Nat Commun ; 13(1): 6458, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309526

RESUMO

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5+ DM are still largely unknown. Here we describe the immune signatures of MDA5+ DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient. We find strong peripheral antibody-secreting cell and CD8+ T cell responses as cellular immune hallmarks, and over-stimulated type I interferon signaling and associated metabolic reprogramming as molecular immune signature in MDA5+ DM. High frequency of circulating ISG15+ CD8+ T cells at baseline predicts poor one-year survival in MDA5+ DM patients. In affected lungs, we find profuse immune cells infiltration, which likely contributes to the pro-fibrotic response via type I interferon production. The importance of type I interferons in MDA5+ DM pathology is further emphasized by our observation in a retrospective cohort of MDA5+ DM patients that combined calcineurin and Janus kinase inhibitor therapy show superior efficacy to calcineurin inhibitor monotherapy. In summary, this study reveals key immune-pathogenic features of MDA5+ DM and provides a potential basis for future tailored therapies.


Assuntos
Dermatomiosite , Interferon Tipo I , Doenças Pulmonares Intersticiais , Humanos , Helicase IFIH1 Induzida por Interferon , Dermatomiosite/tratamento farmacológico , Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Estudos Retrospectivos , Linfócitos T CD8-Positivos/metabolismo , Autoanticorpos
19.
Front Plant Sci ; 13: 928634, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119612

RESUMO

Bemisia tabaci is the main pest of agriculture in many regions of the world. The resistance of whitefly to pesticides has increased as a consequence of the continuous irrational use of wide-spectrum pesticides. Thus, pesticides are no longer always effective as a long-term control method. The agricultural landscape can affect the occurrence of an insect population. The objective of this study was to clarify the occurrence of whitefly and its predators in tomato fields in different agricultural landscapes. Different landscapes are classified into urban, flower, water, and mountain landscapes by the principal component analysis method. In 2018-2019, whitefly had the longest main activity period and the lowest density in the flower landscape. The water landscape helped to maintain the highest densities of whitefly during the main activity period. Nine species of predators were sampled, and Nesidiocoris tenuis, Chrysoperla sinica, Menochilus sexmaculata, and Harmonia axyridis were the dominant species throughout the sampling season in both years. During the main activity period, N. tenuis had the highest density in all sampled landscapes. The density of the dominant predators was the highest in the flower landscape, and each natural predator had the largest temporal niche width in the 2-year sampling period. Bemisia tabaci, N. tenuis, and M. sexmaculata were highly synchronized temporally. The flower landscape showed satisfactory results in suppressing whitefly. Increasing the proportion of flowering plants and increasing the diversity of plant crops in the agricultural landscape can effectively reduce the densities of whitefly during an outbreak.

20.
BMC Med Imaging ; 22(1): 144, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962312

RESUMO

OBJECTIVES: To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury. METHODS: We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ). RESULTS: The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6-10 vs. 5, IQR 3-6, p < 0.001), CTSS2 (8, IQR 7-11 vs. 5, IQR 4-7, p < 0.001) and POS (2, IQR 1-2.5 vs. 1, IQR 1-2, p < 0.001). Comorbidity (OR = 6.15, p = 0.023) and the presence of low PMI (OR = 5.43, p = 0.001) were predictors of lung injury aggravation with ΔCTSS1 > 4. The presence of low PMI (OR = 5.98, p < 0.001) was the predictor of lung injury aggravation with ΔCTSS2 > 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2. CONCLUSIONS: PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.


Assuntos
COVID-19 , Lesão Pulmonar , Idoso , Humanos , Pulmão/diagnóstico por imagem , Lesão Pulmonar/diagnóstico por imagem , Músculos Peitorais , Estudos Retrospectivos , Tórax , Tomografia Computadorizada por Raios X/métodos
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