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1.
Am J Nucl Med Mol Imaging ; 14(2): 110-121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737640

RESUMO

Molecular imaging enables visualization and characterization of biological processes that influence tumor behavior and response to therapy. The TMTP1 (NVVRQ) peptide has shown remarkable affinity to highly metastatic tumors and and its potential receptor is aminopeptidase P2. In this study, we have designed and synthesized a 68Ga-labeled cyclic TMTP1 radiotracer (68Ga-DOTA-TMTP1), for PET imaging of cervical cancer. The goal of this study was to investigate the properties of this radiotracer and its tumor diagnostic potential. The radiochemical yield of 68Ga-DOTA-TMTP1 was high and the radiochemical purity was greater than 95%. The octanol-water partition coefficient for 68Ga-DOTA-TMTP1 was -2.76 ± 0.08 and 68Ga-DOTA-TMTP1 has showed excellent stability in in vitro studies. The cellular uptake and efflux of 68Ga-DOTA-TMTP1 in paired highly metastatic and lowly metastatic cervical cancer cell line HeLa and C-33A as well as normal cervical epithelial cell line End1 were measured in a γ counter. 68Ga-DOTA-TMTP1 exhibited higher uptake in HeLa cells than in C-33A cells. The binding to HeLa and C-33A cells could be blocked by excess TMTP1. On microPET images, HeLa tumors were clearly visualized within 60 min and the uptake of the radiotracer in HeLa tumors was higher than that of C-33A tumors. After blocking with TMTP1, HeLa tumors uptake was significantly reduced and the specificity 68Ga-DOTA-TMTP1 was thus validated. Overall, we have successfully synthesized 68Ga-DOTA-TMTP1 with high yield and high specific activity and have demonstrated its potential role for highly metastatic tumor-targeted diagnosis.

2.
Front Pharmacol ; 15: 1387585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725657

RESUMO

Background: The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis. Methods: The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics. Results: This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference. Conclusion: This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.

3.
Bioresour Technol ; 402: 130802, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718902

RESUMO

A cost-effective, and low-energy room-temperature cascade catalytic carbonization strategy is demonstrated for converting lignin into graphite with a high yield of 87 %, a high surface potential of -37 eV and super-hydrophilicity. This super-hydrophilic feature endows the lignin-derived graphite to be dispersed in a variety of polar solvents, which is important for its future applications. Encapsulating of liquid metals with the graphite for electrical circuit patterning on flexible substrates is also advocated. These written patterns show superb conductivity of 4.9 × 106 S/m, offering good performance stability and reliability while being repeatedly stretched, folded, twisted, and bent. This will offer new designs for flexible electronic devices, sensors, and biomedical devices.

4.
Int J Mol Sci ; 25(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732175

RESUMO

Drought stress globally poses a significant threat to maize (Zea mays L.) productivity and the underlying molecular mechanisms of drought tolerance remain elusive. In this study, we characterized ZmbHLH47, a basic helix-loop-helix (bHLH) transcription factor, as a positive regulator of drought tolerance in maize. ZmbHLH47 expression was notably induced by both drought stress and abscisic acid (ABA). Transgenic plants overexpressing ZmbHLH47 displayed elevated drought tolerance and ABA responsiveness, while the zmbhlh47 mutant exhibited increased drought sensitivity and reduced ABA sensitivity. Mechanistically, it was revealed that ZmbHLH47 could directly bind to the promoter of ZmSnRK2.9 gene, a member of the subgroup III SnRK2 kinases, activating its expression. Furthermore, ZmSnRK2.9-overexpressing plants exhibited enhanced ABA sensitivity and drought tolerance, whereas the zmsnrk2.9 mutant displayed a decreased sensitivity to both. Notably, overexpressing ZmbHLH47 in the zmsnrk2.9 mutant closely resembled the zmsnrk2.9 mutant, indicating the importance of the ZmbHLH47-ZmSnRK2.9 module in ABA response and drought tolerance. These findings provided valuable insights and a potential genetic resource for enhancing the environmental adaptability of maize.


Assuntos
Ácido Abscísico , Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Estresse Fisiológico , Zea mays , Zea mays/genética , Zea mays/fisiologia , Zea mays/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Resistência à Seca
5.
Nutrients ; 16(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732582

RESUMO

Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.


Assuntos
Crataegus , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/microbiologia , Extratos Vegetais/farmacologia , Animais , Crataegus/química , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Etanol , Modelos Animais de Doenças , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Citocinas/metabolismo , Ácidos Graxos Voláteis/metabolismo
6.
Orphanet J Rare Dis ; 19(1): 209, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773661

RESUMO

BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). METHODS: A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. RESULTS: Two cis-compound benign intronic variants of FBN1 (c.3464-4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein's secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel ß sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. CONCLUSIONS: To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.


Assuntos
Fibrilina-1 , Íntrons , Síndrome de Marfan , Mosaicismo , Linhagem , Humanos , Fibrilina-1/genética , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Feminino , Masculino , Adulto , Íntrons/genética , Mutação INDEL/genética , Pessoa de Meia-Idade , Adipocinas
7.
J Mol Neurosci ; 74(2): 55, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776015

RESUMO

The dysregulation of lipid metabolism has been strongly associated with Alzheimer's disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.


Assuntos
Doença de Alzheimer , Metabolismo dos Lipídeos , Transcriptoma , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Encéfalo/metabolismo , Redes Reguladoras de Genes
8.
Adv Healthc Mater ; : e2400899, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752875

RESUMO

Bioorthogonal chemistry has emerged as a powerful tool for manipulating biological processes. However, difficulties in controlling the exact location and on-demand catalytic synthesis limit its application in biological systems. Herein, this work constructs an activatable bioorthogonal system integrating a shielded catalyst and prodrug molecules to combat biofilm-associated infections. The catalytic species is activated in response to the hyaluronidase (HAase) secreted by the bacteria and the acidic pH of the biofilm, which is accompanied by the release of prodrugs, to achieve the bioorthogonal catalytic synthesis of antibacterial molecules in situ. Moreover, the system can produce reactive oxygen species (ROS) to disperse bacterial biofilms, enabling the antibacterial molecules to penetrate the biofilm and eliminate the bacteria within it. This study promotes the design of efficient and safe bioorthogonal catalysts and the development of bioorthogonal chemistry-mediated antibacterial strategies.

9.
Am J Public Health ; : e1-e9, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696735

RESUMO

Objectives. To identify relationships between US states' COVID-19 in-person activity limitation and economic support policies and drug overdose deaths among working-age adults in 2020. Methods. We used county-level data on 140 435 drug overdoses among adults aged 25 to 64 years during January 2019 to December 2020 from the National Vital Statistics System and data on states' COVID-19 policies from the Oxford COVID-19 Government Response Tracker to assess US trends in overdose deaths by sex in 3138 counties. Results. Policies limiting in-person activities significantly increased, whereas economic support policies significantly decreased, overdose rates. A 1-unit increase in policies restricting activities predicted a 15% average monthly increase in overdose rates for men (incident rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.09, 1.20) and a 14% increase for women (IRR = 1.14; 95% CI = 1.09, 1.20). A 1-unit increase in economic support policies predicted a 3% average monthly decrease for men (IRR = 0.97; 95% CI = 0.95, 1.00) and a 4% decrease for women (IRR = 0.96; 95% CI = 0.93, 0.99). All states' policy combinations are predicted to have increased drug-poisoning mortality. Conclusions. The economic supports that states enacted were insufficient to fully mitigate the adverse relationship between activity limitations and drug overdoses. (Am J Public Health. Published online ahead of print May 2, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307621).

10.
Sci Data ; 11(1): 460, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710725

RESUMO

Blood orange (BO) is a rare red-fleshed sweet orange (SWO) with a high anthocyanin content and is associated with numerous health-related benefits. Here, we reported a high-quality chromosome-scale genome assembly for Neixiu (NX) BO, reaching 336.63 Mb in length with contig and scaffold N50 values of 30.6 Mb. Furthermore, 96% of the assembled sequences were successfully anchored to 9 pseudo-chromosomes. The genome assembly also revealed the presence of 37.87% transposon elements and 7.64% tandem repeats, and the annotation of 30,395 protein-coding genes. A high level of genome synteny was observed between BO and SWO, further supporting their genetic similarity. The speciation event that gave rise to the Citrus species predated the duplication event found within them. The genome-wide variation between NX and SWO was also compared. This first high-quality BO genome will serve as a fundamental basis for future studies on functional genomics and genome evolution.


Assuntos
Citrus sinensis , Genoma de Planta , Citrus sinensis/genética , Cromossomos de Plantas , Elementos de DNA Transponíveis , Sintenia
11.
Anal Cell Pathol (Amst) ; 2024: 8972022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715918

RESUMO

Preeclampsia (PE) manifests as a pregnancy-specific complication arising from compromised placentation characterized by inadequate trophoblast invasion. A growing body of evidence underscores the pivotal involvement of pseudogenes, a subset of long noncoding RNAs, in the pathological processes of PE. This study presents a novel finding, demonstrating a significant downregulation of the pseudogene PDIA3P1 in PE placental tissues compared to normal tissues. In vitro functional assays revealed that suppressing PDIA3P1 hindered trophoblast proliferation, invasion, and migration, concurrently upregulating the expression of secreted frizzled-related protein 1 (SFRP1). Further exploration of the regulatory role of PDIA3P1 in PE, utilizing human trophoblasts, established that PDIA3P1 exerts its function by binding to HuR, thereby enhancing the stability of Snail expression in trophoblasts. Overall, our findings suggest a crucial role for PDIA3P1 in regulating trophoblast properties and contributing to the pathogenesis of PE, offering potential targets for prognosis and therapeutic intervention.


Assuntos
Regulação para Baixo , Fenótipo , Pré-Eclâmpsia , RNA Longo não Codificante , Fatores de Transcrição da Família Snail , Trofoblastos , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Feminino , Trofoblastos/metabolismo , Trofoblastos/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Regulação para Baixo/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Proliferação de Células/genética , Movimento Celular/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Adulto
12.
Food Res Int ; 183: 114226, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760145

RESUMO

Highland barley (HB) is an intriguing plateau cereal crop with high nutrition and health benefits. However, abundant dietary fiber and deficient gluten pose challenges to the processing and taste of whole HB products. Extrusion technology has been proved to be effective in overcoming these hurdles, but the association between the structure and physicochemical properties during extrusion remains inadequately unexplored. Therefore, this study aims to comprehensively understand the impact of extrusion conditions on the physicochemical properties of HB flour (HBF) and the multi-scale structure of starch. Results indicated that the nutritional value of HBF were significantly increased (soluble dietary fiber and ß-glucan increased by 24.05%, 19.85% respectively) after extrusion. Typical underlying mechanisms based on starch structure were established. High temperature facilitated starch gelatinization, resulting in double helices unwinding, amylose leaching, and starch-lipid complexes forming. These alterations enhanced the water absorption capacity, cold thickening ability, and peak viscosity of HBF. More V-type complexes impeded amylose rearrangement, thus enhancing resistance to retrogradation and thermal stability. Extrusion at high temperature and moisture exhibited similarities to hydrothermal treatment, partly promoting amylose rearrangement and enhancing HBF peak viscosity. Conversely, under low temperature and high moisture, well-swelled starch granules were easily broken into shorter branch-chains by higher shear force, which enhanced the instant solubility and retrogradation resistance of HBF as well as reduced its pasting viscosity and the capacity to form gel networks. Importantly, starch degradation products during this condition were experimentally confirmed from various aspects. This study provided some reference for profiting from extrusion for further development of HB functional food and "clean label" food additives.


Assuntos
Amilose , Farinha , Manipulação de Alimentos , Hordeum , Amido , Hordeum/química , Amido/química , Farinha/análise , Viscosidade , Amilose/química , Manipulação de Alimentos/métodos , Valor Nutritivo , Fibras na Dieta/análise , Solubilidade , beta-Glucanas/química , Fenômenos Químicos , Temperatura Alta
13.
Cell Death Differ ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762596

RESUMO

Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinß and δ (C/EBPß and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.

14.
ACS Cent Sci ; 10(3): 579-594, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38559310

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, and for full activation of STAT3, the cooperative phosphorylation of both tyrosine 705 (Tyr705) and serine 727 (Ser727) is needed. Further, a selective inhibitor of STAT3 dual phosphorylation has not been developed. Here, we identified a low nanomolar potency and highly selective small-molecule STAT3 inhibitor that simultaneously inhibits both STAT3 Tyr705 and Ser727 phosphorylation. YY002 potently inhibited STAT3-dependent tumor cell growth in vitro and achieved potent suppression of tumor growth and metastasis in vivo. More importantly, YY002 exhibited favorable pharmacokinetics, an acceptable safety profile, and superior antitumor efficacy compared to BBI608 (STAT3 inhibitor that has advanced into phase III trials). For the mechanism, YY002 is selectively bound to the STAT3 Src Homology 2 (SH2) domain over other STAT members, which strongly suppressed STAT3 nuclear and mitochondrial functions in STAT3-dependent cells. Collectively, this study suggests the potential of small-molecule STAT3 inhibitors as possible anticancer therapeutic agents.

15.
Mol Cell Biochem ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581552

RESUMO

Muscle atrophy and skeletal muscle fibrosis are significant pathological manifestations of primary sarcopenia. The regulation of C2C12 myoblast and skeletal muscle fibroblast apoptosis is associated with these pathological changes. Previous studies have indicated that irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), can alleviate primary sarcopenia. However, the mechanisms of the effect of irisin in age-related apoptosis remain unknown. Our present research aimed to explore the effect of irisin and the underlying mechanism of D-galactose (D-gal)-induced apoptosis in skeletal muscle fibroblasts and C2C12 myoblasts. We found the opposite effects of D-gal on C2C12 myoblasts and fibroblasts. We also found that irisin suppressed C2C12 cell apoptosis and promoted fibroblast apoptosis. Mechanistically, irisin altered D-gal-induced apoptosis by increasing caveolin-1 expression. Taken together, these findings further demonstrated that irisin is a potential agent that can treat aged-relative muscle atrophy and fibrosis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38561475

RESUMO

BACKGROUND: Although PM2.5 (fine particulate matter with an aerodynamic diameter less than 2.5 µm) is an air pollutant of great concern in Texas, limited regulatory monitors pose a significant challenge for decision-making and environmental studies. OBJECTIVE: This study aimed to predict PM2.5 concentrations at a fine spatial scale on a daily basis by using novel machine learning approaches and incorporating satellite-derived Aerosol Optical Depth (AOD) and a variety of weather and land use variables. METHODS: We compiled a comprehensive dataset in Texas from 2013 to 2017, including ground-level PM2.5 concentrations from regulatory monitors; AOD values at 1-km resolution based on images retrieved from the MODIS satellite; and weather, land-use, population density, among others. We built predictive models for each year separately to estimate PM2.5 concentrations using two machine learning approaches called gradient boosted trees and random forest. We evaluated the model prediction performance using in-sample and out-of-sample validations. RESULTS: Our predictive models demonstrate excellent in-sample model performance, as indicated by high R2 values generated from the gradient boosting models (0.94-0.97) and random forest models (0.81-0.90). However, the out-of-sample R2 values fall within a range of 0.52-0.75 for gradient boosting models and 0.44-0.69 for random forest models. Model performance varies slightly across years. A generally decreasing trend in predicted PM2.5 concentrations over time is observed in Eastern Texas. IMPACT STATEMENT: We utilized machine learning approaches to predict PM2.5 levels in Texas. Both gradient boosting and random forest models perform well. Gradient boosting models perform slightly better than random forest models. Our models showed excellent in-sample prediction performance (R2 > 0.9).

17.
Adv Mater ; : e2313612, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574762

RESUMO

Continuous monitoring of blood pressure (BP) and multiparametric analysis of cardiac functions are crucial for the early diagnosis and therapy of cardiovascular diseases. However, existing monitoring approaches often suffer from bulky and intrusive apparatus, cumbersome testing procedures, and challenging data processing, hampering their applications in continuous monitoring. Here, a heterogeneously hierarchical piezoelectric composite is introduced for wearable continuous BP and cardiac function monitoring, overcoming the rigidity of ceramic and the insensitivity of polymer. By optimizing the hierarchical structure and components of the composite, the developed piezoelectric sensor delivers impressive performances, ensuring continuous and accurate monitoring of BP at Grade A level. Furthermore, the hemodynamic parameters are extracted from the detected signals, such as local pulse wave velocity, cardiac output, and stroke volume, all of which are in alignment with clinical results. Finally, the all-day tracking of cardiac function parameters validates the reliability and stability of the developed sensor, highlighting its potential for personalized healthcare systems, particularly in early diagnosis and timely intervention of cardiovascular disease.

18.
ACS Omega ; 9(14): 16648-16655, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617661

RESUMO

In order to explore the pressure and flame propagation characteristics of gas-coal dust composite explosions, a semiclosed pipeline explosion test platform was built. The shock wave overpressure and explosion flame propagation law of different concentrations of suspended coal dust participating in gas explosions were studied in depth through experiments, and the coal dust motion law was simulated and analyzed based on Fluent software. The experimental results show that the peak pressure of gas-coal dust composite explosion is significantly higher than that of single-phase gas explosion, and the pressure peak increase ratio at the pipeline outlet is the highest; as the suspended coal dust concentration increases, the pressure rise rate at point 3 gradually decreases. Under the condition of 600 g/m3 coal dust participating in the explosion, the explosion pressure increase speed reduction ratio is 25.65%, the pressure wave secondary peak decreases, and the fluctuation frequency increases. When the explosion flame front passes through the suspended coal dust area, the flame shape changes from 'v' shape to 'finger' shape and propagates forward. The gas-coal dust composite explosion flame propagation speed shows a secondary acceleration phenomenon, after the flame front passes through the coal dust suspension area. As the coal dust concentration increases, the explosion core area moves away from the flame front. The coal dust cloud moves to the right, showing a concave rectangle; the larger the coal dust concentration, the smaller the moving speed. The experimental results and analysis provide an experimental basis for further exploring the mechanism and dynamic mechanism of gas-coal dust coupling explosion.

19.
J Econ Entomol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625052

RESUMO

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

20.
Front Cell Infect Microbiol ; 14: 1376725, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590440

RESUMO

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.


Assuntos
Guanidinas , Piperazinas , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vacinas , Suínos , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Linhagem Celular
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