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1.
Artigo em Inglês | MEDLINE | ID: mdl-38907821

RESUMO

To control the diffusion of high concentrations of coal dust during tunnel boring and minimize the threat to the life and health of coal miners, theoretical analysis, numerical simulations, and field measurements were combined in this study. First, computational fluid dynamic simulation software was used to simulate the generation of dust particles and their transport pattern in the tunnel. Subsequently, an innovative orthogonal test was performed to study the effect of four ventilation parameters [the pressure airflow rate (Q), distance between the air duct center and heading face (LA), distance between the air duct center and tunnel floor (LB), and distance between the air duct center and nearest coal wall (LC)] on dust diffusion. According to the orthogonal test results, the optimal ventilation parameters for effective dust control are as follows: Q = 1400 m3/min, LA = 7 m, LB = 2.8 m, and LC = 1 m. The optimized set of ventilation parameters was applied to the Wangpo 3206 working face. The results show that dust diffusion in the tunnel was effectively controlled and that the air quality was sufficiently improved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38910417

RESUMO

BACKGROUND: Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear. METHODS: In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways. RESULTS: The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway. CONCLUSION: In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.

3.
Sci Rep ; 14(1): 14155, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898215

RESUMO

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.


Assuntos
Ritmo Circadiano , Humanos , Ritmo Circadiano/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Isquemia Miocárdica , Prognóstico , Doença da Artéria Coronariana , Idoso , Biomarcadores , Progressão da Doença
4.
Fitoterapia ; 176: 106010, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38740341

RESUMO

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.


Assuntos
Flores , Farmacologia em Rede , Compostos Fitoquímicos , Pneumonia , Animais , Flores/química , Pneumonia/tratamento farmacológico , Camundongos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Hosta , Anti-Inflamatórios/farmacologia , Mapas de Interação de Proteínas , Masculino , Plantas Medicinais/química , Medicina Tradicional da Mongólia , Lesão Pulmonar Aguda/tratamento farmacológico
5.
Biomaterials ; 309: 122616, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38776592

RESUMO

The gel microsphere culture system (GMCS) showed various advantages for mesenchymal stem cell (MSC) expansion and delivery, such as high specific surface area, small and regular shape, extensive adjustability, and biomimetic properties. Although various technologies and materials have been developed to promote the development of gel microspheres, the differences in the biological status of MSCs between the GMCS and the traditional Petri dish culture system (PDCS) are still unknown, hindering gel microspheres from becoming a culture system as widely used as petri dishes. In the previous study, an excellent "all-in-one" GMCS has been established for the expansion of human adipose-derived MSCs (hADSCs), which showed convenient cell culture operation. Here, we performed transcriptome and proteome sequencing on hADSCs cultured on the "all-in-one" GMCS and the PDCS. We found that hADSCs cultured in the GMCS kept in an undifferentiation status with a high stemness index, whose transcriptome profile is closer to the adipose progenitor cells (APCs) in vivo than those cultured in the PDCS. Further, the high stemness status of hADSCs in the GMCS was maintained through regulating cell-ECM interaction. For application, bilayer scaffolds were constructed by osteo- and chondro-differentiation of hADSCs cultured in the GMCS and the PDCS. The effect of osteochondral regeneration of the bilayer scaffolds in the GMCS group was better than that in the PDCS group. This study revealed the high stemness and excellent functionality of MSCs cultured in the GMCS, which promoted the application of gel microspheres in cell culture and tissue regeneration.


Assuntos
Tecido Adiposo , Diferenciação Celular , Células-Tronco Mesenquimais , Microesferas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Animais , Matriz Extracelular/metabolismo , Células Cultivadas , Alicerces Teciduais/química , Géis/química , Condrogênese , Osteogênese , Técnicas de Cultura de Células/métodos
6.
Math Ann ; 389(2): 1657-1676, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751410

RESUMO

Bohnenblust-Hille inequalities for Boolean cubes have been proven with dimension-free constants that grow subexponentially in the degree (Defant et al. in Math Ann 374(1):653-680, 2019). Such inequalities have found great applications in learning low-degree Boolean functions (Eskenazis and Ivanisvili in Proceedings of the 54th annual ACM SIGACT symposium on theory of computing, pp 203-207, 2022). Motivated by learning quantum observables, a qubit analogue of Bohnenblust-Hille inequality for Boolean cubes was recently conjectured in Rouzé et al. (Quantum Talagrand, KKL and Friedgut's theorems and the learnability of quantum Boolean functions, 2022. arXiv preprint arXiv:2209.07279). The conjecture was resolved in Huang et al. (Learning to predict arbitrary quantum processes, 2022. arXiv preprint arXiv:2210.14894). In this paper, we give a new proof of these Bohnenblust-Hille inequalities for qubit system with constants that are dimension-free and of exponential growth in the degree. As a consequence, we obtain a junta theorem for low-degree polynomials. Using similar ideas, we also study learning problems of low degree quantum observables and Bohr's radius phenomenon on quantum Boolean cubes.

7.
Microorganisms ; 12(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792846

RESUMO

Both pandemic and seasonal influenza are major health concerns, causing significant mortality and morbidity. Current influenza drugs primarily target viral neuraminidase and RNA polymerase, which are prone to drug resistance. Polyoxometalates (POMs) are metal cation clusters bridged by oxide anions. They have exhibited potent anti-tumor, antiviral, and antibacterial effects. They have remarkable activity against various DNA and RNA viruses, including human immunodeficiency virus, herpes simplex virus, hepatitis B and C viruses, dengue virus, and influenza virus. In this study, we have identified sodium polyoxotungstate (POM-1) from an ion channel inhibitor library. In vitro, POM-1 has been demonstrated to have potent antiviral activity against H1N1, H3N2, and oseltamivir-resistant H1N1 strains. POM-1 can cause virion aggregation during adsorption, as well as endocytosis. However, the aggregation is reversible; it does not interfere with virus adsorption and endocytosis. Our results suggest that POM-1 exerts its antiviral activity by inhibiting the nuclear import of viral ribonucleoprotein (vRNP). This distinct mechanism of action, combined with its wide range of efficacy, positions POM-1 as a promising therapeutic candidate for influenza treatment and warrants further investigation.

8.
ACS Catal ; 14(10): 7707-7716, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38779184

RESUMO

Nonthermal plasma (NTP) offers the potential for converting CH4 with CO2 into liquid products under mild conditions, but controlling liquid selectivity and manipulating intermediate species remain significant challenges. Here, we demonstrate the effectiveness of the Cu/UiO-66-NH2 catalyst in promising the conversion of CH4 and CO2 into oxygenates within a dielectric barrier discharge NTP reactor under ambient conditions. The 10% Cu/UiO-66-NH2 catalyst achieved an impressive 53.4% overall liquid selectivity, with C2+ oxygenates accounting for ∼60.8% of the total liquid products. In situ plasma-coupled Fourier-transform infrared spectroscopy (FTIR) suggests that Cu facilitates the cleavage of surface adsorbed COOH species (*COOH), generating *CO and enabling its migration to the surface of Cu particles. This surface-bound *CO then undergoes C-C coupling and hydrogenation, leading to ethanol production. Further analysis using CO diffuse reflection FTIR and 1H nuclear magnetic resonance spectroscopy indicates that in situ generated surface *CO is more effective than gas-phase CO (g) in promoting C-C coupling and C2+ liquid formation. This work provides valuable mechanistic insights into C-C coupling and C2+ liquid production during plasma-catalytic CO2 oxidation of CH4 under ambient conditions. These findings hold broader implications for the rational design of more efficient catalysts for this reaction, paving the way for advancements in sustainable fuel and chemical production.

9.
Sci Rep ; 14(1): 12229, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806533

RESUMO

The effects of moisture and drying shrinkage can lead to uneven settlement, cracking, and other diseases in loess subgrade. The objective of this study was to investigate the effects of amide polymer (AP) on the permeability, mechanical properties and crack resistance of loess by orthogonal experiments. The basic properties of AP and the permeability, mechanical properties, and dry-wet variation properties of polymer-modified loess were tested, and a scale model verification and simulation analysis were conducted. In this paper, water migration in subgrade is regulated by improving the water sensitivity of loess. By reducing the variation range of subgrade water content, the stress accumulation in subgrade caused by water is weakened. The results show that the curing time and mechanical properties of AP are directly affected by the oxidant and reducing agent, and the mechanical properties of AP are compatible with the characteristics of loess. AP filled the grain gap and reduced the permeability of loess by 34.05-280.83%. The ductility of polymer-modified loess is significantly increased, and the strain of peak strength is increased by 17.21-126.36%. AP can regulate moisture change, reduce the surface tension between particles, and reduce stress concentration. The strength loss rate was reduced by 19.98-51.21% by enhancing the cracking resistance and weakening the strength loss caused by dry and wet cycling. The increase of upper layer moisture content in the scale model of polymer-modified loess subgrade is reduced by 31.38-36.11%.

10.
J Gastrointest Surg ; 28(4): 538-547, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583908

RESUMO

BACKGROUND: With the development of endoscopic technology, endoscopic submucosal dissection (ESD) has been widely used in the treatment of gastrointestinal tumors. It is necessary to evaluate the depth of tumor invasion before the application of ESD. The convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist in the classification of the depth of invasion in endoscopic images. This meta-analysis aimed to evaluate the performance of CNN in determining the depth of invasion of gastrointestinal tumors. METHODS: A search on PubMed, Web of Science, and SinoMed was performed to collect the original publications about the use of CNN in determining the depth of invasion of gastrointestinal neoplasms. Pooled sensitivity and specificity were calculated using an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity. RESULTS: A total of 17 articles were included; the pooled sensitivity was 84% (95% CI, 0.81-0.88), specificity was 91% (95% CI, 0.85-0.94), and the area under the curve (AUC) was 0.93 (95% CI, 0.90-0.95). The performance of CNN was significantly better than that of endoscopists (AUC: 0.93 vs 0.83, respectively; P = .0005). CONCLUSION: Our review revealed that CNN is one of the most effective methods of endoscopy to evaluate the depth of invasion of early gastrointestinal tumors, which has the potential to work as a remarkable tool for clinical endoscopists to make decisions on whether the lesion is feasible for endoscopic treatment.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gastrointestinais , Humanos , Inteligência Artificial , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/patologia , Endoscopia Gastrointestinal/métodos , Redes Neurais de Computação , Ressecção Endoscópica de Mucosa/métodos
11.
Cell Mol Life Sci ; 81(1): 189, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643448

RESUMO

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/genética , Fator de Crescimento Transformador beta1 , Glicólise , Neoplasias Colorretais/genética , Células-Tronco , Microambiente Tumoral , Proteína Smad3/genética , Proteína 4 Semelhante a Angiopoietina/genética
12.
Bull World Health Organ ; 102(4): 276-287, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562199

RESUMO

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019. Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines. Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction). Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.


Assuntos
Sarampo , Coqueluche , Criança , Humanos , Lactente , Programas de Imunização , Vacinação , Vacina contra Sarampo/uso terapêutico , Mortalidade da Criança , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche
13.
Sci Total Environ ; 928: 172428, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38615765

RESUMO

The increasing level of mechanization in coal mining means more dust and gas are generated during excavation operations in tunnels. The high concentrations of dust and gas severely affect production efficiency and the physical and mental health of workers. Here, Ansys Fluent simulations were performed to derive the spatiotemporal evolution of coupled airflow-dust-gas diffusion in a low-gas excavation face. The aim was to optimize pollution control by determining the optimal duct distance, L, from the working face in the excavation tunnel. Our results showed that the airflow field affects the coupled diffusion and transport of dust and gas. According to a comparison of the effects of different duct distances from the working face, when L = 6 m, the average dust concentration in the tunnel is low (257.6 mg/m3), and the average gas concentration in the tunnel is 0.28 %, which does not exceed the safety limit. Accordingly, the optimal distance of the duct for pollution control is 6 m. The results of field measurements supported the validity of the simulation. Our findings can be used to improve the air quality in tunnels, thereby keeping miners safe and the working area clean.

14.
Commun Math Phys ; 405(4): 95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606337

RESUMO

We extend three related results from the analysis of influences of Boolean functions to the quantum setting, namely the KKL theorem, Friedgut's Junta theorem and Talagrand's variance inequality for geometric influences. Our results are derived by a joint use of recently studied hypercontractivity and gradient estimates. These generic tools also allow us to derive generalizations of these results in a general von Neumann algebraic setting beyond the case of the quantum hypercube, including examples in infinite dimensions relevant to quantum information theory such as continuous variables quantum systems. Finally, we comment on the implications of our results as regards to noncommutative extensions of isoperimetric type inequalities, quantum circuit complexity lower bounds and the learnability of quantum observables.

15.
ACS Nano ; 18(14): 10031-10044, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38547360

RESUMO

The increasing demand for improving pesticide utilization efficiency has prompted the development of sustainable, targeted, and stimuli-responsive delivery systems. Herein, a multi-stimuli-responsive nano/microcapsule bidirectional delivery system loaded with pyraclostrobin (Pyr) is prepared through interfacial cross-linking from a lignin-based Pickering emulsion template. During this process, methacrylated alkali lignin nanoparticles (LNPs) are utilized as stabilizers for the tunable oil-water (O/W) Pickering emulsion. Subsequently, a thiol-ene radical reaction occurs with the acid-labile cross-linkers at the oil-water interface, leading to the formation of lignin nano/microcapsules (LNCs) with various topological shapes. Through the investigation of the polymerization process and the structure of LNC, it was found that the amphiphilicity-driven diffusion and distribution of cyclohexanone impact the topology of LNC. The obtained Pyr@LNC exhibits high encapsulation efficiency, tunable size, and excellent UV shielding to Pyr. Additionally, the flexible topology of the Pyr@LNC shell enhances the retention and adhesion of the foliar surface. Furthermore, Pyr@LNC exhibits pH/laccase-responsive targeting against Botrytis disease, enabling the intelligent release of Pyr. The in vivo fungicidal activity shows that efficacy of Pyr@LNC is 53% ± 2% at 14 days postspraying, whereas the effectiveness of Pyr suspension concentrate is only 29% ± 4%, and the acute toxicity of Pyr@LNC to zebrafish is reduced by more than 9-fold compared with that of Pyr technical. Moreover, confocal laser scanning microscopy shows that the LNCs can be bidirectionally translocated in plants. Therefore, the topology-regulated bidirectional delivery system LNC has great practical potential for sustainable agriculture.


Assuntos
Lignina , Praguicidas , Estrobilurinas , Animais , Lignina/química , Praguicidas/farmacologia , Cápsulas/química , Emulsões/química , Peixe-Zebra , Água
16.
Antimicrob Agents Chemother ; 68(4): e0135023, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38470034

RESUMO

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.


Assuntos
Doenças Transmissíveis , Influenza Humana , Inibidores de Janus Quinases , Infecções por Orthomyxoviridae , Orthomyxoviridae , Pirimidinas , Sulfonamidas , Humanos , Animais , Camundongos , Influenza Humana/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Citocinas , Infecções por Orthomyxoviridae/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças Transmissíveis/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Antivirais/uso terapêutico , Antivirais/farmacologia , Pulmão
17.
J Hazard Mater ; 469: 134058, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38508106

RESUMO

Most current researches focus solely on reducing soil chromium availability. It is difficult to reduce soil Cr(VI) concentration below 5.0 mg kg-1 using single remediation technology. This study introduced a sustainable soil Cr(VI) reduction and stabilization system, Penicillium oxalicum SL2-nanoscale zero-valent iron (nZVI), and investigated its effect on Cr(VI) reduction efficiency and microbial ecology. Results showed that P. oxalicum SL2-nZVI effectively reduced soil total Cr(VI) concentration from 187.1 to 3.4 mg kg-1 within 180 d, and remained relatively stable at 360 d. The growth curve of P. oxalicum SL2 and microbial community results indicated that γ-ray irradiation shortened the adaptation time of P. oxalicum SL2 and facilitated its colonization in soil. P. oxalicum SL2 colonization activated nZVI and its derivatives, and increased soil iron bioavailability. After restoration, the negative effect of Cr(VI) on soil microorganisms was markedly alleviated. Cr(VI), Fe(II), bioavailable Cr/Fe, Eh, EC and urease (SUE) were the key environmental factors of soil microbiota. Notably, Penicillium significantly stimulated the growth of urease-positive bacteria, Arthrobacter, Pseudarthrobacter, and Microvirga, synergistically reducing soil chromium availability. The combination of P. oxalicum SL2 and nZVI is expected to form a green, economical and long-lasting Cr(VI) reduction stabilization strategy.


Assuntos
Cromo , Recuperação e Remediação Ambiental , Penicillium , Poluentes Químicos da Água , Cromo/análise , Cromo/metabolismo , Ferro , Solo , Urease , Poluentes Químicos da Água/análise
18.
Sci Total Environ ; 925: 171770, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38499093

RESUMO

The exploration of microbial resources to reduce Pb accumulation in rice attracted great attention. In this study, we found Penicillium oxalicum SL2, a Pb-tolerant strain with good capability of dissolving phosphorus and stabilizing Pb in soil, was able to colonize on the root surface of rice seedlings without additional carbon sources, and promoted the secretion of metabolites related to amino acid metabolism, organic acid metabolism, signal transduction and other pathways in rhizosphere exudates, in which the secretion of oxalate increased by 47.7 %. However, P. oxalicum SL2 increased Fe(II) proportion and Fe availability on the root surface, resulting in iron plaque content decrease. Moreover, by converting root surface Pb from Pb-Fe state to PbC2O4 and Pb-P compounds, P. oxalicum SL2 increased Pb intercept capacity of iron plaque by 118.0 %. Furthermore, P. oxalicum SL2 regulated element distribution on the root surface, and reduced the relative content of Pb on the maturation zone of root tip, which was conducive to reducing Pb uptake by apoplastic pathway and the risk of Pb accumulation in root system. Our findings further revealed the interaction between P. oxalicum SL2 and rice root, providing a theoretical basis for the development and application of microbial agents in Pb-contaminated farmland.


Assuntos
Oryza , Penicillium , Poluentes do Solo , Ferro/análise , Chumbo/análise , Poluentes do Solo/análise , Solo/química , Raízes de Plantas/metabolismo
19.
Front Endocrinol (Lausanne) ; 15: 1349041, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476675

RESUMO

Background: Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is still controversy over whether thyroid peroxidase antibody (TPOAb) is related to differentiated thyroid cancer. Methods: We scrutinized relevant studies published up to July 2023 across four major databases including PubMed, Embase, Cochrane Library, and Web of Science, to examine the association between TPOAb and DTC. Clinical outcome measures include the incidence of DTC, tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, recurrence and bilaterality. Results: 12 original studies were included, involving a total of 20,330 subjects. Our analysis of the included studies revealed that TPOAb+ individuals exhibited a higher risk of developing DTC (OR=1.57 [95% CI: 1.00-2.45], p=0.049) than TPOAb- individuals. Furthermore, TPOAb+ DTC patients were more prone to present with bilateral (OR=1.40 [95% CI: 1.21-1.62], p<0.00001) and multifocal (OR=1.40 [95% CI: 1.23-1.60], p<0.00001) tumors than TPOAb- patients. Sensitivity analysis indicated a high sensitivity for these three findings. No significant differences in the risk of extrathyroidal extension and lymph node metastasis, recurrence rate, tumor size, were observed between TPOAb+ and TPOAb- DTC patients. Conclusion: The presence of TPOAb is correlated with an increase prevalence of DTC. However, its effectiveness as a prognostic marker for DTC patients warrants further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023448824.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Metástase Linfática , Neoplasias da Glândula Tireoide/patologia , Bases de Dados Factuais , Iodeto Peroxidase
20.
Res Sq ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38464266

RESUMO

Background: Segmented regression, a common model for interrupted time series (ITS) analysis, primarily utilizes two equation parametrizations. Interpretations of coefficients vary between the two segmented regression parametrizations, leading to occasional user misinterpretations. Methods: To illustrate differences in coefficient interpretation between two common parametrizations of segmented regression in ITS analysis, we derived analytical results and present an illustration evaluating the impact of a smoking regulation policy in Italy using a publicly accessible dataset. Estimated coefficients and their standard errors were obtained using two commonly used parametrizations for segmented regression with continuous outcomes. We clarified coefficient interpretations and intervention effect calculations. Results: Our investigation revealed that both parametrizations represent the same model. However, due to differences in parametrization, the immediate effect of the intervention is estimated differently under the two approaches. The key difference lies in the interpretation of the coefficient related to the binary indicator for intervention implementation, impacting the calculation of the immediate effect. Conclusions: Two common parametrizations of segmented regression represent the same model but have different interpretations of a key coefficient. Researchers employing either parametrization should exercise caution when interpreting coefficients and calculating intervention effects.

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