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1.
iScience ; 27(7): 110144, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38989466

RESUMO

Retinoic acid (RA), derived from retinol (ROL), is integral to cell growth, differentiation, and organogenesis. It is known that RA can inhibit herpes simplex virus (HSV) replication, but the interactions between alphaherpesviruses and RA metabolism are unclear. Our present study revealed that alphaherpesvirus (HSV-1 and Pseudorabies virus, PRV) infections suppressed RA synthesis from ROL by activating P53, which increased retinol reductase 3 (DHRS3) expression-an enzyme that converts retinaldehyde back to ROL. This process depended on the virus-triggered DNA damage response, the degradation of class I histone deacetylases, and the subsequent hyperacetylation of histones H3 and H4. Counteracting DHRS3 or P53 enabled higher RA synthesis and reduced viral growth. RA enhanced antiviral defenses by promoting ABCA1- and ABCG1-mediated lipid efflux. Treatment with the retinoic acid receptor (RAR) agonist palovarotene protected mice from HSV-1 infection, thus providing a potential therapeutic strategy against viral infections.

2.
Urolithiasis ; 52(1): 109, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073726

RESUMO

Impacted proximal ureteral stones (IPUS) present challenging clinical scenarios due to their persistent nature and associated complications. While ureterorenoscopy (URS) lithotripsy is recommended as the primary treatment, controversies exist regarding the optimal management of such stones. In this retrospective analysis, we compared the operative outcomes and long-term results of transperitoneal laparoscopic ureterolithotomy (LU) and percutaneous nephrolithotomy (PCNL) for IPUS larger than 15 mm. Propensity score matching (PSM) was employed to mitigate potential selection biases. Following PSM, 83 patients in each cohort exhibited comparable baseline characteristics. LU demonstrated a superior surgical success rate (100% vs. 96.4%, p = 0.244) and significantly lower perioperative hemoglobin decline (0.6 ± 0.4 g/dL vs. 1.5 ± 0.7 g/dL, p = 0.036) compared to PCNL. Additionally, LU exhibited a higher stone-free rate after 2 months (100% vs. 91.6%, p = 0.043), but a longer duration of catheterization (7.4 ± 1.2 days vs. 3.5 ± 2.2 days vs., p = 0.011). Conversely, PCNL was associated with a higher incidence of total complications (21.7% vs. 9.6%, p = 0.033) and stone recurrence during a mean period of 40-month follow-up (20.5% vs. 8.4%, p = 0.027). Transperitoneal LU and PCNL represent effective interventions for managing IPUS exceeding 15 mm. Notably, LU emerges as a preferable option over PCNL, offering superior stone clearance rates, reduced perioperative complications, and lower recurrence rates.


Assuntos
Laparoscopia , Nefrolitotomia Percutânea , Pontuação de Propensão , Cálculos Ureterais , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Cálculos Ureterais/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Adulto , Seguimentos , Resultado do Tratamento , Fatores de Tempo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Peritônio/cirurgia
3.
J Am Heart Assoc ; 13(13): e032781, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38934873

RESUMO

BACKGROUND: This study assesses the diagnostic utility of strain parameters from cardiovascular magnetic resonance feature tracking across all cardiac chambers in patients with acute myocarditis, stratified by ejection fraction. METHODS AND RESULTS: Our cohort included 65 patients with acute myocarditis and 25 healthy controls; all underwent cardiac magnetic resonance imaging. Patients were divided into 2 groups based on left ventricular ejection fraction (EF)with a 55% cutoff: acute myocarditis with preserved EF, EF ≥55%, n=48; and acute myocarditis with reduced EF, EF <55%, n=17. The control group matched for age and sex. Cardiovascular magnetic resonance feature tracking evaluated strain parameters across all cardiac chambers. Both acute myocarditis with preserved EF and acute myocarditis with reduced EF groups showed significant decreases in left atrial peak early negative strain rate compared with controls. The acute myocarditis with reduced EF group had significantly reduced left ventricular circumferential strain relative to acute myocarditis with preserved EF and controls. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy in distinguishing patients with acute myocarditis with preserved EF from controls, with left atrial peak early negative strain rate achieving 92.9% specificity, left ventricular circumferential strain demonstrating an area under the curve of 0.832, and similarly effective results for left ventricular longitudinal strain and right ventricular longitudinal strain. Additionally, left atrial peak early negative strain rate and left ventricular circumferential strain showed significant correlations with troponin I levels, indicating myocardial injury. CONCLUSIONS: Cardiovascular magnetic resonance feature-tracking-derived strain parameters, particularly left atrial peak early negative strain rate and left ventricular circumferential strain, effectively diagnose acute myocarditis across different EFs, enhancing diagnostic accuracy and facilitating early detection, notably in patients with preserved EF.


Assuntos
Imagem Cinética por Ressonância Magnética , Miocardite , Volume Sistólico , Função Ventricular Esquerda , Humanos , Miocardite/fisiopatologia , Miocardite/diagnóstico por imagem , Miocardite/diagnóstico , Masculino , Feminino , Volume Sistólico/fisiologia , Adulto , Doença Aguda , Função Ventricular Esquerda/fisiologia , Imagem Cinética por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos de Casos e Controles , Estudos Retrospectivos
4.
Bioorg Chem ; 150: 107562, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901282

RESUMO

Accumulating data support the key roles of the NLRP3 inflammasome, an essential component of the innate immune system, in human pathophysiology. As an emerging drug target and a potential biomarker for human diseases, small molecule inhibitors of the NLRP3 inflammasome have been actively pursued. Our recent studies identified a small molecule, MS-II-124, as a potent NLRP3 inhibitor and potential imaging probe. In this report, MS-II-124 was further characterized by an unbiased and comprehensive analysis through Eurofins BioMAP Diversity PLUS panel that contains 12 human primary cell-based systems. The analysis revealed promising activities of MS-II-124 on inflammation and immune functions, further supporting the roles of the NLRP3 inflammasome in these model systems. Further studies of MS-II-124 in mouse model of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and NLRP3 knockout mice demonstrated its target engagement, efficacy to suppress inflammatory cytokines and infiltration of immune cells in the lung tissues. In summary, the results support the therapeutic potential of MS-II-124 as a NLRP3 inhibitor and warrant future studies of this compound and its analogs to develop therapeutics for ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda , Inflamassomos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Bibliotecas de Moléculas Pequenas , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Camundongos , Humanos , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Camundongos Endogâmicos C57BL , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga
5.
J Tradit Complement Med ; 14(3): 321-334, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707923

RESUMO

Background and aim: Most patients with hepatocellular carcinoma (HCC) in China have been diagnosed with spleen deficiency syndrome (SDS), which accelerates the progression of HCC by disrupting the tumor microenvironment homeostasis. This study aimed to investigate the intercellular crosstalk in HCC with SDS. Experimental procedure: An HCC-SDS mouse model was established using orthotopic HCC transplantation based on reserpine-induced SDS. Single-cell data analysis and cancer cell prediction were conducted using Seurat and CopyKAT package, respectively. Intercellular interactions were explored using CellPhoneDB and CellChat and subsequently validated using co-culture assays, ELISA and histological staining. We performed pathway activity analysis using gene set variation analysis and the Seurat package. The extracellular matrix (ECM) remodeling was assessed using a gel contraction assay, atomic force microscopy, and Sirius red staining. The deconvolution of the spatial transcriptomics data using the "CARD" package based on single-cell data. Results and conclusion: We successfully established the HCC-SDS mouse model. Twenty-nine clusters were identified. The interactions between cancer cells and cancer-associated fibroblasts (CAFs) were significantly enhanced via platelet-derived growth factor (PDGF) signaling in HCC-SDS. CAFs recruited in HCC-SDS lead to ECM remodeling and the activation of TGF-ß signaling pathway. Deconvolution of the spatial transcriptome data revealed that CAFs physically surround cancer cells in HCC-SDS. This study reveals that the crosstalk of CAFs-cancer cells is crucial for the tumor-promoting effect of SDS. CAFs recruited by HCC via PDGFA may lead to ECM remodeling through activation of the TGF-ß pathway, thereby forming a physical barrier to block immune cell infiltration under SDS.

6.
BioData Min ; 17(1): 13, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773619

RESUMO

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

7.
Sci Total Environ ; 932: 173029, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38719039

RESUMO

Plant growth regulators (PGR) and plant growth-promoting bacteria (PGPB) have the potential in phytoremediation of heavy metals (HMs) contaminated soils. However, their sole application may not yield the optimal results, thus necessitating the combined application. The present study aimed to enhance the phytoremediation efficiency of Sedum alfredii Hance (S. alfredii) in acidic and alkaline soils through the combination of PGR (Brassinolide, BR) and PGPB (Pseudomonas fluorescens, P. fluorescens). The combination of BR and P. fluorescens (BRB treatment) effectively increased the removal efficiency of S. alfredii for Cd, Pb, and Zn by 355.2 and 155.3 %, 470.1 and 128.9 %, and 408.4 and 209.6 %, in acidic and alkaline soils, respectively. Moreover, BRB treatment led to a substantial increase in photosynthetic pigments contents and antioxidant enzymes activities, resulting in a remarkable increase in biomass (86.71 and 47.22 %) and dry mass (101.49 and 42.29 %) of plants grown in acidic and alkaline soils, respectively. Similarly, BRB treatment significantly elevated the Cd (109.4 and 71.36 %), Pb (174.9 and 48.03 %), and Zn levels (142.8 and 104.3 %) in S. alfredii shoots, along with cumulative accumulation of Cd (122.7 and 79.47 %), Pb (183.8 and 60.49 %), and Zn (150.7 and 117.9 %), respectively. In addition, the BRB treatment lowered the soil pH and DTPA-HMs contents, while augmenting soil enzymatic activities, thereby contributing soil microecology and facilitating the HMs absorption and translocation by S. alfredii to over-ground tissues. Furthermore, the evaluation of microbial community structure in phyllosphere and rhizosphere after remediation revealed the shift in microbial abundance. The combined treatment altered the principal effects on S. alfredii HMs accumulation from bacterial diversity to the soil HMs availability. In summary, our findings demonstrated that synergistic application of BR and P. fluorescens represents a viable approach to strengthen the phytoextraction efficacy of S. alfredii in varying soils.


Assuntos
Biodegradação Ambiental , Metais Pesados , Reguladores de Crescimento de Plantas , Pseudomonas fluorescens , Sedum , Poluentes do Solo , Solo , Sedum/metabolismo , Poluentes do Solo/metabolismo , Metais Pesados/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Solo/química , Pseudomonas fluorescens/metabolismo , Microbiologia do Solo
8.
Gels ; 10(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391450

RESUMO

Aerogels prepared using freeze-drying methods have the potential to be insulation materials or absorbents in the fields of industry, architecture, agriculture, etc., for their low heat conductivity, high specific area, low density, degradability, and low cost. However, their native, poor water resistance caused by the hydrophilicity of their polymer matrix limits their practical application. In this work, a novel, controllable, and efficient templating method was utilized to construct a highly hydrophobic surface for freeze-drying aerogels. The influence of templates on the macroscopic morphology and hydrophobic properties of materials was investigated in detail. This method provided the economical and rapid preparation of a water-resistant aerogel made from polyvinyl alcohol (PVA) and montmorillonite (MMT), putting forward a new direction for the research and development of new, environmentally friendly materials.

9.
Neurospine ; 21(1): 303-313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317550

RESUMO

OBJECTIVE: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). METHODS: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients' clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. RESULTS: During a mean follow-up of 5.5 years (range, 5-7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. CONCLUSION: Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

10.
Phys Chem Chem Phys ; 26(8): 7137-7148, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38348666

RESUMO

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

11.
Pest Manag Sci ; 80(7): 3258-3268, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38358092

RESUMO

BACKGROUND: Detoxifying enzymes are likely involved in lignin feeding and immune defense mechanisms within termites, rendering them potential targets for biological control. However, investigations into the dual functionality of termite detoxification enzymes in vivo have not been documented. RESULTS: In this study, the complete cDNA of the catalase gene (Cfcat) derived from Coptotermes formosanus Shiraki was amplified. CFCAT comprises an open reading frame spanning 1527 bp, encoding a 508-amino acid sequence. The highest expression was observed in the epidermal tissues (including the fat body and hemolymph) followed by the foregut/salivary gland. Furthermore, we confirmed the catalase activity of the recombinant Cfcat protein. Using RNA interference (RNAi) technology, the importance of Cfcat in the lignin-feeding of C. formosanus was demonstrated, and the role of Cfcat in innate immunity was investigated. Survival assays showed that Cfcat RNAi significantly increased the susceptibility of C. formosanus to Metarhizium anisopliae. Irrespective of the infection status, Cfcat inhibition had a significant impact on multiple factors of humoral and intestinal immunity in C. formosanus. Notably, Cfcat RNAi exhibited a more pronounced immunosuppressive effect on humoral immunity than on intestinal immunity. CONCLUSION: Cfcat plays an important role in the regulation of innate immunity and lignin feeding in C. formosanus. Cfcat RNAi can weaken the immune response of termites against M. anisopliae, which may aid the biocontrol efficiency of M. anisopliae against C. formosanus. This study provides a theoretical basis and technical reference for the development of a novel biocontrol strategy targeting detoxifying enzymes of termites. © 2024 Society of Chemical Industry.


Assuntos
Catalase , Proteínas de Insetos , Isópteros , Lignina , Animais , Isópteros/imunologia , Isópteros/microbiologia , Isópteros/genética , Lignina/metabolismo , Catalase/genética , Catalase/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Metarhizium/fisiologia , Metarhizium/genética , Controle de Insetos , Imunidade Inata , Interferência de RNA , Sequência de Aminoácidos
12.
Sci Total Environ ; 913: 169788, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38181951

RESUMO

The phytoremediation efficiency of plants in removing the heavy metals (HMs) might be influenced by their growth status and accumulation capacity of plants. Herein, we conducted a lab-scale experiment and a field try out to assess the optimal plant growth regulators (PGRs) including indole-3-acetic acid (IAA)/brassinolide (BR)/abscisic acid (ABA) in improving the phytoextraction potential of Sedum alfredii Hance (S. alfredii). The results of pot experiment revealed that application of IAA at 0.2 mg/L, BR at 0.4 mg/L, and ABA at 0.2 mg/L demonstrated notable potential as optimal dosage for Cd/Pb/Zn phytoextraction in S. alfredii. The findings of subcellular level of Cd/Pb/Zn in leaves showed that IAA (0.2 mg/L), BR (0.4 mg/L) or ABA (0.2 mg/L) promoted the HMs storage in the soluble and cell wall fraction, therefore contributing HMs subcellular compartmentation. In addition, application of PGRs notably enhanced the antioxidant system (SOD, CAT, POD, APX activities) while reducing lipid peroxidation (MDA content) in S. alfredii, consequently improving HMs tolerance and growth of S. alfredii. Moreover, the results of field trial showed that application of BR, IAA, or ABA+BR substantially improved the growth of S. alfredii by inducing plants biomass and augmenting the levels of photosynthetic pigment contents. Notably, ABA+BR noticed the highest theoretical biomass by 42.9 %, followed by IAA (41.6 %), and BR (36.4 %), as compared with CK. Additionally, ABA+BR treatment showed effectiveness in removing the Cd by 103.4 %, while BR and IAA led to a significant increase of Pb and Zn removal by 239 % and 116 %, respectively, when compared with CK. Overall, the results of this study highlights that the foliar application of IAA, BR, or ABA+BR can serve as viable strategy to boosting phytoremediation efficiency of S. alfredii in contaminated soil by improving the biomass and metal accumulation in harvestable parts.


Assuntos
Metais Pesados , Sedum , Poluentes do Solo , Cádmio/análise , Reguladores de Crescimento de Plantas , Chumbo , Metais Pesados/análise , Ácido Abscísico , Biodegradação Ambiental , Solo , Poluentes do Solo/análise , Raízes de Plantas/química
13.
Bioorg Med Chem Lett ; 99: 129610, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211702

RESUMO

A series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of P1, P1 prime and P2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. 14c demonstrated excellent in-vitro potency (FXIa IC50: 15 nM, 2 x aPTT: 6.8 µM) and good in-vivo efficacy (prolonged in-vivo aPTT by more than 1-fold but not PT). Moreover, the pharmacokinetics property of 14c were evaluated following intravenous administration in rats, which indicated that 14c probably will be a clinical candidate for intravenous administration.


Assuntos
Coagulação Sanguínea , Fator XIa , Animais , Ratos , Tempo de Tromboplastina Parcial
14.
Adv Sci (Weinh) ; 11(8): e2306355, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38115551

RESUMO

Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small-size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas-solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self-similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle-fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era.

15.
Small ; 20(20): e2310240, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105415

RESUMO

Silicon (Si) is regarded as the most potential anode material for next-generation lithium-ion batteries (LIBs). However, huge volume expansion hinders its commercial application. Here, a yolk-shell structural nitrogen-doped carbon coated Si@SiO2 is prepared by SiO2 template and HF etching method. The as-prepared composite exhibits superior cycling stability with a high reversible capacity of 577 mA h g-1 at 1 A g-1 after 1000 cycles. The stress effect of SiO2 on stabilizing the electrochemical performance of Si anode is systematically investigated for the first time. In situ thickness measurement reveals that the volume expansion thickness of Si@SiO2 upon charge-discharge is obviously smaller than Si, demonstrating the electrode expansion can be effectively inhibited to improve the cyclability. The density functional theory (DFT) calculation further demonstrates the moderate young's modulus and enhanced hardness after SiO2 coating contribute significantly to the mechanical reinforcement of overall Si@SiO2@void@NC composite. Various post-cycling electrode analyses also address the positive effects of inner stress from the Si core on effectively relieving the damage to electrode structure, facilitating the formation of a more stable inorganic-rich solid electrolyte interphase (SEI) layer. This study provides new insights for mechanical stability and excellent electrochemical performance of Si-based anode materials.

16.
J Med Chem ; 67(1): 555-571, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38150705

RESUMO

The NOD-like receptor (NLR) family pyrin-domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune system, has been emerging as a viable drug target and a potential biomarker for human diseases. In our efforts to develop novel small molecule NLRP3 inhibitors, a 1-(5-chloro-2-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole scaffold was designed via a rational approach based on our previous leads. Structure-activity relationship studies and biophysical studies identified a new lead compound 8 as a potent (IC50: 0.55 ± 0.16 µM), selective, and direct NLRP3 inhibitor. Positron emission tomography (PET) imaging studies of [11C]8 demonstrated its rapid and high brain uptake as well as fast washout in mice and rhesus macaque. Notably, plasma kinetic analysis of this radiotracer from the PET/magnetic resonance imaging studies in rhesus macaque suggested radiometabolic stability. Collectively, our data not only encourage further studies of this lead compound but also warrant further optimization to generate additional novel NLRP3 inhibitors and suitable central nervous system PET radioligands with translational promise.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Humanos , Macaca mulatta , Cinética , Tomografia por Emissão de Pósitrons
17.
Artigo em Inglês | MEDLINE | ID: mdl-38041745

RESUMO

Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.

18.
Pestic Biochem Physiol ; 196: 105621, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945257

RESUMO

Biocontrol of subterranean termites is largely impeded by their social immune responses. Studies on biocontrol agents combined with natural insecticides and their possible effects on the immune defense mechanisms of termites are limited. In this study, we investigated the effects of a combined biocontrol strategy using a plant-derived insect ATPase inhibitor, α-terpineol, with the entomopathogenic nematodes (EPNs) Steinernema carpocapsae against the subterranean termite Coptotermes formosanus Shiraki. Survival assays showed that even a low lethal concentration of α-terpineol significantly increased the EPNs-induced virulence in C. formosanus. α-terpineol treatment majorly inhibited the activity of Na+- K+- ATPase, which disturbed the EPNs-induced enhancement of locomotor activity and grooming behavior in termites treated with the combined strategy. Furthermore, the combination treatment had a synergistic inhibitory effect on innate immune responses in C. formosanus, which were measured as changes in the expression of immune-related genes and activities of immune system enzymes. In conclusion, α-terpineol can weaken the immune defense of termites against EPNs at low lethal concentrations, and is a suitable non-synthetic insecticide to prove the biocontrol efficiency of EPNs on C. formosanus. This study provides a theoretical basis and technical reference for a novel biocontrol strategy that promises to overcome the problems of host immune defense in termites.


Assuntos
Inseticidas , Isópteros , Nematoides , Animais , Isópteros/fisiologia , Virulência , Inseticidas/farmacologia , Adenosina Trifosfatases
19.
Front Neurol ; 14: 1275715, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954641

RESUMO

Background: Advanced perfusion modalities are increasingly popular for various diseases. However, few studies have focused on contrasting perfusion patterns. Objective: This study aimed to compare the time efficiency and clinical outcomes of patients with acute ischemic stroke (AIS) who underwent endovascular treatment (EVT) before one-stop arterial spin labeling (ASL) and computed tomography perfusion (CTP) protocols. Methods: This study retrospectively included 326 patients with AIS who had accepted EVT within 24 h of onset from four comprehensive stroke centers between October 2017 and September 2022. After 1:1 matching of the propensity scores, 202 patients were separated into two groups: the ASL group (n = 101) and the CTP group (n = 101). Results: Functional independence at 90 days (modified Rankin Scale [mRS] 0-2; p = 0.574), onset-to-puncture time (p = 0.231), door-to-puncture time (p = 0.136), and door-to-perfusion time (p = 0.646) were not significantly different between the two groups. The proportion of EVT complications (31.7% in the ASL group vs. 14.9% in the CTP group, p = 0.005) and symptomatic intracranial hemorrhage (sICH) at 24 h (23.8% in the ASL group vs. 9.9% in the CTP group, p = 0.008) in the CTP group were lower than the ASL group. The ischemic core volume was a common predictor of favorable outcomes in both ASL (p < 0.001) and CTP (p < 0.001) groups. Conclusion: There were no significant differences in time efficiency and efficacy outcomes between the two groups of patients receiving one-stop ASL and CTP. The proportion of sICH at 24 h and EVT complications of patients in the CTP group was lower than the ASL group. The ischemic core volume was an independent predictor for favorable outcomes.

20.
Sci Prog ; 106(4): 368504231205395, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37814534

RESUMO

International Dispute Settlement Bodies (IDSBs), through their judgements, have consistently urged the States to take scientific approaches in ocean governance for marine environmental protection. There has been the development of significant jurisprudence which undertake policy principles with scientific prescription in ocean governance. The jurisprudence relating to maritime dispute resolution has primarily relied on the interpretative criteria of 'integration' for science and policy as specified in the Vienna Convention. Indeed, this principle of 'integration' integrated 'science-policy' through various concepts, and IDSBs applied and endorsed the 'rule of law', 'cooperation', 'precaution' and 'ecosystem-based approach' to lay stress on the progressive ocean governance. This also reflects that the scientific basis in jurisprudence demonstrates a change in the international organisations' interests (of environmental protection and global sustainability). Moreover, it is also suggested at the end how the provisions related to Marine Scientific Research can be purposefully developed and maintained to protect the marine environment and ecosystems in light of the decisions of the IDSBs. This research article analysed the relevant jurisprudence to explain the principles for science-policy integration, which operates in ocean governance for marine environmental protection.

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