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1.
Pest Manag Sci ; 2024 Feb 15.
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.

2.
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.

3.
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.

4.
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.

5.
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
6.
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
7.
J Med Chem ; 67(1): 555-571, 2024 Jan 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
8.
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.

9.
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.

10.
Small ; : e2310240, 2023 Dec 17.
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.

11.
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
12.
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.

13.
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.

14.
Front Cell Dev Biol ; 11: 1191074, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842089

RESUMO

Background: Hepatocellular Carcinoma (HCC) is a common lethal digestive system tumor. The oxidative stress mechanism is crucial in the HCC genesis and progression. Methods: Our study analyzed single-cell and bulk sequencing data to compare the microenvironment of non-tumor liver tissues and HCC tissues. Through these analyses, we aimed to investigate the effect of oxidative stress on cells in the HCC microenvironment and identify critical oxidative stress response-related genes that impact the survival of HCC patients. Results: Our results showed increased oxidative stress in HCC tissue compared to non-tumor tissue. Immune cells in the HCC microenvironment exhibited higher oxidative detoxification capacity, and oxidative stress-induced cell death of dendritic cells was attenuated. HCC cells demonstrated enhanced communication with immune cells through the MIF pathway in a highly oxidative hepatoma microenvironment. Meanwhile, using machine learning and Cox regression screening, we identified PRDX1 as a predictor of early occurrence and prognosis in patients with HCC. The expression level of PRDX1 in HCC was related to dysregulated ribosome biogenesis and positively correlated with the expression of immunological checkpoints (PDCD1LG2, CTLA4, TIGIT, LAIR1). High PRDX1 expression in HCC patients correlated with better sensitivity to immunotherapy agents such as sorafenib, IGF-1R inhibitor, and JAK inhibitor. Conclusion: In conclusion, our study unveiled variations in oxidative stress levels between non-tumor liver and HCC tissues. And we identified oxidative stress gene markers associated with hepatocarcinogenesis development, offering novel insights into the oxidative stress response mechanism in HCC.

15.
Environ Technol ; : 1-13, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37746747

RESUMO

In this study, Chlorella and Scenedesmus were inoculated in biogas slurry medium with initial inoculum (OD680) of 0.05, 0.1, 0.2, and 0.3, respectively, and 5% CO2 was continuously injected. The study aimed to examine the carbon sequestration capacity of Chlorella and Scenedesmus, as well as the effectiveness of removing pollutants such as TN, TP, and COD in biogas slurry medium. Additionally, an economic efficiency analysis of energy consumption was conducted. The group with an initial inoculum (OD680) of 0.3 for both types of microalgae exhibited better tolerance to pollutants, entered the logarithmic growth stage earlier, promoted nutrient removal, achieved higher energy efficiency, and reduced carbon emissions compared to the other groups. The highest carbon sequestration rates were 18.03% for Chlorella and 11.05% for Scenedesmus. Furthermore, Chlorella demonstrated corresponding nutrient removal efficiencies of 83.03% for TN, 99.84% for TP, and 90.06% for COD, while Scenedesmus exhibited removal efficiencies of 66.35% for TN, 98.74% for TP, and 77.71% for COD. The highest energy efficiency for pollutants and CO2 removal rates for Chlorella were 49.51 ± 2.20 and 9.91 ± 0.44 USD-1, respectively. In conclusion, the findings demonstrate the feasibility of using microalgae for simultaneous purification of biogas and biogas slurry.

16.
Curr Protein Pept Sci ; 24(8): 666-683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37587817

RESUMO

AIMS: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC). BACKGROUND: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied. OBJECTIVE: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy. METHODS: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC. RESULTS: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup. CONCLUSION: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.

17.
Front Pharmacol ; 14: 1218679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37502211

RESUMO

We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating drugs with adverse drug events using 1,394 clinical notes of 47 randomly selected patients who received immune checkpoint inhibitors (ICIs) from 2011 to 2018 at The Ohio State University James Cancer Hospital, annotating 189 drug-ADE relations in single sentences within the medical records. We also used data from Harvard's publicly available 2018 National Clinical Challenge (n2c2), which includes 505 discharge summaries with annotations of 1,355 single-sentence drug-ADE relations. We applied classical machine learning (support vector machine (SVM)), deep learning (convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM)), and state-of-the-art transformer-based (bidirectional encoder representations from transformers (BERT) and ClinicalBERT) methods trained and tested in the two different corpora and compared performance among them to detect drug-ADE relationships. ClinicalBERT detected drug-ADE relationships better than the other methods when trained using our dataset and tested in n2c2 (ClinicalBERT F-score, 0.78; other methods, F-scores, 0.61-0.73) and when trained using the n2c2 dataset and tested in ours (ClinicalBERT F-score, 0.74; other methods, F-scores, 0.55-0.72). Comparison among several machine learning methods demonstrated the superior performance and, therefore, the greatest generalizability of findings of ClinicalBERT for the detection of drug-ADE relations from clinical narratives in electronic medical records.

18.
Expert Opin Ther Pat ; 33(6): 455-470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37470439

RESUMO

INTRODUCTION: NOD-like receptor family pyrin domain containing 3 (NLRP3) can sense a plethora of exogenous and endogenous dangers. Upon activation, a multimeric protein complex, the NLRP3 inflammasome, is formed to initiate the innate immune responses. Emerging studies have implicated the pathophysiological roles of this protein complex in human disorders, highlighting that it represents a druggable target for therapeutics development. AREAS COVERED: The current review summarizes the functional facets of the NLRP3 inflammasome, its association with autoimmune diseases, and recent patents on the development of NLRP3 inhibitors. Literature search was conducted using SciFinder and Google Patents with the key word NLRP3 and NLRP3 inhibitors. EXPERT OPINION: Although significant advances have been made in understanding the NLRP3 inflammasome, more studies are still needed to elucidate the molecular mechanisms underlying its roles in autoimmune diseases. A number of NLRP3 inhibitors have been patented, however, none of them have been approved for clinical use. Due to the complex nature of the NLRP3 inflammasome, novel screening assays along with target engagement methods could benefit the drug discovery and clinical translation. In addition, clinical trials on NLRP3 inhibitors are still in their early stages, and continuous investigations are needed to fully assess their safety and effectiveness.


Assuntos
Doenças Autoimunes , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Patentes como Assunto , Imunidade Inata , Doenças Autoimunes/tratamento farmacológico
19.
Ren Fail ; 45(1): 2235015, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37462113

RESUMO

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.


Assuntos
Técnicas de Imagem por Elasticidade , Nefropatias , Transplante de Rim , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Transplante de Rim/efeitos adversos , Técnicas de Imagem por Elasticidade/métodos , Prognóstico , Rim/diagnóstico por imagem , Rim/patologia , Nefropatias/patologia
20.
IEEE J Biomed Health Inform ; 27(9): 4385-4396, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37467088

RESUMO

Medical images such as facial and tongue images have been widely used for intelligence-assisted diagnosis, which can be regarded as the multi-label classification task for disease location (DL) and disease nature (DN) of biomedical images. Compared with complicated convolutional neural networks and Transformers for this task, recent MLP-like architectures are not only simple and less computationally expensive, but also have stronger generalization capabilities. However, MLP-like models require better input features from the image. Thus, this study proposes a novel convolution complex transformation MLP-like (CCT-MLP) model for the multi-label DL and DN recognition task for facial and tongue images. Notably, the convolutional Tokenizer and multiple convolutional layers are first used to extract the better shallow features from input biomedical images to make up for the loss of spatial information obtained by the simple MLP structure. Subsequently, the Channel-MLP architecture with complex transformations is used to extract deep-level contextual features. In this way, multi-channel features are extracted and mixed to perform the multi-label classification of the input biomedical images. Experimental results on our constructed multi-label facial and tongue image datasets demonstrate that our method outperforms existing methods in terms of both accuracy (Acc) and mean average precision (mAP).


Assuntos
Diagnóstico por Imagem , Redes Neurais de Computação , Humanos
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