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1.
J Am Chem Soc ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742912

RESUMO

Composite oxides have been widely applied in the hydrogenation of CO/CO2 to methanol or as the component of bifunctional oxide-zeolite for the synthesis of hydrocarbon chemicals. However, it is still challenging to disentangle the stepwise formation mechanism of CH3OH at working conditions and selectively convert CO2 to hydrocarbon chemicals with narrow distribution. Here, we investigate the reaction network of the hydrogenation of CO2 to methanol over a series of spinel oxides (AB2O4), among which the Zn-based nanostructures offer superior performance in methanol synthesis. Through a series of (quasi) in situ spectroscopic characterizations, we evidence that the dissociation of H2 tends to follow a heterolytic pathway and that hydrogenation ability can be regulated by the combination of Zn with Ga or Al. The coordinatively unsaturated metal sites over ZnAl2Ox and ZnGa2Ox originating from oxygen vacancies (OVs) are evidenced to be responsible for the dissociative adsorption and activation of CO2. The evolution of the reaction intermediates, including both carbonaceous and hydrogen species at high temperatures and pressures over the spinel oxides, has been experimentally elaborated at the atomic level. With the integration of a series of zeolites or zeotypes, high selectivities of hydrocarbon chemicals with narrow distributions can be directly produced from CO2 and H2, offering a promising route for CO2 utilization.

2.
Environ Pollut ; 351: 124079, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692390

RESUMO

With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO2-NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO2-NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO2-NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO2-NPs, while the presence of TiO2-NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO2-NPs and LEV. The results indicate that TiO2-LEV complexes or aggregates can be formed during the co-transportation process of TiO2-NPs and LEV in porous media. As flow velocity increases from 0.204 cm min-1 to 1.630 cm min-1, both the transport capacities of TiO2-NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L-1), the transport capacity of TiO2-NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems.

3.
Nat Prod Res ; : 1-10, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695089

RESUMO

Rubrolides are natural butyrolactones isolated from the tunicate Ritterella rubra, shows antibacterial, antiviral and plant photosynthesis inhibitory activities. In this study, a facile total synthetic method for preparing the rubrolides from benzaldehyde by a Darzens reaction, aldol reaction and vinylogous aldol condensation in five steps is presented. Three natural rubrolides (E, C and F) were synthesised in the total yields of 25-40%. The bioassay results indicate that rubrolides E, C and F exhibit some herbicidal inhibitory effect against rapeseed, in particular, rubrolide F shows the best herbicidal activities against rapeseed root with the growth inhibitory rate of 72.8%. At greenhouse treatment concentrations of 100 and 500 mg/L, rubrolide F show a positive dose-toxicity correlation towards abutilon plants. Collectively, facile total Synthesis strategy provided the base for further bioactivities study of rubrolides family. Rubrolide F may be act as inhibitor of photosynthesis, and this could be lead structure of new herbicide.

4.
J Alzheimers Dis ; 98(4): 1415-1426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578889

RESUMO

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Placa Amiloide/diagnóstico por imagem , Peptídeos beta-Amiloides , Amiloide , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Proteínas tau
6.
Front Integr Neurosci ; 18: 1367593, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560577

RESUMO

[This corrects the article DOI: 10.3389/fnint.2023.1234471.].

7.
Food Chem Toxicol ; 188: 114665, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641045

RESUMO

Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides, amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, ß, and γ-amanitin at concentrations ranging from 0.3 to 100 µM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure.


Assuntos
Amanitinas , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Humanos , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Amanitinas/toxicidade , Células HEK293 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Alfa-Amanitina/toxicidade , Células Hep G2
8.
Cell Death Differ ; 31(5): 635-650, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493248

RESUMO

Diquat (DQ) poisoning is a severe medical condition associated with life-threatening implications and multiorgan dysfunction. Despite its clinical significance, the precise underlying mechanism remains inadequately understood. This study elucidates that DQ induces instability in the mitochondrial genome of endothelial cells, resulting in the accumulation of Z-form DNA. This process activates Z-DNA binding protein 1 (ZBP1), which then interacts with receptor-interacting protein kinase 3 (RIPK3), ultimately leading to RIPK3-dependent necroptotic and ferroptotic signaling cascades. Specific deletion of either Zbp1 or Ripk3 in endothelial cells simultaneously inhibits both necroptosis and ferroptosis. This dual inhibition significantly reduces organ damage and lowers mortality rate. Notably, our investigation reveals that RIPK3 has a dual role. It not only phosphorylates MLKL to induce necroptosis but also phosphorylates FSP1 to inhibit its enzymatic activity, promoting ferroptosis. The study further shows that deletion of mixed lineage kinase domain-like (Mlkl) and the augmentation of ferroptosis suppressor protein 1 (FSP1)-dependent non-canonical vitamin K cycling can provide partial protection against DQ-induced organ damage. Combining Mlkl deletion with vitamin K treatment demonstrates a heightened efficacy in ameliorating multiorgan damage and lethality induced by DQ. Taken together, this study identifies ZBP1 as a crucial sensor for DQ-induced mitochondrial Z-form DNA, initiating RIPK3-dependent necroptosis and ferroptosis. These findings suggest that targeting the ZBP1/RIPK3-dependent necroptotic and ferroptotic pathways could be a promising approach for drug interventions aimed at mitigating the adverse consequences of DQ poisoning.


Assuntos
DNA Mitocondrial , Ferroptose , Necroptose , Proteínas de Ligação a RNA , Proteína Serina-Treonina Quinases de Interação com Receptores , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Ferroptose/efeitos dos fármacos , Animais , Necroptose/efeitos dos fármacos , Camundongos , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Humanos , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Camundongos Endogâmicos C57BL , Masculino
9.
Sci Total Environ ; 925: 171740, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494017

RESUMO

Seawater intrusion (SI) has become a global issue exacerbated by intense anthropogenic activities and climate change. It is imperative to seek a synergistic strategy to reconcile environmental and economic benefits in the coastal regions. However, the intricate SI process and data scarcity present formidable challenges in dynamically assessing the coastal groundwater vulnerability. To address the challenge, this study proposed a novel framework that integrates the existing vulnerability assessment method (GALDIT) and variable-density groundwater model (SEAWAT). The future scenarios from 2019 to 2050 were investigated monthly under climate change (SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) and human activities (80 % and 50 % of current groundwater abstraction) in Longkou city, China, a typical coastal region subject to extensive SI, compared with the status quo in 2018. Results indicated that by 2050, the high vulnerability area, is in a narrow buffer within 1.2 km from the shoreline and exhibits minor changes while the salt concentration here increased by about 2700 mg/L compared with the current situation. The moderate vulnerability zone expands by about 30 km2, and the low vulnerable area decreases proportionally. The groundwater over-abstraction is identified as a more critical factor compared to the regional precipitation under climate change. When groundwater abstraction is reduced to 80 % of the current scale, the expansion rate of the moderate-vulnerable area slows down significantly, with an expansion area of only 18 km2 by 2050. Further reducing groundwater abstraction to 50 % of the current scale shifts the evolution trend of the medium-vulnerable area from expansion to contraction, with the area shrinking by about 11 km2 by 2050. The integrated vulnerability assessment framework can be applied not only in the similar coastal regions but also provides insights into other natural hazards.

10.
Shock ; 61(3): 454-464, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38412105

RESUMO

ABSTRACT: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients.


Assuntos
Interleucina-10 , Sepse , Humanos , Interleucina-10/metabolismo , Células Dendríticas/metabolismo , Lipopolissacarídeos/farmacologia , Tolerância Imunológica , Sepse/metabolismo , Inflamação/metabolismo
12.
Cardiovasc Diabetol ; 23(1): 21, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195542

RESUMO

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3ß, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1ß, IL-6, JAG2, KCNJ2, MALT1, ß-MHC, NF-κB, PCK1, PLCß1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.


Assuntos
Aterosclerose , MicroRNAs , Humanos , Fatores de Ribosilação do ADP , Espessura Intima-Media Carotídea , Diacilglicerol O-Aciltransferase , MicroRNAs/genética , Pró-Proteína Convertase 9 , Proteína Smad7 , Aterosclerose/genética
13.
Neuroradiology ; 66(3): 443-455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183426

RESUMO

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.


Assuntos
Vértebras Lombares , Punção Espinal , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Tomografia Computadorizada por Raios X
14.
Compr Rev Food Sci Food Saf ; 23(1): e13276, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284605

RESUMO

Soy protein gel can be developed into a variety of products, ranging from traditional food (e.g., tofu) to newly developed food (e.g., soy yogurt and meat analog). So far, efforts are still needed to be made on modifying the gel properties of soy protein for improving its sensory properties as animal protein-based food substitutes. Furthermore, there is always a need to regulate its gel properties for designing novel and tailored products of soy protein gels due to the fast-growing plant protein-based product market. This review gave an emphasis on the latest modification strategies and applications of gel properties of soy protein. The modifying methods of soy protein gel properties were reviewed from an aspect of composition or processing. Compositional modification included changing protein composition and gelling conditions and using additives, whereas processing strategies can be achieved through physical, chemical, and enzymatic treatments. Several compositional modification and processing strategies have been both proven to alter the gel properties of soy protein effectively. So far, soy protein gel has been applied in the field of food and biomedicine. In the future, more mechanistic studies on the modification methods are still needed to facilitate the full application of soy protein gel.


Assuntos
Alimentos de Soja , Proteínas de Soja , Animais , Proteínas de Soja/química , Géis/química , Proteínas de Plantas
15.
Chin J Traumatol ; 27(2): 63-70, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38040590

RESUMO

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.


Assuntos
Terapia de Imunossupressão , Sepse , Humanos , Imunoterapia , Sepse/tratamento farmacológico , Tolerância Imunológica
16.
Anal Methods ; 16(2): 179-188, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38047435

RESUMO

A novel multi-functional microfluidic paper-based analytical device (µPAD) integrated with ion imprinted polymers (IIPs) was proposed for specific, portable and low-cost detection of cadmium (Cd(II)) in water. The IIP was grafted on paper and integrated into the µPAD for separation of Cd(II) through multi-layer design. The paper-based screen printed carbon electrode (pSPCE) modified with reduced graphene oxide was fabricated and combined with the µPAD for electrochemical sensing of the separated Cd(II). Reduced graphene oxide (rGO) was prepared via electroreduction on the working electrode surface of the pSPCE (rGO/pSPCE), which provided a sensitization effect with an improved signal for Cd(II) detection. The µPAD developed with the integrated IIP and combined with rGO/pSPCE is able to detect Cd(II) with a linear range from 1 ng ml-1 to 100 ng ml-1 and a detection limit of 0.05 ng ml-1. The accuracy of this µPAD was evaluated with spiked real water samples and compared with that of the inductively coupled plasma mass spectrometry (ICP-MS) method, from which the recovery values ranged from 96.5% to 114.2% with RSDs <10% between the two methods. This µPAD demonstrated its advantages of low-cost, portability, and suitability for highly sensitive detection of Cd(II), making it a valuable tool for on-site analysis.

17.
Poult Sci ; 103(2): 103287, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104412

RESUMO

Remarkable changes have occurred in poultry farming and meat processing in recent years, driven by advancements in breeding technology, feed processing technology, farming conditions, and management practices. The incorporation of probiotics, prebiotics, and phytoextracts has made significant contributions to the development of poultry meat products that promote both health and functionality throughout the growth phase and during meat processing. Poultry fed with these substances improve meat quality, while incorporating probiotics, prebiotics, and phytoextracts in poultry processing, as additives or supplements, inhibits pathogens and offers health benefits to consumers. However, it is vital to assess the safety of functional fermented meat products containing these compounds and their potential effects on consumer health. Currently, there's still uncertainty in these aspects. Additionally, research on utilizing next-generation probiotic strains and synergistic combinations of probiotics and prebiotics in poultry meat products is in its early stages. Therefore, further investigation is required to gain a comprehensive understanding of the beneficial effects and safety considerations of these substances in poultry meat products in the future. This review offered a comprehensive overview of the applications of probiotics and prebiotics in poultry farming, focusing on their effects on nutrient utilization, growth efficiency, and gut health. Furthermore, potential of probiotics, prebiotics, and phytoextracts in enhancing poultry meat production was explored for improved health benefits and functionality, and possible issues associated with the use of these substances were discussed. Moreover, the conclusions drawn from this review and potential future perspectives in this field are presented.


Assuntos
Produtos da Carne , Probióticos , Animais , Prebióticos , Aves Domésticas , Galinhas , Probióticos/farmacologia
18.
Sensors (Basel) ; 23(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38067978

RESUMO

In this work, a flexible electrochemical sensor was developed for the detection of organophosphorus pesticides (OPs). To fabricate the sensor, graphene was generated in situ by laser-induced graphene (LIG) technology on a flexible substrate of polyimide (PI) film to form a three-electrode array, and pralidoxime (PAM) chloride was used as the probe molecule. CeO2 was used to modify the working electrode to improve the sensitivity of the sensor because of its electrocatalytic effect on the oxidation of PAM, and the Ag/AgCl reference electrode was prepared by the drop coating method. The effects of the laser power, laser scanning speed, and CeO2 modification on the electrochemical properties of the sensor were studied in detail. The results prove that the sensor has good repeatability, stability, and anti-interference ability, and it shows an excellent linear response in the chlorpyrifos concentration range from 1.4 × 10-8 M to 1.12 × 10-7 M with the detection limit of 7.01 × 10-10 M.

19.
IEEE Trans Comput Soc Syst ; 10(6): 3602-3608, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38084365

RESUMO

Alzheimer's disease(AD) is being the burden of society and family. Applying computing-aided strategies to reveal its pathology is one of the research highlights. Plasma neurofilament light (NFL) is an emerging noninvasive and economic biomarker for AD molecular pathology. It is valuable to reveal the correlations between the plasma NFL levels and neurodegeneration, especially hippcampal deformations at the preclinical stage. The negative correlation between plasma NFL levels and hippocampal volumes has been documented. However, the relationship between the plasma NFL levels and the hippocampal morphometry details at the preclinical stage is still elusive. This study seeks to demonstrate the capacity of our proposed surface-based hippocampal morphometry system to discern the plasma NFL positive (NFL+>41.9 pg/L) level and plasma NFL negative (NFL-<41.9pg/L) level and illustrate its superiority to the hippocampal volume measurement by drawing the cohort of 154 CU middle aged and elderly adults. We also apply this morphometry measure and a proposed sparse coding based classification algorithm to classify CU individuals with NFL+ and NFL- levels. Experimental results show that the proposed hippocampal morphometry system offers stronger statistical power to discriminate CU subjects with NFL+ and NFL- levels, comparing with the hippocampal volume measure. Furthermore, this system can discriminate plasma NFL levels in CU individuals (Accuracy=0.86). Both the group level and individual level analysis results indicate that the association between plasma NFL levels and the hippocampal shapes can be mapped at the preclinical stage.

20.
Nat Commun ; 14(1): 8396, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110429

RESUMO

Full activation of the NLRP3 inflammasome needs two sequential signals: a priming signal, followed by a second, assembly signal. Several studies have shown that the two signals trigger post-translational modification (PTM) of NLRP3, affecting activity of the inflammasome, however, the PTMs induced by the second signal are less well characterized. Here, we show that the assembly signal involves acetylation of NLRP3 at lysine 24, which is important for the oligomerization and the actual assembly of NLRP3 without affecting its recruitment to dispersed trans-Golgi network (dTGN). Accordingly, NLRP3 inflammasome activation is impaired in NLRP3-K24R knock-in mice. We identify KAT5 as an acetyltransferase able to acetylate NLRP3. KAT5 deficiency in myeloid cells and pharmacological inhibition of KAT5 enzymatic activity reduce activation of the NLRP3 inflammasome, both in vitro and in vivo. Thus, our study reveals a key mechanism for the oligomerization and full activation of NLRP3 and lays down the proof of principle for therapeutic targeting of the KAT5-NLRP3 axis.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Acetilação , Macrófagos/metabolismo , Processamento de Proteína Pós-Traducional
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