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1.
Langmuir ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728752

RESUMO

Porous composites, such as polyimide and polyetheretherketone (PEEK) polymer composites, became more attractive as a result of excellent specific strength, lightweightness, and smart lubrication. However, revealing the influence of a porous filler on the friction behaviors of polymer composites remains a challenge. The current work examines the effects of the pore structure and wettability on the mechanical and tribological performances of polymer composites reinforced with fillers. Three kinds of particles (non-porous, porous, and oleophobic porous) act as fillers within PEEK, respectively. It was identified that adding porous zeolite particles into PEEK slightly decreased the mechanical property. The zeolite particles significantly increased the oil adsorption of the composite, leading to a significant increase in the friction coefficient at 10 wt % content. However, the friction coefficient of the PEEK composite filled with 20 wt % modified zeolite was relatively low as a result of the weak adsorption. The interface analyses indicated that the thickness of the oil film was controlled via porous structures, changing the lubrication regime of the tribopair. The reason is the appropriate adsorption of oil and the release of zeolite from the composites during the friction process. These results can offer technical guidance to control the friction behaviors of composites under oil-lubricating conditions by a porous particle and pore modification.

2.
Fitoterapia ; : 106000, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729248

RESUMO

Five new characteristic cembrane-type diterpenoids (olibacartiols A-E, 1-5) were acquired from the gum resin of Boswellia carterii. The structures of these diterpenoids were characterized by detailed spectroscopic analysis, and compounds 1-3 were unambiguously confirmed by single-crystal X-ray diffraction experiments. The anti-inflammatory activities of the isolated compounds were evaluated using LPS-induced BV2 cell model and compounds 2-5 showed moderate NO inhibitory effects with IC50 values of 8.84 ±â€¯1.02, 9.82 ±â€¯1.95, 9.75 ±â€¯2.24, and 7.39 ±â€¯1.24 µM, respectively.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38743541

RESUMO

Federated learning (FL) aims to collaboratively learn a model by using the data from multiple users under privacy constraints. In this article, we study the multilabel classification (MLC) problem under the FL setting, where trivial solution and extremely poor performance may be obtained, especially when only positive data with respect to a single class label is provided for each client. This issue can be addressed by adding a specially designed regularizer on the server side. Although effective sometimes, the label correlations are simply ignored and thus suboptimal performance may be obtained. Besides, it is expensive and unsafe to exchange user's private embeddings between server and clients frequently, especially when training model in the contrastive way. To remedy these drawbacks, we propose a novel and generic method termed federated averaging (FedAvg) by exploring label correlations (FedALCs). Specifically, FedALC estimates the label correlations in the class embedding learning for different label pairs and utilizes it to improve the model training. To further improve the safety and also reduce the communication overhead, we propose a variant to learn fixed class embedding for each client, so that the server and clients only need to exchange class embeddings once. Extensive experiments on multiple popular datasets demonstrate that our FedALC can significantly outperform the existing counterparts.

4.
Traffic Inj Prev ; : 1-9, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717830

RESUMO

OBJECTIVE: Studying the optimal profile shape and size of deceleration facilities suitable for low-speed environment roads under different speed control intervals. METHODS: Simulation modeling of deceleration facilities with various profile shapes and sizes and for vehicles in different speed intervals was performed using the vehicle dynamics simulation software Carsim. The height jumped by a vehicle's wheels, the vertical force on the wheels, and the vertical acceleration of the vehicle were used as indicators of ride comfort and operational stability for the various deceleration facility profiles. RESULTS: stability and comfort were related to the contour of the deceleration facility. Vertical forces were positively related to vehicle jump height, but the jump heights of vehicles passing through deceleration mounds with different planes at the same speed were not significantly different with increasing height. When the vehicle is traveling slowly, the vertical impact force on the vehicle is not significantly related to the speed loss of the vehicle. CONCLUSIONS: Within the speed range of 20-60 km/h and profile heights of 3-10.5 cm, the effectiveness ratings of circular high width and parabolic were basically at level 2 and level 3, but the circular high width had a more stable jump height and was the best profile form, followed by sinusoidal and parabolic, then isosceles trapezoidal, and lastly conventional speed bumps.

6.
Nat Commun ; 15(1): 3716, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697959

RESUMO

Entanglement serves as the resource to empower quantum computing. Recent progress has highlighted its positive impact on learning quantum dynamics, wherein the integration of entanglement into quantum operations or measurements of quantum machine learning (QML) models leads to substantial reductions in training data size, surpassing a specified prediction error threshold. However, an analytical understanding of how the entanglement degree in data affects model performance remains elusive. In this study, we address this knowledge gap by establishing a quantum no-free-lunch (NFL) theorem for learning quantum dynamics using entangled data. Contrary to previous findings, we prove that the impact of entangled data on prediction error exhibits a dual effect, depending on the number of permitted measurements. With a sufficient number of measurements, increasing the entanglement of training data consistently reduces the prediction error or decreases the required size of the training data to achieve the same prediction error. Conversely, when few measurements are allowed, employing highly entangled data could lead to an increased prediction error. The achieved results provide critical guidance for designing advanced QML protocols, especially for those tailored for execution on early-stage quantum computers with limited access to quantum resources.

7.
Diabetes Obes Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698647

RESUMO

AIM: To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS: At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.

8.
Diabetes Obes Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698649

RESUMO

AIM: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). METHODS: In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 µl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). RESULTS: Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). CONCLUSIONS: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

9.
Heliyon ; 10(8): e29424, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38638958

RESUMO

In this study, the neuroprotective potential of tanshinone IIA (TIIA)-modified mesenchymal stem cells (MSC) were investigated using a murine model of lipopolysaccharide (LPS)-induced neuroinflammation. The cognitive performance of the mice was assessed using the Y-maze and Morris water maze tests, while immunofluorescence and Western blot analyses were employed to evaluate the hippocampal expression of pertinent markers and inflammatory factors, respectively. The results from the behavioral experiments demonstrated discernible differences in learning and memory abilities between the model group and the control group (P < 0.05), confirming the successful induction of neuroinflammation. Both the MSC and TIIA-MSC groups exhibited enhancements in the cognitive abilities of neuroinflammatory mice, with the TIIA-MSC group demonstrating a more pronounced improvement (P < 0.01). Immunofluorescence analysis revealed significant activation of microglia in the model group, while the MSC and TIIA-MSC groups exhibited a reduction in hippocampal microglial activation, with the TIIA-MSC group displaying a more substantial decrease. A statistically significant difference in the expression levels of IL-1, IL-6, and TNF-α was observed between the model and control groups (P < 0.05), indicating that IL-1, IL-6, and TNF-α were downregulated in both the MSC and TIIA-MSC groups. Notably, the downregulatory effect was more prominent in the TIIA-MSC group (P < 0.01). Compared to MSC treatment alone, the administration of TIIA-modified MSC demonstrated a superior protective effect against lipopolysaccharide-induced neuroinflammation. These findings underscore the potential therapeutic efficacy of TIIA-modified MSC in mitigating neuroinflammatory responses.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38651864

RESUMO

CuInTe2 (CIT) is one of the typical ternary chalcogenides known for its characteristic mixed polyanionic/polycationic site defects, making it a subject of continuous interest in the field of thermoelectrics. In this work, we propose a chemical composition modulation strategy for CIT by alloying GeTe and then introducing a copper deficiency (denoted by VCu). This strategy aims to unpin its Fermi level (Fr) and shift Fr into the valence band (VB) while simultaneously enabling coupling between the optical and acoustic phonon, thereby providing an extra phonon scattering path at low frequencies. The simultaneous composition regulations not only enhance the carrier concentration (nH) to 1019-1020 cm-3 but also significantly reduce the lattice thermal conductivity (κL) to ∼0.48 W m-1 K-1, thus effectively realizing electro-acoustic coordination in the present material. As a consequence, the thermoelectric (TE) performance is remarkably improved with the highest TE figure of merit (ZT) of 1.51 at ∼838 K. This value ranks at a higher level among CIT-based materials, which showcases the great significance of chemical composition modulation.

11.
J Vis Exp ; (205)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38557978

RESUMO

Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.


Assuntos
Disfunção Erétil , Induração Peniana , Placa Aterosclerótica , Masculino , Humanos , Animais , Bovinos , Induração Peniana/cirurgia , Pênis , Disfunção Erétil/etiologia , Disfunção Erétil/cirurgia , Fibrose , Placa Amiloide
12.
Clin Appl Thromb Hemost ; 30: 10760296241246004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566600

RESUMO

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.


Assuntos
Tromboembolia Venosa , Trombose Venosa , Humanos , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Coeficiente Internacional Normatizado , Estudos Retrospectivos , Estudos Prospectivos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Administração Oral , Recidiva
13.
Nutr Diabetes ; 14(1): 13, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589353

RESUMO

BACKGROUND: Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS: Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS: Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS: In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.


Assuntos
Diabetes Mellitus Tipo 2 , Glucose , Adulto , Humanos , Glicemia , Hemoglobinas Glicadas , Esvaziamento Gástrico , Controle Glicêmico , Automonitorização da Glicemia , Frutosamina , Refeições , Período Pós-Prandial , Insulina , Estudos Cross-Over
14.
Chin Med ; 19(1): 60, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589903

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

15.
Heliyon ; 10(7): e28838, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596076

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms like bradykinesia, tremors, and balance issues. The pathology is recognized by progressively degenerative nigrostriatal dopaminergic neurons (DANs) loss. Its exact pathogenesis is unclear. Numerous studies have shown that nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) contributes to the pathogenesis of PD. Previous studies have demonstrated that the over-activation of NLRP3 inflammasome in microglia indirectly leads to the loss of DANs, which can worsen PD. In recent years, autopsy analyses of PD patients and studies in PD models have revealed upregulation of NLRP3 expression within DANs and demonstrated that activation of NLRP3 inflammasome in neurons is sufficient to drive neuronal loss, whereas microglial activation occurs after neuronal death, and that inhibition of intraneuronal NLRP3 inflammasome prevents degeneration of DANs. In this review, we provide research evidence related to NLRP3 inflammasome in DANs in PD as well as focus on possible mechanisms of NLRP3 inflammasome activation in neurons, aiming to provide a new way of thinking about the pathogenesis and prevention of PD.

16.
Front Pediatr ; 12: 1347637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596248

RESUMO

The introduction of new internal fixation devices and arthroscopic techniques has led to significant changes in the surgical treatment of tibial eminence fractures (TEFs) in children. In recent years, arthroscopic surgery has arisen as the gold standard for the treatment of TEFs. This popularity of arthroscopic techniques has reduced surgical complications and improved patient prognosis. In this paper, we investigate the current situation of the use of arthroscopic fixation techniques for pediatric TEFs. We searched the PubMed database using the terms "arthroscopic treatment and tibial eminence," "arthroscopic treatment and tibial spine," "tibial eminence avulsion", "tibial spine fracture", with no limit on the year of publication. From these articles, we reviewed the use of various arthroscopic TEFs fixation techniques reported in the current literature. Overall, we found that the choice of fixation method seems to have no effect on clinical outcomes or imaging results. However, if an easy, strong fixation that is less prone to epiphyseal damage is desired, as a junior practitioner, the anchor technique should be mastered first, whereas for senior practitioners, a variety of fixation techniques for TEFs should be mastered, including anchors, sutures, and screws, so that personalized fixation can be achieved with the least amount of trauma, operative time, and complications. Higher quality studies are needed in the future to provide Useful evidence to determine the optimal fixation technique in terms of clinical outcomes, function, and complications.

17.
Environ Sci Technol ; 58(14): 6226-6235, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557021

RESUMO

The updated climate models provide projections at a fine scale, allowing us to estimate health risks due to future warming after accounting for spatial heterogeneity. Here, we utilized an ensemble of high-resolution (25 km) climate simulations and nationwide mortality data from 306 Chinese cities to estimate death anomalies attributable to future warming. Historical estimation (1986-2014) reveals that about 15.5% [95% empirical confidence interval (eCI):13.1%, 17.6%] of deaths are attributable to nonoptimal temperature, of which heat and cold corresponded to attributable fractions of 4.1% (eCI:2.4%, 5.5%) and 11.4% (eCI:10.7%, 12.1%), respectively. Under three climate scenarios (SSP126, SSP245, and SSP585), the national average temperature was projected to increase by 1.45, 2.57, and 4.98 °C by the 2090s, respectively. The corresponding mortality fractions attributable to heat would be 6.5% (eCI:5.2%, 7.7%), 7.9% (eCI:6.3%, 9.4%), and 11.4% (eCI:9.2%, 13.3%). More than half of the attributable deaths due to future warming would occur in north China and cardiovascular mortality would increase more drastically than respiratory mortality. Our study shows that the increased heat-attributable mortality burden would outweigh the decreased cold-attributable burden even under a moderate climate change scenario across China. The results are helpful for national or local policymakers to better address the challenges of future warming.


Assuntos
Temperatura Baixa , Temperatura Alta , Temperatura , Cidades , China/epidemiologia , Mudança Climática , Mortalidade
18.
Clin Transl Med ; 14(3): e1623, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38488468

RESUMO

BACKGROUND: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. METHODS: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. RESULTS: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. CONCLUSIONS: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.


Assuntos
Doença de Alzheimer , Inflamassomos , Humanos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Células HEK293 , Simulação de Acoplamento Molecular , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Camundongos Transgênicos , Acetiltransferases
19.
Chemosphere ; 353: 141635, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447897

RESUMO

The performance of bacterial strains in executing degradative functions under the coexistence of heavy metals/heavy metal-like elements and organic contaminants is understudied. In this study, we isolated a fluorene-degrading bacterium, highly arsenic-resistant, designated as strain 2021, from contaminated soil at the abandoned site of an old coking plant. It was identified as a member of the genus Rhodococcus sp. strain 2021 exhibited efficient fluorene-degrading ability under optimal conditions of 400 mg/L fluorene, 30 °C, pH 7.0, and 250 mg/L trivalent arsenic. It was noted that the addition of arsenic could promote the growth of strain 2021 and improve the degradation of fluorene - a phenomenon that has not been described yet. The results further indicated that strain 2021 can oxidize As3+ to As5+; here, approximately 13.1% of As3+ was converted to As5+ after aerobic cultivation for 8 days at 30 °C. The addition of arsenic could greatly up-regulate the expression of arsR/A/B/C/D and pcaG/H gene clusters involved in arsenic resistance and aromatic hydrocarbon degradation; it also aided in maintaining the continuously high expression of cstA that codes for carbon starvation protein and prmA/B that codes for monooxygenase. These results suggest that strain 2021 holds great potential for the bioremediation of environments contaminated by a combination of arsenic and polycyclic aromatic hydrocarbons. This study provides new insights into the interactions among microbes, as well as inorganic and organic pollutants.


Assuntos
Arsênio , Hidrocarbonetos Policíclicos Aromáticos , Rhodococcus , Poluentes do Solo , Arsênio/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Fluorenos/metabolismo , Biodegradação Ambiental , Poluentes do Solo/metabolismo , Microbiologia do Solo
20.
One Earth ; 7(3): 497-505, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38532982

RESUMO

China's carbon-neutral target could have benefits for ambient fine particulate matter (PM2.5)-associated mortality. Although previous studies have researched such benefits, the potential impact on cardiovascular disease incidence burden is yet to be investigated thoroughly. Here, we first estimate the association between short-term PM2.5 exposure and the incidence of stroke and coronary heart disease (CHD) via a case-crossover study before projecting future changes in short-term PM2.5-associated excess incidence across China from 2025 to 2060 under three different emission scenarios. We find that, compared to the 2015-2020 baseline, average PM2.5 concentrations nationwide in 2060 under SSP119 (an approximation of a carbon-neutral scenario) are projected to decrease by 81.07%. The short-term PM2.5-related excess incidence of stroke and CHD is projected to be reduced to 3,352 cases (95% confidence interval: 939, 5,738)-compared with 34,485 cases under a medium-emissions scenario (SSP245)-and is expected to be accompanied by a 95% reduction in the related economic burden. China's carbon-neutral policies are likely to bring health benefits for cardiovascular disease by reducing short-term PM2.5-related incidence burden.

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