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1.
Trop Med Infect Dis ; 9(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38668533

RESUMO

OBJECTIVE: This study aimed to improve dengue fever predictions in Singapore using a machine learning model that incorporates meteorological data, addressing the current methodological limitations by examining the intricate relationships between weather changes and dengue transmission. METHOD: Using weekly dengue case and meteorological data from 2012 to 2022, the data was preprocessed and analyzed using various machine learning algorithms, including General Linear Model (GLM), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), Decision Tree (DT), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms. Performance metrics such as Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and R-squared (R2) were employed. RESULTS: From 2012 to 2022, there was a total of 164,333 cases of dengue fever. Singapore witnessed a fluctuating number of dengue cases, peaking notably in 2020 and revealing a strong seasonality between March and July. An analysis of meteorological data points highlighted connections between certain climate variables and dengue fever outbreaks. The correlation analyses suggested significant associations between dengue cases and specific weather factors such as solar radiation, solar energy, and UV index. For disease predictions, the XGBoost model showed the best performance with an MAE = 89.12, RMSE = 156.07, and R2 = 0.83, identifying time as the primary factor, while 19 key predictors showed non-linear associations with dengue transmission. This underscores the significant role of environmental conditions, including cloud cover and rainfall, in dengue propagation. CONCLUSION: In the last decade, meteorological factors have significantly influenced dengue transmission in Singapore. This research, using the XGBoost model, highlights the key predictors like time and cloud cover in understanding dengue's complex dynamics. By employing advanced algorithms, our study offers insights into dengue predictive models and the importance of careful model selection. These results can inform public health strategies, aiming to improve dengue control in Singapore and comparable regions.

2.
Nano Lett ; 24(15): 4665-4671, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38587938

RESUMO

Effective bimetallic nanoelectrocatalysis demands precise control of composition, structure, and understanding catalytic mechanisms. To address these challenges, we employ a two-in-one approach, integrating online synthesis with real-time imaging of bimetallic Au@Metal core-shell nanoparticles (Au@M NPs) via electrochemiluminescence microscopy (ECLM). Within 120 s, online electrodeposition and in situ catalytic activity screening alternate. ECLM captures transient faradaic processes during potential switches, visualizes electrochemical processes in real-time, and tracks catalytic activity dynamics at the single-particle level. Analysis using ECL photon flux density eliminates size effects and yields quantitative electrocatalytic activity results. Notably, a nonlinear activity trend corresponding to the shell metal to Au surface atomic ratio is discerned, quantifying the optimal surface component ratio of Au@M NPs. This approach offers a comprehensive understanding of catalytic behavior during the deposition process with high spatiotemporal resolution, which is crucial for tailoring efficient bimetallic nanocatalysts for diverse applications.

3.
ACS Appl Mater Interfaces ; 16(15): 18608-18626, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38565551

RESUMO

Hypoxia, chronic inflammation, and elevated reactive oxygen species (ROS) production induced by hyperglycemia pose formidable challenges to the healing of diabetic chronic wounds, often resulting in impaired recovery. Currently, sustainable and eco-friendly therapeutic approaches targeting this multifaceted problem remain uncharted. Herein, we develop a unique three-functional covalent organic framework (COF)-modified microalgae gel designed for the preparation and treatment of chronic diabetic wounds. The gel comprises an oxygen-releasing basic fibroblast growth factor (bFGF) microalgae matrix, augmented by an ROS-responsive COF. Although two of these components have been reported to be used in wound healing, the combination of all three functions represents an innovative approach to synergize the treatment of chronic diabetic wounds. Therefore, we propose a new concept of "ligand interlocking" with three functional synergistic effects. Specifically, the COF has a similar effect to the "double Excalibur", which binds bFGF to promote angiogenesis and proliferation and inhibit the inflammatory response of chronic wounds and binds live microalgae to eliminate ROS and release dissolved oxygen to alleviate the hypoxia of wounds. Moreover, in vivo experiments and RNA sequencing analyses similarly demonstrated that the COF-modified microalgae gel reduced the inflammatory cascade cycle in the wound site and promoted vascular and tissue regeneration. We posit that the COF-modified microalgae gel represents a promising strategy for the active in vivo delivery of therapeutics to the wound body in intensive care unit settings.


Assuntos
Diabetes Mellitus , Estruturas Metalorgânicas , Microalgas , Humanos , Fator 2 de Crescimento de Fibroblastos , Espécies Reativas de Oxigênio , Géis , Hipóxia , Oxigênio , Hidrogéis
4.
J Agric Food Chem ; 72(15): 8859-8870, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564481

RESUMO

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.


Assuntos
Ácidos Graxos Monoinsaturados , Óleos de Peixe , Água , Triglicerídeos/química , Óleos de Peixe/química , Digestão
5.
Neurourol Urodyn ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558173

RESUMO

INTRODUCTION: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. METHODS: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. RESULTS: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. CONCLUSIONS: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

6.
Nanoscale ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660780

RESUMO

Controlled synthesis of metal clusters through minor changes in surface ligands holds significant interest because the corresponding entities serve as ideal models for investigating the ligand environment's stereochemical and electronic contributions that impact the corresponding structures and properties of metal clusters. In this work, we obtained two Ag(0)-containing nanoclusters (Ag17 and Ag32) with near-infrared emissions by regulating phosphine auxiliary ligands. Ag17 and Ag32 bear similar shells wherein Ag17 features a trigonal bipyramid Ag5 kernel while Ag32 has a bi-icosahedral interpenetrating an Ag20 kernel. Ag17 and Ag32 showed a near-infrared emission (NIR) of around 830 nm. Benefiting from the rigid structure, Ag17 displayed a more intense near-infrared emission than Ag32. This work provides new insight into the construction of novel superatomic silver nanoclusters by regulating phosphine ligands.

7.
Front Microbiol ; 15: 1359797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605713

RESUMO

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites.

8.
Abdom Radiol (NY) ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619611

RESUMO

OBJECTIVE: To investigate multiphase computed tomography (CT) radiomics-based combined with clinical factors to predict overall survival (OS) in patients with bladder urothelial carcinoma (BLCA) who underwent transurethral resection of bladder tumor (TURBT). METHODS: Data were retrospectively collected from 114 patients with primary BLCA from February 2016 to February 2018. The regions of interest (ROIs) of the plain, arterial, and venous phase images were manually segmented. The Cox regression algorithm was used to establish 3 basic models for the plain phase (PP), arterial phase (AP), and venous phase (VP) and 2 combination models (AP + VP and PP + AP + VP). The highest-performing radiomics model was selected to calculate the radiomics score (Rad-score), and independent risk factors affecting patients' OS were analyzed using Cox regression. The Rad-score and clinical risk factors were combined to construct a joint model and draw a visualized nomogram. RESULTS: The combined model of PP + AP + VP showed the best performance with the Akaike Information Criterion (AIC) and Consistency Index (C-index) in the test group of 130.48 and 0.779, respectively. A combined model constructed with two independent risk factors (age and Ki-67 expression status) in combination with the Rad-score outperformed the radiomics model alone; AIC and C-index in the test group were 115.74 and 0.840, respectively. The calibration curves showed good agreement between the predicted probabilities of the joint model and the actual (p < 0.05). The decision curve showed that the joint model had good clinical application value within a large range of threshold probabilities. CONCLUSION: This new model can be used to predict the OS of patients with BLCA who underwent TURBT.

9.
Cancer Cell ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579725

RESUMO

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

10.
Mitochondrial DNA B Resour ; 9(4): 541-545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665928

RESUMO

Pandanus amaryllifolius of Pandanaceae, a plant native to Southeast Asia, has been domesticated for its health benefits and aromatic leaves. It is also used for phytoremediation and soil rehabilitation. However, genetic studies of this species are limited. This study aims to expand its genomic information by assembling and characterizing the complete chloroplast genome of P. amaryllifolius. The chloroplast genome, which was 157,839 bp long, contains a total of 133 genes, including 87 protein-coding (CDS), 38 tRNA, and eight rRNA genes. The overall G/C content was 37.7%. A phylogenetic analysis using 79 shared unique CDS revealed a monophyletic relationship in Pandanales. Based on the limited sampling size, Pandanus amaryllifolius was the first to diverge in Pandanaceae. The genomic data will be useful for future phylogenetic and evolutionary studies of Pandanaceae.

11.
Natl Sci Rev ; 11(4): nwae053, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38666092

RESUMO

The water oxidation half-reaction at anodes is always considered the rate-limiting step of overall water splitting (OWS), but the actual bias distribution between photoanodes and cathodes of photoelectrochemical (PEC) OWS cells has not been investigated systematically. In this work, we find that, for PEC cells consisting of photoanodes (nickel-modified n-Si [Ni/n-Si] and α-Fe2O3) with low photovoltage (Vph < 1 V), a large portion of applied bias is exerted on the Pt cathode for satisfying the hydrogen evolution thermodynamics, showing a thermodynamics-controlled characteristic. In contrast, for photoanodes (TiO2 and BiVO4) with Vph > 1 V, the bias required for cathode activation can be significantly reduced, exhibiting a kinetics-controlled characteristic. Further investigations show that the bias distribution can be regulated by tuning the electrolyte pH and using alternative half-reaction couplings. Accordingly, a volcano plot is presented for the rational design of the overall reactions and unbiased PEC cells. Motivated by this, an unbiased PEC cell consisting of a simple Ni/n-Si photoanode and Pt cathode is assembled, delivering a photocurrent density of 5.3 ± 0.2 mA cm-2.

12.
Nat Ecol Evol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637692

RESUMO

Self-incompatibility and recurrent transitions to self-compatibility have shaped the extant mating systems underlying the nonrandom mating critical for speciation in angiosperms. Linkage between self-incompatibility and speciation is illustrated by the shared pollen rejection pathway between self-incompatibility and interspecific unilateral incompatibility (UI) in the Brassicaceae. However, the pollen discrimination system that activates this shared pathway for heterospecific pollen rejection remains unknown. Here we show that Stigma UI3.1, the genetically identified stigma determinant of UI in Arabidopsis lyrata × Arabidopsis arenosa crosses, encodes the S-locus-related glycoprotein 1 (SLR1). Heterologous expression of A. lyrata or Capsella grandiflora SLR1 confers on some Arabidopsis thaliana accessions the ability to discriminate against heterospecific pollen. Acquisition of this ability also requires a functional S-locus receptor kinase (SRK), whose ligand-induced dimerization activates the self-pollen rejection pathway in the stigma. SLR1 interacts with SRK and interferes with SRK homomer formation. We propose a pollen discrimination system based on competition between basal or ligand-induced SLR1-SRK and SRK-SRK complex formation. The resulting SRK homomer levels would be sensed by the common pollen rejection pathway, allowing discrimination among conspecific self- and cross-pollen as well as heterospecific pollen. Our results establish a mechanistic link at the pollen recognition phase between self-incompatibility and interspecific incompatibility.

13.
JAMA Neurol ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436990

RESUMO

Importance: Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. Objective: To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. Design, Setting, and Participants: This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Exposures: Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. Main Outcomes and Measures: The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. Results: In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. Conclusions and Relevance: These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.

14.
J Health Popul Nutr ; 43(1): 40, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454510

RESUMO

OBJECTIVE: To explore the effect of the hospital-community-home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN). METHOD: A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention. RESULTS: After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05). CONCLUSION: The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/terapia , Glicemia , Cooperação do Paciente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Hospitais
15.
Cerebrovasc Dis ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471482

RESUMO

Introduction The angiotensin-converting enzyme-2 (ACE-2) and its shedding product [soluble ACE-2 (sACE-2)] are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack (TIA). Methods Data were obtained from the Third China National Stroke Registry (CNSR-Ⅲ). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, 494 controls were selected using age- and sex- matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29-45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest quartile versus the lowest quartile was 1.68 (1.12-2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high sensitivity C reactive protein (hsCRP) ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15-4.72]) and neutrophil (NEUT) counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35-5.23]), but not significant in patients with lower systemic inflammation. Discussion Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.

16.
Org Lett ; 26(13): 2523-2528, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38536882

RESUMO

A migratory insertion of carbenes into distal γ-C(sp3)-H bonds of aliphatic amines has been successfully developed. The synergistic interplay among a palladium catalyst, picolinamide directing group, a carefully selected base additive, and an essential ligand proved crucial in achieving high yields. These findings hold significant value for advancing the exploration of regioselective carbene insertions into nonactivated C(sp3)-H bonds.

17.
Exp Cell Res ; 437(1): 113999, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494067

RESUMO

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.


Assuntos
Diabetes Mellitus , NF-kappa B , Humanos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ligamento Periodontal/metabolismo , Transdução de Sinais , Inflamação , Produtos Finais de Glicação Avançada/farmacologia
18.
Molecules ; 29(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542876

RESUMO

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.


Assuntos
Lesão Pulmonar Aguda , Cebolinha-Francesa , Medicamentos de Ervas Chinesas , Saponinas , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Saponinas/farmacologia , Lipopolissacarídeos/toxicidade , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Células Endoteliais da Veia Umbilical Humana , Fator de Necrose Tumoral alfa/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Mediadores da Inflamação/metabolismo
19.
Front Vet Sci ; 11: 1373178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550787

RESUMO

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

20.
BMC Med Educ ; 24(1): 350, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553682

RESUMO

AIM: The transition from medical students to competent physicians requires comprehensive training during residency programs. In China, resident students typically undergo 2- or 3-year training programs. While they learn from patient interactions under the guidance of experienced doctors, integrating theoretical knowledge from textbooks into practical cases remains a challenge. This study aimed to explore the impact of medical interns acting as peer-students on the knowledge mastery of resident students. METHOD: The participants of this study consisted of resident students specializing in respiratory medicine at the Second Affiliated Hospital of Zhejiang University, School of Medicine. Resident students were given the opportunity to volunteer as peer-teachers for medical interns in the respiratory department. Those who chose to instruct interns were automatically placed into the test group, while those who opted not to partake in intern instruction formed the control group. In their role as peer-teachers, resident students assumed the responsibility of guiding interns in patient management throughout the entire continuum, spanning from initial engagement to discharge, a commitment that extended over a minimum period of 2 weeks. The resident students' academic performance was evaluated through a departmental examination consisting of 50 multiple-choice questions, which was administered upon completing their rotation. Statistical analysis was performed to assess the impact of peer-teaching on the resident students' performance. RESULTS: Between January 2023 and June 2023, a total of 158 resident students completed their rotation in the respiratory department. Among them, 40 resident students willingly took on the responsibility of instructing medical interns, while 118 resident students did not participate in intern teaching. With a "one-to-one" teaching policy in place, the overall satisfaction rate of the interns was an impressive 95.35%. Pre-rotation test scores for the test group averaged 81.66 ± 8.325 (Mean ± SD) and the control group averaged 81.66 ± 8.002, without significance. The departmental examination scores of the test group averaged 85.60 ± 7.886, while the control group scored an average of 82.25 ± 8.292, with a statistically significant difference (p = 0.027). CONCLUSION: In conclusion, our study underscores the positive influence of peer-teaching on the knowledge mastery of resident students.


Assuntos
Pessoal de Educação , Internato e Residência , Pneumologia , Estudantes de Medicina , Humanos , Currículo , Ensino
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