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1.
Circ Res ; 133(1): 25-44, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37264926

RESUMEN

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , Aterosclerosis/metabolismo , Inflamación , Proteína Quinasa 7 Activada por Mitógenos/genética , Proteína Quinasa 7 Activada por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo
2.
J Proteome Res ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292827

RESUMEN

The stability of proteins from rates of oxidation (SPROX), thermal proteome profiling (TPP), and limited proteolysis (LiP) techniques were used to profile the stability of ∼2500 proteins in hippocampus tissue cell lysates from 2- and 8-months-old wild-type (C57BL/6J; n = 7) and transgenic (5XFAD; n = 7) mice with five Alzheimer's disease (AD)-linked mutations. Approximately 200-500 protein hits with AD-related stability changes were detected by each technique at each age point. The hit overlap from technique to technique was low, and all of the techniques generated protein hits that were more numerous and largely different from those identified in protein expression level analyses, which were also performed here. The hit proteins identified by each technique were enriched in a number of the same pathways and biological processes, many with known connections to AD. The protein stability hits included 25 high-value conformation biomarkers with AD-related stability changes detected using at least 2 techniques at both age points. Also discovered were subunit- and age-specific AD-related stability changes in the proteasome, which had reduced function at both age points. The different folding stability profiles of the proteasome at the two age points are consistent with a different mechanism for proteasome dysfunction at the early and late stages of AD.

3.
Circulation ; 148(12): 959-977, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37555319

RESUMEN

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified. METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis. RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix-producing, and inflammatory phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. Single-cell sequencing assay for transposase-accessible chromatin analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in proliferation, extracellular matrix, and inflammation. IRF3 (interferon regulatory factor 3), a proinflammatory transcription factor activated by cytosolic DNA, was identified as a key driver of the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING (stimulator of interferon genes)-TBK1 (tank-binding kinase 1) to activate IRF3, which bound and recruited EZH2 (enhancer of zeste homolog 2) to contractile genes to induce repressive H3K27me3 modification and gene suppression. In contrast, double-stranded DNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress-induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations toward diverse directions were detected in human ascending thoracic AAD tissues. CONCLUSIONS: Our study reveals the dynamic epigenetic induction of SMC phenotypic alterations in AAD. DNA damage and cytosolic leakage drive SMCs from a contractile phenotype to an inflammatory phenotype.


Asunto(s)
Aneurisma de la Aorta Torácica , Aneurisma de la Aorta , Disección Aórtica , Humanos , Ratones , Animales , Epigenómica , Fenotipo , Aneurisma de la Aorta Torácica/genética , Aneurisma de la Aorta Torácica/metabolismo , Disección Aórtica/genética , Miocitos del Músculo Liso/metabolismo , ADN/metabolismo , Cromatina/metabolismo , Epigénesis Genética , Células Cultivadas
4.
Chemistry ; : e202402040, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007169

RESUMEN

Visible-light active heterogeneous organophotocatalysts have recently gained considerable interest in organic synthetic community. Ordered mesoporous polymers (OMPs) are highly promising as heterogeneous alternative to traditional precious metal/organic dyes-based photocatalysts. Herein, we report the preparation of a benzothiadiazole functionalized OMPs (BT-MPs) through a "bottom-up" strategy. High ordered periodic porosity, large surface area, excellent stability and rational energy-band structures guarantee the high catalytic activity of BT-MPs. As a result, at least six conversions, e. g., the [3+2] cycloaddition of phenols with olefins, the selective oxidation of sulfides, the C-3 thiocyanation of indole and the aminothiocyanation of ß-keto ester, could be promoted smoothly by BT-MPs. In addition, BT-MPs was readily recovered with well maintaining its photocatalytic activity and could be reused for at least eight times. This study highlights the potential of exploiting photoactive OMPs as recyclable, robust and metal-free heterogeneous photocatalysts.

5.
Curr Atheroscler Rep ; 26(9): 463-483, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38958925

RESUMEN

PURPOSE OF REVIEW: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. RECENT FINDINGS: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Enfermedades Cardiovasculares , Trastorno Depresivo Mayor , Guanilato-Quinasas , Humanos , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/genética , Animales , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Guanilato-Quinasas/genética , Guanilato-Quinasas/metabolismo , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Polimorfismo de Nucleótido Simple
6.
J Appl Microbiol ; 135(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39066493

RESUMEN

AIMS: Microbial transformation to modify saponins and enhance their biological activities has received increasing attention in recent years. This study aimed to screen the strain that can biotransform notoginsenoside R1, identify the product and study its biological activity. METHODS AND RESULTS: A lactic acid bacteria strain S165 with glycosidase-producing activity was isolated from traditional Chinese fermented foods, which was identified and grouped according to API 50 CHL kit and 16S rDNA sequence analysis. Subsequently, notoginsenoside R1 underwent a 30-day fermentation period by the strain S165, and the resulting products were analyzed using High-performance liquid chromatography (HPLC), Ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS)/MS, and 13C-Nuclear magnetic resonance (NMR) techniques. Employing a model of Lipopolysaccharide (LPS)-induced damage to Caco-2 cells, the damage of Caco-2 cells was detected by Hoechst 33 258 staining, and the activity of notoginsenoside R1 biotransformation product was investigated by CCK-8 and western blotting assay. The strain S165 was identified as Lactiplantibacillus plantarum and was used to biotransform notoginsenoside R1. Through a 30-day biotransformation, L. plantarum S165 predominantly converts notoginsenoside R1 into 3ß,12ß-dihydroxydammar-(E)-20(22),24-diene-6-O-ß-D-xylopyranosyl-(1→2)-ß-D-glucopyranoside, temporarily named notoginsenoside T6 (NGT6) according to HPLC, UPLC-MS/MS, and 13C-NMR analysis. Results from CCK-8 and Hoechst 33258 staining indicated that the ability notoginsenoside T6 to alleviate the intestinal injury induced by LPS in the Caco-2 cell was stronger than that of notoginsenoside R1. In addition, Western blotting result showed that notoginsenoside T6 could prevent intestinal injury by protecting tight junction proteins (Claudin-1, Occludin, and ZO-1). CONCLUSION: Notoginsenoside R1 was biotransformed into the notoginsenoside T6 by L. plantarum S165, and the biotransformed product showed an enhanced intestinal protective effect in vitro.


Asunto(s)
Ginsenósidos , Lipopolisacáridos , Ginsenósidos/metabolismo , Ginsenósidos/farmacología , Humanos , Células CACO-2 , Lipopolisacáridos/metabolismo , Fermentación , Biotransformación , Cromatografía Líquida de Alta Presión , Lactobacillus plantarum/metabolismo , Alimentos Fermentados/microbiología
7.
Arch Sex Behav ; 53(6): 2269-2276, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38453777

RESUMEN

BDSM is a type of sexual preference that includes bondage and discipline, dominance and submission, and sadism and masochism. Research has identified three specific power exchange roles in the practice of BDSM: dominance, submission, and switch. It has also been suggested that attachment style potentially influences BDSM interests. This study investigated the potential roles of attachment style in driving BDSM identity. A questionnaire was completed by a cross-sectional Chinese sample (n = 3310, age range 18-30 years), including 1856 BDSM practitioners (436 men, 1420 women). To assess attachment style, the questionnaire included a Chinese translation of the Adult Attachment Scale as well as items surveying BDSM interests. Compared to non-BDSM practitioners, attachment styles were not significantly different from BDSM practitioners. However, practitioners with different BDSM identities showed a significant difference in their attachment styles. Secure and avoidant attachment styles were associated with dominance, whereas submissiveness recorded high average scores of separation anxiety in both males and females. BDSM identities based on gender revealed that 60.5% of female practitioners assumed the role of submissiveness and this group recorded the highest average scores of separation anxiety among all groups. These results show that BDSM identity is related to attachment style. However, the results did not support the hypothesis that attachment styles potentially drive BDSM identities. Further research is needed to explore other psychological processes that drive BDSM identities in order to provide guidance for BDSM practitioners in choosing suitable identities, thereby helping practitioners to choose suitable identity partners and avoid negative experiences during BDSM participation.


Asunto(s)
Masoquismo , Apego a Objetos , Humanos , Masculino , Femenino , Adulto , Estudios Transversales , China , Adolescente , Adulto Joven , Masoquismo/psicología , Encuestas y Cuestionarios , Sadismo/psicología , Conducta Sexual/psicología
8.
Sensors (Basel) ; 24(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39275684

RESUMEN

The adoption of multiprocessor platforms is growing commonplace in Internet of Things (IoT) applications to handle large volumes of sensor data while maintaining real-time performance at a reasonable cost and with low power consumption. Partitioned scheduling is a competitive approach to ensure the temporal constraints of real-time sensor data processing tasks on multiprocessor platforms. However, the problem of partitioning real-time sensor data processing tasks to individual processors is strongly NP-hard, making it crucial to develop efficient partitioning heuristics to achieve high real-time performance. This paper presents an enhanced harmonic partitioned multiprocessor scheduling method for periodic real-time sensor data processing tasks to improve system utilization over the state of the art. Specifically, we introduce a general harmonic index to effectively quantify the harmonicity of a periodic real-time task set. This index is derived by analyzing the variance between the worst-case slack time and the best-case slack time for the lowest-priority task in the task set. Leveraging this harmonic index, we propose two efficient partitioned scheduling methods to optimize the system utilization via strategically allocating the workload among processors by leveraging the task harmonic relationship. Experiments with randomly synthesized task sets demonstrate that our methods significantly surpass existing approaches in terms of schedulability.

9.
J Environ Manage ; 366: 121820, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39003909

RESUMEN

Northwest China has abundant solar energy resources and extensive land, making it a pivotal site for solar energy development. However, restrictions on site selection and severe weather conditions have hindered the establishment and operation of photovoltaic (PV) power stations. Previous studies have not considered meteorological factors when evaluating site suitability, leading to research gaps in identifying suitable areas and establishing indicator systems. We aimed to address these gaps by considering seven factors constraining the construction of centralized PV power stations (CPPS) and developing an indicator system based on terrain, climate, soil, and economic factors. Furthermore, we conducted analyses to quantify the solar energy generation potential (SEGP), carbon emissions reduction benefits, and land utilization potential at different sites. The findings indicate that areas rated as very suitable and extremely suitable comprised the largest proportion (62.35%) of site suitability. The correlation between site suitability and electricity consumption was largely non-significant, highlighting the need for enhanced coordination. Additionally, we forecast the electricity consumption in Xinjiang, Gansu, Inner Mongolia, Qinghai, Ningxia, and Shaanxi for 2030 to be 56.62, 19.86, 54.54, 13.59, 15.96, and 33.34 ( × 1011 kWh), respectively, with corresponding carbon emissions reduction potentials of 20.2, 7.1, 19.4, 4.8, 5.7, and 11.9 ( × 109 kg). Consequently, PV carbon reduction and land utilization potential are substantial.


Asunto(s)
Energía Solar , China , Electricidad
10.
Rev Cardiovasc Med ; 24(7): 205, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39077002

RESUMEN

Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH. Methods: In 182 STEMI patients received PPCI, predictors of IMH were analyzed by logistic regression analysis. The predictive ability of risk factors for IMH were determined by receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index. Results: Overall, 80 patients (44.0%) developed IMH. All 4 biomarkers were independent predictors of IMH [odds ratio [OR] (95% confidence interval [CI]): 0.350 (0.202-0.606) for Treg, 1.004 (1.001-1.006) for pCKMB, 1.060 (1.022-1.100) for hsCRP, and 3.329 (1.346-8.236) for LVESD]. After propensity score matching (PSM), the biomarkers significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05]. Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI. Clinical Trial Registration: NCT03939338.

11.
J Appl Microbiol ; 134(8)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37516440

RESUMEN

AIMS: Probiotics have been proved to be strongly linked to the occurrence and progression of atherosclerosis. This study aimed to investigate the improved effects and mechanisms underlying a potential probiotic, Weizmannia coagulans JA845, on atherosclerosis. METHODS AND RESULTS: Male Sprague-Dawley rats supported on a high-fat diet with vitamin D3 supplementation were subjected to W. coagulans JA845 treatment. W. coagulans JA845 obviously alleviated histological abnormalities of the abdominal aorta. After 6 weeks of W. coagulans JA845 administration, levels of TG, TC, LDL, ox-LDL, ROS, and MDA in the JA845 group decreased significantly, and those of HDL, GSH-Px, and SOD were markedly elevated. Treatment with W. coagulans JA845 also inhibited the secretion of ICAM-1 and VCAM-1 and regulated the plasma NO and eNOS content. In brief, administration of W. coagulans JA845 promoted the expression of the SIRT3/SOD2/FOXO3A pathway, inhibited the lipid metabolism pathway, SREBP-1c/FAS/DGAT2, and suppressed the JNK2/P38 MAPK/VEGF pathway implicated in endothelial injury. CONCLUSIONS: These results indicated W. coagulans JA845 improved atherosclerosis by regulating lipid metabolism, antioxidative stress, and protecting against endothelial injury.


Asunto(s)
Aterosclerosis , Lesiones del Sistema Vascular , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Colecalciferol/farmacología , Metabolismo de los Lípidos , Dieta Alta en Grasa/efectos adversos , Estrés Oxidativo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo
12.
Molecules ; 29(1)2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38202610

RESUMEN

The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.


Asunto(s)
Ginsenósidos , Lactobacillus plantarum , Neoplasias , Animales , Ratones , Fermentación , Caspasa 3 , Ginsenósidos/farmacología , Apoptosis
13.
J Appl Microbiol ; 132(3): 2323-2330, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34689406

RESUMEN

AIMS: This study aimed to explore the therapeutic effects of Lactiplantibacillus plantarum HG20 (HG20) on collagen-induced arthritis (CIA) rats and its mechanism. METHODS AND RESULTS: CIA rats were established by injecting bovine type II collagen for 7 days, and treated by intragastric administration HG20 for 21 days. The foot palm temperature and arthritis score were measured once a week. The pathological changes in the knee joint were observed by hematoxylin and eosin staining. The levels of cytokines were detected by enzyme linked immunosorbent assay, and the effects of HG20 on inflammatory and apoptosis pathway of spleen cells were detected by western blot analysis. The results indicated that HG20 reduced the joint swelling degree and foot palm temperature, inhibited the development of joint histopathology, decreased the levels of pro-inflammatory cytokines, down-regulate the expression of pro-inflammatory cytokines by nuclear factor kappa-B pathway, and inhibited the apoptosis of spleen cells by inhibiting phosphatidylinositol 3-kinase/protein kinase B pathway and regulating apoptosis pathways. CONCLUSIONS: HG20 had an adjuvant therapeutic effect on arthritis in CIA rats, and its mechanism might be related to the inflammatory and apoptosis pathway. SIGNIFICANCE AND IMPACT OF STUDY: These results revealed that HG20 could be used as a functional probiotic in the field of food and medical, and which played a potential role in the prevention and treatment of arthritis.


Asunto(s)
Apoptosis , Artritis Reumatoide , Articulaciones , Lactobacillus plantarum , Probióticos , Animales , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/patología , Artritis Reumatoide/terapia , Bovinos , Colágeno , Citocinas/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Ratas , Ratas Wistar
14.
Nutr Neurosci ; 25(12): 2588-2600, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34755592

RESUMEN

Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer's disease (AD) in D-galactose (D-gal) and AlCl3-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3ß pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Microbioma Gastrointestinal , Lactobacillus plantarum , Animales , Ratones , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Modelos Animales de Enfermedad , Galactosa , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Lactobacillus plantarum/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
15.
Lasers Med Sci ; 37(3): 1531-1537, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34647190

RESUMEN

There are few studies on excimer laser (308 nm) atherectomy in the treatment of infrapopliteal artery disease. The purpose of this retrospective clinical study was to assess the efficacy and safety of excimer laser atherectomy (ELA) in combination with adjuvant drug-coated balloon angioplasty (DCB) compared to DCB for infrapopliteal arterial revascularization in patients with ischemic diabetic foot. From September 2018 to February 2019, a total of 79 patients with diabetic foot were treated for infrapopliteal arterial revascularization at Tianjin First Central Hospital (Tianjin, China). In this project, 35 patients were treated with ELA combined with DCB angioplasty, and 44 patients were treated with DCB angioplasty. The patients' baseline characteristics were similar between the 2 groups. The primary efficacy endpoints through 24 months were clinically driven target lesion revascularization (CD-TLR), wound healing rate, major amputation rate, and target vessel patency rate. The primary safety endpoint through 24 months was all-cause mortality. The primary efficacy results at 24 months of ELA + DCB versus DCB were CD-TLR of 14.3% versus 34.1% (p = 0.044), wound healing rate of 88.6% versus 65.9% (p = 0.019), target vessel patency rate of 80.0% versus 52.3% (p = 0.010), and major amputations rate of 5.7% versus 22.7% (p = 0.036). The safety signal at 24 months of all-cause mortality rate was 2.9% for ELA + DCB group and 4.5% for DCB group (p = 0.957). ELA combined with DCB angioplasty is more effective than DCB in the treatment of infrapopliteal artery disease in patients with ischemic diabetic foot, which can improve the wound healing rate and target vessel patency rate. There was no statistical difference in the safety results between the two groups.


Asunto(s)
Angioplastia de Balón , Diabetes Mellitus , Pie Diabético , Enfermedad Arterial Periférica , Angioplastia de Balón/efectos adversos , Aterectomía/efectos adversos , Aterectomía/métodos , Materiales Biocompatibles Revestidos , Pie Diabético/terapia , Arteria Femoral , Humanos , Láseres de Excímeros/uso terapéutico , Enfermedad Arterial Periférica/cirugía , Arteria Poplítea/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Grado de Desobstrucción Vascular
16.
Sensors (Basel) ; 22(8)2022 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-35459059

RESUMEN

The last decade has seen significant advances in power optimization for IoT sensors. The conventional wisdom considers that if we reduce the power consumption of each component (e.g., processor, radio) into µW-level of power, the IoT sensors could achieve overall ultra-low power consumption. However, we show that this conventional wisdom is overturned, as bus communication can take significant power for exchanging data between each component. In this paper, we analyze the power efficiency of bus communication and ask whether it is possible to reduce the power consumption for bus communication. We observe that existing bus architectures in mainstream IoT devices can be classified into either push-pull or open-drain architecture. push-pull only adapts to unidirectional communication, whereas open-drain inherently fits for bidirectional communication which benefits simplifying bus topology and reducing hardware costs. However, open-drain consumes more power than push-pull due to the high leakage current consumption while communicating on the bus. We present Turbo, a novel approach introducing low power to the open-drain based buses by reducing the leakage current created on the bus. We instantiate Turbo on I2C bus and evaluate it with commercial off-the-shelf (COTS) sensors. The results show a 76.9% improvement in power efficiency in I2C communication.

17.
Entropy (Basel) ; 24(12)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36554225

RESUMEN

Nanorefrigerant is a mixture of nanoparticles and pure refrigerant, which can increase heat transfer characteristics in refrigeration and air conditioning equipment. The performance of four different Al2O3 nanorefrigerants and their pure fluids (R600a, R134a, R1234yf, and R1233zd(E)) is analyzed in a vapor-compression refrigeration cycle. The enthalpy of a nanorefrigerant in the refrigeration cycle is calculated by using the prediction method based on the density of nanorefrigerant. A numerical model is established for the thermodynamic analysis, and the results show that adding nanoparticles to the pure refrigerant enhances heat transfer in heat exchangers, increases cooling capacity, reduces compressor power consumption, and finally improves the performance of the refrigeration system. The COP improvement of R1233zd(E) + Al2O3 nanorefrigerant is the highest, and the COP improvement of R134a + Al2O3 and R1234yf + Al2O3 are close to each other. When the mass fraction of Al2O3 nanoparticles increases to 0.30%, the COP of R1233zd(E) and R600a increases by more than 20%; the maximum exergy efficiency is 38.46% for R1233zd(E) + Al2O3, and the minimum exergy efficiency is 27.06% for pure R1234yf. The results provide a basis for the application of nanorefrigerants in the vapor compression refrigeration cycle.

18.
Int J Neurosci ; 131(2): 135-143, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32083954

RESUMEN

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p < 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Neoplasias de la Mama/complicaciones , Femenino , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad
19.
Org Biomol Chem ; 18(40): 8179-8185, 2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-33026031

RESUMEN

A practical visible-light-induced aerobic oxidative dehydrogenative coupling reaction of glycine derivatives with olefins has been developed to efficiently synthesize quinoline-2-carboxylates. This metal-free process proceeds smoothly under mild conditions and exhibits good tolerance of functional groups. Given the low cost of the catalyst and feedstock materials, the mild reaction conditions and the absence of hazardous byproducts, this protocol should find broad applications in the synthesis of quinoline-2-carboxylate derivatives.

20.
Appl Microbiol Biotechnol ; 104(12): 5273-5282, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32335723

RESUMEN

Gut microbiota dysbiosis, associated with insulin resistance, weak intestinal barrier integrity, and inflammation, may also play a role in the development of dietary-induced nonalcoholic fatty liver disease (NAFLD). This study investigates the effects of dietary Lactobacillus plantarum NA136 administration on gut microbiota composition in an insulin-resistant C57BL/6J mouse NAFLD model. Comparison of mice with and without L. plantarum NA136 treatment revealed that L. plantarum NA136 treatment not only relieved insulin resistance but also significantly increased relative proportions of Desulfovibrio, Alistipes, Prevotella, and Enterorhabdus in gut microbiota of NAFLD mice. Meanwhile, L. plantarum NA136 administration also inhibited pathogenic bacterial growth, while promoting growth of probiotics such as Allobaculum, Lactobacillus, and, most markedly, Bifidobacterium. Moreover, L. plantarum NA136 treatment of NAFLD mice improved intestinal barrier integrity and attenuated high-fat and fructose diet (HFD/F)-induced inflammation. These results implicate gut-liver-axis-dependent microbiota modulation as the underlying mechanism for L. plantarum NA136-induced amelioration of NAFLD.Key points• L. plantarum NA136 corrects gut microbiota disorders caused by a high-fat and fructose diet. • L. plantarum NA136 strengthens the intestinal barrier and reduces inflammation in the liver. • L. plantarum NA136 relieves NAFLD by improving the gut-liver axis.


Asunto(s)
Microbioma Gastrointestinal , Inflamación/prevención & control , Lactobacillus plantarum/fisiología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/terapia , Probióticos/uso terapéutico , Animales , Dieta Alta en Grasa , Células Epiteliales/fisiología , Inflamación/microbiología , Mucosa Intestinal/microbiología , Intestinos/citología , Intestinos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL
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