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1.
Chaos ; 33(1): 013108, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36725659

RESUMO

Gas-liquid two-phase flow is polymorphic and unstable, and characterizing its flow behavior is a major challenge in the study of multiphase flow. We first conduct dynamic experiments on gas-liquid two-phase flow in a vertical tube and obtain multi-channel signals using a self-designed four-sector distributed conductivity sensor. In order to characterize the evolution of gas-liquid two-phase flow, we transform the obtained signals using the adaptive optimal kernel time-frequency representation and build a complex network based on the time-frequency energy distribution. As quantitative indicators, global clustering coefficients of the complex network at various sparsity levels are computed to analyze the dynamic behavior of various flow structures. The results demonstrate that the proposed approach enables effective analysis of multi-channel measurement information for revealing the evolutionary mechanisms of gas-liquid two-phase flow. Furthermore, for the purpose of flow structure recognition, we propose a temporal-spatio convolutional neural network and achieve a classification accuracy of 95.83%.

2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614182

RESUMO

Auxin is a key regulator that virtually controls almost every aspect of plant growth and development throughout its life cycle. As the major components of auxin signaling, auxin response factors (ARFs) play crucial roles in various processes of plant growth and development. In this study, a total of 35 PtrARF genes were identified, and their phylogenetic relationships, chromosomal locations, synteny relationships, exon/intron structures, cis-elements, conserved motifs, and protein characteristics were systemically investigated. We also analyzed the expression patterns of these PtrARF genes and revealed that 16 of them, including PtrARF1, 3, 7, 11, 13-17, 21, 23, 26, 27, 29, 31, and 33, were preferentially expressed in primary stems, while 15 of them, including PtrARF2, 4, 6, 9, 10, 12, 18-20, 22, 24, 25, 28, 32, and 35, participated in different phases of wood formation. In addition, some PtrARF genes, with at least one cis-element related to indole-3-acetic acid (IAA) or abscisic acid (ABA) response, responded differently to exogenous IAA and ABA treatment, respectively. Three PtrARF proteins, namely PtrARF18, PtrARF23, and PtrARF29, selected from three classes, were characterized, and only PtrARF18 was a transcriptional self-activator localized in the nucleus. Moreover, Y2H and bimolecular fluorescence complementation (BiFC) assay demonstrated that PtrARF23 interacted with PtrIAA10 and PtrIAA28 in the nucleus, while PtrARF29 interacted with PtrIAA28 in the nucleus. Our results provided comprehensive information regarding the PtrARF gene family, which will lay some foundation for future research about PtrARF genes in tree development and growth, especially the wood formation, in response to cellular signaling and environmental cues.


Assuntos
Populus , Madeira , Madeira/metabolismo , Populus/metabolismo , Filogenia , Família Multigênica , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo , Hormônios , Regulação da Expressão Gênica de Plantas
3.
Sci Adv ; 9(4): eade2217, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706189

RESUMO

A solid-state zinc-ion battery can fundamentally eliminate dendrite formation and hydrogen evolution on the zinc anode from aqueous systems. However, enabling fast zinc ion + conduction in solid crystals is thought to be impossible. Here, we demonstrated a fluorine-doping approach to achieving fast Zn2+ transport in mesoporous ZnyS1-xFx. The substitutional doping of fluoride ion with sulfide substantially reduces Zn2+ migration barrier in a crystalline phase, while mesopore channels with bounded dimethylformamide enable nondestructive Zn2+ conduction along inner pore surface. This mesoporous conductor features a high room-temperature Zn2+ conductivity (0.66 millisiemens per centimeter, compared with 0.01 to 1 millisiemens per centimeter for lithium solid-state electrolyte) with a superior cycling performance (89.5% capacity retention over 5000 cycles) in a solid zinc-ion battery and energy density (0.04 watt-hour per cubic centimeter) in a solid zinc-ion capacitor. The universality of this crystal engineering approach was also verified in other mesoporous zinc chalcogenide materials, which implies various types of potential Zn2+-conducting solid electrolytes.

4.
Ann Med ; 55(1): 325-334, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36598136

RESUMO

INTRODUCTION: Long-term exposure to air pollution is known to be harmful to preterm birth (PTB), but little is known about the short-term effects. This study aims to quantify the short-term effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2) on PTB. MATERIALS AND METHODS: A total of 18,826 singleton PTBs were collected during the study period. Poisson regression model combined with the distributed lag non-linear model was applied to evaluate the short-term effects of PTBs and air pollutants. RESULTS: Maternal exposure to NO2 was significantly associated increased risk of PTB at Lag1 (RR: 1.025, 95%CI: 1.003-1.047). In the moving average model, maternal exposure to NO2 significantly increased the risk of PTB at Lag01 (RR: 1.029, 95%CI: 1.004-1.054). In the cumulative model, maternal exposure to NO2 significant increased the risk of PTB at Cum01 (RR:1.026, 95%CI: 1.002-1.051), Cum02 (RR: 1.030, 95%CI: 1.003-1.059), and Cum03 (RR: 1.033, 95%CI: 1.002-1.066). The effects of PM2.5, PM10 and NO2 on PTB were significant and greater in the cold season than the warm season. CONCLUSIONS: Maternal exposure to NO2, PM2.5 and PM10 before delivery has a significant risk for PTB, particularly in the cold season.Key messagesMaternal exposure to NO2 was significant associated with an increased risk of preterm birth at the day 1 before delivery.Particle matter (PM2.5 and PM10) showed a significant short-term effect on preterm birth in the cold season.The effects of air pollutants on preterm birth was greater in the cold season compared with the warm season.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Nascimento Prematuro , Feminino , Recém-Nascido , Humanos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , China/epidemiologia
5.
Front Immunol ; 13: 1011264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569894

RESUMO

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape-for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.


Assuntos
Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Hepáticas/genética , Imunoterapia , Ritmo Circadiano/genética
6.
Front Nutr ; 9: 1052820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532540

RESUMO

Introduction: The flavor deterioration blocks the development of melon juice. Methods: The effects of ultra-high temperature (UHT) and high pressure (HP) treatments on the aromatic compound concentrations of melon juice and their mechanisms were explored with fresh juice as the control. Results: A total of 57 volatile compounds were identified by gas chromatography-tandem mass spectrometry analysis. ß-ionone was shown to be the major aromatic component of melon juice for the first time. The HP at 200 MPa for 20 min increased the total volatile concentration of melon juice by 1.54 and 3.77 times the control and UHT, respectively. Moreover, the sum concentration of a major aromatic component in the HP treatment was 1.49 and 5.94 times higher than that of the control and UHT, respectively. Discussion: The HP treatment raised the concentration of volatile and aromatic components of melon juice by reducing their surface tension.

7.
Chin Med J (Engl) ; 135(21): 2563-2569, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36583919

RESUMO

BACKGROUND: Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. METHODS: A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. RESULTS: There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. CONCLUSION: The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.


Assuntos
Dermatophagoides pteronyssinus , Hipersensibilidade , Animais , Humanos , Antígenos de Dermatophagoides , Alérgenos , Testes Cutâneos/métodos
8.
J Biol Phys ; 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36580168

RESUMO

Cell fate decision processes are regulated by networks which contain different molecules and interactions. Different network topologies may exhibit synergistic or antagonistic effects on cellular functions. Here, we analyze six most common small networks with regulatory logic AND or OR, trying to clarify the relationship between network topologies and synergism (or antagonism) related to cell fate decisions. We systematically examine the contribution of both network topologies and regulatory logic to the cell fate synergism by bifurcation and combinatorial perturbation analysis. Initially, under a single set of parameters, the synergism of three types of networks with AND and OR logic is compared. Furthermore, to consider whether these results depend on the choices of parameter values, statistics on the synergism of five hundred parameter sets is performed. It is shown that the results are not sensitive to parameter variations, indicating that the synergy or antagonism mainly depends on the network topologies rather than the choices of parameter values. The results indicate that the topology with "Dual Inhibition" shows good synergism, while the topology with "Dual Promotion" or "Hybrid" shows antagonism. The results presented here may help us to design synergistic networks based on network structure and regulation combinations, which has promising implications for cell fate decisions and drug combinations.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36441890

RESUMO

Traditional pattern recognition models usually assume a fixed and identical number of classes during both training and inference stages. In this paper, we study an interesting but ignored question: can increasing the number of classes during training improve the generalization and reliability performance? For a k-class problem, instead of training with only these k classes, we propose to learn with k+m classes, where the additional m classes can be either real classes from other datasets or synthesized from known classes. Specifically, we propose two strategies for constructing new classes from known classes. By making the model see more classes during training, we can obtain several advantages. Firstly, the added m classes serve as a regularization which is helpful to improve the generalization accuracy on the original k classes. Secondly, this will alleviate the overconfident phenomenon and produce more reliable confidence estimation for different tasks like misclassification detection, confidence calibration, and out-of-distribution detection. Lastly, the additional classes can also improve the learned feature representation, which is beneficial for new classes generalization in few-shot learning and class-incremental learning. Compared with the widely proved concept of data augmentation (dataAug), our method is driven from another dimension of augmentation based on additional classes (classAug). Comprehensive experiments demonstrated the superiority of our classAug under various open-environment metrics on benchmark datasets.

10.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36293351

RESUMO

The plant hormone auxin acts as a signaling molecule to regulate numerous developmental processes throughout all stages of plant growth. Understanding how auxin regulates various physiological and developmental processes has been a hot topic and an intriguing field. Recent studies have unveiled more molecular details into how diverse auxin responses function in every aspect of plant growth and development. In this review, we systematically summarized and classified the molecular mechanisms of diverse auxin responses, and comprehensively elaborated the characteristics and multilevel regulation mechanisms of the canonical transcriptional auxin response. On this basis, we described the characteristics and differences between different auxin responses. We also presented some auxin response genes that have been genetically modified in plant species and how their changes impact various traits of interest. Finally, we summarized some important aspects and unsolved questions of auxin responses that need to be focused on or addressed in future research. This review will help to gain an overall understanding of and some insights into the diverse molecular mechanisms of auxin responses in plant growth and development that are instrumental in harnessing genetic resources in molecular breeding of extant plant species.


Assuntos
Ácidos Indolacéticos , Reguladores de Crescimento de Plantas , Desenvolvimento Vegetal/genética , Plantas/genética , Transdução de Sinais/fisiologia , Regulação da Expressão Gênica de Plantas
11.
Front Nutr ; 9: 946259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211499

RESUMO

This study focused on the association of dietary patterns and Tibetan featured foods with high-altitude polycythemia (HAPC) in Naqu, Tibet, to explore the risk factors of HAPC in Naqu, Tibet, to raise awareness of the disease among the population and provide evidence for the development of prevention and treatment interventions. A 1:2 individual-matched case-control study design was used to select residents of three villages in the Naqu region of Tibet as the study population. During the health examination and questionnaire survey conducted from December 2020 to December 2021, a sample of 1,171 cases was collected. And after inclusion and exclusion criteria and energy intake correction, 100 patients diagnosed with HAPC using the "Qinghai criteria" were identified as the case group, while 1,059 patients without HAPC or HAPC -related diseases were identified as the control group. Individuals were matched by a 1:2 propensity score matching according to gender, age, body mass index (BMI), length of residence, working altitude, smoking status, and alcohol status. Dietary patterns were determined by a principal component analysis, and the scores of study subjects for each dietary pattern were calculated. The effect of dietary pattern scores and mean daily intake (g/day) of foods in the Tibetan specialty diet on the prevalence of HAPC was analyzed using conditional logistic regression. After propensity score matching, we found three main dietary patterns among residents in Naqu through principal component analysis, which were a "high protein pattern," "snack food pattern," and "vegetarian food pattern." All three dietary patterns showed a high linear association with HAPC (p < 0.05) and were risk factors for HAPC. In the analysis of the relationship between Tibetan featured foods and the prevalence of HAPC, the results of the multifactorial analysis following adjustment for other featured foods showed that there was a positive correlation between the average daily intake of tsampa and the presence of HAPC, which was a risk factor. Additionally, there was an inverse correlation between the average daily intake of ghee tea and the presence of HAPC, which was a protective factor.

12.
Cell Biosci ; 12(1): 166, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207723

RESUMO

BACKGROUND: Krüppel-like factor 7 (klf7), a transcription factor in the nervous system to regulate cell proliferation and differentiation, has been recently identified as a causal gene for autism spectrum disorder (ASD), but the mechanism behind remains unknown. RESULT: To uncover this mechanism, in this study we characterized the involvement of klf7 in circadian rhythm by knocking down klf7 in N2A cells and examining the rhythmic expression of circadian genes, especially Clock gene. We constructed klf7-/- mice and then investigated into klf7 regulation on the expression of rhythm genes in vivo as well as the use of melatonin to rescue the autism behavior. Our results illustrated that circadian rhythm was disrupted in klf7 knockdown cells and that klf7-/- mice showed autism-like behavior. Also, we found that Clock gene was downregulated in the brain of these klf7-/- mice and that the downstream rhythm genes of Clock were disturbed. Melatonin, as a circadian regulation drug, could regulate the expression level and amplitude of rhythm genes in klf7 knockout cells and further rescue the autistic behavior of klf7-/- mice. CONCLUSION: Klf7 deficiency causes ASD by disrupting circadian rhythm related genes to trigger rhythm oscillations. To treat ASD, maintaining circadian homeostasis is promising with the use of melatonin.

13.
Oncogene ; 41(42): 4696-4708, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36097193

RESUMO

NY-ESO-1 is a well-known cancer-testis antigen (CTA) with re-expression in numerous cancer types, but its expression is suppressed in myeloid leukemia cells. Patients with acute myeloid leukemia (AML) receiving decitabine (DAC) exhibit induced expression of NY-ESO-1 in blasts; thus, we investigated the effects of NY-ESO-1-specific TCR-engineered T (TCR-T) cells combined with DAC against AML. NY-ESO-1-specific TCR-T cells could efficiently eliminate AML cell lines (including U937, HL60, and Kasumi-1cells) and primary AML blasts in vitro by targeting the DAC-induced NY-ESO-1 expression. Moreover, the incubation of T cells with DAC during TCR transduction (designated as dTCR-T cells) could further enhance the anti-leukemia efficacy of TCR-T cells and increase the generation of memory-like phenotype. The combination of DAC with NY-ESO-1-specific dTCR-T cells showed a superior anti-tumor efficacy in vivo and prolonged the survival of an AML xenograft mouse model, with three out of five mice showing complete elimination of AML cells over 90 days. This outcome was correlated with enhanced expressions of IFN-γ and TNF-α, and an increased proportion of central memory T cells (CD45RO+CD62L+ and CD45RO+CCR7+). Taken together, these data provide preclinical evidence for the combined use of DAC and NY-ESO-1-specific dTCR-T cells for the treatment of AML.


Assuntos
Antígenos de Neoplasias , Leucemia Mieloide Aguda , Linfócitos T , Animais , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Decitabina/farmacologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas de Membrana/metabolismo , Camundongos , Fenótipo , Receptores de Antígenos de Linfócitos T , Receptores CCR7/metabolismo , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Front Genet ; 13: 856636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159992

RESUMO

Objective: Microcephaly with pontine and cerebellar hypoplasia (MICPCH) is a rare X-linked dominant genetic disease, and most MICPCHs are ascribed to CASK mutations, while few are revealed in Chinese patients. This study aims to identify the pathogenic mutation in a Chinese proband with MICPCH. Methods: A 3-year-old female Chinese proband with MICPCH and her parents were included. Clinical data were collected from the medical records and recalled by the proband's mother. Whole genome sequencing and Sanger sequencing were used to find the pathogenic mutation of MICPCH. Results: The proband presented with postnatal progressive microcephaly, cerebellar hypoplasia, intellectual disability, motor and language development retardation and limb hypertonia. Genetic analysis indicated that there was a novel compound heterozygote nonsynonymous mutation, c.755T>C(p.Leu252Pro) in exon8 of CASK gene in the proband, but not in her parents. This CASK mutation has not been reported in other databases. Conclusion: This study broadens the mutation spectrum of the CASK gene and is of great value for precise prenatal diagnosis and genetic counseling.

15.
Dalton Trans ; 51(40): 15330-15338, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36134906

RESUMO

Overexpressed HOCl in tumors can behave as an activator for imaging-guided precision therapy. Herein, a new kind of HOCl-activated molecular platform has been developed aiming at the integration of detection, imaging, and anticancer functions. The design strategy uses a five-membered heterocyclic ring to bridge the fluorescent fluorescein part (FL) and the anticancer ferrocene part (Fc). Three derivatives, namely FL-Fc, FL-NP-Fc and FL-TEG-Fc, were designed with different grafted chains on the fluorescein mother to modulate the hydrophilic and biocompatible capacity. In these molecular platforms, the ferrocene unit serves as the fluorescence emission quencher and masked prodrug. These three could respond to HOCl with good selectivity and sensitivity, showing a turn-on fluorescence signal and anticancer efficacy. FL-TEG-Fc with the highest sensitivity (6.5 × 10-6 M) was successfully used for imaging endogenous HOCl in AGS cells, in which it presented strong toxicity IC50 = 9.5 ± 0.3 µM. The mechanistic study revealed that the five-membered heterocyclic ring of FL-TEG-Fc was broken specifically and effectively by HOCl to release strongly fluorescent fluorescein and a bioactive ferrocene derivative; the obtained ferrocene derivative further generated cytotoxic ˙OH through a Fenton-like reaction. This study provides a potential theranostic strategy against HOCl-overexpressing cancers.


Assuntos
Corantes Fluorescentes , Pró-Fármacos , Compostos Ferrosos , Fluoresceína/farmacologia , Corantes Fluorescentes/farmacologia , Ácido Hipocloroso , Metalocenos/farmacologia , Pró-Fármacos/farmacologia
16.
J Colloid Interface Sci ; 629(Pt B): 227-237, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36152579

RESUMO

With the surging demand for flexible and portable electronic devices featuring high energy and power density, the development of next-generation lightweight, flexible energy storage devices is crucial. However, achieving the expected energy and power density of supercapacitors remains a great challenge. This work reports a facile plasma-enabled method for preparing supercapacitor electrodes made of MoS2 nanosheets grown on flexible and lightweight N-doped carbon cloth (NCC). The MoS2/NCC presents an outstanding specific capacitance of 3834.28 mF/cm2 at 1 mA/cm2 and energy density of 260.94 µWh/cm2 at a power density of 354.48 µW/cm2. An aqueous symmetric supercapacitor fitted with two MoS2/NCC electrodes achieved the maximum energy density of 138.12 µWh/cm2 and the highest power density of 7,417.33 µW/cm2, along with the excellent cycling stability of 83.3 % retention over 10,000 cycles. The high-performance energy storage ASSSs (all-solid-state supercapacitors) are demonstrated to power devices in both rigid and flexible operation modes. This work provides a new perspective for fabricating high-performance all-solid-state flexible supercapacitors for clean energy storage.

17.
Front Genet ; 13: 916281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105108

RESUMO

Previous studies have demonstrated that TRIB3 is closely related to insulin resistance, metabolic disorders and vascular diseases. Recently, it was reported that a 33 bp variable number of tandem repeats (VNTR) located in the TRIB3 promoter could considerably alter its transcriptional activity. Nonetheless, whether the shift of TRIB3 transcriptional activity has the effect of inducing diabetic vascular complications is still unclear. Therefore, in our study, we aimed to explore the relationship between the TRIB3 33bp VNTR and diabetic vascular complications. The TRIB3 33bp VNTR polymorphisms were determined by PCR and Sanger sequencing, a total of 798 eligible Chinese patients with type 2 diabetes (T2DM) were included in our study and then evaluated with clinical data. After adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes, we found that the high number of 33 bp tandem repeats (repeats>8) was significantly associated with an increase in the risk of cerebrovascular diseases compared with the low number of 33 bp tandem repeats (repeats≤6) in patients with T2DM(OR 2.66, 95% CI 1.29-5.47, p = 0.008). The intermediate number of 33bp tandem repeats (6 < repeat≤8) was markedly associated with a decreased risk of diabetic retinopathy compared with the low number of tandem repeats (OR 0.65, 95% CI 0.46-0.91, p = 0.012). Adjusting for gender, age and BMI, there was a significant difference in DBP levels among patients with the number of different 33 bp tandem repeats (Low vs. Intermediate vs. High, 81.6 ± 12.8 vs. 79.8 ± 12.4 vs. 78.7 ± 12.6 mmHg; p = 0.045). Subgroup analysis found that TRIB3 VNTR was significantly correlated with the difference in systolic blood pressure (SBP) in T2DM patients taking ACEI/ARB drugs (Low vs. Intermediate vs. High, 146.27 ± 18.23 vs. 140.01 ± 19.91 vs. 140.77 ± 18.64 mmHg; p = 0.018). Our results indicated that TRIB3 promoter 33bp VNTR is related to vascular diseases in T2DM patients, and may serve as a new biomarker for individualized prevention and therapy of T2DM.

18.
Med Sci Sports Exerc ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36107108

RESUMO

METHODS: We used linear regression to examine cross-sectional associations of accelerometer-measured physical activity and sedentary time with extrinsic and intrinsic epigenetic age acceleration models (EEAA and IEAA) and GrimAge measured from blood samples from Framingham Heart Study participants with accelerometry and DNA methylation data (n = 2435; mean age 54.9 ± 14.3, 46.0% men). Residuals of Hannum-, Horvath-, and GrimAge-predicted epigenetic age were calculated by regressing epigenetic age on chronological age. We took into account blood cell composition for EEAA, IEAA, and AdjGrimAge. Moderate to vigorous physical activity (MVPA) was log-transformed to normalize its distribution. Adjustment models accounted for family structure, age, sex, smoking status, cohort-laboratory indicator, and accelerometer wear time. We additionally explored adjustment for body mass index (BMI). RESULTS: Walking 1500 more steps/day or spending 3 fewer hours sedentary was associated with >10 months lower GrimAge biological age (or ~ 1 month lower AdjGrimAge, after adjusting for blood cells, p < 0.05). Every 5 min/day more MVPA was associated with 19-79 days lower GrimAge (4-23 days lower using EEAA or AdjGrimAge, p < 0.01). Adjusting for BMI attenuated these results, but all statistically significant associations with AdjGrimAge remained. CONCLUSIONS: Greater habitual physical activity and lower sedentary time were associated with lower epigenetic age, which was partially explained by BMI. Further research should explore whether changes in physical activity influence methylation status and whether those modifications influence chronic disease risk.

19.
Adv Healthc Mater ; 11(22): e2201150, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36074801

RESUMO

Stroke patients with diabetes have worse neurological outcomes than non-diabetic stroke patients, and treatments beneficial for non-diabetic stroke patients are not necessarily effective for diabetic stroke patients. While stem cell-derived extracellular vesicles (EVs) show potential for treating stroke, the results remain unsatisfactory due to the lack of approaches for retaining and controlling EVs released into the brain. Herein, a glucose/reactive oxygen species dual-responsive hydrogel showing excellent injectability, biocompatibility, and self-healing capability is introduced as an EVs-loading vehicle and an intelligent EVs sustained releasing system in the brain. These EVs-hydrogels are developed via crosslinking of phenylboronic acid-modified hyaluronic acid and Poly vinyl alcohol, and fusion with neural stem cell-derived EVs. The results show EVs are stably incorporated into the hydrogels and can be controllably released in response to the brain microenvironment after stroke in type 2 diabetic mice. The EVs-hydrogels exert an excellent angiogenic effect, increasing the migration and tube formation of human umbilical vein endothelial cells. In addition, injection of EVs-hydrogels into the ischemic mouse brain enhances EVs retention and facilitates sustained release, promotes angiogenesis, and improves neurobehavioral recovery. These results suggest such a microenvironment responsive and sustained release EVs-hydrogel system offers a safe, and efficient therapy for diabetic stroke.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Acidente Vascular Cerebral , Animais , Camundongos , Humanos , Hidrogéis/farmacologia , Preparações de Ação Retardada , Células Endoteliais da Veia Umbilical Humana , Encéfalo , Acidente Vascular Cerebral/terapia
20.
Cancer Sci ; 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36156330

RESUMO

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti-angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic-related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient-derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET-1), an important regulator of angiogenesis and the hypoxia-related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET-1-induced hypoxia-inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.

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