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1.
Opt Express ; 32(6): 9306-9315, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571168

RESUMEN

Understanding and directing the energy transfer in nanocrystals-chromophore heterostructure is critical to improve the efficiency of their photocatalytic and optoelectronic applications. In this work, we studied the energy transfer process between inorganic-organic molecular complexes composed of cesium halide perovskite nanoplatelets (CsPbBr3 NPLs) and boron dipyrromethene (BODIPY) by photoluminescence spectroscopy (PL), time-correlated single photon-counting (TCSPC) and femtosecond transient absorption spectroscopy. The quenching of PL in CsPbBr3 NPLs occurred simultaneously with the PL enhancement of BODIPY implied the singlet energy transfer process. The rate of energy transfer has been determined by transient absorption spectrum as kET = 3.8 × 109 s-1. The efficiency of Förster energy transfer (FRET) has been quantitatively calculated up to 70%. Our work advances the understanding of the interaction between BODIPY and perovskite nanoplatelets, providing a new solution based on their optoelectronic and photocatalytic applications.

2.
Cardiovasc Diabetol ; 23(1): 61, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336720

RESUMEN

BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Hiperglucemia , Humanos , Femenino , Anciano , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Retrospectivos , Glucemia/análisis , Factores de Riesgo
3.
Cardiovasc Diabetol ; 23(1): 87, 2024 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-38419016

RESUMEN

BACKGROUND: Insulin resistance (IR) is involved in the pathophysiological processes of arrhythmias. Increasing evidence suggests triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are simple and reliable surrogates for IR. Although they have been associated with atrial fibrillation (AF), evidence supporting this is limited. Here, this is the first study to investigate the association between TyG-BMI index and AF recurrence following radiofrequency catheter ablation (RFCA). The performance of the four non-insulin-based IR indexes in predicting AF recurrence after ablation was explored. METHODS: A total of 2242 AF patients who underwent a de novo RFCA between June 2018 to January 2022 at two hospitals in China were included in this retrospective study. The predictive values of IR indexes for AF recurrence after ablation were assessed. RESULTS: During 1-year follow-up, 31.7% of patients experienced AF recurrence. The multivariable analysis revealed that TyG index, METS-IR, and TyG-BMI index were independent risk factors for AF recurrence. Restricted cubic spline analysis revealed a connection between METS-IR, TyG-BMI index, and AF recurrence (P < 0.001). Furthermore, incorporating the METS-IR or TyG-BMI index to the basic risk model with fully adjusted factors considerably enhanced the forecast of AF recurrence, as demonstrated by the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: TyG index, METS-IR, and TyG-BMI index were independently associated with AF recurrence following ablation. Among the four non-insulin-based IR indexes, TyG-BMI had the highest predictive value, followed by METS-IR.


Asunto(s)
Fibrilación Atrial , Resistencia a la Insulina , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Estudios Retrospectivos , Glucosa , Triglicéridos , Glucemia , Biomarcadores
4.
Environ Sci Technol ; 58(11): 5014-5023, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38437169

RESUMEN

Estimates of the land area occupied by wind energy differ by orders of magnitude due to data scarcity and inconsistent methodology. We developed a method that combines machine learning-based imagery analysis and geographic information systems and examined the land area of 318 wind farms (15,871 turbines) in the U.S. portion of the Western Interconnection. We found that prior land use and human modification in the project area are critical for land-use efficiency and land transformation of wind projects. Projects developed in areas with little human modification have a land-use efficiency of 63.8 ± 8.9 W/m2 (mean ±95% confidence interval) and a land transformation of 0.24 ± 0.07 m2/MWh, while values for projects in areas with high human modification are 447 ± 49.4 W/m2 and 0.05 ± 0.01 m2/MWh, respectively. We show that land resources for wind can be quantified consistently with our replicable method, a method that obviates >99% of the workload using machine learning. To quantify the peripheral impact of a turbine, buffered geometry can be used as a proxy for measuring land resources and metrics when a large enough impact radius is assumed (e.g., >4 times the rotor diameter). Our analysis provides a necessary first step toward regionalized impact assessment and improved comparisons of energy alternatives.


Asunto(s)
Fuentes Generadoras de Energía , Viento , Humanos , Granjas , Fenómenos Físicos
5.
Yi Chuan ; 46(5): 408-420, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763775

RESUMEN

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.


Asunto(s)
Sistemas CRISPR-Cas , Modelos Animales de Enfermedad , Hipoxantina Fosforribosiltransferasa , Síndrome de Lesch-Nyhan , Animales , Conejos , Síndrome de Lesch-Nyhan/genética , Hipoxantina Fosforribosiltransferasa/genética , Hipoxantina Fosforribosiltransferasa/metabolismo , Femenino , Edición Génica , ARN Guía de Sistemas CRISPR-Cas/genética , Masculino , Fenotipo
6.
Mol Ther ; 30(7): 2443-2451, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35443934

RESUMEN

Predictable DNA off-target effect is one of the major safety concerns for the application of cytosine base editors (CBEs). To eliminate Cas9-dependent DNA off-target effects, we designed a novel effective CBE system with dual guiders by combining CRISPR with transcription activator-like effector (TALE). In this system, Cas9 nickase (nCas9) and cytosine deaminase are guided to the same target site to conduct base editing by single-guide RNA (sgRNA) and TALE, respectively. However, if nCas9 is guided to a wrong site by sgRNA, it will not generate base editing due to the absence of deaminase. Similarly, when deaminase is guided to a wrong site by TALE, base editing will not occur due to the absence of single-stranded DNA. In this way, Cas9- and TALE-dependent DNA off-target effects could be completely eliminated. Furthermore, by fusing TALE with YE1, a cytidine deaminase with minimal Cas9-independent off-target effect, we established a novel CBE that could induce efficient C-to-T conversion without detectable Cas9- or TALE-dependent DNA off-target mutations.


Asunto(s)
Citosina , ARN Guía de Kinetoplastida , Sistemas CRISPR-Cas , ADN/genética , Edición Génica , ARN Guía de Kinetoplastida/genética , Efectores Tipo Activadores de la Transcripción/genética
7.
Altern Ther Health Med ; 29(8): 863-869, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37708558

RESUMEN

When a medical device or surgical instrument comes into contact with the patient's sterile tissue or mucous membrane during the various processes, the risk of introducing infections into the patient's body increases. Furthermore, an infection may be transmitted from one patient to another, from a patient to a member of the medical staff and vice versa or from the environment to the patient via improperly sterilized or disinfected equipment. A number of outbreaks and diseases have been documented in the hospital setting as a result of poorly sanitized devices. As a result, adequate disinfection procedures for medical and surgical items are required in all healthcare facilities. It is equally the responsibility of healthcare providers to reduce and eliminate such infections. Each hospital should have its own standards for sterilization and disinfection of equipment based on the intended use of medical devices and associated infections. In order to reduce the risk of both endogenous and exogenous infections, infection control procedures must be implemented in general practice. Using a formulation containing alcohol alone or in combination with other agents to properly wash hands after each patient's checkup and before any procedure reduces the likelihood of transmitting infections to and from patients. Sterilization and disinfection are the most important aspects of infection control. The most common sterilization methods are steam sterilizers and ethylene dioxide sterilizers. Trash generated during practice should be handled according to protocol and rules, as it may be a source of nosocomial infections. Trained personnel are required to carry out these procedures.


Asunto(s)
Infección Hospitalaria , Desinfección , Humanos , Desinfección/métodos , Infección Hospitalaria/prevención & control , Instrumentos Quirúrgicos , Personal de Salud , Resultado del Tratamiento
8.
Phys Chem Chem Phys ; 24(27): 16538-16544, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35788232

RESUMEN

Excitonic devices based on two-dimensional (2D) transition metal dichalcogenides (TMDCs) can combine spintronics with valleytronics due to its special energy band structure. In this work, we studied the generation and relaxation processes of spin/valley polarized excitons dynamics in monolayer WSe2 and its van der Waals (vdW) heterojunction with graphene using a circularly polarized femtosecond pump-probe system. The spin/valley depolarization dynamics of the A exciton in monolayer WSe2 is found to exhibit a biexponential decay. The fast relaxation process is due to the ultrafast intervalley electron-hole spin-flip exchange coupling and electron-phonon scattering. And the slow relaxation process originates from the recombination and relaxation of the trion states. Graphene has an electron extraction effect on WSe2, which prevents the formation of trions. Therefore, the spin/valley depolarization process of the A exciton in the heterojunction exhibits only a fast relaxation process. In both monolayer WSe2 and its heterojunction with graphene, B/A' excitons exhibit a negative spin/valley polarization which is mainly due to two-photon absorption and excited Bose scattering. Our work systematically studied the spin/valley depolarization dynamics of excitons and revealed possible mechanisms of their differences in isolated 2D WSe2 and vdW heterojunctions.

9.
Acta Biochim Biophys Sin (Shanghai) ; 54(10): 1540-1551, 2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36239356

RESUMEN

In recent decades, EGFR-targeted tyrosine kinase inhibitors (TKIs) have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer (NSCLC). However, resistance to EGFR-TKIs limits their clinical application. In the present study, we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, cyy-287, in NSCLC. We find that cyy-287 has a high affinity for lung tissue and inhibits the proliferation of NSCLC cells. Interestingly, the significant suppression of migration and induction of apoptosis by cyy-287 are only observed in EGFR-driven but not in EGFR-wild-type (wt) cells. According to the RNA sequencing and KEGG enrichment analysis results, cyy-287 markedly inhibits the MAPK pathway in EGFR-driven PC9 cells, and western blot analysis results further indicate that cyy-287 selectively blocks the ERK pathway in EGFR-driven cells. Meanwhile, apoptosis induced by cyy-287 could be partially reversed by ERK pathway inhibition. Further experiment indicates that cyy-287 inhibits the EGFR pathway in both EGFR-driven and EGFR-overexpressing cells. Interestingly, it only induces apoptosis in EGFR-driven cells, not in EGFR-overexpressing cells. The growth of EGFR-driven cells is suppressed by cyy-287 in vivo, with fewer side effects. Our results suggest that cyy-287 may be a potential therapeutic drug with promising antitumor effects against NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Sistema de Señalización de MAP Quinasas , Receptores ErbB , Transducción de Señal , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Línea Celular Tumoral , Pirimidinas/farmacología , Resistencia a Antineoplásicos , Proliferación Celular , Apoptosis
10.
Int J Mol Sci ; 23(19)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36233332

RESUMEN

As an important forage legume with high values in feed and medicine, Melilotus albus has been widely cultivated. The AP2/ERF transcription factor has been shown to play an important regulatory role in plant drought resistance, but it has not been reported in the legume forage crop M. albus. To digger the genes of M. albus in response to drought stress, we identified and analyzed the ERF gene family of M. albus at the genome-wide level. A total of 100 MaERF genes containing a single AP2 domain sequence were identified in this study, named MaERF001 to MaERF100, and bioinformatics analysis was performed. Collinearity analysis indicated that segmental duplication may play a key role in the expansion of the M. albus ERF gene family. Cis-acting element predictions suggest that MaERF genes are involved in various hormonal responses and abiotic stresses. The expression patterns indicated that MaERFs responded to drought stress to varying degrees. Furthermore, four up-regulated ERFs (MaERF008, MaERF037, MaERF054 and MaERF058) under drought stress were overexpressed in yeast and indicated their biological functions to confer the tolerance to drought. This work will advance the understanding of the molecular mechanisms underlying the drought response in M. albus. Further study of the promising potential candidate genes identified in this study will provide a valuable resource as the next step in functional genomics studies and improve the possibility of improving drought tolerance in M. albus by transgenic approaches.


Asunto(s)
Sequías , Melilotus , Regulación de la Expresión Génica de las Plantas , Melilotus/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
11.
Mol Pharmacol ; 96(5): 589-599, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31462456

RESUMEN

Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.


Asunto(s)
Chalconas/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Glycyrrhiza , Leucemia Mieloide Aguda/tratamiento farmacológico , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Administración Oral , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucemia Mieloide Aguda/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Simulación del Acoplamiento Molecular/métodos , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Tirosina Quinasa 3 Similar a fms/metabolismo
12.
Anal Bioanal Chem ; 410(27): 7007-7017, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30232522

RESUMEN

A highly selective and sensitive probe for the detection of hypochlorous acid (HClO) in real samples was designed and synthesized by using the specific reaction between HClO and phenyl azo group. Upon reaction with HClO, the nonfluorescent probe generated a highly fluorescent 2-(2-hydroxy-4-chlorophenyl)benzimidazole (HBI-Cl) fluorophore, which underwent the excited state intramolecular proton transfer process to give strong fluorescence turn-on. The sensing mechanism, conversion of the nonfluorescent azo moiety into the fluorescent derivative of HBI upon reaction with HClO, was verified by independent synthesis of HBI-Cl (ϕfl ≈ 0.75). The theoretical computing results were in agreement with the experimental results that the azo moiety was the reactive site to realize fluorescence detection for HClO. Additionally, the probe was successfully utilized to determine HClO in tap water, exogenous HClO in HeLa cells, and endogenous HClO in MCF-7 cells with a low detection limit and cytotoxicity. Graphical abstract ᅟ.


Asunto(s)
Bencimidazoles/química , Colorantes Fluorescentes/química , Ácido Hipocloroso/análisis , Imagen Óptica/métodos , Células HeLa , Humanos , Células MCF-7 , Microscopía Fluorescente/métodos , Modelos Moleculares
13.
Phys Chem Chem Phys ; 20(27): 18837-18843, 2018 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-29966027

RESUMEN

In this work, segmented silver nanowires (AgNWs) with an average diameter of 60 nm have been successfully synthesized by a typical polyol method without any templates and seeds. The synthesized segmented AgNWs were strongly dependent on the reaction temperature and time. It was found from high-resolution transmission electron microscopy and selected area electron diffraction measurements that the connection node of segmented AgNWs was in the form of a twinned crystal. We speculated that these segmented AgNWs were possibly derived from end-to-end self-connection and self-concrescence of two neighbouring Ag nanorods or nanowires at a suitable reaction temperature and time, which is further confirmed by the secondary growth of AgNWs. In addition, segmented AgNWs were blended into hole transporting layers to enhance the performance of polymer solar cells (PSCs) by utilizing their localized surface plasmon resonance and optical scattering effects. As a result, the power conversion efficiency (PCE) and short-circuit current density (Jsc) of PSCs with segmented AgNWs increased from 2.81% and 8.99 mA cm-2 to 3.30% and 9.95 mA cm-2, respectively.

14.
Opt Express ; 25(21): 24861-24871, 2017 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-29041159

RESUMEN

The chirality of photons plays a fundamental role in light-matter interactions. However, a limiting factor in photonic integrated circuits is the lack of a miniaturized component, which can distinguish the chirality in a low cost and integrated manner. Herein we numerically demonstrate a chirality-distinguishing beamsplitter that can address this challenge. It consists of an integrated polarization rotator and a linear polarization beamsplitter, which together can fulfill the task of distinguishing and splitting left- and right-handed quasi-circularly polarized modes on a chip with an ultra-broadband operation range from 1.45 µm to 1.65 µm. Owning to the reciprocity, the device can emit photons with selectable spin angular momentum depending on the chosen feeding waveguide. The device is compatible with complementary metal-oxide semiconductor technology and it may open up new avenues in the fields of on-chip nano-photonics, bio-photonics and quantum information science.

15.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(12): 3178-82, 2014 Dec.
Artículo en Zh | MEDLINE | ID: mdl-25881403

RESUMEN

With the methods of compound-melting and high-temperature molding, PC/YAG:Ce fluorescent resin pieces were prepared. The transmittance of the prepared PC/YAG:Ce fluorescent resin in 500~800 nm reaches approximately 65% (0.71 mm thick, double sides polished). The fluorescent resin was characterized by XRD, SEM and PL. The X-ray diffraction (XRD) patterns demonstrated that the fluorescent resin was pure Y3Al5O12 phase. The scanning electron microscopy (SEM) images showed that YAG phosphor was distributed evenly in the fluorescent resin. The excitation spectra had a weak peak at 342 nm and a strong band at 448 nm. The broad emission peaks at about 532 nm can be attributed to 5d-->4f transition of Ce3+ ions. Decay curves for the fluorescence of PC/YAG:Ce fluorescent resin show that the lifetime of the fluorescent resin was 61.5 ns. The luminous efficacy of the white LED packaged by the fluorescent resin and blue LED chip was 81.12 lm · W(-1) at 100 mA. All results above of PC/YAG:Ce fluorescent resin indicate a promising fluorescent material for white LEDs.

16.
Commun Biol ; 7(1): 1069, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215079

RESUMEN

Cellular senescence is widely acknowledged as having strong associations with cancer. However, the intricate relationships between cellular senescence-related (CSR) genes and cancer risk remain poorly explored, with insights on causality remaining elusive. In this study, Mendelian Randomization (MR) analyses were used to draw causal inferences from 866 CSR genes as exposures and summary statistics for 18 common cancers as outcomes. We focused on genetic variants affecting gene expression, DNA methylation, and protein expression quantitative trait loci (cis-eQTL, cis-mQTL, and cis-pQTL, respectively), which were strongly linked to CSR genes alterations. Variants were selected as instrumental variables (IVs) and analyzed for causality with cancer using both summary-data-based MR (SMR) and two-sample MR (TSMR) approaches. Bayesian colocalization was used to unravel potential regulatory mechanisms underpinning risk variants in cancer, and further validate the robustness of MR results. We identified five CSR genes (CNOT6, DNMT3B, MAP2K1, TBPL1, and SREBF1), 18 DNA methylation genes, and LAYN protein expression which were all causally associated with different cancer types. Beyond causality, a comprehensive analysis of gene function, pathways, and druggability values was also conducted. These findings provide a robust foundation for unravelling CSR genes molecular mechanisms and promoting clinical drug development for cancer.


Asunto(s)
Senescencia Celular , Metilación de ADN , Análisis de la Aleatorización Mendeliana , Neoplasias , Sitios de Carácter Cuantitativo , Humanos , Neoplasias/genética , Senescencia Celular/genética , Predisposición Genética a la Enfermedad , Teorema de Bayes
17.
Angiology ; 75(3): 219-230, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37658802

RESUMEN

Liver fibrosis scores have been demonstrated to be associated with poor prognosis after percutaneous coronary intervention (PCI). However, no studies have compared the prognostic value of these scores in acute myocardial infarction (AMI) patients with and without diabetes. We retrospectively enrolled 1576 AMI patients who underwent PCI. There were 177 all-cause deaths and 111 cardiac deaths during follow-up (median 3.8 years). The non-alcoholic fatty liver disease fibrosis score (NFS) showed a better prognostic value than the fibrosis-8 (FIB-8) score (Harrell's C-index: 0.703 vs 0.671, P = .014) and the fibrosis-4 (FIB-4) score (Harrell's C-index: 0.703 vs 0.648, P < .001) in the overall population. In the time-dependent receiver operating characteristic analysis, the NFS also had the highest area under the curve across all time points. Consistent results were observed in diabetic and non-diabetic populations. Adding the NFS to traditional cardiovascular risk factors significantly improved the prediction both for all-cause mortality (Harrell's C-index: 0.806 vs 0.771, P < .001) and cardiac death (Harrell's C-index: 0.800 vs 0.771, P = .014). The NFS showed a better prognostic value than the FIB-8 score and the FIB-4 score in patients with AMI undergoing PCI, which might be preferable for estimating the risk of mortality regardless of the presence or absence of diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Enfermedad del Hígado Graso no Alcohólico , Intervención Coronaria Percutánea , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Pronóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia
18.
Biomed Pharmacother ; 175: 116790, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38776677

RESUMEN

Diabetic cardiomyopathy (DCM) is a cardiac microvascular complication caused by metabolic disorders. It is characterized by myocardial remodeling and dysfunction. The pathogenesis of DCM is associated with abnormal cellular metabolism and organelle accumulation. Autophagy is thought to play a key role in the diabetic heart, and a growing body of research suggests that modulating autophagy may be a potential therapeutic strategy for DCM. Here, we have summarized the major signaling pathways involved in the regulation of autophagy in DCM, including Adenosine 5'-monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), Forkhead box subfamily O proteins (FOXOs), Sirtuins (SIRTs), and PTEN-inducible kinase 1 (PINK1)/Parkin. Given the significant role of autophagy in DCM, we further identified natural products and chemical drugs as regulators of autophagy in the treatment of DCM. This review may help to better understand the autophagy mechanism of drugs for DCM and promote their clinical application.


Asunto(s)
Autofagia , Cardiomiopatías Diabéticas , Transducción de Señal , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Humanos , Autofagia/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacos
19.
Clin Appl Thromb Hemost ; 30: 10760296241266607, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39129349

RESUMEN

The model for end-stage liver disease (MELD) and the model for end-stage liver disease excluding international normalized ratio (INR) (MELD-XI) scores, which reflect dysfunction of liver and kidneys, have been reported to be related to the prognosis of patients with right-sided "backward" failure. However, the relationship between the MELD/MELD-XI score and the in-hospital adverse events in pulmonary embolism (PE) patients was unknown. Normotensive PE patients were retrospectively enrolled at China-Japan friendship hospital from January 2017 to February 2020. The primary outcome was defined as death and clinical deterioration during hospitalization. Multivariate logistic analysis was used to explore the association between the MELD and MELD-XI scores for in-hospital adverse events. We also compared the accuracy of the MELD, MELD-XI, and the pulmonary embolism severity index (PESI) score using the time-dependent receiver operating characteristic curve and corresponding areas under the curve (AUC). A total of 222 PE patients were analyzed. Logistic regression analysis showed that the MELD score was independently associated with in-hospital adverse events (odds ratio = 1.115, 95% confidential interval = 1.022-1.217, P = .014). The MELD score has an AUC of 0.731 and was better than PESI (AUC of 0.629) in predicting in-hospital adverse events. Among PE patients with normal blood pressure on admission, the MELD score was associated with increased in-hospital adverse events.


Asunto(s)
Embolia Pulmonar , Humanos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Valor Predictivo de las Pruebas , Pronóstico , Enfermedad Aguda
20.
Diabetes Res Clin Pract ; 209: 111595, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38408613

RESUMEN

AIMS: Variability of metabolic parameters, such as glycemic variability (GV) and systolic blood pressure variability (SBPV), are associated with adverse cardiovascular outcomes. However, whether these parameters have additive effects on mortality in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU) remains unclear. METHODS: We retrospectively enrolled patients with CAD from the Medical Information Mart for Intensive Care-IV database. The highest tertile of variability was defined as high variability. A variability scoring system was established, which assigned 0 points to tertile 1, 1 point to tertile 2, and 2 points to tertile 3 for GV and SBPV. RESULTS: Among 4237 patients with CAD, 400 patients died in hospital, and 967 patients died during 1-year follow-up. High GV and high SBPV were associated with an increased risk of mortality. The effects of GV and SBPV on in-hospital mortality were partially mediated by ventricular arrhythmias (18.0 % and 6.6 %, respectively). The risk of mortality gradually increased with the number of high-variability parameters and increasing variability scores. CONCLUSIONS: GV and SBPV have additive effects on the risk of mortality in patients with CAD hospitalized in the ICU. Ventricular arrhythmias partially mediate the effects of GV and SBPV on in-hospital mortality.


Asunto(s)
Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Presión Sanguínea/fisiología , Glucemia , Estudios Retrospectivos , Mortalidad Hospitalaria
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