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1.
Cell ; 153(4): 773-84, 2013 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-23663777

RESUMEN

5-methylcytosine is a major epigenetic modification that is sometimes called "the fifth nucleotide." However, our knowledge of how offspring inherit the DNA methylome from parents is limited. We generated nine single-base resolution DNA methylomes, including zebrafish gametes and early embryos. The oocyte methylome is significantly hypomethylated compared to sperm. Strikingly, the paternal DNA methylation pattern is maintained throughout early embryogenesis. The maternal DNA methylation pattern is maintained until the 16-cell stage. Then, the oocyte methylome is gradually discarded through cell division and is progressively reprogrammed to a pattern similar to that of the sperm methylome. The passive demethylation rate and the de novo methylation rate are similar in the maternal DNA. By the midblastula stage, the embryo's methylome is virtually identical to the sperm methylome. Moreover, inheritance of the sperm methylome facilitates the epigenetic regulation of embryogenesis. Therefore, besides DNA sequences, sperm DNA methylome is also inherited in zebrafish early embryos.


Asunto(s)
Metilación de ADN , Embrión no Mamífero/metabolismo , Oocitos/metabolismo , Espermatozoides/metabolismo , Pez Cebra/embriología , Pez Cebra/genética , 5-Metilcitosina/análisis , Animales , Epigénesis Genética , Femenino , Células Germinativas/metabolismo , Masculino , Pez Cebra/metabolismo
2.
Nat Mater ; 23(3): 331-338, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37537355

RESUMEN

The properties of two-dimensional (2D) van der Waals materials can be tuned through nanostructuring or controlled layer stacking, where interlayer hybridization induces exotic electronic states and transport phenomena. Here we describe a viable approach and underlying mechanism for the assisted self-assembly of twisted layer graphene. The process, which can be implemented in standard chemical vapour deposition growth, is best described by analogy to origami and kirigami with paper. It involves the controlled induction of wrinkle formation in single-layer graphene with subsequent wrinkle folding, tearing and re-growth. Inherent to the process is the formation of intertwined graphene spirals and conversion of the chiral angle of 1D wrinkles into a 2D twist angle of a 3D superlattice. The approach can be extended to other foldable 2D materials and facilitates the production of miniaturized electronic components, including capacitors, resistors, inductors and superconductors.

3.
BMC Bioinformatics ; 25(1): 41, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267858

RESUMEN

BACKGROUND: With the development of single-cell technology, many cell traits can be measured. Furthermore, the multi-omics profiling technology could jointly measure two or more traits in a single cell simultaneously. In order to process the various data accumulated rapidly, computational methods for multimodal data integration are needed. RESULTS: Here, we present inClust+, a deep generative framework for the multi-omics. It's built on previous inClust that is specific for transcriptome data, and augmented with two mask modules designed for multimodal data processing: an input-mask module in front of the encoder and an output-mask module behind the decoder. InClust+ was first used to integrate scRNA-seq and MERFISH data from similar cell populations, and to impute MERFISH data based on scRNA-seq data. Then, inClust+ was shown to have the capability to integrate the multimodal data (e.g. tri-modal data with gene expression, chromatin accessibility and protein abundance) with batch effect. Finally, inClust+ was used to integrate an unlabeled monomodal scRNA-seq dataset and two labeled multimodal CITE-seq datasets, transfer labels from CITE-seq datasets to scRNA-seq dataset, and generate the missing modality of protein abundance in monomodal scRNA-seq data. In the above examples, the performance of inClust+ is better than or comparable to the most recent tools in the corresponding task. CONCLUSIONS: The inClust+ is a suitable framework for handling multimodal data. Meanwhile, the successful implementation of mask in inClust+ means that it can be applied to other deep learning methods with similar encoder-decoder architecture to broaden the application scope of these models.


Asunto(s)
Cromatina , Transcriptoma , Fenotipo
4.
J Biol Chem ; 299(3): 103000, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36764522

RESUMEN

Microbially derived, protein-based biopesticides offer a more sustainable pest management alternative to synthetic pesticides. Vegetative insecticidal proteins (Vip3), multidomain proteins secreted by Bacillus thuringiensis, represent a second-generation insecticidal toxin that has been preliminarily used in transgenic crops. However, the molecular mechanism underlying Vip3's toxicity is poorly understood. Here, we determine the distinct functions and contributions of the domains of the Vip3Aa protein to its toxicity against Spodoptera frugiperda larvae. We demonstrate that Vip3Aa domains II and III (DII-DIII) bind the midgut epithelium, while DI is essential for Vip3Aa's stability and toxicity inside the protease-enriched host insect midgut. DI-DIII can be activated by midgut proteases and exhibits cytotoxicity similar to full-length Vip3Aa. In addition, we determine that DV can bind the peritrophic matrix via its glycan-binding activity, which contributes to Vip3Aa insecticidal activity. In summary, this study provides multiple insights into Vip3Aa's mode-of-action which should significantly facilitate the clarification of its insecticidal mechanism and its further rational development.


Asunto(s)
Bacillus thuringiensis , Insecticidas , Animales , Bacillus thuringiensis/química , Insecticidas/química , Proteínas Bacterianas/metabolismo , Péptido Hidrolasas/metabolismo , Larva/metabolismo , Spodoptera/metabolismo , Control Biológico de Vectores
5.
J Biol Chem ; 299(8): 104964, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37364687

RESUMEN

The epithelium of the pulmonary airway is composed of several distinct cell types that differentiate from common progenitor cells to provide defense against environmental insults. Epigenetic mechanisms regulating lineage differentiation of airway epithelial progenitors remain poorly understood. Protein arginine methyltransferase 5 (Prmt5) is a predominant type II arginine methyltransferase that methylates >85% of symmetric arginine residues. Here, we provide evidence for the function of Prmt5 in promoting ciliated cell fate specification of airway epithelial progenitors. We show that lung epithelial-specific deletion of Prmt5 resulted in a complete loss of ciliated cells, an increased number of basal cells, and ecotopic-expressed Tp63-Krt5+ putative cells in the proximal airway. We further identified that transcription factor Tp63 is a direct target of Prmt5, and Prmt5 inhibited Tp63 transcription expression through H4R3 symmetric dimethylation (H4R3sme2). Moreover, inhibition of Tp63 expression in Prmt5-deficient tracheal progenitors could partially restore the ciliated cell deficient phenotype. Together, our data support a model where Prmt5-mediated H4R3sme2 represses Tp63 expression to promote ciliated cell fate specification of airway progenitors.


Asunto(s)
Regulación de la Expresión Génica , Factores de Transcripción , Animales , Humanos , Ratones , Diferenciación Celular , Línea Celular Tumoral , Pulmón/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Factores de Transcripción/metabolismo , Ratones Endogámicos C57BL
6.
N Engl J Med ; 385(14): 1268-1279, 2021 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-34491661

RESUMEN

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).


Asunto(s)
Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Hipertensión/complicaciones , Hipotensión/inducido químicamente , Incidencia , Masculino , Persona de Mediana Edad , Nivel de Atención , Sístole
7.
Anal Chem ; 96(1): 67-75, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38153001

RESUMEN

Origins of pH effects on the kinetics of electrocatalytic reactions involving the transfer of both protons and electrons, including the hydrogen evolution reaction (HER) considered in this study, are heatedly debated. By taking the HER at Au(111) in acid solutions of different pHs and ionic concentrations as the model systems, herein, we report how to derive the intrinsic kinetic parameters of such reactions and their pH dependence through the measurement of j-E curves and the corresponding kinetic simulation based on the Frumkin-Butler-Volmer theory and the modified Poisson-Nernst-Planck equation. Our study reveals the following: (i) the same set of kinetic parameters, such as the standard activation Gibbs free energy, charge transfer coefficient, and Gibbs adsorption energy for Had at Au(111), can simulate well all the j-E curves measured in solutions with different pH and temperatures; (ii) on the reversible hydrogen electrode scale, the intrinsic rate constant increases with the increase of pH, which is in contrast with the decrease of the HER current with the increase of pH; and (iii) the ratio of the rate constants for HER at Au(111) in x M HClO4 + (0.1 - x) M NaClO4 (pH ≤ 3) deduced before properly correcting the electric double layer (EDL) effects to the ones estimated with EDL correction is in the range of ca. 10 to 40, and even in a solution of x M HClO4 + (1 - x) M NaClO4 (pH ≤ 2) there is a difference of ca. 5× in the rate constants without and with EDL correction. The importance of proper correction of the EDL effects as well as several other important factors on unveiling the intrinsic pH-dependent reaction kinetics are discussed to help converge our analysis of pH effects in electrocatalysis.

8.
Small ; 20(3): e2304327, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37699748

RESUMEN

Flexible composite films have attracted considerable attention due to great potential for healthcare, telecommunication, and aerospace. However, it is still challenging to achieve high conductivity and multifunctional integration, mainly due to poorly designed composite structures of these films. Herein, a novel sandwich-structured assembly strategy is proposed to fabricate flexible composite thin films made of Ag nanowire (AgNW) core and MXene layers by combination of spray coating and vacuum filtration process. In this case, ultrathin MXene layers play crucial roles in constructing compact composite structures strongly anchored to substrate with extensive hydrogen-bonding interactions. The resultant sandwich-structured MXene/AgNW composite thin films (SMAFs) exhibit ultrahigh electrical conductivity (up to 27193 S cm-1 ), resulting in exceptional electromagnetic interference shielding effectiveness of 16 223.3 dB cm2 g-1 and impressive Joule heating performance with rapid heating rate of 10.4 °C s-1 . Moreover, the uniform SMAFs can also be facilely cut into kirigami-patterned interconnects, which indicate superior strain-insensitive conductance even after long-term exposure to extreme temperatures. The demonstrated strategy offers a significant paradigm to construct multifunctional composite thin films for next-generation integrated flexible electronics with practical applications.

9.
Small ; 20(5): e2305511, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37726230

RESUMEN

Microorganisms have attracted much attention to act as biotemplates for fabricating micro/nanostructured functional particles. However, it is still challenging to produce tunable hierarchical particles based on microorganisms with intricate architectures and superior stability. Herein, a novel strategy is developed to fabricate biohybrid urchin-like magnetic ZnO microspheres based on Chlorella (Ch.) with tunable hierarchical core-shell structures. Using Ch. cells as microspherical templates, Fe3 O4 nanoparticles and ZnO nanorod (NR) arrays are deposited in sequence to form the final biohybrid heterostructure microspheres (Ch.@Fe3 O4 @ZnO NRs). Ordered growth and structural regulation of 3D ZnO NR arrays are achieved via a facile and controllable manner. Compared with the prepared microspheres with diverse structure configurations of ZnO shells, the Ch.@Fe3 O4 @ZnO NRs possess excellent light absorption and photoelectrocatalysis performance toward tetracycline degradation (normalized apparent rate constant, k = 366.3 h-1 g-1 ), which is significantly larger than that of ZnO nanoflower/nanoparticle loaded types. It also proves that the synergistic enhancement of well-oriented ZnO NR arrays, heterojunction structures, and biomass features is the fundamental reason for outstanding photoelectrocatalytic activity. Due to the remarkable stability and versatility, this work provides abundant opportunities to construct biohybrid multilevel micro/nanostructures with significant potentials for practical applications.

10.
Plant Physiol ; 193(2): 1126-1141, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37350495

RESUMEN

Transfer RNA (tRNA) can produce smaller RNA fragments called tRNA-derived fragments (tRFs). tRFs play critical roles in multiple cellular programs, although the functional mechanisms of tRFs remain largely unknown in plants. In this study, we examined the phenotype associated with 5' tRF-Ala (tRF-Ala, produced from tRNA-Ala) overexpression and knockdown lines (tDR-Ala-OE and tDR-Ala-kd, respectively) and the mechanisms by which tRF-Ala affects mRNA levels in Arabidopsis (Arabidopsis thaliana). We investigated the candidate proteins associated with tRF-Ala by quantitative proteomics and confirmed the direct interaction between tRF-Ala and the splicing factor SERINE-ARGININE RICH PROTEIN 34 (SR34). A transcriptome sequencing analysis showed that 318 genes among all the genes (786) with substantial alternative splicing (AS) variance in tDR-Ala-OE lines are targets of SR34. tRF-Ala diminished the binding affinity between SR34 and its targets by direct competition for interaction with SR34. These findings reveal the critical roles of tRF-Ala in regulating mRNA levels and splicing.


Asunto(s)
Arabidopsis , ARN de Transferencia , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , ARN/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Expresión Génica
11.
Toxicol Appl Pharmacol ; 489: 117007, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901695

RESUMEN

We are facing a rapidly growing geriatric population (65+) that will live for multiple decades and are challenged with environmental pollution far exceeding that of previous generations. Consequently, we currently have a poor understanding of how environmental pollution will impact geriatric health distinctly from younger populations. Few toxicology studies have considered age differences with geriatric individuals. Critically, all top ten most prevalent age-related diseases are linked to metal exposures. Hexavalent chromium [Cr(VI)] is a metal of major environmental health concern that can induce aging phenotypes and neurotoxicity. However, there are many knowledge gaps for Cr(VI) neurotoxicity, including how Cr(VI) impacts behavior. To address this, we exposed male rats across three ages (3-, 7-, and 18-months old) to Cr(VI) in drinking water (0, 0.05, 0.1 mg/L) for 90 days. These levels reflect the maximum contaminant levels determined by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (US EPA). Here, we report how these Cr(VI) drinking water levels impacted rat behaviors using a battery of behavior tests, including grip strength, open field assay, elevated plus maze, Y-maze, and 3-chamber assay. We observed adult rats were the most affected age group and memory assays (spatial and social) exhibited the most significant effects. Critically, the significant effects were surprising as rats should be particularly resistant to these Cr(VI) drinking water levels due to the adjustments applied in risk assessment from rodent studies to human safety, and because rats endogenously synthesize vitamin C in their livers (vitamin C is a primary reducer of Cr[VI] to Cr[III]). Our results emphasize the need to broaden the scope of toxicology research to consider multiple life stages and suggest the current regulations for Cr(VI) in drinking water need to be revisited.


Asunto(s)
Envejecimiento , Conducta Animal , Cromo , Animales , Cromo/toxicidad , Masculino , Conducta Animal/efectos de los fármacos , Ratas , Síndromes de Neurotoxicidad/etiología , Aprendizaje por Laberinto/efectos de los fármacos , Factores de Edad , Agua Potable , Contaminantes Químicos del Agua/toxicidad
12.
Biotechnol Bioeng ; 121(5): 1642-1658, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38381097

RESUMEN

Bacillus licheniformis formulations are effective for environmental remediation, gut microbiota modulation, and soil improvement. An adequate spore quantity is crucial for the activity of B. licheniformis formulations. This study investigated the synergistic effects of carbon/nitrogen source consumption and concentration on B. licheniformis BF-002 cultivation, with the aim of developing an automatic co-feeding strategy to enhance spore production. Initial glucose (10 g/L) and amino nitrogen (1.5 g/L) concentrations promote cell growth, followed by reduced glucose (2.0 g/L) and amino nitrogen (0.5 g/L) concentrations for sustained spore generation. The spore quantity reached 2.59 × 1010 CFU/mL. An automatic co-feeding strategy was developed and implemented in 5 and 50 L cultivations, resulting in spore quantities of 2.35 × 1010 and 2.86 × 1010 CFU/mL, respectively, improving by 6.81% and 30.00% compared to that with a fixed glucose concentration (10.0 g/L). The culture broth obtained at both the 5 and 50 L scales was spray-dried, resulting in bacterial powder with cell viability rates of 85.94% and 82.68%, respectively. Even after exposure to harsh conditions involving high temperature and humidity, cell viability remained at 72.80% and 69.89%, respectively. Employing the automatic co-feeding strategy increased the transcription levels of the spore formation-related genes spo0A, spoIIGA, bofA, and spoIV by 7.42%, 8.46%, 8.87%, and 9.79%, respectively. The proposed strategy effectively promoted Bacillus growth and spore formation, thereby enhancing the quality of B. licheniformis formulations.


Asunto(s)
Bacillus licheniformis , Bacillus , Carbono , Nitrógeno , Esporas Bacterianas , Bacillus/genética , Bacillus licheniformis/genética , Glucosa
13.
Clin Chem Lab Med ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38687473

RESUMEN

OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

14.
Surg Endosc ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981881

RESUMEN

BACKGROUND: Laparoscopic distal gastrectomy (LDG) has become a common procedure for treating advanced gastric cancer (AGC) in China. However, there is uncertainty regarding its oncological outcomes compared to open distal gastrectomy (ODG). This study aims to compare the 3-year disease-free survival (DFS) rates among patients who underwent surgery for AGC in northern China. METHODS: A multicenter, non-inferiority, open-label, parallel, randomized clinical trial was conducted to evaluate patients with AGC who were eligible for distal gastrectomy at five tertiary hospitals in North China. In this trial, patients were randomly assigned preoperatively to receive either LDG or ODG in a 1:1 allocation ratio. The primary endpoint was postoperative morbidity and mortality within 30 days and the secondary endpoint was the 3-year DFS rate. This trial has been registered at ClinicalTrials.gov (Identifier: NCT02464215). RESULTS: A total of 446 patients were randomly allocated to LDG (n = 223) or ODG group (n = 223) between March 2014 and August 2017. After screening, a total of 214 patients underwent the open surgical approach, while 216 patients underwent laparoscopic surgery. The 3-year DFS rate was 85.9% for the LDG group and 84.72% for the ODG group, with no significant statistical difference (Hazard ratio 1.12; 95% CI 0.68-1.84, P = 0.65). Body mass index (BMI) < 25 kg/m2, advanced pathologic T4, and pathologic N2-3 category were confirmed as independent risk factors for DFS in the Cox regression. CONCLUSIONS: In comparison to ODG, LDG with D2 lymphadenectomy yielded similar outcomes in terms of 3-year DFS rates among patients diagnosed with AGC.

15.
Pathol Int ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940569

RESUMEN

Exosomes from cancer cells function as carriers to spread or transport specific microRNAs (miRNAs) to distant sites to exert their effects, but the mechanism of exosomal miRNA action in esophageal squamous cell carcinoma (ESCC) has not been fully explained. Therefore, in this study, we were interested in the impact of exosomal miR-196a-5p in ESCC progression. We found that miR-196a-5p was expressed enriched in clinical tissues, ESCC cells, and exosomes. Functionally, depletion of miR-196a-5p impeded ESCC cell growth, migration, and invasion, whereas overexpression of miR-196a-5p produced the opposite results. Moreover, enhancement of exosomal miR-196a-5p in recipient ESCC cells triggered more intense proliferation and migration. Mechanistically, we identified integral membrane protein 2B (ITM2B) as a direct target of miR-196a-5p. Silencing of ITM2B partially counteracted the inhibitory effect of miR-196a-5p inhibitors on the malignant phenotype of ESCC. Furthermore, in vivo, lower miR-196a-5p levels triggered by the introduction of antagomiR-196a-5p resulted in the generation of smaller volume and weight xenograft tumors. Thus, our results demonstrated novel mechanisms of exosomal and intracellular miR-196a-5p-mediated ESCC growth and migration and identify the interaction of miR-196a-5p with ITM2B. These works might provide new targets and basis for the development of clinical treatment options for ESCC.

16.
Mediators Inflamm ; 2024: 8360538, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549715

RESUMEN

Objective: The association between vitamin D status and inflammation remains unclear in hospitalized patients. Materials and Methods: We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (<12 ng/mL), insufficiency (12-20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. Results: A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m2, respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 109/mL (95% CI: 0.2 × 109/mL, 0.06 × 109/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. Conclusions: The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.


Asunto(s)
Deficiencia de Vitamina D , Masculino , Adulto , Humanos , Femenino , Estudios Transversales , Polipéptido alfa Relacionado con Calcitonina , Vitamina D , Biomarcadores , Proteína C-Reactiva/metabolismo , Inflamación
17.
Biomed Chromatogr ; 38(6): e5855, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38442715

RESUMEN

Metabolite profiling has the potential to comprehensively bridge phenotypes and complex heterogeneous physiological and pathological states. We performed a metabolomics study using parallel liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis to screen for biomarkers of primary aldosteronism (PA) from a cohort of 111 PA patients and 218 primary hypertension (PH) patients. Hydrophilic interaction chromatography and reversed-phase liquid chromatography separations were employed to obtain a global plasma metabolome of endogenous metabolites. The satisfactory classification between PA and PH patients was obtained using the MVDA model. A total of 35 differential metabolites were screened out and identified. A diagnostic biomarker panel was established using the least absolute shrinkage and selection operator (LASSO) binary logistic regression model and receiver operating characteristic analysis. Joint analysis with clinical indicators, including plasma supine aldosterone level, plasma orthostatic aldosterone level, body mass index, and blood potassium, revealed that the combination of metabolite biomarker panel and plasma supine aldosterone has the best clinical diagnostic efficacy.


Asunto(s)
Biomarcadores , Hiperaldosteronismo , Espectrometría de Masas , Metabolómica , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Metabolómica/métodos , Biomarcadores/sangre , Femenino , Persona de Mediana Edad , Masculino , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos , Metaboloma/fisiología , Adulto , Aldosterona/sangre , Cromatografía Líquida con Espectrometría de Masas
18.
BMC Biol ; 21(1): 83, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-37061721

RESUMEN

Breathing is a singularly robust behavior, yet this motor pattern is continuously modulated at slow and fast timescales to maintain blood-gas homeostasis, while intercalating orofacial behaviors. This functional multiplexing goes beyond the rhythmogenic function that is typically ascribed to medullary respiration-modulated networks and may explain lack of progress in identifying the mechanism and constituents of the respiratory rhythm generator. By recording optically along the ventral respiratory column in medulla, we found convergent evidence that rhythmogenic function is distributed over a dispersed and heterogeneous network that is synchronized by electrotonic coupling across a neuronal syncytium. First, high-speed recordings revealed that inspiratory onset occurred synchronously along the column and did not emanate from a rhythmogenic core. Second, following synaptic isolation, synchronized stationary rhythmic activity was detected along the column. This activity was attenuated following gap junction blockade and was silenced by tetrodotoxin. The layering of syncytial and synaptic coupling complicates identification of rhythmogenic mechanism, while enabling functional multiplexing.


Asunto(s)
Bulbo Raquídeo , Neuronas , Ratones , Animales , Bulbo Raquídeo/fisiología , Neuronas/fisiología , Respiración
19.
Sensors (Basel) ; 24(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38203120

RESUMEN

Systematically and comprehensively enhancing road traffic safety using artificial intelligence (AI) is of paramount importance, and it is gradually becoming a crucial framework in smart cities. Within this context of heightened attention, we propose to utilize machine learning (ML) to optimize and ameliorate pedestrian crossing predictions in intelligent transportation systems, where the crossing process is vital to pedestrian crossing behavior. Compared with traditional analytical models, the application of OpenCV image recognition and machine learning methods can analyze the mechanisms of pedestrian crossing behaviors with greater accuracy, thereby more precisely judging and simulating pedestrian violations in crossing. Authentic pedestrian crossing behavior data were extracted from signalized intersection scenarios in Chinese cities, and several machine learning models, including decision trees, multilayer perceptrons, Bayesian algorithms, and support vector machines, were trained and tested. In comparing the various models, the results indicate that the support vector machine (SVM) model exhibited optimal accuracy in predicting pedestrian crossing probabilities and speeds, and it can be applied in pedestrian crossing prediction and traffic simulation systems in intelligent transportation.

20.
Nano Lett ; 23(23): 10939-10945, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-37976291

RESUMEN

Two-dimensional (2D) materials hold great promise for future complementary metal-oxide semiconductor (CMOS) technology. However, the lack of effective methods to tune the Schottky barrier poses a challenge in constructing high-performance complementary circuits from the same material. Here, we reveal that the polarity of pristine MoTe2 field-effect transistors (FETs) with minimized air exposure is n-type, irrespective of the metal contact type. The fabricated n-FETs with palladium contact can reach electron currents up to 275 µA/µm at VDS = 2 V. For p-FETs, we introduce a novel nitric oxide doping strategy, allowing a controlled transition of MoTe2 FETs from n-type to unipolar p-type. By doping only in the contact region, we demonstrate hole currents up to 170 µA/µm at VDS= -2 V with preserved Ion/Ioff ratios of 105. Finally, we present a complementary inverter circuit comprising the high-performance n- and p-type FETs based on MoTe2, promoting the application of 2D materials in future electronic systems.

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