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1.
Acta Biochim Biophys Sin (Shanghai) ; 56(8): 1145-1155, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39099413

RESUMEN

Glycosylation, a crucial posttranslational modification, plays a significant role in numerous physiological and pathological processes. Lectin microarrays, which leverage the high specificity of lectins for sugar binding, are ideally suited for profiling the glycan spectra of diverse and complex biological samples. In this review, we explore the evolution of lectin detection technologies, as well as the applications and challenges of lectin microarrays in analyzing the glycome profiles of various clinical samples, including serum, saliva, tissues, sperm, and urine. This review not only emphasizes significant advancements in the high-throughput analysis of polysaccharides but also provides insight into the potential of lectin microarrays for diagnosing and managing diseases such as tumors, autoimmune diseases, and chronic inflammation. We aim to provide a clear, concise, and comprehensive overview of the use of lectin microarrays in clinical settings, thereby assisting researchers in conducting clinical studies in glycobiology.


Asunto(s)
Glicómica , Lectinas , Polisacáridos , Humanos , Lectinas/metabolismo , Lectinas/química , Polisacáridos/metabolismo , Polisacáridos/análisis , Glicómica/métodos , Análisis por Micromatrices/métodos , Glicosilación , Neoplasias/metabolismo , Neoplasias/diagnóstico , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/diagnóstico
2.
Front Nutr ; 11: 1399390, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149545

RESUMEN

Introduction: In Northeast China, Dorper and Australian White rams are commonly crossbred with small-tailed Han (STH) ewes to improve the offspring's meat yield and quality. However, the differences in traits and the flavor between the crossbred sheep and STH sheep remain unclear. In addition, the candidate genes potentially influencing the meat quality in the three sheep breeds require further verification. Methods: A total of 18 2-month-old healthy rams were raised over a period of 5 months, which included 6 STH, 6 Dorper and small-tailed Han crossbred (Do × STH), and 6 Australian white and small-tailed Han crossbred (Au × STH) offspring. The differences in slaughter, meat quality traits, fatty acid and amino acid composition in the muscular longissimus dorsi (MLD), and volatile compounds in the semitendinosus muscle were compared between the sheep breeds. The candidate genes related to intramuscular fat (IMF) content and fatty acids were validated. Results: The results of this study revealed that the crossbred sheep had higher body weight, carcass weight, bone weight, net meat weight, and IMF content than the STH sheep (p < 0.05). The Do × STH offspring had a higher pH value (24 h), moisture content, and cooking percentage; they also had redder and brighter meat color. The content of myristate, palmitic, and margaric acids in the crossbred sheep was higher than that in the STH sheep (p < 0.05). The Do × STH offspring had the highest saturated fatty acid content (p < 0.05). The Au × STH offspring had the highest protein content (p < 0.05). The arachidonic acid and amino acid (Asp, Ala, Ile, Leu, Lys, Thr, and essential amino acid) contents were higher in the STH sheep than in the crossbred sheep (p < 0.05). The odor activity value (OAV) analysis showed that most of the aldehydes in the Au × STH offspring had higher values. The PDK4 gene expression was positively associated with the IMF content and was negatively correlated with the linoleic acid content in the Do × STH sheep (p < 0.05). The TMEM273 gene expression was positively associated with linoleic and arachidonic acid contents and was negatively correlated with oleic and palmitic acid contents in the Do × STH sheep (p < 0.05). Discussion: The results showed the differences between the crossbred sheep and STH sheep and provided the candidate genes related to meat quality in sheep.

3.
JACS Au ; 4(8): 3205-3216, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39211596

RESUMEN

Accurate description of the static correlation poses a persistent challenge in electronic structure theory, particularly when it has to be concurrently considered with the dynamic correlation. We develop here a method in the generalized Kohn-Sham density functional theory (DFT) framework, named R-xDH7-SCC15, which achieves an unprecedented accuracy in capturing the static correlation, while maintaining a good description of the dynamic correlation on par with the state-of-the-art DFT and wave function theory methods, all grounded in the same single-reference black-box methodology. Central to R-xDH7-SCC15 is a general-purpose static correlation correction (SCC) model applied to the renormalized XYG3-type doubly hybrid method (R-xDH7). The SCC model development involves a hybrid machine learning strategy that integrates symbolic regression with nonlinear parameter optimization, aiming to achieve a balance between generalization capability, numerical accuracy, and interpretability. Extensive benchmark studies confirm the robustness and broad applicability of R-xDH7-SCC15 across a diverse array of main-group chemical scenarios. Notably, it displays exceptional aptitude in accurately characterizing intricate reaction kinetics and dynamic processes in regions distant from equilibrium, where the influence of static correlation is most profound. Its capability to consistently and efficiently predict the whole energy profiles, activation barriers, and reaction pathways within a user-friendly "black-box" framework represents an important advance in the field of electronic structure theory.

4.
Emerg Microbes Infect ; 13(1): 2387447, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39082740

RESUMEN

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2- to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.


Asunto(s)
Vacunas contra el Adenovirus , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Ratones Endogámicos BALB C , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Ratones , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas contra el Adenovirus/inmunología , Vacunas contra el Adenovirus/administración & dosificación , Femenino , Humanos , Inmunogenicidad Vacunal , Vacunación , Adenoviridae/genética , Adenoviridae/inmunología
5.
Angew Chem Int Ed Engl ; 63(40): e202410743, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38963024

RESUMEN

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

6.
Front Vet Sci ; 11: 1388532, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988981

RESUMEN

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn't impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

8.
Aquat Toxicol ; 272: 106967, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38833998

RESUMEN

Microplastics (MPs) are ubiquitous in aquatic environments, which can act as carriers to affect the bioavailability of heavy metals. The aging process in the environment changes the physicochemical properties of MPs, thereby affecting their environmental behavior and co-toxicity with other pollutants. However, relevant research is limited. In this study, we compared the properties and Cu2+ adsorption capacity of pristine and aged polytetrafluoroethylene (PTFE) MPs and further explored the influence on copper bioavailability and bio-effects on Microcystis aeruginosa. Aging process induced surface oxidation and cracks of PTFE MPs, and decreased the stability of MPs in water by increasing zeta potential. PTFE MPs had a strong adsorption capacity for Cu2+ and increased the bioavailability of copper to microalgae, which was not affected by the aging process. Pristine and aged PTFE MPs adhered to cyanobacterium surfaces and caused shrinkage and deformation of cells. Inhibition of cyanobacterium growth, photosynthesis and reduction of total antioxidant capacity were observed in the treatment of PTFE MPs. Combined exposure of pristine MPs and Cu2+ had stronger toxic effects to cyanobacterium, and increased Microcystin-LR release, which could cause harm to aquatic environment. Aging reduced the toxic effects of PTFE MPs on microalgae. Furthermore, soluble exopolysaccharide (EPS) content was significantly higher in co-exposure of aged MPs and Cu2+, which could reduce the toxicity to cyanobacterium cells. These results indicate that aging process alleviates the toxicity to microalgae and environmental risks caused by PTFE MPs. This study improves understanding of the combined toxicity of aged MPs and metals in freshwater ecosystems.


Asunto(s)
Disponibilidad Biológica , Cobre , Microcystis , Microplásticos , Politetrafluoroetileno , Contaminantes Químicos del Agua , Microcystis/efectos de los fármacos , Cobre/toxicidad , Contaminantes Químicos del Agua/toxicidad , Microplásticos/toxicidad , Politetrafluoroetileno/química , Politetrafluoroetileno/toxicidad , Rayos Ultravioleta , Adsorción , Microalgas/efectos de los fármacos
9.
Front Psychol ; 15: 1331425, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873500

RESUMEN

Background: Occupational commitment (OC) is a multidimensional construct that predicts turnover intentions. The interindividual variability of nurses' OC merits further exploration. Therefore, this study aims to examine patterns of OC and its relationship with psychological empowerment and job crafting in nurses. Methods: A sample of 1,061 nurses was recruited from February 2022 to April 2022 by using a stratified four-stage cluster sampling procedure. A self-report survey included the Psychological Empowerment Scale, Job Crafting Scale, and Occupational Commitment Scale. Latent profile analysis (LPA) was used to examine the patterns of OC. Associations of the latent class membership with individual characteristics, psychological empowerment and job crafting were examined using multinomial logistic regression. Results: Three patterns of OC were identified: (1) "Low OC group" (n = 224, 21.1%); (2) "Moderate OC group" (n = 665, 62.7%); (3) "High OC group" (n = 172, 16.2%). Nurses with higher education, fewer years of service, working in medicine, lower psychological empowerment and lower job crafting had a higher likelihood of belonging to Class 1 (Low OC group). In contrast, nurses working in emergency and with higher psychological empowerment and job crafting were more likely to belong to Class 3 (High OC group). Conclusion: The findings revealed the heterogeneity of occupational commitment among nurses in China and could guide the identification and early intervention of nurses with low level of occupational commitment.

10.
Org Lett ; 26(26): 5528-5533, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38901007

RESUMEN

This paper outlines an innovative three-component coupling strategy for the 1,4-difunctionalization of 1,3-butadiene, utilizing sodium decatungstate (NaDT) as a hydrogen atom transfer (HAT) photocatalyst. The photoinduced process efficiently generates homoallylic amino acid esters with 100% atom economy, employing readily available components under mild reaction conditions. This light-induced protocol eliminates the need for an additional transition metal catalysts, additives, or equivalent reducing agents. The study explored various C(sp3)-H bearing partners, butadienes, and α-iminoesters, demonstrating the versatility and synthetic utility of this method.

11.
Food Res Int ; 187: 114345, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763637

RESUMEN

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.


Asunto(s)
Chenopodium quinoa , Dieta Occidental , Fermentación , Microbioma Gastrointestinal , Hordeum , Lactobacillus , Ratas Sprague-Dawley , Animales , Hordeum/química , Masculino , Lactobacillus/metabolismo , Chenopodium quinoa/química , Ratas , Hígado/metabolismo , Disbiosis , Metabolómica , Alimentos Fermentados , Multiómica
12.
J Biomed Res ; 38(4): 397-412, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38807380

RESUMEN

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia (AML), the identification of biomarkers for prognostic assessment and therapeutic guidance is critical. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In the current study, we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas (TCGA) based on differential gene expression analysis and univariable Cox proportional hazards regression analysis. By using multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we constructed a 9-CSMs prognostic model for risk stratification of the AML patients. The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels. Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients. The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores. Notably, single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance. Furthermore, PI3K inhibitors were identified as potential treatments for these high-risk patients. In conclusion, we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

13.
Heliyon ; 10(9): e30131, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707430

RESUMEN

Utilizing city-level data from China, the paper employs a spatial econometric analysis to investigate the impact of fiscal decentralization on urban pollution. Empirical evidence indicates: (1) In the context of the emphasis of ecological civilization construction in China, an increase of fiscal autonomy for local governments is conducive to mitigating urban pollution intensity. Specifically, fiscal decentralization in one city not only promotes a reduction in local pollution intensity but alleviates environmental pollution problems in adjacent cities through spatial spillover effects. (2) Industrial structure upgrading and green technology progress become crucial measures for local governments to realize pollution reduction targets through fiscal expenditure. (3) Heterogeneity analysis reveals that the positive significance of decentralization is most prominent in the eastern China, while local governments with fiscal autonomy in central region tend to transfer pollution to neighboring cities. (4) There is a threshold characteristic for fiscal decentralization to promote a reduction in urban pollution intensity, and its marginal effect becomes more significant accompanied by continuous introduction of sophisticated foreign direct investment. Finally, the paper summarizes the potential significance of fiscal decentralization among Chinese local governments against the background of "Chinese-style decentralization" and proposes corresponding policy recommendations.

14.
Front Psychol ; 15: 1308863, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38659680

RESUMEN

Introduction: The mental health of university students is influenced by a variety of factors, including self-esteem and personality traits, with resilience playing a crucial role in mediating and moderating these relationships. This study investigates the intricate dynamics affecting mental well-being in Chinese university students, focusing on the roles of self-esteem, personality traits, and the interventional effects of resilience. Methods: A cross-sectional survey was conducted with 689 students, aged on average 20.3 years, between April and July 2022. The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) was used to assess mental well-being, while resilience, personality traits, and self-esteem were evaluated using the revised Connor-Davidson Resilience Scale (CD-RISC), the Chinese version of the Big Five Inventory-2 (BFI-2), and the Texas Social Behavior Inventory (TSBI), respectively. Results: Analysis revealed significant correlations between self-esteem, personality traits, and both resilience and mental well-being. Resilience was found to partially mediate the relationship between self-esteem and mental well-being and fully mediate certain aspects of the relationship between personality traits and mental well-being. Additionally, tenacity and autonomy were identified as moderators in the link between specific personality traits and mental well-being. Discussion: The findings highlight the complex interplay between self-esteem, personality traits, resilience, and mental well-being, underscoring the critical role of resilience. This insight is pivotal for developing targeted interventions to bolster mental well-being among university students, emphasizing the need for multifaceted support strategies to enhance student mental health.

15.
J Am Chem Soc ; 146(17): 12053-12062, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38622809

RESUMEN

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

16.
Clin Epigenetics ; 16(1): 48, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38528641

RESUMEN

BACKGROUND: miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. METHODS: To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. RESULTS: miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. CONCLUSIONS: Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.


Asunto(s)
Antineoplásicos , MicroARNs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adulto , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Metilación de ADN/genética , Linfocitos/metabolismo , Ratones Noqueados , MicroARNs/genética , MicroARNs/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Sulfonamidas/uso terapéutico , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo
17.
Commun Biol ; 7(1): 280, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38448784

RESUMEN

X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.


Asunto(s)
Investigación , Tomografía Computarizada por Rayos X , Rayos X , Radiografía , Imagen Óptica
18.
Heliyon ; 10(5): e27417, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486755

RESUMEN

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

19.
J Phys Chem A ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477590

RESUMEN

Zero-dimensional kinetic modeling of atmospheric pressure Ar-N2-H2 nonthermal plasma was carried out to gain mechanistic insights into plasma-assisted catalytic synthesis of ammonia. Ar dilution is a common technique for tailoring plasma discharge properties and has been shown to enhance NH3 formation when added to N2-H2 plasma. The kinetic model was developed for a coaxial dielectric barrier discharge quartz wool-packed bed reactor operating at near room temperature using a kHz-frequency plasma source. With 30% Ar mixed in a 1:1 N2-H2 plasma at 760 Torr, we find that NH3 production is dominated by Eley-Rideal (E-R) surface reactions, which heavily involve surface NHx species derived from N and H radicals in the gas phase, while the influence of excited N2 molecules is negligible. This is contrary to the commonly proposed mechanism that excited N2 molecules created by Penning excitation of N2 by Ar(4s) and Ar(4p) play a significant role in assisting NH3 formation. Our model shows that the enhanced NH3 formation upon Ar dilution is unlikely due to the interactions between Ar and H species, as excited Ar atoms have a weak effect on H radical formation through H2 dissociation compared to electrons. We find that excited Ar atoms contribute to 28% of the N radical production in the gas phase via N2 dissociation, while the rest are dominated by electron-impact dissociation. Furthermore, Ar species play a negligible role in the product NH3 dissociation. N2 conversion sensitivity analyses were carried out for electron number density (ne) and reduced electric field (E/N), and contributions from Ar to gas-phase N radical production were quantified. The model can provide guidance on potential reasons for observing enhanced NH3 formation upon Ar dilution in N2-H2 plasma beyond changes in the discharge characteristics.

20.
J Assist Reprod Genet ; 41(3): 591-608, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38315418

RESUMEN

Precise extravillous trophoblast (EVT) invasion is crucial for successful placentation and pregnancy. This review focuses on elucidating the mechanisms that promote heightened EVT invasion. We comprehensively summarize the pivotal roles of hormones, angiogenesis, hypoxia, stress, the extracellular matrix microenvironment, epithelial-to-mesenchymal transition (EMT), immunity, inflammation, programmed cell death, epigenetic modifications, and microbiota in facilitating EVT invasion. The molecular mechanisms underlying enhanced EVT invasion may provide valuable insights into potential pathogenic mechanisms associated with diseases characterized by excessive invasion, such as the placenta accreta spectrum (PAS), thereby offering novel perspectives for managing pregnancy complications related to deficient EVT invasion.


Asunto(s)
Trofoblastos Extravellosos , Trofoblastos , Embarazo , Femenino , Humanos , Trofoblastos/metabolismo , Placentación/fisiología , Células Epiteliales , Placenta/metabolismo
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