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1.
Small ; : e2404829, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388497

RESUMEN

In the general analysis of thin-film growth processes, it is often assumed that the temperature of the film growth surface is the same as the temperature of the film growth substrate. However, a temperature gradient exists between the film growth surface and film growth substrate. Using the growth surface of TiO2 thin films as an example, the temperature gradient of the film growth surface is tested and analyzed. A NiCr/NiSi thin-film thermocouple is fabricated using the direct-current pulse magnetron sputtering method. A three-layer NiCr/NiSi thin-film thermocouple temperature measurement system is established to measure the temperature gradient of the film growth surface. The growth surface temperature and substrate temperature of the TiO2 thin films are measured. For a sputtering power density of 0.83 W cm- 2, the temperature difference between the first and second layers is 104.79 °C, while the temperature difference between the second and third layers is 39.92 °C. A standard K-type thermocouple is used to measure the substrate temperature, which is recorded to be 132.05 °C, consistent with common measurements of substrate temperature. The heat conduction on the film growth surface in the vacuum chamber is examined and a model for the temperature measurement device during film growth is constructed.

2.
Biochim Biophys Acta Mol Cell Res ; 1871(8): 119853, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39353470

RESUMEN

We previously reported that a bioactive peptide (pep3) can potently inhibit the enzyme activity of purified calcineurin (CN). In this paper, we further demonstrate that transfected pep3 can strongly inhibit CN enzyme activity in HEK293 cells. Transcription factor EB (TFEB) plays an important role in the autophagy-lysosome pathway (ALP) as one of the substrates of CN, so we study the effect of pep3 on the CN-TFEB-ALP pathway. Pep3 can significantly inhibit the mRNA levels of the TFEB downstream genes and the expression of the autophagy-associated proteins, and autophagy flux in HEK293 cells. We also validated the inhibitory effect of pep3 on autophagy in mice. These findings may provide a new idea for discovering more CN inhibitors and autophagy inhibitory drugs.


Asunto(s)
Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Calcineurina , Péptidos , Calcineurina/metabolismo , Calcineurina/genética , Humanos , Autofagia/efectos de los fármacos , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Células HEK293 , Ratones , Péptidos/farmacología , Péptidos/metabolismo , Transducción de Señal/efectos de los fármacos , Lisosomas/metabolismo
3.
Cell Rep ; 43(10): 114800, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39365703

RESUMEN

Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPirGlu) innervate GABAergic neurons in the IC (ICGABA) to inhibit local glutamatergic neurons (ICGlu) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPirGlu→ICGABA→Glu pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPirGlu neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain.


Asunto(s)
Lavandula , Aceites Volátiles , Aceites de Plantas , Animales , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Ratones , Masculino , Dolor , Neuronas GABAérgicas/metabolismo , Ratones Endogámicos C57BL , Analgésicos/farmacología , Corteza Cerebral/efectos de los fármacos , Inflamación/patología , Adyuvante de Freund
4.
ACS Nano ; 18(43): 29469-29478, 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39405579

RESUMEN

Nonvolatile memristors offer a salient platform for artificial neural network (ANN), yet the integration of different function and algorithm blocks into one hardware system remains challenging. Here we demonstrate the brain-like synaptic (SOT-S) and neuronal (SOT-N) functions in the Bi2Te3/CrTe2 heterostructure-based spin-orbit torque (SOT) device. The SOT-S unit exhibits highly linear and symmetrical long-term potentiation/depression process, resulting in a fast-training of the MNIST data set with the classification accuracy above 90%. Meanwhile, the Sigmoid-shape transition curve inherited in the SOT-N cell replaces the software-based activation function block, hence reducing the system complexity. On this basis, we employ a serial-connected, voltage-mode sensing ANN architecture to enhance the vector-matrix multiplication signal strength with low reading error of 0.61% while simplifying the peripheral circuitry. Furthermore, the trainable activation function of SOT-N enables the implementation of the Batch Normalization algorithm and activation operation within one clock cycle, which bring about improved on/off-chip training performance close to the ideal baseline.

5.
BMC Gastroenterol ; 24(1): 385, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39478467

RESUMEN

OBJECTIVE: Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. METHODS: We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. RESULTS: Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36-69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. CONCLUSION: Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.


Asunto(s)
Colitis Ulcerosa , Estudio de Asociación del Genoma Completo , Hipotiroidismo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Colitis Ulcerosa/genética , Humanos , Hipotiroidismo/genética , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Factor de Transcripción STAT4/genética , Causalidad , Predisposición Genética a la Enfermedad
6.
J Neurooncol ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39325339

RESUMEN

PURPOSE: Spinal laser interstitial thermal therapy (sLITT) is a less invasive alternative to surgery for metastatic epidural spinal cord compression. Here, we analyze outcomes of patients treated with sLITT either in conjunction with radiotherapy or as a standalone salvage therapy. METHODS: We included patients with thoracic vertebral metastatic cord compression treated with sLITT. Outcomes included freedom from local failure (FFLF) and overall survival (OS). Factors associated with FFLF were identified with univariable and multivariable analyses via a Cox proportional hazards model. RESULTS: Between 2013-2022, 129 patients received sLITT to 144 vertebral segments; 69% were radiotherapy naïve, 81% were radioresistant histologies, and 74% were centered in the vertebral body. Median age was 61 years. Pre-sLITT Bilsky score was 3 in 28%, 2 in 33%, and 1c in 37%. Radiotherapy was delivered in conjunction with sLITT for 80% of cases, including 68% that received stereotactic radiotherapy, at a median of 5 days after sLITT. Median follow-up was 9.1 months. One-year FFLF and OS was 80% and 78%, respectively. On multivariable analysis, variables independently associated with adverse FFLF included paraspinal/foraminal disease location (p = 0.001), and post-sLITT imaging Bilsky score of 2 (p = 0.073) or 3 (p = 0.011). Prior radiotherapy, technique of radiotherapy, and time between radiotherapy and sLITT were not associated with FFLF. CONCLUSION: sLITT with radiotherapy is an effective minimally invasive treatment approach for thoracic metastatic epidural spinal cord compression. Early treatment response may serve as a prognostic imaging biomarker.

7.
Int J Mol Sci ; 25(15)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39125770

RESUMEN

Enhancing stalk strength is a crucial strategy to reduce lodging. We identified a maize inbred line, QY1, with superior stalk mechanical strength. Comprehensive analyses of the microstructure, cell wall composition, and transcriptome of QY1 were performed to elucidate the underlying factors contributing to its increased strength. Notably, both the vascular bundle area and the thickness of the sclerenchyma cell walls in QY1 were significantly increased. Furthermore, analyses of cell wall components revealed a significant increase in cellulose content and a notable reduction in lignin content. RNA sequencing (RNA-seq) revealed changes in the expression of numerous genes involved in cell wall synthesis and modification, especially those encoding pectin methylesterase (PME). Variations in PME activity and the degree of methylesterification were noted. Additionally, glycolytic efficiency in QY1 was significantly enhanced. These findings indicate that QY1 could be a valuable resource for the development of maize varieties with enhanced stalk mechanical strength and for biofuel production.


Asunto(s)
Hidrolasas de Éster Carboxílico , Pared Celular , Regulación de la Expresión Génica de las Plantas , Tallos de la Planta , Zea mays , Zea mays/genética , Zea mays/metabolismo , Pared Celular/metabolismo , Pared Celular/genética , Tallos de la Planta/metabolismo , Tallos de la Planta/genética , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/genética , Lignina/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Celulosa/metabolismo , Transcriptoma
8.
ACS Appl Mater Interfaces ; 16(34): 45687-45694, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39162076

RESUMEN

Magnetoresistance effects are crucial for understanding the charge-spin transport as well as propelling the advancement of spintronic applications. Here, we report the coexistence of magnetic-moment-dependent (MD) and magnetic-field-driven (FD) unidirectional magnetoresistance (UMR) effects in CoFeB/InSb/CdTe heterostructures. The strong spin-orbital coupling of InSb and the matched impedance at the CoFeB/InSb interface warrant a distinct MD-UMR effect at room temperature, while the interaction between the in-plane magnetic field and the Rashba effect at the InSb/CdTe interface induces the marked FD-UMR signal that dominates the high-field region. Moreover, owning to different spin scattering mechanisms, these two types of non-reciprocal charge transports show opposite polarities with respect to the magnetic field direction, which further enables an effective phase modulation of the angular-dependent magnetoresistance. The demonstration of the tunable UMR response validates our CoFeB/InSb/CdTe system as a suitable integrated building block for multifunctional spintronic memory and sensor designs.

9.
J Adv Res ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39084404

RESUMEN

INTRODUCTION: Exaggerated neutrophil recruitment and activation are the major features of pathological alterations in periodontitis, in which neutrophil extracellular traps (NETs) are considered to be responsible for inflammatory periodontal lesions. Despite the critical role of NETs in the development and progression of periodontitis, their specific functions and mechanisms remain unclear. OBJECTIVES: To demonstrate the important functions and specific mechanisms of NETs involved in periodontal immunopathology. METHODS: We performed single-cell RNA sequencing on gingival tissues from both healthy individuals and patients diagnosed with periodontitis. High-dimensional weighted gene co-expression network analysis and pseudotime analysis were then applied to characterize the heterogeneity of neutrophils. Animal models of periodontitis were treated with NETs inhibitors to investigate the effects of NETs in severe periodontitis. Additionally, we established a periodontitis prediction model based on NETs-related genes using six types of machine learning methods. Cell-cell communication analysis was used to identify ligand-receptor pairs among the major cell groups within the immune microenvironment. RESULTS: We constructed a single-cell atlas of the periodontal microenvironment and obtained nine major cell populations. We further identified a NETs-related subgroup (NrNeu) in neutrophils. An in vivo inhibition experiment confirmed the involvement of NETs in gingival inflammatory infiltration and alveolar bone absorption in severe periodontitis. We further screened three key NETs-related genes (PTGS2, MME and SLC2A3) and verified that they have the potential to predict periodontitis. Moreover, our findings revealed that gingival fibroblasts had the most interactions with NrNeu and that they might facilitate the production of NETs through the MIF-CD74/CXCR4 axis in periodontitis. CONCLUSION: This study highlights the pathogenic role of NETs in periodontal immunity and elucidates the specific regulatory relationship by which gingival fibroblasts activate NETs, which provides new insights into the clinical diagnosis and treatment of periodontitis.

10.
J Exp Clin Cancer Res ; 43(1): 208, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39061061

RESUMEN

BACKGROUND: Colorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis. METHODS: We conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects. RESULTS: SLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-ß/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TßRII and stabilized TßRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-ß/Smad signaling. Furthermore, TGF-ß1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1's transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers. CONCLUSIONS: Our findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-ß/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.


Asunto(s)
Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Pronóstico , Factor de Crecimiento Transformador beta/metabolismo
11.
Diabetes Metab Res Rev ; 40(5): e3830, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38873748

RESUMEN

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/cirugía , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Cirugía Bariátrica/métodos , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/cirugía , Pronóstico , Resultado del Tratamiento
12.
J Biomed Inform ; 156: 104676, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876451

RESUMEN

Biomedical relation extraction has long been considered a challenging task due to the specialization and complexity of biomedical texts. Syntactic knowledge has been widely employed in existing research to enhance relation extraction, providing guidance for the semantic understanding and text representation of models. However, the utilization of syntactic knowledge in most studies is not exhaustive, and there is often a lack of fine-grained noise reduction, leading to confusion in relation classification. In this paper, we propose an attention generator that comprehensively considers both syntactic dependency type information and syntactic position information to distinguish the importance of different dependency connections. Additionally, we integrate positional information, dependency type information, and word representations together to introduce location-enhanced syntactic knowledge for guiding our biomedical relation extraction. Experimental results on three widely used English benchmark datasets in the biomedical domain consistently outperform a range of baseline models, demonstrating that our approach not only makes full use of syntactic knowledge but also effectively reduces the impact of noisy words.


Asunto(s)
Procesamiento de Lenguaje Natural , Semántica , Minería de Datos/métodos , Algoritmos , Humanos
13.
Chem Commun (Camb) ; 60(53): 6793-6796, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38869018

RESUMEN

We report an integrated ratiometric lysosomal nitric oxide (NO) nanoprobe based on engineered semiconducting polymer dots (Pdots), LyNO-Pdots, which consist of a newly designed NO-responsive dye, a fluorescent conjugated polymer and two functional polymers. The developed probe LyNO-Pdots exhibit high specificity and stability, good photostability and favorable blood-brain barrier (BBB) penetration ability. The LyNO-Pdots are successfully applied to ratiometric imaging of lysosomal NO variations in brain-derived endothelial cells, brain tissues and mice brains with Alzheimer's disease (AD). The results demonstrate that the NO content in the brains of AD mice is considerably higher than that in normal mice.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Colorantes Fluorescentes , Lisosomas , Óxido Nítrico , Imagen Óptica , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Lisosomas/química , Lisosomas/metabolismo , Ratones , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Polímeros/química , Barrera Hematoencefálica/metabolismo , Puntos Cuánticos/química
14.
Nat Commun ; 15(1): 4534, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806482

RESUMEN

We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

15.
Br J Cancer ; 131(2): 347-360, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38822145

RESUMEN

BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.


Asunto(s)
Carcinoma de Células Renales , Resistencia a Antineoplásicos , Neoplasias Renales , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Sunitinib , Sunitinib/farmacología , Sunitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Animales , Resistencia a Antineoplásicos/genética , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , MicroARNs/genética , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Ratones Desnudos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo
16.
J Agric Food Chem ; 72(18): 10163-10178, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38653191

RESUMEN

Oxalate decarboxylase (OXDC) is a typical Mn2+/Mn3+ dependent metal enzyme and splits oxalate to formate and CO2 without any organic cofactors. Fungi and bacteria are the main organisms expressing the OXDC gene, but with a significantly different mechanism of gene expression and regulation. Many articles reported its potential applications in the clinical treatment of hyperoxaluria, low-oxalate food processing, degradation of oxalate salt deposits, oxalate acid diagnostics, biocontrol, biodemulsifier, and electrochemical oxidation. However, some questions still remain to be clarified about the role of substrate binding and/or protein environment in modulating the redox properties of enzyme-bound Mn(II)/Mn(III), the nature of dioxygen involved in the catalytic mechanism, and how OXDC acquires Mn(II) /Mn(III). This review mainly summarizes its biochemical and structure characteristics, gene expression and regulation, and catalysis mechanism. We also deep-mined oxalate decarboxylase gene data from National Center for Biotechnology Information to give some insights to explore new OXDC with diverse biochemical properties.


Asunto(s)
Bacterias , Carboxiliasas , Carboxiliasas/genética , Carboxiliasas/metabolismo , Carboxiliasas/química , Bacterias/genética , Bacterias/enzimología , Bacterias/metabolismo , Hongos/genética , Hongos/enzimología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Biocatálisis , Oxalatos/metabolismo , Oxalatos/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Regulación Enzimológica de la Expresión Génica , Humanos , Catálisis , Animales
17.
Foods ; 13(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38472789

RESUMEN

This study systematically investigates the impact of corn starch molecular structures on the quality attributes of surimi gel products. Employing molecular analyses to characterize corn starch, three amylopectin fractions (A, B1, and B2), categorized by the degree of polymerization ranges (6 < X ≤ 12, 12 < X ≤ 24, and 24 < X ≤ 36, respectively) were specifically focused on. The surimi gel quality was comprehensively assessed through texture profile analysis, nuclear magnetic resonance, scanning electron microscopy, stained section analysis, and Fourier transform infrared spectroscopy. Results indicated the substantial volume expansion of corn amylopectin upon water absorption, effectively occupying the surimi gel matrix and fostering the development of a more densely packed protein network. Starch gels with higher proportions of A, B1, and B2 exhibited improved hardness, chewiness, and bound water content in the resultant surimi gels. The weight-average molecular weight and peak molecular weight of corn starch showed a strong positive correlation with surimi gel hardness and chewiness. Notably, the secondary structure of proteins within the surimi gel was found to be independent of corn starch's molecular structure. This study provides valuable insights for optimizing formulations in surimi gel products, emphasizing the significance of elevated A, B1, and B2 content in corn starch as an optimal choice for crafting dense, chewy, water-retaining surimi gels.

18.
J Phys Condens Matter ; 36(25)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38467073

RESUMEN

Achieving all electrical control of magnetism without assistance of an external magnetic field has been highly pursued for spintronic applications. In recent years, the manipulation of magnetic states through spin-orbit torque (SOT) has emerged as a promising avenue for realizing energy-efficient spintronic memory and logic devices. Here, we provide a review of the rapidly evolving research frontiers in all electrical control of magnetization by SOT. The first part introduces the SOT mechanisms and SOT devices with different configurations. In the second part, the developments in all electrical SOT control of magnetization enabled by spin current engineering are introduced, which include the approaches of lateral symmetry breaking, crystalline structure engineering of spin source material, antiferromagnetic order and interface-generated spin current. The third part introduces all electrical SOT switching enabled by magnetization engineering of the ferromagnet, such as the interface/interlayer exchange coupling and tuning of anisotropy or magnetization. At last, we provide a summary and future perspectives for all electrical control of magnetization by SOT.

19.
Talanta ; 271: 125754, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38335846

RESUMEN

Developing a simple, reliable, and sensitive hepatitis C virus (HCV) genetic sensing platform is of great significance for diagnosing diseases and selecting appropriate antiviral treatments. Herein, a tandem nucleic acid amplification strategy for sensitive detection of HCV genotype 1b (HCV-1b) was developed by stringing the catalytic hairpin assembly (CHA) and the triggered DNAzyme amplifier. The hairpin reactants were initiated by the target to produce lots of triggering double-stranded DNA sequences which can efficiently activate the subsequent blocked DNAzyme. Thereby, the continuous cleavage of substrate was realized, resulting in the fluorescence signal amplification. The DNA-based isothermal CHA-DNAzyme (CDz) sensing platform was successfully applied for sensitive detection of HCV-1b with the limit of detection (84 pM) and showed good selectivity. Moreover, the practical detection of target DNA in the complex biologic matrix indicated that the developing strategy had good potential for early HCV infection diagnosis.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , Hepatitis C , Humanos , ADN Catalítico/genética , Hepacivirus/genética , Retroalimentación , Técnicas Biosensibles/métodos , ADN/genética , Hepatitis C/diagnóstico , Genotipo , Límite de Detección
20.
Heliyon ; 10(4): e25515, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38375258

RESUMEN

Facing the growing issue of cardiovascular diseases, metallic materials with higher tensile strength and fatigue resistance play an important role in treating diseases. This review lists the advantages and drawbacks of commonly used medical metallic materials for vascular stents. To avoid post-procedural threats such as thrombosis and in-stent restenosis, surface treatments, and coating methods have been used to further improve the biocompatibility of these materials. Surface treatments including laser, plasma treatment, polishing, oxidization, and fluorination can improve biocompatibility by modifying the surface charges, surface morphology, and surface properties of the material. Coating methods based on polymer coatings, carbon-based coatings, and drug-functional coatings can regulate the surface properties, and also serve as an effective barrier to the interaction of metallic biomaterial surfaces with biomolecules, which can be used to improve corrosion resistance and stability, as well as improve their biocompatibility. Biocompatibility serves as the most fundamental property of cardiovascular stents, and maintaining the excellent and stable biocompatibility of cardiovascular stent surfaces is a current research bottleneck. Few reviews have been published on metallic biomaterials as cardiovascular stents and their surface treatments. For the purpose of advancing research on cardiovascular stents, common metal biomaterials, surface treatment methods, and coating methods to improve biocompatibility and comprehensive properties of the materials are described in this review. Finally, we suggest future directions for stent development, including continuously improving the durability and stability of permanent stents, accelerating the development of biodegradable stents, and strengthening feedback to improve the safety and reliability of cardiovascular stents.

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