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Represented herein is the first 1,3-difunctionalization of alkenes via photocatalysis. A single cobaloxime is used to carry out two catalytic cycles in which cobaloxime is used not only as a photocatalyst to initiate the reaction but also as a metal catalyst for the ß-H elimination process. Electron-deficient alkenes, electron-rich alkenes, and unactivated alkenes could be directly converted to 1,3-bisphosphorylated products, even unsymmetric 1,3-bisphosphorylated products, with only H2 as a byproduct under extremely mild reaction conditions.
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INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.
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In this study, pectin extracted from pomelo peel was investigated using three different combination methods of pulsed electric field (PEF) and cellulase. Three action sequences were performed, including PEF treatment followed by enzymatic hydrolysis, enzymatic hydrolysis followed by PEF treatment, and enzymatic hydrolysis simultaneously treated by PEF. The three corresponding pectins were namely PEP, EPP and SP. The physiochemical, molecular structural and functional properties of the three pectins were determined. The results showed that PEP had excellent physiochemical properties, with the highest yield (12.08 %), total sugar (80.17 %) and total phenol content (38.20 %). The monosaccharide composition and FT-IR analysis indicated that the three pectins were similar. The molecular weights of PEP, EPP and SP were 51.13, 88.51 and 40.00 kDa, respectively. PEP showed the best gel properties, emulsification stability and antioxidant capacity among the three products, due to its high galacturonic acid and total phenol content, appropriate protein and low molecular weight. The mechanism of PEF-assisted cellulase hydrolysis of pomelo peel was also revealed by SEM analysis. These results suggested that PEF pretreatment was the best method, which not only improved the efficiency of enzymatic extraction, but also reduced resource waste and increased financial benefits.
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BACKGROUND: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.
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Estadificación de Neoplasias , Tumores Neuroendocrinos , Nomogramas , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/diagnóstico , Estudios Retrospectivos , China/epidemiología , Pronóstico , Anciano , Factores de Riesgo , Adulto , Curva ROC , Supervivencia sin Progresión , Clasificación del Tumor , Medición de Riesgo/métodos , Modelos de Riesgos Proporcionales , Valor Predictivo de las Pruebas , Evaluación Nutricional , Pueblos del Este de AsiaRESUMEN
Acrolein is a ubiquitous gaseous air pollutant and endogenous toxicant, which poses strong risk for oxidative stress-related diseases such as cardiovascular disease. Adenosine has been identified as potential therapeutic agent for age-related cardiovascular disease, while the molecular mechanisms underlying its cardioprotection remain elusive. In the present study, we investigated the myocardial protective effects and the mechanism of adenosine on acrolein-induced toxicity in H9c2 cells and primary neonatal rat cardiomyocytes. We found that acrolein caused apoptosis of cardiomyocytes resulting from oxidative damage, autophagy defect, and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential, impairment of mitochondrial biogenesis, dynamics, and oxidative phosphorylation, decrease of mitochondrial deoxyribonucleic acid (mtDNA) copy number and adenosine 5'-triphosphate (ATP) production. Adenosine pretreatment protected against acrolein-induced cardiotoxicity by maintaining mitochondrial homeostasis, activating the phase II detoxifying enzyme system, promoting autophagic flux, and alleviating mitochondrial-dependent apoptosis. We further demonstrated that the up-regulation of forkhead box protein O1 (FoxO1) mediated by extracellular regulated protein kinases (ERK) activation contributes to the cardioprotection of adenosine. These results expand the application of adenosine in cardioprotection to preventing myocardial damages induced by environmental pollutant acrolein exposure, and uncover the adenosine-ERK-FoxO1 axis as the underlying mechanism mediating the protection of mitochondrial homeostasis, Nrf2-mediated antioxidant defense and autophagic flux, shedding light on the better understanding about the pathological mechanism of cardiovascular disease caused by environmental pollutants and applications of adenosine in cardioprotection.
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Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin ß2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.
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Apoptosis , Médula Ósea , Citarabina , Sistemas de Liberación de Medicamentos , Células Madre Hematopoyéticas , Leucemia , Liposomas , Animales , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Ratones , Citarabina/farmacología , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Médula Ósea/metabolismo , Apoptosis/efectos de los fármacos , Leucemia/tratamiento farmacológico , Leucemia/patología , Humanos , Diferenciación Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Línea Celular Tumoral , Antígenos CD18/metabolismo , Proliferación Celular/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/química , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismoRESUMEN
Background and Aims: Hepatic fibrosis (HF) is a critical step in the progression of hepatocellular carcinoma (HCC). Gene associated with retinoid-IFN-induced mortality 19 (GRIM19), an essential component of mitochondrial respiratory chain complex I, is frequently attenuated in various human cancers, including HCC. Here, we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis. Methods: GRIM19 expression was evaluated in normal liver tissues, hepatitis, hepatic cirrhosis, and HCC using human liver disease spectrum tissue microarrays. We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo. We performed flow cytometry, immunofluorescence, immunohistochemistry, western blotting, and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF. Results: Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues, including hepatitis, cirrhosis, and HCC tissues. Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice. In addition, GRIM19 loss caused chronic liver injury through reactive oxygen species (ROS)-mediated oxidative stress, resulting in aberrant NF-кB activation via an IKK/IкB partner in hepatocytes. Furthermore, GRIM19 loss activated NLRP3-mediated IL33 signaling via the ROS/NF-кB pathway in hepatocytes. Intraperitoneal administration of the NLRP3 inhibitor MCC950 dramatically alleviated GRIM19 loss-driven HF in vivo. Conclusions: The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-кB signaling, providing potential therapeutic approaches for earlier HF prevention.
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Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4-nitroquinoline 1-oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single-cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor-promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor-promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment-associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.
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BACKGROUND: The regulatory role of gut microbiota and gut-derived metabolites through the gut-liver axis in the development of cirrhotic portal hypertension (PH) has received increasing attention. METHODS: The review summarized a series of investigations on effects of metabolites derived from microbiota and medicines targeting microbiome including rifaximin, VSL#3, statins, propranolol, FXR agonists as well as drugs derived from bile acids (BAs) on PH progression. RESULTS: Patients with PH exhibit alterations in gut microbial richness and differential overall microbiota community, and several results clearly displayed the correlation of PH with enrichment of Veillonella dispar or depletion of Clostridiales, Peptostreptococcaceae, Alistipes putredinis, Roseburia faecis and Clostridium cluster IV. The gut-derived metabolites including hydrogen sulfide, tryptophan metabolites, butyric acid, secondary BAs and phenylacetic acid (PAA) participate in a range of pathophysiology process of PH through modulating intrahepatic vascular resistance and portal blood flow associated with the formation and progression of PH. Established and emerging drugs targeting on bacterial translocation and intestinal eubiosis are gradually identified as potential strategies for treatments of liver cirrhosis and PH by modulating intestinal inflammation, splanchnic arterial vasodilation and endothelial dysfunction. CONCLUSIONS: Future explorations should further characterize the alteration of the fecal microbiome and metabolite profiles in PH and elucidate the regulatory mechanism of the intestinal microbiome, gut-derived metabolites and gut microbiota targeted pharmaceutical treatments involved in PH.
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RIPK1 plays a key role in necroptosis and is associated with various inflammatory diseases. Using structure-based virtual screening, a novel hit with 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole scaffold was identified as an RIPK1 inhibitor with an IC50 value of 1.3 µM. Further structure-activity relationship study was performed based on similarity research and biological evaluation. The molecular dynamics simulation of compound 2 with RIPK1 indicated that it may act as a type II kinase inhibitor. This study provides a highly efficient way to discover novel scaffold RIPK1 inhibitors for further development.
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Simulación de Dinámica Molecular , Oxadiazoles , Inhibidores de Proteínas Quinasas , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Humanos , Relación Estructura-Actividad , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Oxadiazoles/farmacología , Oxadiazoles/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Simulación del Acoplamiento Molecular , Imidazoles/farmacología , Imidazoles/química , Evaluación Preclínica de Medicamentos , Descubrimiento de Drogas/métodosRESUMEN
Inspired by the structure characteristics of natural products, the size and morphology of particles are carefully controlled using a bottom-up approach to construct nanomaterials with specific spatial unit distribution. Animal polysaccharide nanomaterials, such as chitosan and chondroitin sulfate nanomaterials, exhibit excellent biocompatibility, degradability, customizable surface properties, and novel physical and chemical properties. These nanomaterials hold great potential for development in achieving a sustainable bio-economy. This paper provides a summary of the latest research results on the preparation of nanomaterials from animal polysaccharides. The mechanism for preparing nanomaterials through the bottom-up method from different sources of animal polysaccharides is introduced. Furthermore, this paper discusses the potential hazards posed by industrial applications to the environment and human health, as well as the challenges and future prospects associated with using animal polysaccharides in nanomaterials.
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The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.
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Metanol , Methylobacterium , Methylobacterium/metabolismo , Methylobacterium/genética , Methylobacterium/enzimología , Methylobacterium/crecimiento & desarrollo , Metanol/metabolismo , Simbiosis , Mutación , Aldehído-Liasas/metabolismo , Aldehído-Liasas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Hojas de la Planta/microbiología , Hojas de la Planta/crecimiento & desarrollo , Methylobacterium extorquens/genética , Methylobacterium extorquens/metabolismo , Methylobacterium extorquens/crecimiento & desarrollo , Methylobacterium extorquens/enzimología , Desarrollo de la Planta , Microbiota/genética , BiomasaRESUMEN
Light-flavor Baijiu (LFB) is widely cherished for its flavor. This study identified the thresholds of 14 aroma compounds in a 52% ethanol-water matrix and conducted a comprehensive analysis of the interactions among key aroma compounds in LFB using the Feller additive model and odor activity values approach. Among them, the interactions of ß-damascenone with ester and alcohol compounds were primarily promotive, while the interaction with acid compounds was predominantly masking. Furthermore, for the first time, the electroencephalogram (EEG) technology was used to characterize the interactions between aroma compounds. The results showed that the brain activity in the alpha frequency band demonstrated heightened olfactory sensitivity. The EEG could not only display the additive effect of odor intensity but also reflect the differences in aroma similarity between different odors. This study demonstrated that the EEG can serve as an effective tool for olfactory assessment.
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Electroencefalografía , Aromatizantes , Odorantes , Olfato , Odorantes/análisis , Humanos , Masculino , Adulto , Aromatizantes/química , Femenino , Compuestos Orgánicos Volátiles/química , Adulto Joven , Gusto , Percepción Olfatoria , Encéfalo/fisiologíaRESUMEN
PURPOSE: This study aimed to evaluate the relationships of separate and mixed exposure of neonicotinoids on cardiometabolic risk at baseline and follow-up and its change over 3 years, and further explore whether inflammatory markers levels and platelet traits (PLT) mediate these relationships. METHODS: In this prospective cohort study from the Henan Rural Cohort Study, 2315 participants were involved at baseline, and 1841 participants completed cardiometabolic risk predictors determinations during the 3-year follow-up. Each neonicotinoid pesticide was normalized to imidacloprid (IMIeq) using the relative potency factor approach. Quantile-based g-computation (Qgcomp) regression was used to evaluate the effect of the mixtures of neonicotinoids mediation analysis was employed to explore whether inflammatory markers levels and platelet traits mediated these relationships. A two-sample mendelian randomization (MR) study was further used to causal association. RESULTS: Qgcomp regression revealed a statistically positive relationship between neonicotinoids mixture exposure and cardiometabolic risk score at baseline and follow-up over 3 years. Both neutrophils/monocytes and PLT were mediators in the relationship between IMIeq and cardiometabolic risk score at baseline and follow-up over 3 years. The causal risk effect of pesticide exposure were 2.50 (0.05, 4.95) and 5.24 (1.28, 9.19) for cardiometabolic risk indicators including insulin resistance and triglyceride, respectively. Nevertheless, there was no correlation discovered between pesticide exposure and other markers of cardiometabolic risk. CONCLUSION: Neonicotinoid insecticides exposure was connected to an increased cardiometabolic risk, especially in individuals with T2DM. Furthermore, inflammatory markers and PLT seem to be two vital mediators of these associations. Additionally, genetic evidence on pesticide exposure and cardiometabolic risk still needs to be validated by multiregional and multiethnic GWAS studies.
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Insecticidas , Análisis de la Aleatorización Mendeliana , Neonicotinoides , Población Rural , Humanos , Neonicotinoides/toxicidad , China , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Insecticidas/toxicidad , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo Cardiometabólico , Pueblos del Este de Asia , NitrocompuestosRESUMEN
miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.
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Adenosina , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , MicroARNs , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Regiones no Traducidas 3'/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
Soy protein is a promising nutritional source with improved functionality and bioactivities due to conjugation with polyphenols (PP)-the conjugates between soy protein and PP held by covalent and noncovalent bonds. Different approaches, including thermodynamics, spectroscopy, and molecular docking simulations, can demonstrate the outcomes and mechanism of these conjugates. The soy protein, PP structure, matrix properties (temperature, pH), and interaction mechanism alter the ζ-potential, secondary structure, thermal stability, and surface hydrophobicity of proteins and also improve the techno-functional properties such as gelling ability, solubility, emulsifying, and foaming properties. Soy protein-PP conjugates also reveal enhanced in vitro digestibility, anti-allergic, antioxidant, anticancer, anti-inflammatory, and antimicrobial activities. Thus, these conjugates may be employed as edible film additives, antioxidant emulsifiers, hydrogels, and nanoparticles in the food industry. Future research is needed to specify the structure-function associations of soy protein-PP conjugates that may affect their functionality and application in the food industry.
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OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.
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MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.
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Complejo del Señalosoma COP9 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , FN-kappa B , Transducción de Señal , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/metabolismo , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Complejo del Señalosoma COP9/metabolismo , Complejo del Señalosoma COP9/genética , FN-kappa B/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Animales , Línea Celular Tumoral , Ratones , Ratones Desnudos , Ubiquitinación , Péptido Hidrolasas/metabolismo , Péptido Hidrolasas/genética , Progresión de la Enfermedad , Ratones Endogámicos BALB C , Femenino , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Péptidos y Proteínas de Señalización IntracelularRESUMEN
This study aims to investigate the effect of pulsed electric field (PEF) assisted OSA esterification treatment on the multi-scale structure and digestive properties of cassava starch and structure-digestion relationships. The degree of substitution (DS) of starch dually modified at 1.5-4.5 kV/cm was 37.6-55.3 % higher than that of starch modified by the conventional method. Compared with native starch, the resistant starch (RS) content of esterified starch treated with 3 kV/cm significantly increased by 17.13 %, whereas that of starch produced by the conventional method increased by only 5.91 %. Furthermore, assisted esterification at low electric fields (1.5-3 kV/cm) promotes ester carbonyl grafting on the surface of starch granules, increases steric hindrance and promotes the rearrangement of the amorphous regions of starch, which increases the density of the double-helical structure. These structural changes slow down starch digestion and increase the RS content. Therefore, this study presents a potential method for increasing the RS content of starch products using PEF to achieve the desired digestibility.
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High power 509 nm continuous-wave (CW) lasers have important applications in science and communication. Here we demonstrate a robust high-power single-frequency 509 nm laser system based on nonlinear phase demodulation technique and single-pass second harmonic generation (SHG) configuration. In experiments, the single-frequency fundamental wave at 1018 nm was linewidth-broadened by an electro-optical modulator and then amplified to 207 W in a ytterbium-doped fiber amplifier. In subsequent single-pass SHG stage, over 20 W CW single-frequency 509 nm laser was generated in a LiB3O5 crystal with a SHG efficiency of 9.7%. To the best of our knowledge, this is the highest reported power for CW single-frequency 509 nm laser, which could be used for advanced underwater optical communication and preparation of cesium Rydberg state.