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Topology1-3 and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a 'hybrid' topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a conjoined strong and higher-order topology that stabilizes a hybrid topological phase. Although momentum-space spectroscopy measurements show signs of topological surface states, real-space microscopy measurements unravel a unique geometry of topologically induced step-edge conduction channels revealed on various natural nanostructures on the surface. Using theoretical models, we show that the existence of gapless step-edge states in arsenic relies on the simultaneous presence of both a non-trivial strong Z2 invariant and a non-trivial higher-order topological invariant, which provide experimental evidence for hybrid topology. Our study highlights pathways for exploring the interplay of different band topologies and harnessing the associated topological conduction channels in engineered quantum or nano-devices.
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G-protein coupled receptors (GPCRs), crucial in various diseases, are targeted of over 40% of approved drugs. However, the reliable acquisition of experimental GPCRs structures is hindered by their lipid-embedded conformations. Traditional protein-ligand interaction models falter in GPCR-drug interactions, caused by limited and low-quality structures. Generalized models, trained on soluble protein-ligand pairs, are also inadequate. To address these issues, we developed two models, DeepGPCR_BC for binary classification and DeepGPCR_RG for affinity prediction. These models use non-structural GPCR-ligand interaction data, leveraging graph convolutional networks and mol2vec techniques to represent binding pockets and ligands as graphs. This approach significantly speeds up predictions while preserving critical physical-chemical and spatial information. In independent tests, DeepGPCR_BC surpassed Autodock Vina and Schrödinger Dock with an area under the curve of 0.72, accuracy of 0.68 and true positive rate of 0.73, whereas DeepGPCR_RG demonstrated a Pearson correlation of 0.39 and root mean squared error of 1.34. We applied these models to screen drug candidates for GPR35 (Q9HC97), yielding promising results with three (F545-1970, K297-0698, S948-0241) out of eight candidates. Furthermore, we also successfully obtained six active inhibitors for GLP-1R. Our GPCR-specific models pave the way for efficient and accurate large-scale virtual screening, potentially revolutionizing drug discovery in the GPCR field.
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Descoberta de Drogas , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Ligantes , Descoberta de Drogas/métodos , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Sítios de LigaçãoRESUMO
The mechanistic target of rapamycin complex 1 (mTORC1) is indispensable for preserving cellular and organismal homeostasis by balancing the anabolic and catabolic processes in response to various environmental cues, such as nutrients, growth factors, energy status, oxygen levels, and stress. Dysregulation of mTORC1 signaling is associated with the progression of many types of human disorders including cancer, age-related diseases, neurodegenerative disorders, and metabolic diseases. The way mTORC1 senses various upstream signals and converts them into specific downstream responses remains a crucial question with significant impacts for our perception of the related physiological and pathological process. In this review, we discuss the recent molecular and functional insights into the nutrient sensing of the mTORC1 signaling pathway, along with the emerging role of deregulating nutrient-mTORC1 signaling in cancer and age-related disorders.
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In this study, a really simple and efficient catalytic protocol for the construction of quinazolines from alcohol and diamine has been developed based on CuCoAl layered double hydroxide (CuCoAl-LDH). The developed CuCoAl-LDH catalyst could accelerate the cascade reactions without any additives and tolerate various alcohols with satisfactory yields. Cooperation between the Cu+ and Cu2+ species in CuCoAl-LDH was observed in the cascade reaction, and they are believed to be responsible for the oxidation of alcohol and dehydrogenation of the intermediate, respectively. The promoting effect of the substrate diamine was observed in the oxidation of alcohol, which simplifies the reaction system by eliminating the requirement for a base additive. The catalytic system exhibited highly practical potential for the synthesis of quinazolines, as demonstrated through recyclability investigations and scale-up experiments. A possible catalytic mechanism has been proposed based on a series of control experiments and EPR analysis.
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Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.
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Produtos Biológicos , Relação Dose-Resposta a Droga , Descoberta de Drogas , Receptores Histamínicos H4 , Humanos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Receptores Histamínicos H4/antagonistas & inibidores , Receptores Histamínicos H4/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Fenantrenos/farmacologia , Fenantrenos/química , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/química , Simulação de Acoplamento Molecular , FenótipoRESUMO
Lactarius hatsudake (LH), a great wild endemic fungus, contains rich nutritional components with medicinal properties. The effects of LH on body weight, liver weight, liver injury, blood lipids, and gut microbiota in C57BL/6 mice fed a high-fat diet (HFD) for 8 weeks was examined in this research. Though there was no clear impact on weight loss, the findings indicate that LH treatment effectively decreased liver damage caused by HFD, as well as lowered serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels. Additionally, it positively influenced gut microbiota to resemble that of mice on a normal diet. In HFD-fed mice, LH markedly boosted the levels of Parabacteroides, unclassified Muribaculaceae, Oscillibacter, and unclassified Oscillospiraceae, while reducing the abundance of Lachnospiraceae NK4A136 group and Erysipelatoclostridium, as well as the ratio of Firmicutes to Bacteroidetes. Further analysis of correlation indicate a possible connection between obesity and gut microbiota. Obesity-related indices show a positive association with unclassified Eubacterium coprostanoligenes group, Blautia, and Erysipelatoclostridium, while displaying a negative correlation with unclassified Muribaculaceae, unclassified Clostridia vadinBB60 group, Helicobacter, Oscillibacter, unclassified Ruminococcaceae, Parabacteroides, and unclassified Oscillospiraceae. The results suggest that LH can help combat obesity and may have the potential to be utilized as a functional food.
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Taste, dietary choices, and gut microbiota are often analyzed as major factors of metabolic health. Populations living in cold or hot regions have different dietary habits. This study aims to investigate the potential association among ambient temperature, food taste preferences, and cecal microbiota community profiles in mice. By exposing mice to mixed diets containing sweet, sour, salty, and bitter flavors at low (4 °C) and high (37 °C) ambient temperatures, the taste preferences of mice at both ambient temperatures were in the order of saltiness > sweetness > bitterness > sourness. Exposing mice to sweet, sour, salty, and bitter diets, respectively, revealed that in a low-temperature environment, mice consuming salty (5.00 ± 1.49 g), sweet (4.99 ± 0.35 g), and sour (3.90 ± 0.61 g) diets had significantly higher weight gain compared to those consuming normal feeds (2.34 ± 0.43 g, p < 0.05). Conversely, in a high-temperature environment, no significant changes in body weight were observed among mice consuming different flavored diets (p > 0.05). In a low-temperature environment, mice fed sour and sweet diets showed a significant difference in the gut microbiota composition when compared to those fed a normal diet. A higher abundance of Lachnospiraceae, UBA1819, and Clostridiales was identified as the most significant taxa in the sour group, and a higher abundance of Ruminiclostridium was identified in the sweet group. These differences were associated with microbial pathways involved in carbohydrate metabolism, amino acid metabolism, and energy metabolism. A high-temperature environment exhibited only minor effects on the gut microbiota profile. Overall, our findings provide evidence for temperature-modulated responses to the taste, gut microbiota functions, and body weight changes in mice.
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The high concentration of chloride ions in desulphurization wastewater is the primary limiting factor for its reusability. Monovalent anion selective electrodialysis (S-ED) enables the selective removal of chloride ions, thereby facilitating the reuse of desulfurization wastewater. In this study, different concentrations of NaCl and Na2SO4 were used to simulate different softened desulfurization wastewater. The effects of current density and NaCl and Na2SO4 concentration on ion flux, permselectivity (PSO42-Cl-) and specific energy consumption were studied. The results show that Selemion ASA membrane exhibits excellent permselectivity for Cl- and SO42-, with a significantly lower flux observed for SO42- compared to Cl-. Current density exerts a significant influence on ion flux; as the current density increases, the flux of SO42- also increases but at a lower rate than that of Cl-, resulting in an increase in permselectivity. When the current density reaches 25 mA/cm2, the permselectivity reaches a maximum of 50.4. The increase in NaCl concentration leads to a decrease in the SO42- flux; however, the permselectivity is reduced due to the elevated Cl-/SO42- ratio. The SO42- flux increases with the increase in Na2SO4 concentration, while the permselectivity increases with the decrease in Cl-/SO42- ratio.
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Konjac glucomannan (KGM) is a water-soluble dietary fiber and is used for weight management. However, there is a lack of research on KGM for weight management in nonobese groups and the effects of high-dose KGM supplementation on liver function. This study investigated the metabolic responses to KGM intervention in obese and nonobese mice and explored the underlying mechanisms based on lipidomics. The findings demonstrated that KGM supplementation decreased body weight and mitigated lipid metabolism disorders at the mRNA and protein levels in obese mice. In contrast, no significant impact on these parameters was observed in nonobese mice. Interestingly, KGM had a more significant impact on remodeling hepatic lipid composition in obese mice compared to nonobese mice, leading to reducing harmful lipids and increasing beneficial lipids. However, high-dose KGM increased the risk of hepatocyte bile acid toxicity in obese mice and did not promote liver antioxidant status in nonobese mice. In summary, this study identified distinct metabolic responses to KGM intervention between obese and nonobese mice, providing insights for weight management using KGM.
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Lipidômica , Mananas , Animais , Camundongos , Camundongos Obesos , Fígado , Obesidade/tratamento farmacológico , LipídeosRESUMO
Much evidence has accumulated to show that inflammation and nutritional status are associated with the prognosis of patients with various cancers. The present study was designed to explore the prognostic role of the LANR in NPC patients receiving definitive radiotherapy and to construct a nomogram for predicting patient survival. This study retrospectively reviewed 805 NPC patients (604 in the training cohort and 201 in the validation cohort) who received definitive radiotherapy between January 2013 and December 2019. The clinical data and pretreatment laboratory test data, including lymphocyte count, neutrophil count, and serum ALB concentration, were collected for all patients. The LANR was calculated as the albumin × lymphocyte/neutrophil ratio. Patients in the training cohort and validation cohort were categorized into high-LANR and low-LANR groups according to the corresponding cutoff values. The independent prognostic factors for overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and metastasis-free survival (MFS) were evaluated by univariate and multivariate Cox regression analyses, and a nomogram was subsequently constructed. The performance of the nomogram was evaluated by the concordance index (C-index) and calibration curve. A low LANR (< 14.3) was independently associated with worse OS, PFS and MFS in NPC patients. A prognostic prediction nomogram was established based on T stage, N stage, Eastern Cooperative Oncology Group (ECOG) score, treatment modality, and LANR and was validated. The C-indices of the nomograms for OS and PFS in the training cohort were 0.729 and 0.72, respectively. The C-indices of the nomograms for OS and PFS in the validation cohort were 0.694 and 0.695, respectively. The calibration curve revealed good consistency between the actual survival and the nomogram prediction. Patients with NPC with low pretreatment LANR had a poor prognosis. The nomogram established on the basis of the LANR was efficient and clinically useful for predicting survival in NPC patients who underwent definitive radiotherapy.
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Neoplasias Nasofaríngeas , Nomogramas , Humanos , Neutrófilos , Carcinoma Nasofaríngeo/radioterapia , Estudos Retrospectivos , Prognóstico , Linfócitos , Albuminas , Neoplasias Nasofaríngeas/radioterapiaRESUMO
Eggs, with their high nutritional value, are great carriers for enriching nutrients. In this study, selenium- and/or zinc-enriched eggs (SZE) were obtained and their effects on ameliorating oxidative stress injury, alleviating cognitive impairment, and maintaining intestinal flora balance in a D-gal-induced aging mice model were investigated. As determined by the Y-maze test, SZE restored the learning and memory abilities and increased the Ach level and AChE activity of aging mice (p < 0.05). Meanwhile, supplementation of low-dose SZE increased antioxidant levels and decreased inflammation levels (p < 0.05). High-dose SZE increased anti-inflammatory levels but were less effective than low dose. Additionally, SZE maintained the intestinal flora balance and significantly increased the ratio of Firmicutes and Bacteroidota. Blautia, as a probiotic, was negatively correlated with pro-inflammatory factors and positively correlated with antioxidant levels (p < 0.05). These results suggest that SZE might improve organ damage and cognitive function by attenuating oxidative stress and inflammatory response and maintaining healthy gut flora.
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Microbioma Gastrointestinal , Selênio , Camundongos , Animais , Selênio/farmacologia , Antioxidantes/farmacologia , Zinco/farmacologia , Estresse Oxidativo , Envelhecimento , Dieta , Galactose/farmacologiaRESUMO
BACKGROUND: Serum biomarkers have a significant impact on the prediction of treatment outcomes in patients diagnosed with nasopharyngeal carcinoma (NPC). The primary aim of this study was to develop and validate a nomogram that incorporates hemoglobin, albumin, and globulin ratio (HAGR) and clinical data to accurately forecast treatment outcomes in patients with NPC. METHODS: A total of 796 patients diagnosed with NPC were included in the study. RESULTS: The results of the multivariate Cox analysis revealed that TNM stage and HAGR were found to be significant independent prognostic factors for OS and PFS. Furthermore, the utilization of the nomogram demonstrated a significant improvement in the evaluation of OS, PFS compared with the eighth TNM staging system. Additionally, the implementation of Kaplan-Meier curves and decision curve analysis curves further confirmed the discriminability and clinical effectiveness of the nomogram. CONCLUSIONS: The HAGR, an innovative prognostic factor grounded in the realm of immunonutrition, has emerged as a promising prognostic marker for both OS and PFS in individuals afflicted with NPC.
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The aim of this study was to obtain egg-derived peptides with facilitating alcohol metabolism (EPs) by enzymolysis, to identify their structures, and screen small polypeptides with higher activity by molecular docking. The optimum conditions for preparing EPs with facilitating alcohol metabolism were obtained by a single factor experiment, adding 2% Protamex and performing enzymolysis for 3 h with a liquid-material ratio of 35:1. The dose-response relationship experiment showed that 800 mg/kg·bw EPs played a better role in facilitating alcohol metabolism. EPs contained 40% hydrophobic amino acids (HAA), including 9.24% Leu. Eighty-four peptides were identified by HPLC-MS/MS and four peptides with potential activation of alcohol dehydrogenase were further selected by molecular docking. The tetrapeptide Trp-Ile-Val-Asp (WIVD) with the highest binding energy reached -7.16 kcal/mol. These findings suggest that egg is a good source for the preparation of peptides with facilitating alcohol metabolism activity.
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Konjac glucomannan (KGM), high-viscosity dietary fiber, is utilized in weight management. Previous investigations on the appetite-suppressing effects of KGM have centered on intestinal responses to nutrients and gastric emptying rates, with less focus on downstream hypothalamic neurons of satiety hormones. In our studies, the molecular mechanisms through which KGM and its degradation products influence energy homeostasis via the adipocyte-hypothalamic axis have been examined. It was found that high-viscosity KGM more effectively stimulates enteroendocrine cells to release glucagon-like peptide-1 (GLP-1) and reduces ghrelin production, thereby activating hypothalamic neurons and moderating short-term satiety. Conversely, low-viscosity DKGM has been shown to exhibit stronger anti-inflammatory properties in the hypothalamus, enhancing hormone sensitivity and lowering the satiety threshold. Notably, both KGM and DKGM significantly reduced leptin signaling and fatty acid signaling in adipose tissue and activated brown adipose tissue thermogenesis to suppress pro-opiomelanocortin (POMC) expression and activate agouti-related protein (AgRP) expression, thereby reducing food intake and increasing energy expenditure. Additionally, high-viscosity KGM has been found to activate the adipocyte-hypothalamus axis more effectively than DKGM, thereby promoting greater daily energy expenditure. These findings provide novel insights into the adipocyte-hypothalamic axis for KGM to suppress appetite and reduce weight.
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Adipócitos , Regulação do Apetite , Dieta Hiperlipídica , Metabolismo Energético , Hipotálamo , Camundongos Endogâmicos C57BL , Animais , Camundongos , Metabolismo Energético/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Masculino , Regulação do Apetite/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Humanos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Grelina/metabolismo , Leptina/metabolismo , Proteína Relacionada com Agouti/metabolismo , Proteína Relacionada com Agouti/genética , Termogênese/efeitos dos fármacos , Pró-Opiomelanocortina/metabolismo , Pró-Opiomelanocortina/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/dietoterapia , MananasRESUMO
Washed red blood cells (RBCs) can be used to treat immune-related diseases. However, whether the washing process changes the quality of RBCs and affects the curative effect of transfusion therapy remains unclear. We retrospectively analysed the clinical data of patients who received blood transfusion. The physiological and biochemical parameters of RBCs were tested on an automated haematology-biochemical analyser. CD47 and phosphatidylserine (PS) plasma membrane expression were analysed using flow cytometry. Morphological changes in RBCs were observed using scanning electron microscopy. The results showed that the curative effect on patients who received washed RBCs was weaker than that on those who received non-washed RBCs. Physiological and biochemical parameters of RBCs were not significantly different. RBC immune indices changed significantly after washing. The expression of "don't eat me" signals was weakened, whereas the intensity of "eat me" signals was enhanced. This study suggests that the current use of physiological and biochemical parameters as indicators to evaluate the quality of RBCs may not be comprehensive and that evaluation of the real status of RBCs requires other effective parameters. Immune molecules in RBCs are expected to become supplementary markers for evaluating RBC quality.
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BACKGROUND: Higher magnesium intake was linked to lower risk of hepatocellular carcinoma (HCC). However, the relationship between blood magnesium level and HCC has not been fully characterized, especially among liver cirrhosis patients who are at higher risk for HCC. METHODS: In the Mass General Brigham Biobank, we developed a new prospective cohort of 1,460 liver cirrhosis patients without liver cancer history using the validated International Classification of Diseases codes. We used Cox proportional hazard models to generate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident HCC, and used generalized estimating equations to compare changes in liver biomarkers according to baseline blood magnesium, adjusting for age, sex, race, lifestyles, body mass index, type 2 diabetes, model for end-stage liver disease score, and hepatitis infection. RESULTS: During a median follow-up period of 4.26 years, 109 developed HCC. Magnesium deficiency (<1.70mg/dL; N = 158) was associated with a higher risk of HCC (HR =1.88; 95%CI:1.10-3.22) compared to magnesium sufficiency. This association remained robust in the 1-year lag analysis (HR=2.19; 95%CI:1.12-4.29) and in sensitivity analysis excluding patients with alcoholic liver disease (HR=2.26; 95%CI:1.16-4.42). Magnesium in the lowest quartile was associated with a faster increase in alanine transaminase (ß=3.74; 95%CI:0.51-6.97), direct bilirubin (ß=0.18; 95%CI:0.01-0.35), and total bilirubin (ß=0.20; 95%CI:0.02-0.37), compared to the highest quartile. CONCLUSIONS: Lower blood magnesium level is associated with higher HCC risk and unfavorable liver biomarkers changes. IMPACT: If confirmed, our findings may potentially enable better identification of high-risk patients for HCC and inform better management strategies for liver cirrhosis.
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Detecting airflow turbulence precursors promptly is crucial for ensuring flight safety and control. The initial stages of turbulence involve small reverse flows with random velocities and directions, which are not easily detected by existing airflow sensors. In this study, we designed a bionic, sensitivity-enhanced, bi-directional airflow sensor (BSBA) by incorporating bio-inspired circular tip slits and enlarging the central part of the cruciform beam structure. The BSBA exhibits a rapid response time (24.1 ms), high sensitivity (1.36 mV m-1 s-1), consistent detection of forward and backward airflow (correlation coefficient of 0.9854), and a low airflow detection threshold (1 ml). With these features, the proposed sensor can rapidly and accurately measure slight variations in the oscillating airflow, flow field, and contact force. The BSBA also achieves transparent obstacle detection on a quadrotor, even in visually challenging environments, by capturing minute changes in the flow fields produced by the quadrotor when encountering obstacles. The sensor's high sensitivity, consistent bi-directional detection, and fast response give it significant potential for enhancing safety in aircraft control systems.
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The physicochemical properties of dietary fiber in the gastrointestinal tract, such as hydration properties, adsorption properties, rheological properties, have an important influence on the physiological process of host digestion and absorption, leading to the differences in satiety and glucose and lipid metabolisms. Based on the diversified physicochemical properties of konjac glucomannan (KGM), it is meaningful to review the relationship of structural characteristics, physicochemical properties and glycose and lipid metabolism. Firstly, this paper bypassed the category of intestinal microbes, and explained the potential of dietary fiber in regulating glucose and lipid metabolism during nutrient digestion and absorption from the perspective of colloidal nutrition. Secondly, the modification methods of KGM to regulate its physicochemical properties were discussed and the relationship between KGM's molecular structure types and glycose and lipid metabolism were summarized. Finally, based on the characteristics of KGM, the application of KGM in the main material and ingredients of fat reduction food was reviewed. We hope this work could provide theoretical basis for the study of dietary fiber colloid nutrition science.
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Metabolismo dos Lipídeos , Mananas , Ciências da Nutrição , Fibras na Dieta , GlucoseRESUMO
In this paper, three Pd-coated Cu (PCC) wires with different Pd-layer thicknesses were used to make bonding samples, and the influence of Pd-layer thickness on the reliability of bonded points before and after a high-temperature storage test was studied. The results show that smaller bonding pressure and ultrasonic power lead to insufficient plastic deformation of the ball-bonded point, which also leads to small contact area with the pad and low bonding strength. Excessive bonding pressure and ultrasonic power will lead to 'scratch' on the surface of the pad and large-scale Ag spatter. The wedge-bonded point has a narrowed width when the bonding pressure and ultrasonic power are too small, and the tail edge will be cocked, resulting in false bonding and low strength. When the bonding pressure or ultrasonic power is too large, it will cause stress concentration, and the pad will appear as an 'internal injury', which will improve the failure probability; a high-temperature environment can make Cu-Ag intermetallic compounds (IMCs) grow and improve the bonding strength. With the extension of high-temperature storage time, the shear force of Pd100 gradually reaches the peak and then decreases, due to Kirkendall pores caused by excessive growth of IMCs, while the shear force of Pd120 continued to increase due to the slow growth rate of IMCs. In the high-temperature storage test, the thicker the Pd layer of the bonding wire, the higher the bonding strength; in the cold/hot cycle test, the sample with the largest Pd-layer thickness has the lowest failure rate. The thicker the Pd layer, the stronger its ability to resist changes in the external environment, and the higher its stability and reliability.
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ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. MATERIALS AND METHODS: Jinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. RESULTS: Seventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 µM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. CONCLUSIONS: This study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.