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2.
Phytomedicine ; 130: 155398, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38788390

RESUMEN

BACKGROUND: The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. HYPOTHESIS/PURPOSE: This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. STUDY DESIGN: A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. RESULTS: Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (ß, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (ß, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (ß, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. CONCLUSION: Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.


Asunto(s)
Alanina Transaminasa , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/microbiología , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Método Doble Ciego , Alanina Transaminasa/sangre , Adulto , Microbioma Gastrointestinal/efectos de los fármacos , Hígado/efectos de los fármacos , Medicina Tradicional China/métodos
3.
Clin Transl Gastroenterol ; 15(3): e00680, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38240390

RESUMEN

INTRODUCTION: In metabolic dysfunction-associated steatotic liver disease, the diagnostic efficacy of controlled attenuation parameter (CAP) was not very accurate in evaluating liver fat content. The aim of this study was to develop a score, based on CAP and conventional clinical parameters, to improve the diagnostic performance of CAP regarding liver fat content. METHODS: A total of 373 participants from 2 independent Chinese cohorts were included and divided into derivation (n = 191), internal validation (n = 75), and external validation (n = 107) cohorts. Based on the significant difference index between the 2 groups defined by the magnetic resonance imaging-proton density fat fraction (MRI-PDFF) in derivation cohort, the optimal model (CAP-BMI-AST score [CBST]) was screened by the number of parameters and the area under the receiver operating characteristic curve (AUROC). In the internal and external validation cohorts, the AUROC and corresponding 95% confidence intervals (CIs) were used to compare the diagnostic performance of CBST with that of CAP. RESULTS: We constructed the CBST = -14.27962 + 0.05431 × CAP - 0.14266 × body mass index + 0.01715 × aspartate aminotransferase. When MRI-PDFF was ≥20%, ≥10%, and ≥5%, the AUROC for CBST was 0.77 (95% CI 0.70-0.83), 0.89 (95% CI 0.83-0.94), and 0.93 (95% CI 0.88-0.98), which was higher than that for CAP respectively. In the internal validation cohort, the AUROC for CBST was 0.80 (95% CI 0.70-0.90), 0.95 (95% CI 0.91-1.00), and 0.98 (95% CI 0.94-1.00). The optimal thresholds of CBST were -0.5345, -1.7404, and -1.9959 for detecting MRI-PDFF ≥20%, ≥10%, and ≥5%, respectively. DISCUSSION: The CBST score can accurately evaluate liver steatosis and is superior to the CAP.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Imagen por Resonancia Magnética , Curva ROC
4.
Nat Commun ; 14(1): 5451, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37673856

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Masculino , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , PPAR alfa/genética , Ácidos y Sales Biliares , Citoplasma , Ratones Noqueados , Ácidos Grasos
5.
J Cell Sci ; 136(18)2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37622462

RESUMEN

Triple-negative breast cancer (TNBC) is the most aggressive and poorly treated subtype of breast cancer. Identifying novel drivers and mechanisms for tumor progression is essential for precise targeted therapy of TNBC. Immunoglobulin-like transcript 4 (ILT4; also known as LILRB2) is a classic myeloid suppressor for their activation and immune response. Our recent results found that ILT4 is also highly expressed in lung cancer cells, where it has a role in promoting immune evasion and thus tumor formation. However, the expression and function of ILT4 in breast cancer remains elusive. Here, using our patient cohort and public database analysis, we found that TNBC displayed the most abundant ILT4 expression among all breast cancer subtypes. Functionally, enriched ILT4 promoted TNBC cell proliferation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Our study identified a novel driver for TNBC progression and proposed a promising strategy to combat TNBC by targeting ILT4.


Asunto(s)
Neoplasias Pulmonares , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , Transportador de Glucosa de Tipo 3 , Proliferación Celular/genética , Glucosa
6.
PeerJ Comput Sci ; 9: e1467, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37547422

RESUMEN

Semantic segmentation for extracting buildings and roads from uncrewed aerial vehicle (UAV) remote sensing images by deep learning becomes a more efficient and convenient method than traditional manual segmentation in surveying and mapping fields. In order to make the model lightweight and improve the model accuracy, a lightweight network using object attention (LOANet) for buildings and roads from UAV aerial remote sensing images is proposed. The proposed network adopts an encoder-decoder architecture in which a lightweight densely connected network (LDCNet) is developed as the encoder. In the decoder part, the dual multi-scale context modules which consist of the atrous spatial pyramid pooling module (ASPP) and the object attention module (OAM) are designed to capture more context information from feature maps of UAV remote sensing images. Between ASPP and OAM, a feature pyramid network (FPN) module is used to fuse multi-scale features extracted from ASPP. A private dataset of remote sensing images taken by UAV which contains 2431 training sets, 945 validation sets, and 475 test sets is constructed. The proposed basic model performs well on this dataset, with only 1.4M parameters and 5.48G floating point operations (FLOPs), achieving excellent mean Intersection-over-Union (mIoU). Further experiments on the publicly available LoveDA and CITY-OSM datasets have been conducted to further validate the effectiveness of the proposed basic and large model, and outstanding mIoU results have been achieved. All codes are available on https://github.com/GtLinyer/LOANet.

7.
Front Pharmacol ; 14: 1097835, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817150

RESUMEN

The incidence of obesity and associated metabolic diseases is increasing globally, adversely affecting human health. Dietary fats, especially triglycerides, are an important source of energy for the body, and the intestine absorbs lipids through a series of orderly and complex steps. A long-term high-fat diet leads to intestinal dysfunction, inducing obesity and metabolic disorders. Therefore, regulating dietary triglycerides absorption is a promising therapeutic strategy. In this review, we will discuss diverse aspects of the dietary triglycerides hydrolysis, fatty acid uptake, triglycerides resynthesis, chylomicron assembly, trafficking, and secretion processes in intestinal epithelial cells, as well as potential targets in this process that may influence dietary fat-induced obesity and metabolic diseases. We also mention the possible shortcomings and deficiencies in modulating dietary lipid absorption targets to provide a better understanding of their administrability as drugs in obesity and related metabolic disorders.

8.
Med Phys ; 50(3): 1635-1646, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36303466

RESUMEN

BACKGROUND: Automatic segmentation of lesion, organ, and tissue from the medical image is an important part of medical image analysis, which are useful for improving the accuracy of disease diagnosis and clinical analysis. For skin melanomas lesions, the contrast ratio between lesions and surrounding skin is low and there are many irregular shapes, uneven distribution, and local and boundary features. Moreover, some hair covering the lesions destroys the local context. Polyp characteristics such as shape, size, and appearance vary at different development stages. Early polyps with small sizes have no distinctive features and could be easily mistaken for other intestinal structures, such as wrinkles and folds. Imaging positions and illumination conditions would alter polyps' appearance and lead to no visible transitions between polyps and surrounding tissue. It remains a challenging task to accurately segment the skin lesions and polyps due to the high variability in the location, shape, size, color, and texture of the target object. Developing a robust and accurate segmentation method for medical images is necessary. PURPOSE: To achieve better segmentation performance while dealing with the difficulties above, a U-shape network based on the encoder and decoder structure is proposed to enhance the segmentation performance in target regions. METHODS: In this paper, a novel deep network of the encoder-decoder model that combines HarDNet, dual attention (DA), and reverse attention (RA) is proposed. First, HarDNet68 is employed to extract the backbone features while improving the inference speed and computational efficiency. Second, the DA block is adopted to capture the global feature dependency in spatial and channel dimensions, and enrich the contextual information on local features. At last, three RA blocks are exploited to fuse and refine the boundary features to obtain the final segmentation results. RESULTS: Extensive experiments are conducted on a skin lesion dataset which consists of ISIC2016, ISIC2017, and ISIC 2018, and a polyp dataset which consists of several public datasets, that is, Kvasir, CVC-ClinicDB, CVC-ColonDB, ETIS, Endosece. The proposed method outperforms some state-of-art segmentation models on the ISIC2018, ISIC2017, and ISIC2016 datasets, with Jaccard's indexes of 0.846, 0.881, and 0.894, mean Dice coefficients of 0.907, 0.929, and 03939, precisions of 0.908, 0.977, and 0.968, and accuracies of 0.953, 0.975, and 0.972. Additionally, the proposed method also performs better than some state-of-art segmentation models on the Kvasir, CVC-ClinicDB, CVC-ColonDB, ETIS, and Endosece datasets, with mean Dice coefficients of 0.907, 0.935, 0.716, 0.667, and 0.887, mean intersection over union coefficients of 0.850, 0.885, 0.644, 0.595, and 0.821, structural similarity measures of 0.918, 0.953, 0.823, 0.807, and 0.933, enhanced alignment measures of 0.952, 0.983, 0.850, 0.817, and 0.957, mean absolute errors of 0.026, 0.007, 0.037, 0.030, and 0.009. CONCLUSIONS: The proposed deep network could improve lesion segmentation performance in polyp and skin lesion images. The quantitative and qualitative results show that the proposed method can effectively handle the challenging task of segmentation while revealing the great potential for clinical application.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Procesamiento de Imagen Asistido por Computador , Iluminación , Piel , Neoplasias Cutáneas/diagnóstico por imagen
9.
Front Pharmacol ; 13: 1027628, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36467028

RESUMEN

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are prevalent in China. According to traditional Chinese medicine (TCM) theory, damp-heat (DH) syndrome is common in chronic liver disease. However, the biological characteristics related to quantitative diagnosis remain to be determined. This study aimed to identify the consistent alterations in the gut microbiota associated with DH syndrome in patients with CHB or NAFLD. Methods: A total of 405 individuals were recruited, of which 146 were participants who met the consistent TCM diagnosis by three senior TCM physicians and were typical syndromes. All participants were required to provide fresh stool and serum samples. The gut microbiota was assessed by fecal 16S rRNA gene sequencing, and the serum metabolite profiles of participants were quantified by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. DH syndrome-related bacteria taxa were identified based on the 146 individuals with typical syndromes and validated in all 405 volunteers. Results: The results showed that CHB and NAFLD patients with typical TCM DH syndrome had consistently elevated serum total bile acid (TBA) levels. Significant alterations in microbial community were observed according to TCM syndromes identification. A total of 870 microbial operational taxonomic units and 21 serum metabolites showed the same variation trends in both the CHB and NAFLD DH syndrome groups. The functional analysis predicts consistent dysregulation of bile acid metabolism. Five genera (Agathobacter, Dorea, Lachnospiraceae_NC2004_group, Subdoligranulum, and unclassified_c__Clostridia) significantly decreased in abundance in patients with DH syndrome. We utilize these five genera combined with TBA to construct a random forest classifier model to predict TCM diagnosis. The diagnostic receiver-operator characteristic (ROC) areas for DH syndrome were 0.818 and 0.791 in internal tenfold cross-validation and the test set based on all 405 individuals, respectively. Conclusion: There are common signatures of gut microbiota associated with DH syndrome in patients with different chronic liver diseases. Serum TBA combined with DH-related genera provides a good diagnostic potential for DH syndrome in chronic liver disease.

10.
Cell Host Microbe ; 30(7): 944-960.e8, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35654045

RESUMEN

The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. Thus, our findings provide evidence that small molecules released from the gut microbiome can directly bind genomic DNA and act as transcriptional coregulators by recruiting transcription factors. These findings further unveil a molecular mechanism that connects gut metabolism to gene expression in the brain with implications for disease development.


Asunto(s)
Bacteriófagos , Disfunción Cognitiva , Microbioma Gastrointestinal , Aminas , Animales , Bacterias , Bacteriófagos/genética , Humanos , Ratones , Microglía , Proteína p53 Supresora de Tumor
11.
RSC Adv ; 12(12): 7189-7198, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35424694

RESUMEN

Organic solvents are widely used in pharmaceutical and chemical industries. Their separation and recovery account for a large part of energy consumption and capital cost in many industrial processes. MoS2 membranes with varying pore sizes (0.6 nm pore with S atoms, 0.7 nm pore with Mo atoms, 1.3 nm pore with S atoms, 1.4 nm pore with Mo atoms) were investigated as organic solvent nanofiltration (OSN) membranes using molecular simulation in this study. The fluxes of five polar solvents (methanol, ethanol, propanol, acetonitrile and acetone) and a nonpolar solvent (n-hexane) were predicted. Although the 0.6 nm S pore has a smaller pore size, it has a better flux for some organic solvents than the 0.7 nm Mo pore. This selective behavior of molybdenum disulfide was confirmed by calculating the potential of mean force (PMF) of each solvent molecule. The PMFs show that polar solvents face a higher energy barrier through the pore, and greater resistance needs to be overcome. After testing the permeability of solvent by experiment and simulation, the flux changes of different solvents have the same trend in experiment and simulation. The solvent permeability was slightly affected in the presence of solute (acetaminophen), and MoS2 membranes with small pores demonstrated 100% rejection rate for acetaminophen. This study confirmed that pore chemistry and pore size play important roles in OSN, and MoS2 is a promising OSN membrane for the recovery of organic solvents.

12.
Hepatol Commun ; 6(8): 1975-1986, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35384367

RESUMEN

We used cross-sectional and longitudinal studies to comprehensively compare hepatic steatosis measurements obtained with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and controlled attenuated parameter (CAP) in hepatic steatosis in adults with nonalcoholic fatty liver disease (NAFLD). A total of 185 participants with NAFLD and 12 non-NAFLD controls were recruited. CAP and MRI-PDFF data were collected at baseline from all participants and from 95 patients included in the longitudinal study after 24 weeks of drug or placebo intervention. Pearson correlation, linear regression, and piecewise linear regression analyses were used to evaluate the relationship between the two modalities. Linear analysis suggested a positive correlation between CAP and MRI-PDFF (r = 0.577, p < 0.0001); however, piecewise linear regression showed no correlation when CAP was ≥331 dB/m (p = 0.535). In the longitudinal study, both the absolute and relative change measurements were correlated between the two modalities; however, the correlation was stronger for the relative change (relative r = 0.598, absolute r = 0.492; p < 0.0001). Piecewise linear regression analysis revealed no correlation when CAP was reduced by more than 53 dB/m (p = 0.193). Conclusions: We found a correlation between CAP and MRI-PDFF measurements for grading hepatic steatosis when CAP was <331 dB/m. While the measured absolute change and relative change were correlated, it was stronger for the relative change. These findings have implications for the clinical utility of CAP or MRI-PDFF in the clinical diagnosis and assessment of NAFLD.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Adulto , Antígenos CD36 , Estudios Transversales , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Protones , Curva ROC
13.
Small ; 18(6): e2105385, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34897972

RESUMEN

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plant-derived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited. Here an alcohol-induced chronic brain inflammation model is used to identify that the microglial cell is the novel target of oat nanoparticles (oatN). Oral administration of oatN inhibits brain inflammation and improves brain memory function of mice that are fed alcohol. Mechanistically, ethanol activates dectin-1 mediated inflammatory pathway. OatN is taken up by microglial cells via ß-glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN ß-glucan to dectin-1. Subsequently endocytosed ß-glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rab11a. This complex then sequesters the dectin-1 in the ERC in an oatN ß-glucan dependent manner and alters the location of dectin-1 from Golgi to early endosomes and lysosomes and increases exportation of dectin-1 into exosomes in an Rab11a dependent manner. Collectively, these cascading actions lead to preventing the activation of the alcoholic induced brain inflammation signing pathway(s). This coordinated assembling of the HPCA/Rab11a/dectin-1 complex by oral administration of oatN may contribute to the prevention of brain inflammation.


Asunto(s)
Exosomas , Lectinas Tipo C , Memoria , Microglía , Nanopartículas , Animales , Avena , Encéfalo , Etanol/administración & dosificación , Lectinas Tipo C/metabolismo , Memoria/fisiología , Ratones , Microglía/metabolismo
14.
Diabetes Metab Syndr Obes ; 14: 4241-4251, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34703257

RESUMEN

PURPOSE: White adipose tissue (WAT) has positive effects on peripheral metabolism parameters and liver energy metabolism. This study aimed to explain the pharmacological mechanism of Qushi Huayu (QSHY) granules in the treatment of nonalcoholic fatty liver disease (NALFD) mice based on branched-chain amino acid (BCAA) catabolism and WAT browning. PATIENTS AND METHODS: Thirty C57BL/6J mice were randomly divided into a (Ctrl) control group, fed with a control diet, a NAFLD model group, fed with a high-fat and high-sugar (HFHS) diet, and a QSHY granules treatment (HFHS+QSHY) group, administered with QSHY granules. After 14 weeks of feeding, HFHS+QSHY group mice were administered QSHY granules through oral gavage for 6 weeks. The metabolic parameters were assessed, the circular and fecal BCAA content was observed, and liver and epididymal WAT (eWAT) were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses. RESULTS: Compared with the HFHS group, mice in the HFHS+QSHY group demonstrated restored liver histological changes, ameliorated hepatocyte steatosis, and alleviated inflammatory cell infiltration. Consistent with the pathological changes, QSHY granules significantly reduced the elevated levels of liver triglycerides, and serum alanine aminotransferase, and it relieved hypercholesterolemia and insulin resistance in mice with HFHS-induced NAFLD. Furthermore, it corrected BCAA metabolic disorders in serum and feces and promoted the expression of BCAA catabolic genes in the eWAT of HFHS mice. QSHY granules also increased the expression of phosphorylated AMP-activated protein kinase (AMPK) protein, up-regulating the protein expression of the AMPK/SIRT1/UCP-1 pathway in the eWAT. CONCLUSION: QSHY granules improved hepatic steatosis and corrected the BCAA disorder in NAFLD mice, and the related mechanisms regulated the AMPK/SIRT1/UCP-1 pathway and promoted WAT browning.

15.
Mol Ecol ; 30(16): 4023-4038, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34107131

RESUMEN

The study of balancing selection, as a selective force maintaining adaptive genetic variation in gene pools longer than expected by drift, is currently experiencing renewed interest due to the increased availability of new data, methods of analysis, and case studies. In this investigation, evidence of balancing selection operating on conserved enhancers of the olfactory receptor (OR) genes is presented for the Chinese sleeper (Bostrychus sinensis), a coastal marine fish that is emerging as a model species for evolutionary studies in the Northwest Pacific marginal seas. Coupled with tests for Gene Ontology enrichment and transcription factor binding, population genomic data allow for the identification of an OR cluster in the sleeper with a downstream flanking region containing three enhancers that are conserved with human and other fish species. Phylogenetic and population genetic analyses indicate that the enhancers are under balancing selection as evidenced by their translineage polymorphisms, excess common alleles, and increased within-group diversities. Age comparisons between the translineage polymorphisms and most recent common ancestors of neutral genealogies substantiate that the former are old, and thus, due to ancient balancing selection. The survival and reproduction of vertebrates depend on their sense of smell, and thereby, on their ORs. In addition to locus duplication and allelic variation of structural genes, this study highlights a third mechanism by which receptor diversity can be achieved for detecting and responding to the huge variety of environmental odorants (i.e., by balancing selection acting on OR gene expression through their enhancer variability).


Asunto(s)
Peces/genética , Receptores Odorantes , Alelos , Animales , China , Proteínas de Peces/genética , Variación Genética , Filogenia , Polimorfismo Genético , Receptores Odorantes/genética , Selección Genética
17.
RSC Adv ; 11(14): 8356-8361, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35423333

RESUMEN

The rhodium-catalyzed olefination and deuteration of tetrahydrocarbazoles in water with the aid of an N,N-dimethylcarbamoyl-protected group is presented. This olefination method features a broad substrate scope, good functional-group tolerance, and high efficiency in water. Practical applications of the protocol are illustrated by the synthesis of various evodiamine derivatives. As such, this environmentally friendly approach to directly modify natural products will attract much attention in academic and industrial research.

18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 1045-1055, 2020 Dec 25.
Artículo en Chino | MEDLINE | ID: mdl-33369344

RESUMEN

In order to solve the problems of insufficient stimulation channels and lack of stimulation effect feedback in the current electrical stimulation system, a functional array electrode electrical stimulation system with surface electromyography (sEMG) feedback was designed in this paper. Firstly, the effectiveness of the system was verified through in vitro and human experiments. Then it was confirmed that there were differences in the number of amperage needed to achieve the same stimulation stage among individuals, and the number of amperage required by men was generally less than that of women. Finally, it was verified that the current required for square wave stimulation was smaller than that for differential wave stimulation if the same stimulation stage was reached. This system combined the array electrode and sEMG feedback to improve the accuracy of electrical stimulation and performed the whole process recording of feedback sEMG signal in the process of electrical stimulation, and the electrical stimulation parameters could change with the change of the sEMG signal. The electrical stimulation system and sEMG feedback worked together to form a closed-loop electrical stimulation working system, so as to improve the efficiency of electrical stimulation rehabilitation treatment. In conclusion, the functional array electrode electrical stimulation system with sEMG feedback developed in this paper has the advantages of simple operation, small size and low power consumption, which lays a foundation for the introduction of electrical stimulation rehabilitation treatment equipment into the family, and also provides certain reference for the development of similar products in the future.


Asunto(s)
Neurorretroalimentación , Estimulación Eléctrica , Electrodos , Electromiografía , Retroalimentación , Femenino , Humanos , Masculino
19.
Medicine (Baltimore) ; 99(33): e21085, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32871979

RESUMEN

The lymph nodal invasion diagnosis is critical for therapeutic-decision and follows up in gastric cancer. However, the number of nodes to be examined for nodal invasion diagnosis is still under controversy, and the model for quantifying risk of missing positive node is currently not reported yet. We analyzed the nodal invasion status of 13,857 gastric cancer samples with records of primary tumor stage, the number of examined and positive lymph nodes in the surveillance, epidemiology, and end results (SEER) database, fitting a beta-binomial model. The nodes need to be examined with different primary tumor stage were determined based on the model. Overall, examining 11 lymph nodes reduces the probability of missing positive nodes to <10%, and the currently median nodes dissected is adequate (12 nodes). While the number of nodes demands to be dissected for T1, T2, T3, and T4 subgroups are 6, 19, 40, and 66, respectively. The currently implemented median value for these samples was 12, 12, 13, and 16, separately. It implies that the number of nodes to be examined is sufficient for early gastric cancer (T1), but it is inadequate for middle and advanced gastric cancer (T2-T3). The clinical significance of nodal staging score was validated with survival information. In summary, we first quantified the lymph nodes to be examined during surgery using a beta-binomial model, and validated with survival information.


Asunto(s)
Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Estadificación de Neoplasias/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Reacciones Falso Negativas , Femenino , Humanos , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Probabilidad , Estudios Retrospectivos , Programa de VERF , Sensibilidad y Especificidad , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/cirugía , Análisis de Supervivencia
20.
ACS Omega ; 5(16): 9204-9211, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32363272

RESUMEN

The kinetics of benzophenone (BP) and its derivatives have been widely studied in different solvents by nanosecond laser flash photolysis as well as in the polymer matrix. With the development of functional polymer coating, BP, as well as other photocross-linkers, has been incorporated into the polymer backbone or side chain to form the covalent connection between polymer coatings and substrates, which can improve the mechanical and chemical stability of the coatings. In this work, a series of BP pendent zwitterionic copolymer kinetics were investigated using UV-vis for the first time. Because of the high hydrophilicity of the zwitterionic monomer, the influence of the polymer matrix's polarity on the cross-linking rate was observed. With a higher zwitterionic percentage in the copolymer, the polarity of the copolymer increases, BP reactivity decreases, and a hypothesis between the BP rate constant and partial coefficient log P was raised. Moreover, the thermal property is also an important factor affecting the BP reactivity. For polymers with high glass-transition temperature, the reactivity was not dominated by the chemical environment such as polarity, and the restricted segment movement reduces the cross-linking rate. Additionally, the ring substituents show similar effects to BP pendent copolymers as with small molecules. Electron-withdrawing groups help to stabilize the BP triplet radical and facilitate cross-linking, while electron-donating groups work conversely. Therefore, polarity, thermal properties, and substituents should be taken into consideration when designing BP-containing functional polymers.

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