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PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.
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Antineoplásicos , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Carcinoma de Células Transicionales/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo U , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: Sonographic features are associated with pathological and immunohistochemical characteristics of triple-negative breast cancer (TNBC). To predict the biological property of TNBC, the performance using quantitative high-throughput sonographic feature analysis was compared with that using qualitative feature assessment. METHODS: We retrospectively reviewed ultrasound images, clinical, pathological, and immunohistochemical (IHC) data of 252 female TNBC patients. All patients were subgrouped according to the histological grade, Ki67 expression level, and human epidermal growth factor receptor 2 (HER2) score. Qualitative sonographic feature assessment included shape, margin, posterior acoustic pattern, and calcification referring to the Breast Imaging Reporting and Data System (BI-RADS). Quantitative sonographic features were acquired based on the computer-aided radiomics analysis. Breast cancer masses were manually segmented from the surrounding breast tissues. For each ultrasound image, 1688 radiomics features of 7 feature classes were extracted. The principal component analysis (PCA), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were used to determine the high-throughput radiomics features that were highly correlated to biological properties. The performance using both quantitative and qualitative sonographic features to predict biological properties of TNBC was represented by the area under the receiver operating characteristic curve (AUC). RESULTS: In the qualitative assessment, regular tumor shape, no angular or spiculated margin, posterior acoustic enhancement, and no calcification were used as the independent sonographic features for TNBC. Using the combination of these four features to predict the histological grade, Ki67, HER2, axillary lymph node metastasis (ALNM), and lymphovascular invasion (LVI), the AUC was 0.673, 0.680, 0.651, 0.587, and 0.566, respectively. The number of high-throughput features that closely correlated with biological properties was 34 for histological grade (AUC 0.942), 27 for Ki67 (AUC 0.732), 25 for HER2 (AUC 0.730), 34 for ALNM (AUC 0.804), and 34 for LVI (AUC 0.795). CONCLUSION: High-throughput quantitative sonographic features are superior to traditional qualitative ultrasound features in predicting the biological behavior of TNBC. KEY POINTS: ⢠Sonographic appearances of TNBCs showed a great variety in accordance with its biological and clinical characteristics. ⢠Both qualitative and quantitative sonographic features of TNBCs are associated with tumor biological characteristics. ⢠The quantitative high-throughput feature analysis is superior to two-dimensional sonographic feature assessment in predicting tumor biological property.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Metástasis Linfática , Curva ROC , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , UltrasonografíaRESUMEN
CO2-assisted oxidative dehydrogenation of propane (CO2-ODHP) is an attractive strategy to offset the demand gap of propylene due to its potentiality of reducing CO2 emissions, especially under the demands of peaking CO2 emissions and carbon neutrality. The introduction of CO2 as a soft oxidant into the reaction not only averts the over-oxidation of products, but also maintains the high oxidation state of the redox-active sites. Furthermore, the presence of CO2 increases the conversion of propane by coupling the dehydrogenation of propane (DHP) with the reverse water gas reaction (RWGS) and inhibits the coking formation to prolong the lifetime of catalysts via the reverse Boudouard reaction. An effective catalyst should selectively activate the C-H bond but suppress the C-C cleavage. However, to prepare such a catalyst remains challenging. Chromium-based catalysts are always applied in industrial application of DHP; however, their toxic properties are harmful to the environment. In this aspect, exploring environment-friendly and sustainable catalytic systems with Cr-free is an important issue. In this review, we outline the development of the CO2-ODHP especially in the last ten years, including the structural information, catalytic performances, and mechanisms of chromium-free metal-based catalyst systems, and the role of CO2 in the reaction. We also present perspectives for future progress in the CO2-ODHP.
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Deoxynivalenol (DON) or "vomitoxin" is a mycotoxin produced by Fusarium species. Few food poisoning cases caused by DON have been reported since the 1990s in China. However, on May 16, 2019, the Zhuhai Center for Disease Control and Prevention received a case report from primary school "S" that many students began vomiting after eating breakfast. To discern the cause and control the outbreak effectively, an epidemiological investigation was carried out. This retrospective cohort study defined both suspected and probable cases of food poisoning using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry to detect 16 mycotoxins simultaneously. A total of 101 cases (14 suspected and 87 probable) were identified, with an overall attack rate of 8.1%. All cases were in grades 1-3. The main symptoms of probable cases were vomiting (100%) and nausea (63%). The average incubation time was 25 min after eating. Comparison of students who ate breakfast provided by the school with those who did not revealed the relative risk was 6.0 (95% confidence intervals [CI] = 2.2-16) among students in grades 1-3. The concentration of DON in the leftover raw breakfast noodles ranged from 6856 to 11,982 µg/kg and 878.3 to 1074.2 µg/kg in leftover cooked noodles. DON exposure was 1.3-1.6 µg/kg body weight for grades 1-2 and 1.7-2.1 µg/kg body weight for grade 3. The attack rate of grade 3 was 4.3 times higher than that for grades 1-2 (95% CI = 3.0-6.3). The food poisoning outbreak on May 16, 2019 in primary school "S" in China, was determined to be caused by DON-contaminated commercial raw noodles.
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Contaminación de Alimentos/análisis , Microbiología de Alimentos/estadística & datos numéricos , Enfermedades Transmitidas por los Alimentos/microbiología , Micotoxinas/toxicidad , Tricotecenos/toxicidad , Niño , China , Cromatografía Líquida de Alta Presión , Femenino , Servicios de Alimentación , Enfermedades Transmitidas por los Alimentos/epidemiología , Humanos , Masculino , Micotoxinas/análisis , Estudios Retrospectivos , Servicios de Salud Escolar , Instituciones Académicas , Espectrometría de Masas en Tándem , Tricotecenos/análisisRESUMEN
There is a growing interest in the use of hybrid liposomes for various biochemical and biomedical applications. In this study, we report the first preparation and characterization of a class of TiO2-reinforced liposomes by a one-step assembly approach. The amphiphilic natural structure of lipids is exploited to localize a hydrophobic molecule, namely, precursor tetrabutyl titanate (TBOT), in the mid-plane of the liposomal bilayer assemblies in the aqueous phase. In situ TiO2 nanoshell formation is driven by subsequent interfacial hydrolysis of TBOT and the ensuing condensation within the hydrophobic interstices of the lipid bilayer. The core-shell structure, like cell and wall, is demonstrated by means of scanning electron microscopy and transmission electron microscopy images, and the formation of the TiO2 shell is confirmed using energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. To study the structural evolution of the hybrid liposomes during titania formation, fluorescence probe technique and surface pressure versus molecular area (π- A) isotherms are designed. The results demonstrate that the incorporation of TBOT into the mid-membrane of the lipid and titania in the core of the membrane strengthened the assembly of the lipid bilayer. We further demonstrate that titania shell improved the stability and release property of liposomes. We expect that the reported new TiO2-coated liposomes by co-assembly will be valuable in designing hybrid liposomes, exhibiting integrative capacity for drug encapsulation, compartment reaction, and photocatalysis.
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Membrana Dobles de Lípidos/química , Nanoestructuras , Titanio/química , Interacciones Hidrofóbicas e Hidrofílicas , Liposomas , Microscopía Electrónica de Rastreo , Nanoestructuras/química , Nanoestructuras/ultraestructura , Espectrometría por Rayos XRESUMEN
A novel, high-efficiency and high-selectivity construction of ß-trifluoromethyl enol ether via base-induced/promoted C-O coupling of trifluoromethylated vinyl chloride and phenols is presented with a broad substrate scope. The reaction mechanism, especially the significantly high selectivity, was excavated and understood via DFT calculation and is well supported by the experimental observation.
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BACKGROUND: Numerous case-control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (-765G > C), rs689466 (-1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. METHODS: We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. RESULTS: Finally 8 case-control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. CONCLUSION: Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association.
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Carcinoma de Células Escamosas/genética , Ciclooxigenasa 2/genética , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/genética , Humanos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
The Kazak ethnic minority is a large ethnic group in the Xinjiang Uygur Autonomous Region of China and is valuable resource for the study of ethnogeny. In the present study, 24 Y-chromosomal short tandem repeat (Y-STR) loci were analyzed in 201 unrelated Kazak male individuals from Ili Kazak Autonomous Prefecture, Xinjiang, China. The gene diversity of the 24 Y-STR loci in the studied Kazak group ranged from 0.0050 to 0.9104. According to haplotypic analysis of the 24 Y-STR loci, 113 different haplotypes were obtained, 96 of which were unique. The haplotype diversity and discrimination capacity in Kazak group were 0.9578 and 0.5622 at 24 STR loci, respectively. The haplotype diversity and discrimination capacity at Y-filer 17 loci, extended 11 loci, and minimal 9 loci were reduced to 0.9274 and 0.4279, 0.8459 and 0.3284, and 0.8354 and 0.2985, respectively, which could indicate that the more loci were detected, the higher forensic efficacy was obtained. We evaluated the application value of the 24 loci in forensic sciences and analyzed interpopulation differentiations by making comparisons between the Kazak1 (represent our samples from Ili Kazak Autonomous Prefecture) group and other 14 groups. The results of pairwise genetic distances, multidimensional scaling plot, and neighbor-joining tree at the same set of 17 Y-filer loci indicated that the Kazak1 group had the closer genetic relationships with Kazak2 (represent samples from the whole territory of Xinjiang Uygur Autonomous Region), Mongolian, and Uygur ethnic groups. The present results may provide useful information for paternal lineages in forensic cases and can also increase our understanding of the genetic relationships between Kazak1 and other groups.
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Cromosomas Humanos Y , Etnicidad/genética , Genética de Población , Haplotipos , Repeticiones de Microsatélite , China , Variación Genética , Humanos , MasculinoRESUMEN
A single-tube multiplex assay of a small set of ancestry-informative markers (AIMs) for effectively estimating individual ancestry and admixture is an ideal forensic tool to trace the population origin of an unknown DNA sample. We present a newly developed 27-plex single nucleotide polymorphism (SNP) panel with highly robust and balanced differential power to perfectly assign individuals to African, European, and East Asian ancestries. Evaluating 968 previously described intercontinental AIMs from three HapMap population genotyping datasets (Yoruban in Ibadan, Nigeria (YRI); Utah residents with Northern and Western European ancestry from the Centre de'Etude du Polymorphism Humain (CEPH) collection (CEU); and Han Chinese in Beijing, China (CHB)), the best set of markers was selected on the basis of Hardy-Weinberg equilibrium (p > 0.00001), population-specific allele frequency (two of three δ values >0.5), according to linkage disequilibrium (r (2) < 0.2), and capable of being multiplexed in one tube and detected by capillary electrophoresis. The 27-SNP panel was first validated by assigning the ancestry of the 11 populations in the HapMap project. Then, we tested the 27-plex SNP assay with 1164 individuals from 17 additional populations. The results demonstrated that the SNP panel was successful for ancestry inference of individuals with African, European, and East Asian ancestry. Furthermore, the system performed well when inferring the admixture of Eurasians (EUR/EAS) after analyzing admixed populations from Xinjiang (Central Asian) as follows: Tajik (68:27), Uyghur (49:46), Kirgiz (40:57), and Kazak (36:60). For individual analyses, we interpreted each sample with a three-ancestry component percentage and a population match probability sequence. This multiplex assay is a convenient and cost-effective tool to assist in criminal investigations, as well as to correct for the effects of population stratification for case-control studies.
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Dermatoglifia del ADN/métodos , Genética de Población , Reacción en Cadena de la Polimerasa Multiplex , Polimorfismo de Nucleótido Simple , Grupos Raciales/genética , Frecuencia de los Genes , Proyecto Mapa de Haplotipos , Humanos , Repeticiones de MicrosatéliteRESUMEN
Previously, we developed and validated a multiplex assay of 27 ancestry-informative markers (AIMs) for analyzing African (AFR), European (EUR), and East Asian (EAS) ancestry components. In this study, we typed and collectively analyzed a large Uyghur sample of 979 individuals to estimate the genetic coefficients of the 27 AIMs and investigate differentiation parameters between Uyghur and Han. The Uyghur allele frequencies ranged from 0.243 to 0.952, and heterozygosities ranged from 0.091 to 0.500. Values of F st 3 and I n 3 for EUR, Uyghur, and EAS ranged from 0.028 to 0.550 and 0.0002 to 0.345, respectively. The Uyghur population displays a substantial ancestry contribution of 50.3:49.7 (EUR:EAS) and was efficiently discriminated from Han Chinese with an accuracy of 99.285 %. All populations were clustered into AFR, EUR, EAS, and admixture groups of these three ancestries. Central Asian was obviously stratified from the other admixture populations of South Asians, North Asians, and the Americans. The 27 SNPs yield a circle with an average distance of 0.936 from the center (0, 0) in PCA analysis. Using this set, Chinese Uyghur and Han populations achieved accurate differentiation, and our updated genotype database (by citing 1000 Genomes data) of 43 worldwide populations is a useful resource for forensic applications and disease association studies.
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Etnicidad/genética , Polimorfismo de Nucleótido Simple , China , Frecuencia de los Genes , Genética de Población , Genotipo , Heterocigoto , Humanos , Análisis de Componente PrincipalRESUMEN
OBJECTIVE: To identify the predictors of the positive results of transrectal ultrasound (TRUS)-guided biopsy for prostate cancer. METHODS: We performed univariate and multivariate logistic regression analyses on the relevant data on 385 male patients that underwent TRUS-guided biopsy for prostate cancer, including such potential predictors as age, body mass index (BMI), symptoms, results of digital rectal examination (DRE), tPSA, fPSA, free/total PSA ratio (f/tPSA), prostate volume (PV), and PSA density (PSAD) for identification of the risk factors related to the positive rate of biopsy. Then we constructed a scoring system as a tool for predicting prostate cancer in repeat biopsies and determined the sensitivity of the system by calculating the false positive rate using the receiver operating characteristic curve. RESULTS: Among the 385 patients, 139 (36.1%) were diagnosed with prostate cancer. On multivariate analysis, age (P < 0.01), DRE (P < 0.01), tPSA (P < 0.01), fPSA (P < 0.01), f/tPSA (P < 0.01), PV (P < 0.01), and PSAD (P < 0.01) were all significant predictors of prostate cancer. Multivariate logistic regression analysis showed age, tPSA, f/tPSA, PV, and PSAD to be independent predictors, with ORs and 95% CIs of 1.07 (1.05-1.16), 1.05 (1.02-1.15), 0.97 (0.86-0.99), 0.98 (0.87-0.96), and 1.79 (1.48-2.06), respectively. Moreover, patients with the risk score of 3-5 had a significantly higher rate of prostate cancer than those with 0-2 (64% vs 11%, P < 0.001). CONCLUSION: The scoring system on the key predictors of prostate cancer can help urologists to identify the men in need of prostatic biopsy.
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Próstata/patología , Neoplasias de la Próstata/patología , Anciano , Tacto Rectal , Humanos , Biopsia Guiada por Imagen/métodos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/química , Curva ROC , Factores de Riesgo , Ultrasonografía Intervencional/métodosRESUMEN
The first examples of a Pd-catalyzed carbonylation of aryl boronic acids with sp(3) carbon partners are presented. Various boronic acids were shown to react with 1,3-diesters and 1,3-diketones to afford structurally unique carbonyl compounds. By employing 2-substituted 1,3-diesters, synthetically-challenging quaternary carbon centres were accessed. In total, 42 examples of aryl carbonyl compounds were prepared in moderate to good yields. The catalytic system features the use of a bidentated phosphine ligand and a relatively low CO pressure (5 atm), providing an easy, alternative method for the preparation of triketones.
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Phytochemical investigation of the 70% ethanol extract from Viburnum ternatum resulted in the isolation of three new compounds, vibsanol-9'-al (1), 4-methoxy-vibsanol (2), and 5,7-dihydroxy-4'-methoxyflavanone(8 â 3')-5,7-dihydroxy-4'-methoxyflavone (4), together with a known compound vibsanol (3). Their structures were determined on the basis of spectroscopic analyses, including 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses.
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Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Etanol/química , Viburnum/química , Diterpenos/química , Medicamentos Herbarios Chinos/química , Flavonoides , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Objective: To compare low- vs high-power HoLEP effects on coagulation in patients on antiplatelet (AP) therapy via thromboelastography (TEG). Methods: 210 patients was retrospectively analyzed and stratificated into three discrete groups, specifically: Group A (AP therapy, high-power HoLEP, n = 72); Group B (AP therapy, low-power HoLEP, n=73); Group C (no AP therapy, low-power HoLEP, n = 65). Baseline characteristics and coagulation profiles via TEG were compared. Univariate and multivariate analyses were conducted to identify independent risk factors associated with hematuria. Furthermore, parameters such as IPSS, Qmax, post-void residual volume V2 and PSA levels were recorded during 1year follow-up. Results: No differences in terms of baseline characteristics across all groups. Significant differences were observed in the duration of enucleation, morcellation, bladder irrigation, post-operative catheterization, length of hospital stay and the extent of hemoglobin reduction (F = 54.06, 8.54, 6.68, 9.24, 17.06, 5.97, p < 0.05). No differences were noted in postoperative hematuria, urine retention, transfusion rates, and SUI (x1 2 = 1.082 ; x2 2 = 0.197,; x3 2 = 3.981;x4 2 = 0.816, p > 0.05). Univariate and multivariate analyses revealed that prostate volume emerged as an independent risk factor for hematuria (OR 1.080, 95% CI: 1.007-1.158, p = 0.031). Clinical outcomes including Qmax, IPSS, V2, and PSA demonstrated significant enhancement during 1 year follow-up. Conclusion: Compared to HP-HoLEP, LP-HoLEP effectively reduces surgical and subsequent processing times, decreases hospital stay duration, and diminishes hemoglobin decline, offering a viable option without discontinuing AP therapy.
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Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.
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Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD is prevalent in about 30% of people worldwide. The lack of physical activity is considered as one of the risks for NAFLD, and approximately one-third of NAFLD patients hardly engage in physical activity. It is acknowledged that exercise is one of the optimal non-pharmacological methods for preventing and treating NAFLD. Different forms of exercise such as aerobic exercise, resistance exercise and even simply physical activity in a higher level can be beneficial in reducing liver lipid accumulation and disease progression for NAFLD patients. In NAFLD patients, exercise is helpful in lowering steatosis and enhancing liver function. The mechanisms underlying the prevention and treatment of NAFLD by exercise are various and complex. Current studies on the mechanisms have focused on the pro-lipolytic, anti-inflammatory, and antioxidant and lipophagy. Promotion of lipophagy is regarded as an important mechanism for prevention and improvement of NAFLD by exercise. Recent studies have investigated the above mechanism, yet the potential mechanism has not been completely elucidated. Thus, in this review, we cover the recent advances of exercise-promoted lipophagy in NAFLD treatment and prevention. Furthermore, given the fact that exercise activates SIRT1, we discuss the possible regulatory mechanisms of lipophagy by SIRT1 during exercise. These mechanisms need to be verified by further experimental studies.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Sirtuina 1/metabolismo , Lipólisis , Autofagia , Ejercicio Físico , Hígado/metabolismoRESUMEN
Compound cross-sections with vegetated floodplains are a common type of cross-section in debris-flow gullies. Floodplain vegetation participates in large-scale debris flow events and regulates debris-flow discharge. Extensive research has been conducted on the water flow characteristics of compound rivers. However, few studies have investigated the debris flow characteristics of compound channels in mountainous areas, particularly those of debris flow and flash flood inundation areas with vegetation. This study discusses the section characteristics of debris flow gullies with vegetated floodplains, gully evolution processes, and their influence on debris flow. The results show that the compound debris flow gully with a vegetated floodplain is formed in the gully from the mature stage to the old-mature stage. The compound sections are developed in flow areas with a gentle slope, which can be bilateral floodplain, unilateral floodplain, and multi-main gully floodplain types. Owing to the vegetation of the floodplain, the roughness of the channel increases, which makes the beach roughness coefficient much larger than that for the main channel. In the integrated Manning coefficient method, the error in resolving the flow velocity and discharge is large and cannot reflect the difference in velocities of the floodplain and main channel, therefore the sectional splitting method is most applicable. Influencing debris flow movement, limiting channel migration, and retaining debris flow to the main channel were the main contributions of the riparian forest zone.
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Owing to the feature of strong α-glucosidase inhibitory activity, 1-deoxynojirimycin (1-DNJ) has broad application prospects in areas of functional food, biomedicine, etc., and this research wants to construct an efficient strain for 1-DNJ production, basing on Bacillus amyloliquefaciens HZ-12. Firstly, using the temperature-sensitive shuttle plasmid T2 (2)-Ori, gene ptsG in phosphotransferase system (PTS) was weakened by homologous recombination, and non-PTS pathway was strengthened by deleting its repressor gene iolR, and 1-DNJ yield of resultant strain HZ-S2 was increased by 4.27-fold, reached 110.72 mg/L. Then, to increase precursor fructose-6-phosphate (F-6-P) supply, phosphofructokinase was weaken, fructose phosphatase GlpX and 6-phosphate glucose isomerase Pgi were strengthened by promoter replacement, moreover, regulator gene nanR was deleted, 1-DNJ yield was further increased to 267.37 mg/L by 2.41-fold. Subsequently, promoter of 1-DNJ synthetase cluster was optimized, as well as 5'-UTRs of downstream genes in synthetase cluster, and 1-DNJ produced by the final strain reached 478.62 mg/L. Last but not the least, 1-DNJ yield of 1632.50 mg/L was attained in 3 L fermenter, which was the highest yield of 1-DNJ reported to date. Taken together, our results demonstrated that metabolic engineering was an effective strategy for 1-DNJ synthesis, this research laid a foundation for industrialization of functional food and drugs based on 1-DNJ.