OsGEX3 affects anther development and improves osmotic stress tolerance in rice.

MAIN CONCLUSION: Overexpression and loss of function of OsGEX3 reduce seed setting rates and affect pollen fertility in rice. OsGEX3 positively regulates osmotic stress response by regulating ROS scavenging. GEX3 proteins are conserved in plants. AtGEX3 encodes a plasma membrane protein that plays a crucial role in pollen tube guidance. However, the function of its homolog in rice, OsGEX3, has not been determined. Our results demonstrate that OsGEX3 is localized in the plasma membrane and the nucleus as shown by a transiently transformed assay using Nicotiana benthamiana leaves. The up-regulation of OsGEX3 was detected in response to treatments with polyethylene glycol (PEG) 4000, hydrogen peroxide, and abscisic acid (ABA) via RT-qPCR analysis. Interestingly, we observed a significant decline in the seed setting rates of OsGEX3-OE lines and mutants, compared to the wild type. Further investigations reveal that overexpression and loss of function of OsGEX3 affect pollen maturation. TEM observation revealed a significant decrease in the fertile pollen rates of OsGEX3-OE transgenic lines and Osgex3 mutants due to a delay in pollen development at the late vacuolated stage. Overexpression of OsGEX3 improved osmotic stress and oxidative stress tolerance by enhancing reactive oxygen species (ROS) scavenging in rice seedlings, whereas Osgex3 mutants exhibited an opposite phenotype in osmotic stress. These findings highlight the multifunctional roles of OsGEX3 in pollen development and the response to abiotic stress. The functional characterization of OsGEX3 provides a fundamental basis for rice molecular breeding and can facilitate efforts to cultivate drought resistance and yield-related varieties.

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis.

BACKGROUND: Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed. METHODS: In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples. RESULTS: We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density. CONCLUSION: Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity.

BACKGROUND: The discovery of a potent photosensitizer with desirable immunogenic cell death (ICD) ability can prominently enhance antitumor immunity in photodynamic therapy (PDT). However, majority of commercially-available photosensitizers suffer from serious aggregation and fail to elicit sufficient ICD. Pyroptosis as a newly identified pattern for potent ICD generation is rarely disclosed in reported photosensitizers. In addition, the photosensitizer with excellent mitochondria-anchored ability evokes prominent mitochondria oxidative stress, and consequently induces ICD. RESULTS: Herein, a novel supramolecular photosensitizer LDH@ZnPc is reported, without complicated preparation, but reveals desirable pyroptosis-triggered ability with mitochondria anchoring feature. LDH@ZnPc is obtained through isolation of ZnPc using positive charged layered double hydroxides (LDH), and excellent mitochondria-anchored ability is achieved. More importantly, LDH@ZnPc-mediated PDT can effectively initiate gasdermin D (GSDMD)-dependent pyroptosis of tumor cells. In vitro and in vivo results verify robust ICD ability and potent tumor inhibition efficacy, and antitumor immunity towards distant tumor inhibition. CONCLUSIONS: This study reveals that LDH@ZnPc can act as an excellent pyroptosis inducer with simultaneous mitochondria anchoring ability for enhancing photodynamic therapy and boosting antitumor immunity.

Interactions between Gut Microbiota and Polyphenols: New Insights into the Treatment of Fatigue.

Fatigue seriously affects people's work efficiency and quality of life and has become a common health problem in modern societies around the world. The pathophysiology of fatigue is complex and not fully clear. To some degree, interactions between gut microbiota and host may be the cause of fatigue progression. Polyphenols such as tannin, tea polyphenols, curcumin, and soybean isoflavones relieve fatigue significantly. Studies have shown that the gut microbiota is able to convert these active compounds into more active metabolites through intestinal fermentation. However, the mechanism of anti-fatigue polyphenols is currently mainly analyzed from the perspective of antioxidant and anti-inflammatory effects, and changes in gut microbiota are rarely considered. This review focuses on gut microecology and systematically summarizes the latest theoretical and research findings on the interaction of gut microbiota, fatigue, and polyphenols. First, we outline the relationship between gut microbiota and fatigue, including changes in the gut microbiota during fatigue and how they interact with the host. Next, we describe the interactions between the gut microbiota and polyphenols in fatigue treatment (regulation of the gut microbiota by polyphenols and metabolism of polyphenols by the gut microbiota), and how the importance of potential active metabolites (such as urolithin) produced by the decomposition of polyphenols by gut microbiota is emerging. Based on the new perspective of gut microbiota, this review provides interesting insights into the mechanism of polyphenols in fatigue treatment and clarifies the potential of polyphenols as targets for anti-fatigue product development, aiming to provide a useful basis for further research and design.

Studies on endoscopic submucosal dissection in the past 15 years: A bibliometric analysis.

Background and aims: Endoscopic submucosal dissection (ESD) is an advanced minimally invasive technique for en bloc resection of superficial gastrointestinal lesions, which is drawn an increasing attention from its emergence. This bibliometric analysis is to evaluate the origin, current hotspots, and research trends on ESD. Methods: A total of 2,131 publications on ESD from 2006 to 2020 were obtained from the Web of Science Core Collection (WoSCC) database. Bibliometric visualization analyses of countries/regions, institutes, authors, journals, references and keywords were performed by CiteSpace V.5.8.R3. Results: The quantity of publications on ESD increased significantly during the past 15 years. Japan occupied the leading position in terms of research power. Professor Yutaka Saito, together with the institute he belongs, the Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan, were the most productive author and institute, respectively. Colorectal ESD led the main thematic concentrations in ESD research. The most prolific journal was Gastrointestinal Endoscopy. European ESD Guideline was the most frequently co-cited reference. Guideline, meta-analysis, endoscopic resection, poly-glycolic acid sheet, Barrett's esophagus, fibrin glue, risk and colorectal neoplasm will be the active research hotspots in the future. Conclusions: These findings provide the trends and frontiers in the field of ESD, as well as valuable information for clinicians and scientists to discover the future perspectives with potential collaborators.

Contrast-enhanced ultrasound in the assessment of Crohn's disease activity: comparison with computed tomography enterography.

BACKGROUND AND OBJECTIVE: Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD. MATERIALS AND METHODS: Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard. RESULTS: The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE. CONCLUSION: CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.

Characterization of Two Key Flavonoid 3-O-Glycosyltransferases Involved in the Formation of Flower Color in Rhododendron Delavayi.

Flower color, largely determined by anthocyanin, is one of the most important ornamental values of Rhododendron delavayi. However, scant information of anthocyanin biosynthesis has been reported in R. delavayi. We found that anthocyanidin 3-O-glycosides were the predominant anthocyanins detected in R. delavayi flowers accounting for 93.68-96.31% of the total anthocyanins during its development, which indicated the key role of flavonoid 3-O-glycosyltransferase (3GT) on R. delavayi flower color formation. Subsequently, based on correlation analysis between anthocyanins accumulation and Rd3GTs expressions during flower development, Rd3GT1 and Rd3GT6 were preliminarily identified as the pivotal 3GT genes involved in the formation of color of R. delavayi flower. Tissue-specific expressions of Rd3GT1 and Rd3GT6 were examined, and their function as 3GT in vivo was confirmed through introducing into Arabidopsis UGT78D2 mutant and Nicotiana tabacum plants. Furthermore, biochemical characterizations showed that both Rd3GT1 and Rd3GT6 could catalyze the addition of UDP-sugar to the 3-OH of anthocyanidin, and preferred UDP-Gal as their sugar donor and cyanidin as the most efficient substrate. This study not only provides insights into the biosynthesis of anthocyanin in R. delavayi, but also makes contribution to understand the mechanisms of its flower color formation.

Simultaneous detection of multiple phenolic compounds in fish by gas chromatography-mass spectrometry following a modified QuEChERS cleanup.

Phenolic compounds can cause health problems in humans through the food chain. Considering that fish play an important role in human diets, we established a rapid, simple and high-throughput method for the determination of 18 phenolic compounds in fish based on a modified QuEChERS sample preparation method combined with GC-MS. The average recovery of the 18 phenolic compounds was 81.3-116% at 3 spiked levels, and the relative standard deviations, RSDr and RSDwR, were in the range of 1.1-11.3% and 1.5-12.2%, respectively. The limit of detection was 2.0-10.1 µg/kg. Satisfactory linear relationships (R2 > 0.998) were observed for the phenolic compounds in their corresponding concentration ranges. Moreover, the established method exhibited a high sensitivity, good stability, and reliability. The development of this method has an important theoretical and practical significance for establishing standards and to control the residue levels of phenolic compounds in fish.

[Determination of 19 chlorophenols in fish by QuEChERS-gas chromatography-mass spectrometry].

With the increasing use of chlorine-containing pesticides, hypochlorous acid disinfection water as well as aquatic product insecticides and fungicides are widely used in the cultivation of fish. This has led to the contamination of fish by chlorophenol compounds. However, currently, there is no standard method for the simultaneous determination of 19 chlorophenol compounds in fish. In this study, the optimum chromatography and mass spectrometry conditions were determined by investigating the instrument parameters. The 19 chlorophenol compounds were well separated using the DB-5MS capillary chromatographic column (30 m×0.25 mm×0.25 µm) with a carrier gas flow rate of 1 mL/min. Under this condition, the chromatographic peak was sharp and symmetric. An analytical method was developed for the simultaneous determination of the 19 chlorophenol compounds in fish using gas chromatography-mass spectrometry coupled with QuEChERS pretreatment. The improved QuEChERS method was used in sample preparation. The 19 chlorophenol compounds were extracted with organic solvents and purified with purifying agents. During the experiment, the effect of the kinds and volumes of the extraction solvent, as well as the types and dosages of the purifying agent, on the recoveries of the 19 chlorophenol compounds were investigated. Moreover, the temperature and time of derivatization, as well as the dosage of the derivatization agent, were optimized. All aforementioned analyses were conducted with the aim of determining the optimal pretreatment method. Finally, the optimized gas chromatography-mass spectrometry conditions were employed for the quantitative determination of 19 chlorophenol compounds in fish samples. Based on the experimental results, the best extraction method was determined to be the one where the extraction agent (10 mL ethyl acetate) was added to 3 g sodium chloride and 5 g anhydrous magnesium sulfate in the test tube, followed by ultrasonication for 15 min. The sample was centrifuged at 4500 r/min for 5 min, and 500 mg C18 was selected as the purifying agent to purify the supernatant. The purified supernatant was blown with nitrogen to less than 1 mL at 45 ℃, and then redissolved with ethyl acetate to 1 mL. Subsequently, the sample solution was passed through a 0.22 µm organic filter membrane, following which 50 µL bis(trimethylsilyl)trifluoroacetamide was added for derivatization at 45 ℃ for 30 min. Lastly, the 19 chlorophenol compounds were determined by gas chromatography-mass spectrometry with an electrospray ionization source and selecting ion monitoring mode. The 19 chlorophenol compounds were then quantitatively analyzed by the external standard method. The compounds showed good linearity in the concentration range of 0.4-10 µg/L, with correlation coefficients (R2) greater than 0.998. The limits of detection and limits of quantification were 0.01-0.05 µg/kg and 0.04-0.16 µg/kg, respectively. Moreover, the average recoveries of the 19 chlorophenol compounds were in the range of 70.6%-115.0% at three spiked levels, and the relative standard deviations were in the range of 2.6%-10.5%. The established method in this study was applied to detect and analyze chlorophenol compounds in actual samples. The experimental results showed that various levels of chlorophenol compounds could be detected in different fishes. Among them, the total amount of chlorophenol compounds detected in the Corvina was 8.74 µg/kg, followed by the Crucian carp at 7.59 µg/kg, and the minimum detected amount in rice fish (1.59 µg/kg). With its simple operation, high sensitivity, and good repeatability, the established method simplifies the pre-treatment of fish samples. It can also meet the requirements for the high-throughput detection of 19 chlorophenol compounds in fish, thereby significantly improving the detection efficiency of chlorophenols. Moreover, the method provides crucial technical support and a theoretical basis for the establishment of feasible detection standards for chlorophenols in China, as well as for the control of residue levels of chlorophenol compounds in fish. The findings have important practical significance to implement management measures during fish breeding and transportation.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/ß-catenin signaling in mice.

The mucosa microenvironment is critical for intestinal stem cell self-renewal and reconstruction of the epithelial barrier in inflammatory bowel disease (IBD), where the mechanisms underlying cross-talk between intestinal crypts and the microenvironment remain unclear. Here, we firstly identified miR-494-3p as an important protector in colitis. miR-494-3p levels were decreased and negatively correlated with the severity in human IBD samples, as well as in colitis mice. In colitis crypts, a notable cytokine-cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting ß-catenin/c-Myc. In differentiated IECs, miR-494-3p inhibits macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKß/NF-κB in colitis. A miR-494-3p agomir system notably ameliorated the severity of colonic colitis in vivo. Collectively, our findings uncover a miR-494-3p-mediated cross-talk mechanism by which macrophage-induced intestinal stem cell impairment aggravates intestinal inflammation.

Involvement of a novel Ca2+-independent C-type lectin from Sinonovacula constricta in food recognition and innate immunity.

Bivalve lectins perform a crucial function in recognition of foreign particles, such as microalgae and pathogenic bacteria. In this study, a novel C-type lectin form Sinonovacula constricta (ScCL) was characterized. The full-length cDNA of ScCL was 1645 bp, encoding a predicted polypeptide of 273 amino acids with one typical carbohydrate-recognition domain. ScCL has the highest similarity and closest phylogenetic relationship with the C-type lectin from Solen grandis. Real-time PCR analysis showed that ScCL was expressed in all tested tissues, with the highest expression in the foot and the lowest expression in hemocytes. Agglutination activity of ScCL was Ca2+-independent. ScCL showed the strongest agglutination on Chlorella vulgaris, the modest agglutination on Platymonas subcordiformis, Nannochloropsis sp., and Thalassiosira pseudonana, the weakest agglutination on Chaetoceros sp., and no agglutination on Isochrysis zhanjiangensis. Meanwhile, agglutination tests and western blot analysis revealed that the recombinant ScCL protein could agglutinate Staphylococcus aureus and Vibrio harveyi, but could not agglutinate Vibrio anguillarum, Bacillus cereus, or Vibrio parahaemolyticus. Furthermore, ScCL had a high binding activity with LPS and mannose, a low binding activity with LTA, and no binding activity with PGN. The expression of ScCL in the gill of S. constricta fed with C. vulgaris and T. pseudonana was significantly increased at 1 and/or 3 h. After injection with S. aureus, the expression of ScCL in the gill was significantly increased at 3, 6, and 24 h. These results indicated that ScCL was involved in food particle recognition and immunity of S. constricta.

Correlation between ultrasound consolidated score and simple endoscopic score for determining the activity of Crohn's disease.

OBJECTIVES: The aim of this study was to develop an ultrasound consolidated score (UCS) in determining the activity of Crohn's disease (CD) and evaluate it with reference to simple endoscopic score (SES). METHODS: From June 2014 to June 2017, 66 patients with CD were retrospectively enrolled in this study. Each patient underwent endoscopy and transabdominal ultrasound (US) examination. The morphological symmetry, echogenicity of bowel wall, bowel wall layer structure, echogenicity of peri-bowel fat, bowel wall thickness (BWT), and Limberg type on power Doppler US were assessed with transabdominal US, and an UCS scoring system was developed based on these characteristics. Endoscopic results were used as the reference standard and SES was calculated to determine the CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance for determining CD activity and the correlation between UCS and SES was assessed using Spearman correlation analysis. RESULTS: 330 intestinal segments in 66 patients were included. The UCS of the segments in the remission phase ranged from 3.0 to 9.0 (mean, 3.6 ± 0.9) whereas in the active phase from 3.0 to 20.0 (mean, 10.6 ± 4.0) (p < 0.001). The cut-off value of UCS was 6. The associated area under ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.980, 88.3%, 95.5%, 93.8%, 91.3%, and 92.3%, respectively. The correlation coefficient between UCS and SES was 0.90, which was higher than the correlation coefficient of 0.83 between BWT and SES. CONCLUSIONS: The newly developed UCS with transabdominal US has a good performance and potentially provides an effective alternative for evaluating the activity of CD. ADVANCES IN KNOWLEDGE: UCS is an effective method to evaluate the activity of CD because it provides comprehensive information of the disease. Therefore, it could be employed as an alternative for diagnosis of CD.

[Overview and prospects of traditional Chinese medicine blending technology oriented by quality consistency].

The consistency of drug quality is related to the clinical efficacy and safety,which is highly valued by the government and relevant industries. Compared with chemical medicine,traditional Chinese medicine originates from the nature,and is greatly influenced by natural factors,such as the place of origin,cultivation and processing technology,climate. The quality consistency of traditional Chinese medicine is poor. The quality consistency has become the pain point and difficulty of the development of the traditional Chinese medicine industry,which seriously affects the stability and controllability of clinical efficacy and the reproducibility or recognition of modern research results. It is also a bottleneck for Chinese patent medicine to enter the international market. Mixed batch blending technology is an effective method for the scientific guarantee of the quality consistency in other industries and disciplines,and widely applied in liquor making industry,tobacco industry and perfume industry. Overseas,mixed batch blending technology has been successfully applied in guaranteeing the quality consistency of Ginkgo biloba preparations Jinnado. It has been used in the production of Chinese formulations in Japan for more than 30 years. In recent years,mixed batch blending technology has been introduced into the pharmaceutical field to ensure the quality consistency of traditional Chinese medicine,and relevant research has gradually increased.This manuscript reviews the application of blending technology in other disciplines,summarizes the algorithm principles and software systems of mixed batch blending in traditional Chinese medicine or natural medicine,explains the specific implementation process of mixed batch blending technology,and looks forward to the application prospects of artificial intelligence and other new technologies,in the hope of providing new ideas and technologies for breaking through the problem of quality consistency,and boosting the high-quality and high-level development of Chinese medicine industry in the new era.

A Potential Anti-Tumor Herb Bred in a Tropical Fruit: Insight into the Chemical Components and Pharmacological Effects of Momordicae Semen.

Gac fruit (Momordica cochinchinensis Spreng) is a popular tropical fruit in southeast Asia. What is amazing is that its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1000 years. In recent years, its anti-tumor activity has received extensive attention and research. This manuscript summarized the chemical composition of saponins, fatty acids, volatile constituents, proteins, peptides, and other components from Momordicae Semen (MSE). The effect and mechanism of MSE and its extract on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were discussed. In addition, its antioxidant, anti-inflammatory, and other pharmacological effects were also analyzed. We hope that this review will provide new ideas for the treatment of cancer and other diseases, and become a reference for the further research into complementary and alternative medicine.

Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities.

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two.

Natural medicines for the treatment of fatigue: Bioactive components, pharmacology, and mechanisms.

It is a common phenomenon that people are in a sub-health condition and facing "unexplained fatigue", which seriously affects their health, work efficiency and quality of life. Meanwhile, fatigue is also a common symptom of many serious diseases such as HIV/AIDS, cancer, and schizophrenia. However, there are still no official recommendations for the treatment of various forms of fatigue. Some traditional natural medicines are often used as health care products, such as ginseng, Cordyceps militaris (L.ex Fr.Link) and Rhodiola rosea L., and these have been reported to have specific anti-fatigue effects with small toxic and side effects and rich pharmacological activities. It may be promising treatment strategy for sub-health. In this review, we first outline the generation of fatigue. Furthermore, we put emphasis on the anti-fatigue mechanism, bioactive components, and clinic trials of natural medicines, which will contribute to the development of potential anti-fatigue agents and open up novel treatments for sub-health.

Usefulness of Strain Elastography, ARFI Imaging, and Point Shear Wave Elastography for the Assessment of Crohn Disease Strictures.

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of strain elastography, acoustic radiation force impulse (ARFI) imaging and point shear wave elastography (p-SWE) for assessment of the predominant types of intestinal stenosis in Crohn disease. METHODS: Twenty-five patients were enrolled in this study, among whom 25 suspicious stenoses in 25 intestinal segments were studied using gray scale ultrasonography. All 3 elastography methods were performed, and all patients underwent endoscopy within 24 hours with pathologic biopsy. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), Youden index, and area under the receiver operating characteristic curve (AUROC) were calculated. Pathologic findings were regarded as the gold standard. RESULTS: For SE, the optimal cutoff value was a score of 4 or greater (sensitivity, 75%; specificity, 66.7%; accuracy, 68%; PPV, 30%; NPV, 93.3%; AUROC, 0.708; however, P > .05). The results of ARFI imaging were similar: the optimal cutoff value was a score of 4 or greater (sensitivity, 50%; specificity, 81%; accuracy, 76%; PPV, 33.3%; NPV, 89.4%; AUROC, 0.669; P < .05). However, for p-SWE, the optimal cutoff value was reached when the shear wave velocity exceeded 2.73 m/s (sensitivity, 75%; specificity, 100%; accuracy, 96%; PPV, 100%; NPV, 95.5%; AUROC, 0.833; P < .05). CONCLUSIONS: p-SWE had the best performance for evaluating and differentiating intestinal stenosis in Crohn disease, while neither SE nor ARFI imaging achieved satisfactory outcomes for evaluating inflammatory stenosis and fibrotic stenosis of Crohn disease.

Long-chain polyunsaturated fatty acid biosynthesis and its response to cadmium exposure in silver pomfret.

Despite a close interaction between cadmium (Cd) and long-chain polyunsaturated fatty acid (LC-PUFA) metabolism, the influence of Cd exposure on the endogenous synthesis of LC-PUFA has received little attention. In the present study, we hypothesized that Cd exposure would affect the synthesis of LC-PUFA in the marine fish silver pomfret (Pampus argenteus). Therefore, the molecular basis of LC-PUFA biosynthesis and regulation was investigated as the first step to understanding the mechanisms underpinning the effects of Cd exposure. Thereafter, transcriptional regulation of the genes that participate in LC-PUFA biosynthesis and regulation by Cd exposure were also explored. Our results showed that fatty acyl desaturase 2 (Fads2) and elongases of very long-chain fatty acids 5 (Elovl5), two key enzymes involved in LC-PUFA biosynthesis, enabled silver pomfret to biosynthesize 20:3n-6 and 20:4n-3 from 18:2n-6 and 18:3n-3. The results also raise the possibility that silver pomfret may have the ability to produce docosahexaenoic acid (DHA, 22:6n-3) from endogenous eicosapentaenoic acid (EPA, 20:5n-3). The expression of silver pomfret fads2 and elovl5 was transcriptionally regulated by the peroxisome proliferator activated receptor α (Pparα). The expression of fads2, elovl5 and pparα in the brain was significantly increased in response to Cd exposure. In addition, Cd exposure significantly reduced the DHA concentration and significantly increased the malondialdehyde concentration in the brain of silver pomfret. Cd exposure likely increases brain-specific DHA synthesis from EPA by transcriptionally activating fads2 and elovl5 via Pparα in silver pomfret. This regulation may be a coping mechanism for the reduction of DHA caused by Cd-oxidative stress in the brains of silver pomfret.