Multiomics analysis reveals the molecular mechanisms underlying virulence in Rhizoctonia and jasmonic acid-mediated resistance in Tartary buckwheat (Fagopyrum tataricum).

Rhizoctonia solani is a devastating soil-borne pathogen that seriously threatens the cultivation of economically important crops. Multiple strains with a very broad host range have been identified, but only 1 (AG1-IA, which causes rice sheath blight disease) has been examined in detail. Here, we analyzed AG4-HGI 3 originally isolated from Tartary buckwheat (Fagopyrum tataricum), but with a host range comparable to AG1-IA. Genome comparison reveals abundant pathogenicity genes in this strain. We used multiomic approaches to improve the efficiency of screening for disease resistance genes. Transcriptomes of the plant-fungi interaction identified differentially expressed genes associated with virulence in Rhizoctonia and resistance in Tartary buckwheat. Integration with jasmonate-mediated transcriptome and metabolome changes revealed a negative regulator of jasmonate signaling, cytochrome P450 (FtCYP94C1), as increasing disease resistance probably via accumulation of resistance-related flavonoids. The integration of resistance data for 320 Tartary buckwheat accessions identified a gene homolog to aspartic proteinase (FtASP), with peak expression following R. solani inoculation. FtASP exhibits no proteinase activity but functions as an antibacterial peptide that slows fungal growth. This work reveals a potential mechanism behind pathogen virulence and host resistance, which should accelerate the molecular breeding of resistant varieties in economically essential crops.

Glutathionylation of a glycolytic enzyme promotes cell death and vigor loss during aging of elm seeds.

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial proapoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N,N,N',N'-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a proapoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.

Multi-omics identification of a key glycosyl hydrolase gene FtGH1 involved in rutin hydrolysis in Tartary buckwheat (Fagopyrum tataricum).

Rutin, a flavonoid rich in buckwheat, is important for human health and plant resistance to external stresses. The hydrolysis of rutin to quercetin underlies the bitter taste of Tartary buckwheat. In order to identify rutin hydrolysis genes, a 200 genotypes mini-core Tartary buckwheat germplasm resource was re-sequenced with 30-fold coverage depth. By combining the content of the intermediate metabolites of rutin metabolism with genome resequencing data, metabolite genome-wide association analyses (GWAS) eventually identified a glycosyl hydrolase gene FtGH1, which could hydrolyse rutin to quercetin. This function was validated both in Tartary buckwheat overexpression hairy roots and in vitro enzyme activity assays. Mutation of the two key active sites, which were determined by molecular docking and experimentally verified via overexpression in hairy roots and transient expression in tobacco leaves, exhibited abnormal subcellular localization, suggesting functional changes. Sequence analysis revealed that mutation of the FtGH1 promoter in accessions of two haplotypes might be necessary for enzymatic activity. Co-expression analysis and GWAS revealed that FtbHLH165 not only repressed FtGH1 expression, but also increased seed length. This work reveals a potential mechanism behind rutin metabolism, which should provide both theoretical support in the study of flavonoid metabolism and in the molecular breeding of Tartary buckwheat.

Extracellular vesicles of Bacteroides fragilis regulated macrophage polarization through promoted Sema7a expression.

Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage. BF-EV promote macrophage M1/M2 polarization significantly, and increase Sting expression significantly. Bioinformatics analysis found that Sema7a is an important gene involving in macrophage polarization. The expression of Sema7a can be induced by BF-EV and can be inhibited after C-176 treated. The inhibition expression of Sema7a prevent BF-EV to induce macrophage polarization. Further analysis reveals that there is no direct interaction between Sting and Sema7a, but Sgpl1 can interact with Sting or Sema7a. BF-EV promote the expression of Sgpl1, which the phenomenon can be inhibited after C-176 treated. Importantly, overexpression of Sgpl1 reversed the effect of C-176 for Sema7a expression, while inhibit Sema7a expression has limitation influence for Sting and Sgpl1 expression. In conclusion, this study confirms that Sting-Sgpl1-Sema7a is a key mechanism by which BF-EV regulates macrophage polarization.

Nomogram for assistant diagnosing acute suppurative cholangitis: a case-control study.

BACKGROUND: Acute suppurative cholangitis (ASC) lacks sensitive and specific preoperative diagnostic criteria. Some researchers suggest treating ASC as severe cholangitis. This study aimed to explore the relationship between the Tokyo Guidelines 2018 (TG18) grading system for acute cholangitis (AC) and the diagnosis of acute suppurative cholangitis (ASC), searching for independent risk factors of ASC and develop a nomogram to discriminate ASC from acute nonsuppurative cholangitis (ANSC) accurately. METHODS: After applying the inclusion and exclusion criteria, 401 patients with acute cholangitis (AC) were retrospectively analyzed at Nanjing First Hospital between January 2015 and June 2023. SPSS version 27.0 and R studio software were used to analyze data obtained from medical records. The results were validated in a prospective cohort of 82 AC patients diagnosed at Nanjing First Hospital between July 2023 and February 2024. RESULTS: Among the 401 patients, 102 had suppurative bile (the ASC group; AC grade I: 40 [39.2%], AC grade II: 27 [26.5%], AC grade III: 35 [34.3%]), whereas 299 did not have (the ANSC group; AC grade I: 157 [52.5%], AC grade II: 92 [30.8%], AC grade III: 50 [16.7%]). The specificity of ASC for diagnosing moderate-to-severe cholangitis is 79.7%. Multivariate logistic regression analysis identified concurrent cholecystitis, CRP, PCT, TBA, and bile duct diameter as independent risk factors for suppurative bile, and all of these factors were included in the nomogram. The calibration curve exhibited consistency between the nomogram and the actual observation, and the area under the curve was 0.875 (95% confidence interval: 0.835-0.915), sensitivity was 86.6%, and specificity was 75.5%. CONCLUSION: Suppurative bile is a specific indicator for diagnosing moderate-to-severe cholangitis. However, diagnosing ASC with AC grade II and AC grade III has the risk of missed diagnosis as the sensitivity is only 60.8%. To improve the diagnostic rate of ASC, this study identified concurrent cholecystitis, CRP, PCT, TBA, and preoperative bile duct diameter as independent risk factors for ASC, and a nomogram was developed to help physicians recognize patients with ASC.

Construction of in vitro liver-on-a-chip models and application progress.

The liver is the largest internal organ of the human body. It has a complex structure and function and plays a vital role in drug metabolism. In recent decades, extensive research has aimed to develop in vitro models that can simulate liver function to demonstrate changes in the physiological and pathological environment of the liver. Animal models and in vitro cell models are common, but the data obtained from animal models lack relevance when applied to humans, while cell models have limited predictive ability for metabolism and toxicity in humans. Recent advancements in tissue engineering, biomaterials, chip technology, and 3D bioprinting have provided opportunities for further research in in vitro models. Among them, liver-on-a-Chip (LOC) technology has made significant achievements in reproducing the in vivo behavior, physiological microenvironment, and metabolism of cells and organs. In this review, we discuss the development of LOC and its research progress in liver diseases, hepatotoxicity tests, and drug screening, as well as chip combinations. First, we review the structure and the physiological function of the liver. Then, we introduce the LOC technology, including general concepts, preparation materials, and methods. Finally, we review the application of LOC in disease modeling, hepatotoxicity tests, drug screening, and chip combinations, as well as the future challenges and directions of LOC.

New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7∼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.

Abnormal functional connectivity of the reward circuit associated with early satiety in patients with postprandial distress syndrome.

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

Resequencing of global Lotus corniculatus accessions reveals population distribution and genetic loci, associated with cyanogenic glycosides accumulation and growth traits.

BACKGROUND: Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. RESULT: Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. CONCLUSION: This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.

Quantitative analysis of six sesquiterpene glycosides from Dendrobium nobile Lindl. under different growth conditions by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry in MRM mode.

INTRODUCTION: The sesquiterpene glycosides (SGs) from Dendrobium nobile Lindl. have immunomodulatory effects. However, there are no studies on the growth conditions affecting its contents and quantitative analysis methods. OBJECTIVE: In the present study, a quantitative analysis method for six SGs from D. nobile was established. We explored which growth conditions could affect the contents of SGs, providing a basis for the cultivation and clinical application of D. nobile. METHODS: Firstly, based on the optimization of mass spectrometry parameters and extraction conditions for six SGs in D. nobile, a method for the determination of the contents of six SGs was established using high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS) in multiple reaction monitoring (MRM) mode. Then, the methodology of the established method was validated. Secondly, the established method was applied to determine the contents of six SGs from 78 samples of D. nobile grown under different growth conditions. Finally, chemometrics analysis was employed to analyze the results and select optimal growth conditions for D. nobile. RESULTS: The results indicated significant variations in the contents of SGs from D. nobile grown under different growth conditions. The primary factors influencing SG contents included age, geographical origin, altitude, and epiphytic pattern. CONCLUSION: Therefore, the established method for determining SG contents from D. nobile is stable. In particular, the SG contents were relatively high in samples of 3-year-old D. nobile grown at an altitude of approximately 500 m on Danxia rocks in Chishui, Guizhou.

Gypensapogenin A-Liposomes Efficiently Ameliorates Hepatocellular Lipid Accumulation via Activation of FXR Receptor.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases encountered in clinical practice, which is characterized by the excessive accumulation of triglycerides (steatosis), and a variety of metabolic abnormalities including lipid metabolism and bile acid metabolism are closely related to NAFLD. In China, Gynostemma pentaphyllum is used as functional food and Chinese medicine to treat various diseases, especially NAFLD, for a long time. However, the active components that exert the main therapeutic effects and their mechanisms remain unclear. In this study, Gypensapogenin A was isolated from the total saponins of G. pentaphyllum and prepared as a liposomal delivery system. Gypensapogenin A liposomes could activate FXR, inhibit the expression of CYP7A1 and CYP8B1, increase the expression of CYP27A1, modulate the ratio of CA and CDCA, decrease the content of CA, and increase the content of CDCA, thus forming a virtuous cycle of activating FXR to play a role in lowering blood lipid levels.

Hypoglycemic Effects and Quality Marker Screening of Dendrobium nobile Lindl. at Different Growth Years.

(1) Background: The effect of Dendrobium nobile Lindl. (D. nobile) on hyperglycemic syndrome has only been recently known for several years. Materials of D. nobile were always collected from the plants cultivated in various growth ages. However, regarding the efficacy of D. nobile on hyperglycemic syndrome, it was still unknown as to which cultivation age would be selected. On the other hand, with the lack of quality markers, it is difficult to control the quality of D. nobile to treat hyperglycemic syndrome. (2) Methods: The effects of D. nobile cultivated at year 1 and year 3 were checked on alloxan-induced diabetic mice while their body weight, diet, water intake, and urinary output were monitored. Moreover, levels of glycosylated serum protein and insulin were measured using Elisa kits. The constituents of D. nobile were identified and analyzed by using UPLC-Q/trap. Quality markers were screened out by integrating the data from UPLC-Q/trap into a network pharmacology model. (3) Results: The D. nobile cultivated at both year 1 and year 3 showed a significant effect on hyperglycemic syndrome at the high dosage level; however, regarding the significant level, D. nobile from year 1 showed the better effect. In D. nobile, most of the metabolites were identified as alkaloids and sesquiterpene glycosides. Alkaloids, represented by dendrobine, were enriched in D. nobile from year 1, while sesquiterpene glycosides were enriched in D. nobile from year 3. Twenty one metabolites were differentially expressed between D. nobile from year 1 and year 3. The aforementioned 21 metabolites were enriched to 34 therapeutic targets directly related to diabetes. (4) Conclusions: Regarding the therapy for hyperglycemic syndrome, D. nobile cultivated at year 1 was more recommended than that at year 3. Alkaloids were recommended to be used as markers to control the quality of D. nobile for hyperglycemic syndrome treatment.

JA-induced FtBPM3 accumulation promotes FtERF-EAR3 degradation and rutin biosynthesis in Tartary buckwheat.

Buckwheat accumulates abundant flavonoids, which exhibit excellent health-promoting value. Flavonoids biosynthesis is mediated by a variety of phytohormones, among which jasmonates (JAs) induce numerous transcription factors, taking part in regulation of flavonoids biosynthesis genes. However, some transcriptional repressors appeared also induced by JAs. How these transcriptional repressors coordinately participate in JA signaling remains unclear. Here, we found that the disruption of the GCC-box in FtF3H promoter was associated with flavonoids accumulation in Tartary buckwheat. Further, our study illustrated that the nucleus-localized FtERF-EAR3 could inhibit FtF3H expression and flavonoids biosynthesis through binding the GCC-box in the promoter of FtF3H. The JA induced FtERF-EAR3 gene expression while facilitating FtERF-EAR3 protein degradation via the FtBPM3-dependent 26S proteasome pathway. Overall, these results illustrate a precise modulation mechanism of JA-responsive transcription suppressor participating in flavonoid biosynthesis, and will further help to improve the efficiency of flavonoids biosynthesis in Tartary buckwheat.

The fate and prospects of stem cell therapy in the treatment of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).

Asia-Pacific Colorectal Screening Score Combined With Stool DNA Test Improves the Detection Rate for Colorectal Advanced Neoplasms.

BACKGROUND & AIMS: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to stratify the risk of colorectal advanced neoplasm (AN). We aimed to evaluate the performance of the APCS score combined with a stool DNA test used for colorectal cancer screening. METHODS: A total of 2842 subjects who visited outpatient clinics or cancer screening centers were enrolled. Age, sex, smoking status, and family history were recorded and APCS scores were calculated in 2439 participants. A stool DNA test (SDC2 and SFRP2 tests) and fecal immunochemical test (FIT) were performed and colonoscopy was used as the gold standard among 2240 subjects who completed all study procedures. We used a threshold of 4.4 µg/g for the FIT, in addition to the manufacturer's recommended threshold of 20 µg/g to match the specificity of a stool DNA test. RESULTS: Based on the APCS score, 38.8% (946 of 2439) of the subjects were categorized as high risk, and they had a 1.8-fold increase in risk for AN (95% CI, 1.4-2.3) compared with low and moderate risk. The APCS combined with the stool DNA test detected 95.2% of invasive cancers (40 of 42) and 73.5% of ANs (253 of 344), while the colonoscopy workload was only 47.1% (1056 of 2240). The sensitivity for AN of APCS combined with stool DNA test was significantly higher than that of APCS combined with FIT (73.5% vs 62.8% with FIT cut-off value of 20 µg/g, and 73.5% vs 68.0% with FIT cut-off value of 4.4 µg/g; both P < .01). CONCLUSIONS: The APCS score combined with a stool DNA test significantly improved the detection of colorectal ANs, while limiting colonoscopy resource utilization (Chictr.org.cn, ChiCTR-DDD-17011169).

The alteration of drug metabolism enzymes and pharmacokinetic parameters in nonalcoholic fatty liver disease: current animal models and clinical practice.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The whole concept of NAFLD has now moved into metabolic dysfunction-associated fatty liver disease (MAFLD) to emphasize the strong metabolic derangement as the basis of the disease. Several studies have suggested that hepatic gene expression was altered in NAFLD and NAFLD-related metabolic comorbidities, particularly mRNA and protein expression of phase I and II drug metabolism enzymes (DMEs). NAFLD may affect the pharmacokinetic parameters. However, there were a limited number of pharmacokinetic studies on NAFLD at present. Determining the pharmacokinetic variation in patients with NAFLD remains challenging. Common modalities for modeling NAFLD included: dietary induction, chemical induction, or genetic models. The altered expression of DMEs has been found in rodent and human samples with NAFLD and NAFLD-related metabolic comorbidities. We summarized the pharmacokinetic changes of clozapine (CYP1A2 substrate), caffeine (CYP1A2 substrate), omeprazole (Cyp2c29/CYP2C19 substrate), chlorzoxazone (CYP2E1 substrate), midazolam (Cyp3a11/CYP3A4 substrate) in NAFLD. These results led us to wonder whether current drug dosage recommendations may need to be reevaluated. More objective and rigorous studies are required to confirm these pharmacokinetic changes. We have also summarized the substrates of the DMEs aforementioned. In conclusion, DMEs play an important role in the metabolism of drugs. We hope that future investigations should focus on the effect and alteration of DMEs and pharmacokinetic parameters in this special patient population with NAFLD.

Rewiring of the seed metabolome during Tartary buckwheat domestication.

Crop domestication usually leads to the narrowing genetic diversity. However, human selection mainly focuses on visible traits, such as yield and plant morphology, with most metabolic changes being invisible to the naked eye. Buckwheat accumulates abundant bioactive substances, making it a dual-purpose crop with excellent nutritional and medical value. Therefore, examining the wiring of these invisible metabolites during domestication is of major importance. The comprehensive profiling of 200 Tartary buckwheat accessions exhibits 540 metabolites modified as a consequence of human selection. Metabolic genome-wide association study illustrates 384 mGWAS signals for 336 metabolites are under selection. Further analysis showed that an R2R3-MYB transcription factor FtMYB43 positively regulates the synthesis of procyanidin. Glycoside hydrolase gene FtSAGH1 is characterized as responsible for the release of active salicylic acid, the precursor of aspirin and indispensably in plant defence. UDP-glucosyltransferase gene FtUGT74L2 is characterized as involved in the glycosylation of emodin, a major medicinal component specific in Polygonaceae. The lower expression of FtSAGH1 and FtUGT74L2 were associated with the reduction of salicylic acid and soluble EmG owing to domestication. This first large-scale metabolome profiling in Tartary buckwheat will facilitate genetic improvement of medicinal properties and disease resistance in Tartary buckwheat.

Endoscopic resection of gastric low-grade dysplasia with high risk factors is associated with decreased advanced neoplasia: a single-center retrospective cohort study.

BACKGROUND: The natural course of gastric low-grade dysplasia (LGD) remains unclear, and there are inconsistent management recommendations among guidelines and consensus. OBJECTIVE: This study aimed to investigate the incidence of advanced neoplasia in patients with gastric LGD and identify the related risk factors. METHODS: Cases of biopsy demonstrated LGD (BD-LGD) at our center from 2010 to 2021 were reviewed retrospectively. Risk factors related to histological progression were identified, and outcomes of patients based on risk stratification were evaluated. RESULTS: Ninety-seven (23.0%) of 421 included BD-LGD lesions were diagnosed as advanced neoplasia. Among 409 superficial BD-LGD lesions, lesion in the upper third of the stomach, H. pylori infection, larger size, and narrow band imaging (NBI)-positive findings were independent risk factors of progression. NBI-positive lesions and NBI-negative lesions with or without other risk factors had 44.7%, 1.7%, and 0.0% risk of advanced neoplasia, respectively. Invisible lesions, visible lesions (VLs) without a clear margin, and VLs with a clear margin and size ≤ 10 mm, or > 10 mm had 4.8%, 7.9%, 16.7%, and 55.7% risk of advanced neoplasia, respectively. In addition, endoscopic resection decreased the risk of cancer (P < 0.001) and advanced neoplasia (P < 0.001) in patients with NBI-positive lesions, but not in NBI-negative patients. Similar results were found in patients with VLs with clear margin and size > 10 mm. Moreover, NBI-positive lesions had higher sensitivity and lower specificity for predicting advanced neoplasia than VLs with a clear margin and size > 10 mm determined by white-light endoscopy (97.6% vs. 62.7%, P < 0.001; and 63.0% vs. 85.6%, P < 0.001, respectively). CONCLUSION: Progression of superficial BD-LGD is associated with NBI-positive lesions, as well as with VLs with a clear margin (size > 10 mm) if NBI is unavailable, and selective resection of those lesions offers benefits for patients by decreasing the risk of advanced neoplasia.

New dammarane-type triterpenoids from hydrolyzate of total Gynostemma pentaphyllum saponins with protein tyrosine phosphatase 1B inhibitory activity.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Widely Targeted Metabolomics Analysis of Dendrobium officinale at Different Altitudes.

In order to investigate the differences in the chemical composition of Dendrobium officinale at different altitudes, we collected Dendrobium officinale from different altitudes in Guizhou Province, China, and firstly determined its polysaccharide content by using a sulfuric acid-phenol color development method with reference to the Chinese Pharmacopoeia, and further determined its metabolites by using widely targeted metabolomics, and explored the differences in the chemical composition of Dendrobium officinale at different altitudes using multivariate statistical analysis. We found that the polysaccharide content was higher in plants growing at 1122 m, a total of 902 secondary metabolites were detected by wildly targeted metabolomics, and amino acids and their derivatives were more highly expressed at 1122 m, while other metabolites were more highly expressed at 835 m. Furthermore, we found that the phenolic acid compound nerugein was only present in plants at 835 m, and two lipid compounds, namely Lyso PE 20 : 4 and its isomer, were only present at 1122 m. Taken together, these results may provide a basis for the selection and clinical application of D. officinale cultivated at different altitudes.