EGC enhances tumor antigen presentation and CD8+ T cell-mediated antitumor immunity via targeting oncoprotein SND1.

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Insights into the Molecular Mechanism of Endothelial Glycocalyx Dysfunction during Heart Surgery.

The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.

Comparable prognosis of early gastric cancer between intestinal type and diffuse type in patients of age 75 and older: a SEER-based cohort study.

Background: The prognostic significance of Lauren's classification in elderly early gastric cancer (EGC) patients remains largely unknown. We aim to investigate the characteristics and clinical implications of Lauren's classification in elderly EGC patients. Methods: Patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database based on the inclusion and exclusion criteria. Univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment were utilized to evaluate the association between Lauren's classification and cancer-specific survival (CSS) in elderly EGC patients. Stratification and interaction analyses were used to reveal the effects of confounding factors on the association between Lauren's classification and CSS. Results: The diffuse type (median, 41.0 months) showed a similar survival (37.0 months), and was mainly distributed in female group (62.5% vs. 42.2%) with poorly differentiated or undifferentiated components (89.1% vs. 27.0%) compared with intestinal type in elderly EGC patients. Analyses of univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment showed that Lauren's classification was not significantly CSS in elderly EGC patients (P>0.05). Subgroup and interaction analyses confirmed the stability of the results. Conclusions: Diffuse type was mainly distributed in female patients with more poorly differentiated/undifferentiated components and similar prognosis compared with intestinal type in age 75 and older EGC patients. No significant association was observed between diffuse type and CSS of the elderly EGC patients.

Robust Micro-Sized and Defect-Rich Carbon-Carbon Composites as Advanced Anodes for Potassium-Ion Batteries.

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

The Enterotoxin Gene Profiles and Enterotoxin Production of Staphylococcus aureus Strains Isolated from Artisanal Cheeses in Belgium.

A Staphyloccoccus aureus is one of the leading causes of food poisoning outbreaks (FPOs) worldwide. Staphylococcal food poisoning (SFP) is induced by the ingestion of food containing sufficient levels of staphylococcal enterotoxins (SEs). Currently, 33 SEs and SE-like toxins (SEls) have been described in the literature, but only five named "classical" enterotoxins are commonly investigated in FPOs due to lack of specific routine analytical techniques. The aims of this study were to (i) establish the genetic profile of strains in a variety of artisanal cheeses (n = 30) in Belgium, (ii) analyze the expression of the SE(l)s by these strains and (iii) compare the output derived from the different analytical tools. Forty-nine isolates of S. aureus were isolated from ten Belgian artisanal cheeses and were analyzed via microbiological, immunological, liquid chromatography mass spectrometry, molecular typing and genetic methods. The results indicated that classical SEs were not the dominant SEs in the Belgian artisanal cheeses that were analyzed in this study, and that all S. aureus isolates harbored at least one gene encoding a new SE(l). Among the new SE(l)s genes found, some of them code for enterotoxins with demonstrated emetic activity and ecg-enterotoxins. It is worth noting that the involvement of some of these new SEs has been demonstrated in SFP outbreaks. Thus, this study highlighted the importance of the development of specific techniques for the proper investigation of SFP outbreaks.

Development of a deep learning model for early gastric cancer diagnosis using preoperative computed tomography images.

Background: Gastric cancer is a highly prevalent and fatal disease. Accurate differentiation between early gastric cancer (EGC) and advanced gastric cancer (AGC) is essential for personalized treatment. Currently, the diagnostic accuracy of computerized tomography (CT) for gastric cancer staging is insufficient to meet clinical requirements. Many studies rely on manual marking of lesion areas, which is not suitable for clinical diagnosis. Methods: In this study, we retrospectively collected data from 341 patients with gastric cancer at the First Affiliated Hospital of Wenzhou Medical University. The dataset was randomly divided into a training set (n=273) and a validation set (n=68) using an 8:2 ratio. We developed a two-stage deep learning model that enables fully automated EGC screening based on CT images. In the first stage, an unsupervised domain adaptive segmentation model was employed to automatically segment the stomach on unlabeled portal phase CT images. Subsequently, based on the results of the stomach segmentation model, the image was cropped out of the stomach area and scaled to a uniform size, and then the EGC and AGC classification models were built based on these images. The segmentation accuracy of the model was evaluated using the dice index, while the classification performance was assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic (ROC), accuracy, sensitivity, specificity, and F1 score. Results: The segmentation model achieved an average dice accuracy of 0.94 on the hand-segmented validation set. On the training set, the EGC screening model demonstrated an AUC, accuracy, sensitivity, specificity, and F1 score of 0.98, 0.93, 0.92, 0.92, and 0.93, respectively. On the validation set, these metrics were 0.96, 0.92, 0.90, 0.89, and 0.93, respectively. After three rounds of data regrouping, the model consistently achieved an AUC above 0.9 on both the validation set and the validation set. Conclusion: The results of this study demonstrate that the proposed method can effectively screen for EGC in portal venous CT images. Furthermore, the model exhibits stability and holds promise for future clinical applications.

Epidemiological and molecular evidence of foodborne poisoning outbreak caused by enterotoxin gene cluster-harboring Staphylococcus aureus of new sequence type 7591.

OBJECTIVES: This paper presented a detailed analysis of the epidemiology and molecular characteristics of staphylococcal food poisoning (SFP) that occurred in a hotel in Hangzhou. METHODS: A total of 46 guests at the hotel underwent an epidemiological survey. Samples of stool from patients, vomit, swabs from the kitchen, leftover food items, and anal swabs from food handlers were taken and investigated for the presence of potential pathogenic bacteria. Molecular techniques and whole genome sequencing were performed to track the evolution of Staphylococcus aureus associated with the outbreak of SFP. RESULTS: Forty-six individuals displayed gastrointestinal symptoms. Seventeen isolates of S. aureus were discovered to carry the seg, sei, sem, sen, seo, and selu genes found in a specific enterotoxin gene cluster (egc) operon, but without the presence of classical enterotoxins such as SEA ∼ SEE. All egc-positive isolates shared identical pulsed-field gel electrophoresis profiles and were classified under new ST7591 (Clonal Complex 72) with identical spa typing t148. In addition, some isolates of S. aureus obtained from food sources sold in Hangzhou over the past 3 years and carrying egc genes were grouped under the ST72 lineage (CC72). Through whole genome sequencing, a strong genetic connection was revealed between these egc-positive isolates and clinical ST72 S. aureus found in China. CONCLUSIONS: S. aureus with non-classical egc enterotoxins was suggested to be a potential cause of SFP in humans.

Characteristic analysis of early gastric cancer after Helicobacter pylori eradication: a multicenter retrospective propensity score-matched study.

BACKGROUND: Helicobacter pylori (H. pylori) is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after H. pylori eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after H. pylori eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis. METHODS: A total of 81 patients of EGC after H. pylori eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of H. pylori infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images. RESULTS: There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group (p < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group (p = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy (p = 0.047), map-like redness (p < 0.001) and mild activity (p < 0.001). The predominant histopathological types differed between the two groups (p < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group (p = 0.025). But different eradication intervals of H. pylori have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year (p = 0.005), mucosal map-like redness (p < 0.001), moderate mucosal atrophy (p = 0.017), and mild activity of gastric mucosa (p = 0.005) were independent characteristics of EGC after H. pylori eradication. CONCLUSION: Our multicenter study revealed that EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.

EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.H. pylori-positive patients at OLGA stages I-II are also more likely to progress to EGC.According to the current data, different eradication intervals of H. pylori have little effect on the characteristics of EGC.

Bonding Properties between Fly Ash/Slag-Based Engineering Geopolymer Composites and Concrete.

Concrete infrastructure repair remains a formidable challenge. The application of engineering geopolymer composites (EGCs) as a repair material in the field of rapid structural repair can ensure the safety of structural facilities and prolong their service life. However, the interfacial bonding performance of existing concrete with EGCs is still unclear. The purpose of this paper is to explore a kind of EGC with good mechanical properties, and to evaluate the bonding performance of EGCs with existing concrete using a tensile bonding test and single shear bonding test. At the same time, X-ray diffraction (XRD) and Scanning electron microscopy (SEM) were adopted to study the microstructure. The results showed that the bond strength increased with the increase in interface roughness. For polyvinyl alcohol (PVA)-fiber-reinforced EGCs, the bond strength increased with the increase in FA content (0-40%). However, with the change of FA content (20-60%), the bond strength of polyethylene (PE) fiber-reinforced EGCs have little change. The bond strength of PVA-fiber-reinforced EGCs increased with the increase in water-binder ratio (0.30-0.34), while that of PE-fiber-reinforced EGCs decreased. The bond-slip model of EGCs with existing concrete was established based on the test results. XRD studies showed that when the FA content was 20-40%, the content of C-S-H gels was high and the reaction was sufficient. SEM studies showed that when the FA content was 20%, the PE fiber-matrix bonding was weakened to a certain extent, so the ductility of EGC was improved. Besides, with the increase in the water-binder ratio (0.30-0.34), the reaction products of the PE-fiber-reinforced EGC matrix gradually decreased.

Hormetic effects of EGC and EGCG on CES1 activity and its rescue from oxidative stress in rat liver S9.

Carboxylesterase 1 (CES1) is a hydrolytic enzyme that plays an important role in the activation or deactivation of many therapeutic agents, thus affecting their pharmacokinetic and pharmacodynamic outcomes. Using rat liver S9 as an enzyme source and enalapril as a CES1 substrate, the present study examined effects of a number of flavonoids on the formation of enalaprilat (the active form of enalapril) produced by CES1-mediated hydrolysis. While a majority of flavonoids tested showed inhibition on CES1, an unexpected hormetic effect was observed for epigallocatechin (EGC) and epigallocatechin gallate (EGCG), i.e., stimulatory effect at low concentrations and enzyme inhibition at high concentrations. Further experiments revealed that oxidative stress caused by hydrogen peroxide, arachidonic acid plus iron, and oxidized low density lipoproteins (oxLOL) reduced CES1 activity in rat liver S9 and the loss of CES1 enzyme activity could be rescued largely by EGC or EGCG. In contrast, such effects were minimal in human liver S9, probably due to the presence of a higher ratio of reduced vs oxidized forms of glutathione. The above findings suggest that the polyphenolic nature of EGC or EGCG might be responsible for rescuing CES1 activity under oxidative stress. Because of the importance of CES1 in drug activation or deactivation and rat liver S9 as a versatile in vitro system used for drug metabolism studies and drug safety assessment, caution should be exercised to avoid potential biases for data interpretation and decision making when CES1 activity in rat liver S9 is evaluated with dependency on experimental conditions.

Predictive factors of lymphatic metastasis and evaluation of the Japanese treatment guidelines for endoscopic resection of early gastric cancer in a high-volume center in Perú.

Purpose: This study aimed to identify the predictive factors of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) and to evaluate the applicability of the Japanese treatment guidelines for endoscopic resection in the western population. Methods: Five hundred-one patients with pathological diagnoses of EGC were included. Univariate and multivariate analyses were conducted to identify the predictive factors of LNM. EGC patients were distributed according to the indications for endoscopic resection of the Eastern guidelines. The incidence of LNM was evaluated in each group. Results: From 501 patients with EGC, 96 (19.2%) presented LNM. In 279 patients with tumors with submucosal infiltration (T1b), 83 (30%) patients had LNM. Among 219 patients who presented tumors > 3 cm, 63 (29%) patients had LNM. Thirty-one percent of patients with ulcerated tumors presented LMN (33 out of 105). In 76 patients and 24 patients with lymphovascular and perineural invasion, the percentage of LMN was 84% and 87%, respectively. In the multivariate analysis, a tumor diameter >3 cm, submucosal invasion, lymphovascular, and perineural invasion were independent predictors of LMN in EGC. No patient with differentiated, non-ulcerated mucosal tumors presented LNM regardless of tumor size. Three of 17 patients (18%) with differentiated, ulcerated mucosal tumors and ≤ 3 cm presented LNM. No LNM was evidenced in patients with undifferentiated mucosal tumors and ≤ 2 cm. Conclusions: The presence of LNM in Western EGC patients was independently related to larger tumors (>3 cm), submucosal invasion, lymphovascular and perineural invasion. The Japanese absolute indications for EMR are safe in the Western population. Likewise, Western patients with differentiated, non-ulcerated mucosal tumors, and larger than 2 cm are susceptible to endoscopic resection. Patients with undifferentiated mucosal tumors smaller than 2 cm presented encouraging results and ESD could be recommended only for selected cases.

Research trends in endoscopic applications in early gastric cancer: A bibliometric analysis of studies published from 2012 to 2022.

Background: Endoscopy is the optimal method of diagnosing and treating early gastric cancer (EGC), and it is therefore important to keep up with the rapid development of endoscopic applications in EGC. This study utilized bibliometric analysis to describe the development, current research progress, hotspots, and emerging trends in this field. Methods: We retrieved publications about endoscopic applications in EGC from 2012 to 2022 from Web of Science™ (Clarivate™, Philadelphia, PA, USA) Core Collection (WoSCC). We mainly used CiteSpace (version 6.1.R3) and VOSviewer (version 1.6.18) to perform the collaboration network analysis, co-cited analysis, co-occurrence analysis, cluster analysis, and burst detection. Results: A total of 1,333 publications were included. Overall, both the number of publications and the average number of citations per document per year increased annually. Among the 52 countries/regions that were included, Japan contributed the most in terms of publications, citations, and H-index, followed by the Republic of Korea and China. The National Cancer Center, based in both Japan and the Republic of Korea, ranked first among institutions in terms of number of publications, citation impact, and the average number of citations. Yong Chan Lee was the most productive author, and Ichiro Oda had the highest citation impact. In terms of cited authors, Gotoda Takuji had both the highest citation impact and the highest centrality. Among journals, Surgical Endoscopy and Other Interventional Techniques had the most publications, and Gastric Cancer had the highest citation impact and H-index. Among all publications and cited references, a paper by Smyth E C et al., followed by one by Gotoda T et al., had the highest citation impact. Using keywords co-occurrence and cluster analysis, 1,652 author keywords were categorized into 26 clusters, and we then divided the clusters into six groups. The largest and newest clusters were endoscopic submucosal dissection and artificial intelligence (AI), respectively. Conclusions: Over the last decade, research into endoscopic applications in EGC has gradually increased. Japan and the Republic of Korea have contributed the most, but research in this field in China, from an initially low base, is developing at a striking speed. However, a lack of collaboration among countries, institutions, and authors, is common, and this should be addressed in future. The main focus of research in this field (i.e., the largest cluster) is endoscopic submucosal dissection, and the topic at the frontier (i.e., the newest cluster) is AI. Future research should focus on the application of AI in endoscopy, and its implications for the clinical diagnosis and treatment of EGC.

Intensive Systematic "Train-the-Trainer" Course as an Effective Strategy to Improve Detection of Early Gastric Cancer: A Multicenter Retrospective Study.

BACKGROUND: To improve the diagnosis of early gastric cancer (EGC), a train-the-trainer (TTT) course was developed. This trial aimed to investigate whether TTT courses from trained trainers could improve trainees' EGC detection. METHODS: In this multi-center, retrospective study, the training was carried out 8 times in one year. Clinical records one year before ("2016"), during ("2017"), and after ("2018") the course were collected. The primary endpoint was the improvement of EGC detection rate after TTT courses. RESULTS: Twenty-four trainees from 17 hospitals were included in this study. A total of 123,416 esophagogastroduodenoscopy and 65,570 colonoscopy procedures were analyzed. The early gastric cancer detection rate (EDR) was 0.101% in 2016, which significantly increased to 0.338% in 2018 (p = 0.015). The early gastric cancer ratio (ECR, ratio of newly detected EGCs to all newly detected gastric cancers) in 2016 was 8.440%, which consistently increased to 11.853% and 19.778% in 2017 and 2018 (p = 0.006), respectively. In contrast, the advanced gastric cancer detection rate (ADR) was similar before, during, or after the course (p = 0.987). The 3-year EDR, ECR, and ADR in esophageal and colorectal cancer were not significantly different. CONCLUSIONS: The systematic training course can improve EGC detection rate and may be an effective educational strategy to reduce gastrointestinal cancers mortality.

The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC50 values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.

Improving flavor of summer Keemun black tea by solid-state fermentation using Cordyceps militaris revealed by LC/MS-based metabolomics and GC/MS analysis.

Cordyceps militaris (C. militaris) has been approved and widely used in healthy food. The present study aimed to improve the flavor of summer Keemun black tea (KBT) using C. militaris solid-state fermentation. Combined with sensory evaluation, the volatile and non-volatile components of solid-state fermentation of KBT (SSF-KBT) and KBT were analyzed. The results showed that after the solid-state fermentation, the contents of total polyphenol, total flavonoid, and total free amino acids were significantly reduced. Further non-targeted metabolomics analysis revealed that the contents of non-galloylated catechins and d-mannitol increased, while the galloylated catechins and flavonoid glycosides decreased as did the bitterness and astringency of KBT. Dihydro-ß-ionone and ß-ionone (OAV = 59321.97 and 8154.17) were the aroma-active compounds imparting woody and floral odors in SSF-KBT, respectively. Current study provides a new avenue to develop summer-autumn KBT.

CO2 transoral laser microsurgery for early glottic carcinoma with anterior commissure involvement.

OBJECTIVE: Anterior commissure (AC) involvement is an unfavorable factor for transoral laser microsurgery (TLM) treatment of early glottic carcinoma (EGC). This study aimed to evaluate the therapeutic efficacy of TLM treatment for EGC with AC involvement. METHODS: From 2008 to 2017, 177 patients with T1-T2 EGC with AC involvement were retrospectively included and divided into the TLM group (n=115) receiving CO2 laser TLM and the control group undergoing open surgery (n=62). The survival outcomes, postoperative complications, laryngeal preservation rate, recurrence and the phonological results were compared between groups. RESULT: The TLM group had significantly reduced hospital stay, hospitalization costs, and intraoperative blood loss as compared with the control group. The tracheotomy rate was significantly higher in the control group (96.8% vs. 0%). The 5-year overall survival (OS) was 89.6% and 85.5% in the TLM group and control group, respectively. Log-rank test showed no difference in survival rate between the two groups. There was no significant difference in laryngeal preservation rate and overall recurrence rate between groups. In postoperative vocal function evaluation, there were significant differences in the overall grade (G), the roughness (R), the breathiness (B), Voice Handicap Index-10 (VHI-10), Jitter, Shimmer, noise/harmonic ratio (NHR), maximum phonation time (MPT), phonation threshold pressure (PTP) between the two groups. CONCLUSION: For EGC with AC involvement, TLM has similar survival outcomes with the open surgery, but has better postoperative voice outcomes. Meanwhile, TLM can effectively reduce intraoperative blood loss, hospitalization time, hospitalization costs and postoperative complications.

Advancement in Aptamer-based Biosensors for Gastric Cancer and Therapeutic Strategies / 中国生物化学与分子生物学报

The timely diagnosis of early gastric cancer is important for guiding the choice of treatment and prolonging the survival of patients. However, current screening of early gastric cancer still relies on endoscopic examination due to the lack of sensitive, accurate, and convenient screening tools. The cost of large-scale screening through gastrointestinal endoscopy is high and many countries and regions cannot afford it. At present, many types of biomarkers have been proved to own the ability to predict and diagnose tumors. Aptamer, as single-stranded oligonucleotides DNA or RNA, can be used to construct sensitive and reliable biosensors based on fluorometry, colorimetric, electrochemistry, etc. through label modification, coupling with various novel materials, etc. Additionally, it is also widely used in the field of precision medicine due to its small molecular weight, high specificity, and natural biological properties. We summarized and concluded aptamer-based gastric cancer diagnostic and therapeutic studies to help researchers quickly get access to tumor-related aptamers screening process, biosensor construction and optimization methods, and therapeutic strategies. This study aimed to provide a reference for the subsequent development of gastric cancer-related aptamers that meet clinical needs and assist in the endoscopic examination, diagnosis, and follow-up.

Geographical origin identification of Chinese white teas, and their differences in tastes, chemical compositions and antioxidant activities among three production regions.

The producing area of Chinese white tea has been expanded to Xinyang and Yunnan from Fuding region. In this study, six sensory tastes and fifty-one chemical components including seventeen phenolic compounds, three purine alkaloids and twenty amino acids were determined in eighteen Bai mudan sub-type of white tea by electronic tongue, high performance liquid chromatography and amino acid analyzer for geographical identification, respectively. Additionally, in vitro antioxidant activities were evaluated by five various assays. Multivariate statistical analyses such as PCA, HCA and PLS-DA, completely divided these white teas into Xinyang, Yunnan and Fuding groups, indicating the feasibility of white tea classification by the production region. Twelve characteristic compounds (VIP > 1.0, P < 0.05) like gallic acid, theaflavin and L-glutamic acid contributed to the geographical identification. In conclusion, this study explored the chemical, taste and antioxidant capacity differences among three main production regions, and revealed their potential relations in white tea.

Automatic detection of early gastric cancer in endoscopy based on Mask region-based convolutional neural networks (Mask R-CNN)(with video).

The artificial intelligence (AI)-assisted endoscopic detection of early gastric cancer (EGC) has been preliminarily developed. The currently used algorithms still exhibit limitations of large calculation and low-precision expression. The present study aimed to develop an endoscopic automatic detection system in EGC based on a mask region-based convolutional neural network (Mask R-CNN) and to evaluate the performance in controlled trials. For this purpose, a total of 4,471 white light images (WLIs) and 2,662 narrow band images (NBIs) of EGC were obtained for training and testing. In total, 10 of the WLIs (videos) were obtained prospectively to examine the performance of the RCNN system. Furthermore, 400 WLIs were randomly selected for comparison between the Mask R-CNN system and doctors. The evaluation criteria included accuracy, sensitivity, specificity, positive predictive value and negative predictive value. The results revealed that there were no significant differences between the pathological diagnosis with the Mask R-CNN system in the WLI test (χ2 = 0.189, P=0.664; accuracy, 90.25%; sensitivity, 91.06%; specificity, 89.01%) and in the NBI test (χ2 = 0.063, P=0.802; accuracy, 95.12%; sensitivity, 97.59%). Among 10 WLI real-time videos, the speed of the test videos was up to 35 frames/sec, with an accuracy of 90.27%. In a controlled experiment of 400 WLIs, the sensitivity of the Mask R-CNN system was significantly higher than that of experts (χ2 = 7.059, P=0.000; 93.00% VS 80.20%), and the specificity was higher than that of the juniors (χ2 = 9.955, P=0.000, 82.67% VS 71.87%), and the overall accuracy rate was higher than that of the seniors (χ2 = 7.009, P=0.000, 85.25% VS 78.00%). On the whole, the present study demonstrates that the Mask R-CNN system exhibited an excellent performance status for the detection of EGC, particularly for the real-time analysis of WLIs. It may thus be effectively applied to clinical settings.