Search

The role of vitamin C in sepsis is still controversial, we aimed to systematically review the efficacy of intravenous vitamin C supplementation in the treatment of sepsis.MEDLINE, EmBase, Web of Science, WanFang Data and CNKI were comprehensively searched to collect randomized controlled trails (RCTs) of vitamin C supplementation for patients with sepsis or sepsis shock from January 2000 to March 2021. Two researchers independently screened the literature, extracted the data and accessed the risk of bias in the included studies; meta-analysis was then performed by using Revman 5.4 software.A total of 10 RCTs involving 1400 participants were included. The results of meta-analysis showed that intravenous vitamin C supplementation can improve SOFA (ΔSOFA) within 72 h [RR = 1.32,95% CI(0.80,1.85), P0.0001] of septic patients. There were no difference on short term mortality (28-30d)[RR = 0.83,95% CI(0.65,1.05), P = 0.11], long term mortality (90d) [RR = 1.16,95% CI(0.82,1.66), P = 0.40], hospital LOS[RR = 0.15,95% CI(-0.73,1.03), P = 0.55], ventilator-free days[RR = 0.09,95% CI(-0.24,0.42), P = 0.60], ICU-LOS[RR = 0.22,95% CI(-0.13,0.57), P = 0.22], between two groups. The results of Subgroup analysis showed that intravenous vitamin C alone can reduce the risk of short term mortality (28-30d) [RR = 0.61,95% CI(0.47,0.79), P = 0.0002]of sepsis patients.Based on current RCTs, our work indicated that mono-intravenous vitamin C therapy may reduce short-term mortality of sepsis patients, and it may protect organ functions. Due to the limitation of the quantity and quality of included studies, the above conclusions need to be verified by more large scale and high quality randomized control trials.

The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis and eosinophilic gastritis in a geographically diverse cohort of patients compared to controls.We conducted a prospective study of individuals with eosinophilic gastrointestinal disease in the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative PCR. Community composition was determined by small subunit rRNA gene amplicons.139 mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased (Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE (Streptococcus, Gemella) and EoG (Leptotrichia), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability amongst individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls.Dominant community members (Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS.

Eight phenolic compounds (1–8), including two new compounds (1 and 2), were isolated from the twigs of Gardenia jasminoides. Their structures were determined by means of extensive 1D and 2D NMR spectroscopic studies. Compounds 1–4 were tested for their antimethicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1–4 showed good inhibition with IZD of 12.2 ± 2.2, 13.8 ± 2.4, 15.2 ± 2.8, and 12.9 ± 2.5 mm, respectively.

Two new isobenzofuranone derivatives (1 and 2) together with six known compounds (3–8) were isolated from the roots of Phlomis betonicoides, a highly sweet plant in China. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–8 were tested for their anti-rotavirus activity. The results showed that compounds 1–8 exhibited potent anti-rotavirus activity with therapeutic index value 7.5–16.4.

Mutation of p53 is the most common genetic alteration in human cancer. The vast majority of p53 mutations found in cancer are missense mutations, with some single nucleotide point mutations leading to the accumulation of mutant p53 protein with potential gain of oncogenic function. The mechanism for stabilization and accumulation of missense mutant p53 protein in malignant cells is not fully understood. It is thought that DNAJA1 plays a crucial role as a co-chaperone protein by stabilizing mutant p53 and amplifying oncogenic potential. As such, identifying small molecule inhibitors to disrupt the protein-protein interaction between mutant p53 and DNAJA1 may lead to an effective treatment for preventing carcinogenesis. Studying protein-protein interactions and identifying potential druggable hotspots has historically been limited-protein-protein binding sites require more complex characterization than those of single proteins and the crystal structures of many proteins have not been identified. Due to these issues, identifying salient druggable targets in protein-protein interactions through bench research may take years to complete. However, in silico modeling approaches allow for rapid characterization of protein-protein interfaces and the druggable binding sites they contain. In this chapter, we first review the oncogenic potential of mutant p53 and the crucial role of DNAJA1 in stabilizing missense mutant p53. We then detail our methodology for using in silico modeling and molecular biology to identify druggable protein-protein interaction sites/pockets between mutant p53 and DNAJA1. Finally, we discuss screening for and validating the utility of a small molecule inhibitor identified through our in silico framework. Specifically, we describe GY1-22, a unique compound with activity against mutant p53 that demonstrates therapeutic potential to inhibit cancer cell growth both in vivo and in vitro.

Three new anthraquinones (1–3), together with four known analogues (4–7) were isolated from the twigs of Cassia auriculata Linn.. Their structures were elucidated by extensive spectroscopic analysis and comparison of spectroscopic data with those reported in literatures. All compounds were tested for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. Compounds 1, 2 and 7 showed modest antibacterial activity against MRSA with MIC values of 4.2, 5.0, 4.7 μg/mL, and compounds 3, 4, 5 and 6 showed weak antibacterial activity against MRSA with MIC valves of 9.2, 7.6, 7.1, 9.6 μg/mL, respectively.

Background Since Nicotiana tabacum (tobacco) has important significance to humans for their medicinal uses, to find antivirus activities inhibitors from tobacco, increase its medicinal value, and comprehensive utilization of its by-products, our group had investigated the chemical constituents of the stems of Y-202, a cultivar of tobacco which high resistance to tobacco mosaic virus (TMV). Results Four new isoindolinone-type alkaloids, nicoisoindoles A–D (1–4), along with four known isoindole derivatives (5–8) were isolated. Compounds 1–4 represent a new subclass of isoindolinone alkaloids with rare cyclopenta[f]isoindole-1-one frameworks. Among them, nicoisoindole C (3) possesses an unusual N-2-(5-methoxy-6-methylpyridin-2-yl) ethyl moiety, while nicoisoindole D (4) has a novel a N-(3-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl substituent. Interestingly, compounds 1, 3, and 4 showed high anti-TMV activities with inhibition rates of 43.8%, 58.8%, and 67.8% at the concentration of 20 μM, and IC50 values of 23.6, 19.5 and 15.4 μM, respectively, even more potent than that of positive control. Conclusions The successful isolation and structure identification of new oxocyclopenta[f]isoindole-1-ones provide materials for the screening of antivirus activities inhibitors, and contribute to the development and utilization of the waste from tobacco cultivation. Graphical Abstract

BACKGROUND Acute pancreatitis is the most common gastrointestinal disease worldwide for hospital admission, and infected pancreatic and peripancreatic necrosis is a potentially lethal complication, which is the most dreadful one associated with a poor prognosis: mortality is approximately 15% and up to 30–39%. Depending on the very high mortality and morbidity, infected necrotizing pancreatitis always requires intervention at the early stage. The current standard approach for infected necrotizing pancreatitis is a minimally invasive step-up approach with catheter drainage as the first step. International guidelines advise delay in catheter drainage and antibiotics treatment until the infected collection has become a “wall-off”, which takes 4 weeks to develop. However, no clear evidence from clinical studies was seen to suggest superiority for the postponed catheter drainage. We will perform the first systematic review and meta-analysis to explore whether immediate catheter drainage improves the survival rate of patients with infected necrotizing pancreatitis compare with postponed catheter drainage. Methods We will search the randomized controlled trial (RCT) literature involving and nonrandomized clinical cohort studies of immediate catheter drainage in patients with infected necrotizing pancreatitis in 5 electric databases, including PubMed, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM). Studies including patients under 18 years of age or pregnant women will be excluded. We will define the overall mortality of patients with infected necrotizing pancreatitis as the primary outcome. Besides, the incidences of bleeding resulting in intervention, perforation of a visceral organ leading to intervention, enterocutaneous fistula, pancreatic cutaneous fistula, incisional hernia and wound infection, the total length of stay, endocrine and exocrine pancreatic insufficiency, and severe complications will be regarded as the secondary outcomes. Quality assessment of the included studies will be independently performed according to the Version 2 of the Cochrane tool for assessing the risk of bias in a randomized trial (RoB2) for RCTs and the Non-Randomized Studies-of Interventions (ROBINS-I) Tool for Observational Studies. Meanwhile, the level of evidence for results will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. All analyses will be conducted by using the RevMan (Version 5.4; Cochrane, Oxford, UK). Results From our study, we will ascertain whether immediate catheter drainage improves the survival rate of patients with infected necrotizing pancreatitis compare with postponed catheter drainage. Trial registration: PROSPERO registration number CRD42021291734.

Engineering of glycosyltransferases (GTs) with desired substrate specificity for the synthesis of complex oligosaccharides has been of great scientific and industrial interest. Here we describe an ultra-high-throughput fluorescence activated cell sorting (FACS) method for the directed evolution of GTs, at the single cell level. This assay relies on the exquisite substrate specificity of lactose permeases (LacY) that are located in the cell membrane, which distinguish selectively the fluorescent glycosylated products from the unreacted substrates. The method described here allows facile screening 10

Two new (1 and 2) compounds, together with five known (3–7) chromone derivatives, were isolated from the whole plants of Cassia pumila. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1–7 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1, 2, 5, and 6 showed good inhibition with IZD of 13.4 ± 2.5, 12.2 ± 2.0, 14.6 ± 2.2, and 14.2 ± 2.6 mm, and compounds 3, 4, and 7 showed weak inhibition with IZD of 10.7 ± 2.2, 11.3 ± 2.0, and 10.8 ± 2.1 mm, respectively.

Two new chromone derivatives (1 and 2), together with four known (3–6) ones, were isolated from the stems of a local sun cured tobacco (Fenghuang tobacco, widely cultivated in Shifang prefecture, Sichuan Province). Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were tested for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compounds 1 and 2 exhibited high anti-TMV activities with inhibition rates of 35.8 and 28.6% at the concentration of 20 μM. These rates are close to that of the positive control.

Two new naphthalene derivatives, 1-(3-hydroxy-1-(hydroxymethyl)-2-methoxy-6-methylnaphthalen-7-yl) propan-2-one (1) and 1-(3-hydroxy-1-(hydroxymethyl)-6-methylnaphthalen-7-yl)propan-2-one (2), together three known naphthalene derivatives (3–5) were isolated from the fermentation products of the endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results showed that compounds 1 and 2 showed weak inhibition with IZD of 10.2 ± 1.8 and 11.3 ± 2.0 mm, respectively.

Transmural fibrosis and stricture formation are key pathogenic processes for Crohn's disease that underlies clinical refractoriness, resulting in severe morbidity. The mechanisms for fibroplasia in Crohn's are not fully elucidated. In this study, we identified a cohort of refractory Crohn's disease with surgically resected bowel specimens including cases with bowel stricture and age-/sex-matched refractory disease without bowel stricture. Via immunohistochemistry, density and distribution of IgG4+ plasma cells in resected cases were analyzed. The histologic severity of fibrosis and association with gross evidence of stricture formation and IgG4+ plasma cells were comprehensively analyzed. Our results showed that density of IgG4+ plasma cells/high-power field (IgG4+ PCs/HPF) was significantly associated with increasing histologic fibrosis score (15 IgG4+ PCs/HPF in specimens with fibrosis score 0 vs 31 IgG4+ PC/HPF in fibrosis score 2 and 3, P = .039). Patients with gross evidence of stricture had significantly higher fibrosis scores compared to those without gross evidence of stricture ( P = .044). There was a trend that mean IgG4+ plasma cell count was higher in Crohn's disease with gross stricture formation ( P = .26), although it did not reach statistical significance (likely due to multiple pathogenesis events involved in bowel stricture formation besides IgG4+ plasma cells; such as transmural fibrosis, muscular hypertrophy, transmural ulcer/scar formation, and muscular–neural dysfunction). Our findings indicate IgG4+ plasma cells are associated with increasing histologic fibrosis in Crohn's. Further research is needed to establish a role for IgG4+ plasma cells in fibroplasia with an eye toward potential medical therapies targeting IgG4+ plasma cells to prevent transmural fibrosis.

Extended survival of liver transplant recipients has brought rejection management to the forefront of liver transplant research. This article discusses T-cell-mediated rejection, antibody-mediated rejection, and chronic rejection. We focus on the prevention and then discuss treatment options. Future directions of rejection management include biomarkers of rejection, which may allow for monitoring of patients who are considered high risk for rejection and detection of rejection before there is any clinical evidence to improve graft and patient survival. With improved graft life and survival of liver transplant recipients, the new frontier of rejection management focuses on immunosuppression minimization, withdrawal, and personalization.

Endoscopic eradication therapy (EET) is an effective treatment for Barrett’s esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET

Objectives To evaluate the pharmacokinetics, pharmacodynamics, and tolerability of JY09, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, in healthy subjects. Materials and methods Healthy subjects were enrolled into 5 cohorts (0.3, 0.7, 1.5, 3.0, and 6.0 mg JY09) and received subcutaneous JY09 or placebo according to a randomized, double-blind, placebo-controlled, single-center, dose-escalating phase I trial design. Blood samples were collected over a 42-day period, and JY09 in plasma was determined by an electrochemical luminescence method. For the pharmacodynamic evaluation, oral glucose tolerance tests (OGTTs) were conducted predose and on day 5 after the target dose, during which plasma glucose, insulin, C-peptide, and glucagon concentrations were analyzed. Tolerability was assessed using physical examination and queries, vital sign measurements, laboratory analysis, and detection of immunogenicity. Results In healthy Chinese subjects, JY09 exhibited a dose-dependent increase in AUC0-inf and Cmax from 0.7 to 6.0 mg JY09. The half-life of JY09 was ~ 9.3 days, and the peak concentration was reached at ~ 60 - 72 hours. Following the OGTT, an increase in C-peptide concentration was observed after exposure to JY09 at the dose of 6.0 mg compared to the placebo group. JY09 was well tolerated in healthy Chinese subjects following a single dose of up to 6.0 mg. No symptomatic hypoglycemia was reported, and the most commonly observed adverse event was suppressed appetite, and its incidence was dose-dependent. Four subjects (13%) developed anti-JY09 antibodies. Conclusion JY09 has a long half-life of ~ 9.3 days, with an acceptable safety profile.

Two new isobenzofurans, 5-(methoxymethyl)-2,2-dimethyl-2H-furo[3,4-h]chromen-7(9H)-one (1) and 5-(2-methoxyethyl)-2,2-dimethyl-2H-furo[3,4-h]chromen-7(9H)-one (2), together with two known isobenzofurans (3 and 4), were isolated from the roots of Yunnan local sun cured tobacco. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–4 were tested for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compound 4 showed strong inhibition with IZD of 16.5 ± 2.2. Compounds 1–3 also showed good inhibition with IZD of 13.6 ± 2.0, 14.0 ± 2.3, and 11.8 ± 1.6 mm, respectively. Compounds 1–4 were also tested for their antioxidant activity, and they showed good antioxidant activity with IC50 value of 4.38, 4.57, 4.46, and 4.28 μg/mL, respectively.

Colorectal carcinoma (CRC) is the third most common cancer type in the United States. While the incidence of CRC is decreasing among an older population undergoing screening, the incidence of early-onset CRC is rising. There is a growing understanding that the molecular underpinnings of colorectal carcinoma vary by age. In this study, we report the genetic alterations and clinicopathologic features of a single-institution colorectal carcinoma cohort over a 2-year period using a next-generation sequencing (NGS) approach and microsatellite stability (MS) status determined by immunohistochemical staining. Forty cases were identified in an early-onset colorectal carcinoma cohort (eCRC) defined by age 70 years. eCRC was more often-left-sided/rectal and more likely to present high rates of lymph node positivity with metastatic disease. NGS mutational analysis revealed distinct differences between eCRC and arCRC, with eCRC being characterized by low frequency of PIK3CA mutations, elevated frequency of KRAS and CTNNB1 mutations in microsatellite instability high tumors, and very low frequency of BRAF mutations.

Two new pentenyl coumarins (1 and 2), together with three known pentenyl coumarins (3–5), were isolated from the roots and stems of Nicotiana rustica. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1–5 were tested for their anti-rotavirus activity. The results revealed that compounds 1–5 exhibited potent anti-rotavirus activity with therapeutic index (TI) value in the range of 11.1–15.7.

This study aimed to employ plant print identification to screen a wild-type soybean (Glycine soja Seib. and Zucc.) and then hybridize it with a cultivated soybean (Glycine max (L.) Merr.) (Lu, Chin Sci Bull 43:2074–2078, 1998) with a view to produce a salt-resistant variety. Scanning electron microscopy, optical microscopy, and paraffin sectioning were employed to compare two varieties of wild soybeans (#028 and #029) captured from different eco-environments, and the one with a salt gland present –– wild soybean #029 – was chosen as the male parent for hybridization. Considering a soybean variety with low stem as female parent, hybridization was performed and a new variety of salt-resistant soybean resulted, Ji-Yu59, which opened up a new, cost-efficient way of soybean breeding. Under saline-alkali stress, our salt-tolerant wild soybean is anticipated to exhibit antagonism by evolving a series of salt-resistant structures, including a salt-containing vacuolar package and a salt gland. The salt gland would help eliminate salts from the soybean plant; upon maturity, a salt gland is known to be able to break up salts to release their respective ions, effectively reducing salt and alkali stress. Therefore, a wild soybean with salt gland is an excellent choice for the hybridization of salt-resistant soybean varieties.

Two new coumarins, 6-hydroxymethyl-3-prenyl-7-methoxycoumarin (1) and 6-hydroxyethyl-3-prenyl-7- methoxycoumarin (2), together with three known coumarins (3–5), were isolated from the roots and stems of Yunyan-300, a variety of Nicotiana tabacum L. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were tested for their anti-methicillinresistant Staphylococcus aureus (anti-MRSA) activity and their antioxidant activity. The results revealed that compounds 1 and 2 showed good anti-MRSA inhibitions with IZD of 12.2 ± 1.8 and 11.8 ± 1.5 mm, respectively, and antioxidant activity with an IC50 value of 4.65 and 4.85 μg/mL, respectively.

Two new furan-2-carboxylic derivatives (1 and 2), together with three known compounds (3–5), were isolated from the leaves of Nicotiana tabacum. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1 and 2 were tested for their anti-TMV activities. The results showed that compounds 1 and 2 exhibited high anti-TMV activity with inhibition rates of 33.2 and 30.8%. These rates are close to that of positive control.

Liver biopsy and histologic examination are the mainstay for diagnosing liver diseases, despite advances in imaging and molecular procedures. Liver biopsy can provide useful information regarding the structural integrity and type and degree of injury, disease activity, response to treatment, progression of disease and degree/staging of fibrosis. Liver biopsies evaluate acute and chronic liver diseases, and mass-forming lesions. The role of the pathologist is to integrate clinical, serologic, and biochemical data with morphologic changes and provide a comprehensive diagnosis. This review focuses on basic principles necessary for proper interpretation of liver biopsy specimens in patients with chronic liver disease.

Two new tricyclic alkaloids (1 and 2), together with three known (3–5) alkaloids, were isolated from the whole plants of Thalictrum cultratum. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–5 were tested for their anti-rotavirus activity. The results revealed that compounds 1–5 exhibited potent anti-rotavirus activity with therapeutic index (TI) values in the range 10.7–17.7.

This study focused on utilizing a boron nitride (BN) layer to improve the photoelectric property stability of the flexible Al/Cu/ZnO multilayer thin film, which was prepared on a polyethylene terephthalate (PET) substrate by radio frequency (RF) magnetron sputtering. By analyzing surface morphology, chemical composition and photoelectric properties of flexible BN/Al/Cu/ZnO multilayer films with different BN layer thicknesses, the BN/Al/Cu/ZnO film with a 100-nm-thick BN layer (BN100/Al/Cu/ZnO), which had the best comprehensive photoelectric property with a figure of merit of 0.82 × 10−3 Ω−1, was chosen to further study the performance stability with storage temperature and time. It was found that as compared to the Al/Cu/ZnO film, the BN100/Al/Cu/ZnO film had more stable photoelectric properties at different storage temperatures and times, which was inferred to be attributed to the excellent heat and oxidation resistances of the BN layer that were conducive to avoiding surface damage and oxidation of the film. The results in this work demonstrate the key role of the BN layer in enhancing photoelectric property stability of the flexible Al/Cu/ZnO film, and may provide a feasible strategy for improving thermal and long-time stability of single-layer or multilayer flexible transparent conductive films.

Two new (1 and 2), together with two known (3 and 4), isoquinoline alkaloids were isolated from the whole plants of Thalictrum cirrhosum. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–4 were tested for their antirotavirus activity. The results revealed that compounds 2 exhibited high antirotavirus activity with a therapeutic index (TI) value of 19.3. This value is close to that of positive control (TI value 20.4). Compounds 1, 3, and 4 also exhibited potent antirotavirus activity with TI value above 10.

Swarming behavior facilitates pair formation, and therefore mating, in many eusocial termites. However, the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightless insect forms are still unclear. Here, we found that the dispersal flight of the eusocial termite Reticulitermes chinensis Snyder led to a gradual decrease in adenosine triphosphate supply from oxidative phosphorylation, as well as a reduction in the activities of critical mitochondrial respiratory enzymes from preflight to dealation. Correspondingly, using three-dimensional reconstruction and transmission electron microscopy (TEM), the flight muscles were found to be gradually deteriorated during this process. In particular, two tergo-pleural muscles (IItpm5 and III-tpm5) necessary to adjust the rotation of wings for wing shedding behavior were present only in flying alates. These findings suggest that flight muscle systems vary in function and morphology to facilitate the swarming flight procedure, which sheds light on the important role of swarming in successful extension and fecundity of eusocial termites.

BACKGROUND: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need in EG for more precise diagnostic tools. OBJECTIVE: We aimed to develop tissue- and blood-based diagnostic platforms for EG. METHODS: Patients with EG and non-EG controls were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. The EGDP(18) scores were derived from the expression of 18 highly dysregulated genes and Blood EG scores from dysregulated cytokines/chemokine levels. RESULTS: Gastric biopsies and blood samples from 185 subjects (EG 74, non-EG 111) were analyzed. The EGDP a) identified patients with active EG (P < .0001, AUC ≥0.95); b) effectively monitored disease activity in longitudinal samples (P = .0078); c) highly correlated in same-patient samples (antrum vs. body, r = 0.85, P < .0001); and d) inversely correlated with gastric peak eosinophil levels (r = −0.83, P < .0001), periglandular circumferential collars (r = − 0.73, P < .0001), and endoscopic nodularity (r = −0.45, P < .0001). For blood-based platforms, eotaxin-3, TARC, IL-5, and TSLP levels were significantly increased. Blood EG scores a) distinguished patients with EG from non-EG controls (P < .0001, AUC ≥0.91); b) correlated with gastric eosinophil levels (plasma r = 0.72, P = .0002; serum r = 0.54, P = .0015); and c) inversely correlated with EGDP(18) scores (plasma r = −0.64, P = .0015; serum r = −0.46, P = .0084). Plasma eotaxin-3 strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). CONCLUSION: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and tools for this emerging rare disease.

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.

Two new (1 and 2) and two known arylbenzofuran lignans (3 and 4) were isolated from the seeds of Arctium lappa. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1–4 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compound 3 showed good inhibition with IZD of 13.5 ± 1.5 mm), and compounds 1, 2, and 4 showed weak inhibition with IZD of 9.6 ± 1.0, 11.6 ± 1.2, and 10.8 ± 1.2 mm, respectively. Compounds 1–4 were also tested for the antioxidant activity, and they show good antioxidant activity with an IC50 values of 4.38, 4.22, 3.96, and 4.15 μg/mL, respectively.

Recent advances in rare disease research are accelerated by the work of consortia that have been supported by the National Institutes of Health. Development of such consortia rely on multidisciplinary relationships and engagement with patient advocacy groups, as well as the National Institutes of Health and industry and academic partners. In this rostrum we present the development of such a process that focuses on eosinophilic gastrointestinal diseases. Principal investigators, patient advocacy groups, research assistants, and trainees work together to perform natural history studies that promote clinical trial readiness tools, conduct clinical trials, train a new generation of investigators, and perform innovative pilot studies.

Differentiating NSAID enteropathy from Crohn disease can be challenging on terminal ileum biopsy. It is important to distinguish these two entities for management. In this study, clinical, radiographic, endoscopic, and histologic features of 30 patients diagnosed with NSAID enteropathy and 30 patients diagnosed with Crohn disease on terminal ileal biopsy were compared. None of the patients in the NSAID cohort demonstrated significant changes on imaging performed prior to biopsy. Depending on disease severity, patients with Crohn disease showed imaging findings ranging from minimal changes to significant bowel wall and/or luminal changes. Endoscopically, erythema, erosions, and/or ulcers in the terminal ileum were observed in a majority of NSAID cases. Patients with active Crohn disease were noted to have erythema, ulcers, strictures, and/or visible inflammation throughout the distal ileum and colon. Histologically, at least 80% of cases in each cohort showed ulceration/erosion and cryptitis/crypt abscesses. The Crohn disease cohort had significantly higher degree of lymphoplasmacytic inflammation in the lamina propria compared to the NSAID cohort. In contrast, a significantly higher percentage of the NSAID cohort had gland/crypt atrophy. A decrease in number of Paneth cells was found in the NSAID cohort. Decreased lamina propria lymphoplasmacytic inflammation was the most specific and the presence of gland atrophy the most sensitive feature favoring NSAID enteropathy. In summary, the combination of gland/crypt/Paneth cell atrophy with decreased lamina propria lymphoplasmacytic inflammation can aid in differentiating NSAID enteropathy from Crohn disease in terminal ileal biopsies; however, correlation with clinical, radiographic, and endoscopic findings is still required.

Nicotiana tabacum (tobacco) has attracted interest as one of the most economically important industrial crops widely cultivated in China, whose dried leaves are popularly consumed medicinally and recreationally by human societies. In this study, five undescribed alkaloids derivatives, isoaspergillines A-E, together with eight known alkaloids, notoamide D, (1R,4S)-4-benzyl-1-isopropyl-2,4-dihydro-1H-pyrazino-[2,1-b]quinazoline-3,6-dione, protuboxepin K, notoamide C, notoamide M, deoxybrevianamide E, cyclo (D-Pro-L-Trp), and versicolamide B, were obtained from the culture of the Nicotiana tabacum-derived fungus Aspergillus versicolor. Their structures were mainly elucidated through comprehensive analyses of spectroscopic data. Bioactivity evaluation of all isolated compounds revealed that isoaspergilline A and notoamide M exhibited anti-TMV activities with IC

BackgroundIndividualized neoantigen-specific immunotherapy (iNeST) requires robustly expressed clonal neoantigens for efficacy, but tumor mutational heterogeneity, loss of neoantigen expression, and variable tissue sampling present challenges. It is assumed that clonal neoantigens are preferred targets for immunotherapy, but the distributions of clonal neoantigens are not well characterized across cancer types.MethodsWe combined multiregion sequencing (MR-seq) analysis of five untreated, synchronously sampled metastatic solid tumors with re-analysis of published MR-seq data from 103 patients in order to characterize their globally clonal neoantigen content and factors that would impact neoantigen targeting.ResultsBranching evolution in colorectal cancer and renal cell carcinoma led to fewer clonal neoantigens and to clade-specific neoantigens (those shared across a subset of tumor regions but not fully clonal), with the latter not being readily distinguishable in single tumor samples. In colorectal, renal, and bladder cancer, most tumors had few globally clonal neoantigens. Prioritizing mutations with higher purity-adjusted and ploidy-adjusted variant allele frequency enriched for globally clonal neoantigens (those found in all tumor regions), whereas estimated cancer cell fraction derived from clustering-based tools, surprisingly, did not. Neoantigen quality was associated with loss of neoantigen expression in the bladder cancer case, and HLA-allele loss was observed in the renal and non-small cell lung cancer cases.ConclusionsWe show that tumor type, multilesion sampling, neoantigen expression, and HLA allele retention are important factors for iNeST targeting and patient selection, and may also be important factors to consider in the development of biomarker strategies.

Background: Crohn’s disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. Summary: Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.

Background: To explore the best pretreatment method of colorectal cancer tissue samples for metabolomics research based on solid-phase nuclear magnetic resonance. Method: Taking mucosal tissues of colorectal cancer and divide it into 5 groups of 0.2cm*0.2cm*0.2cm. Pretreatment was performed as follows: I. Liquid nitrogen storage; II. Transfer to the -80℃ refrigerator after storing in liquid nitrogen for 10 minutes; III. Transfer to the -80℃ refrigerator after storing in liquid nitrogen for 20 minutes; IV. Transfer to the -80℃ refrigerator after storing in liquid nitrogen for 30 minutes; V. -80℃ refrigerator storage. The interval between tumor sample separation to pretreatment is less than 30 minutes. The tissue sample testing process is carried out on Bruker AVII-600 Spectrometer equipped with a high-resolution probe having a 1H/13C magical angle rotation. The tissue samples were put into the NMR which run at a speed of 5000Hz for 10 minutes. NMR signals were collected and analyzed by Fourier transform, partial least squares discrimination analysis (PLS-DA). Corresponding metabolites and metabolic pathways were found in Human Metabolome Database (HMDB) according to the ppms with variable importance of projection (VIP) ＞1. Results: The content of pelargonic acid, stearic acid, D-Ribose, heptadecanoic acid, pyruvic acid, succinate, sarcosine, glycine, creatine, and L-lactate in liquid nitrogen storage group were significantly lower than the other groups (PConclusion: Liquid nitrogen storage can slow down the glucose and choline phospholipid metabolism process of colorectal cancer tissue samples in vitro; liquid nitrogen can preserve tissue sample’s metabolic state in the body. It is therefore the better way to store tissue sample than the other methods. clinical trial registry website: http://www.chictr.org.cn/index.aspx. Trial number: ChiCTR1900024640

Two new compounds (1 and 2), together with three known chromone derivatives (3–5), were isolated from Cassia leschenaultiana. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compounds 1 and 2 showed potential anti-TMV activities with inhibition rates of 35.6% and 38.7% at the concentration of 20 μM, respectively. These rates are higher than that of the positive control.

Two new xanthones (1 and 2), together with three known xanthones (3–5), were isolated from the whole plants of Comastoma pulmonarium. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were also evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compounds 1 and 2 showed high anti-TMV activity with inhibition rates of 42.8% and 52.4%, respectively. These rates are higher than that of positive control.

Two new diphenyl ethers (1 and 2) were isolated from the fermentation products of an endophytic fungus Phomopsis asparagi. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1 and 2 showed good inhibition with IZD 10.8 ± 2.0 and 11.4 ± 1.8 mm, respectively.