Impact of short-term proton pump inhibitors vs. histamine-2 receptor antagonists on gut microbiota in patients with acute coronary syndrome: A multicenter randomized trial.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs has been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S rRNA gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION: www.chictr.org.cn/ (ChiCTR2000029552).

Association between serum potassium, risk and prognosis of peritonitis in peritoneal dialysis patients - results from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study.

BACKGROUND: Hypokalemia has been associated with an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testing whether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. METHODS: A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. RESULTS: During a median follow-up of 25.7 months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0 mmol/L compared to those with higher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0 mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5 mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. CONCLUSION: Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.

Persistence of Lugol-unstaining is Associated With an Increased Risk of Progression to Malignancy in the Esophagus.

BACKGROUND & AIMS: The aim of this study was to investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore their association with progression to malignancy. METHODS: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy reexamination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during reexamination at the documented location (±2 cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma identified over 6.78 years of follow-up, and the secondary outcome was re-examination-detected severe dysplasia and above lesions. The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs. RESULTS: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted odds ratio [OR], 6.16; 95% confidence interval [CI], 2.70-17.80), large LULs (adjusted OR, 1.90; 95% CI, 1.18-3.15), and irregularly shaped LULs (adjusted OR, 1.63; 95% CI, 1.03-2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage esophageal squamous cell carcinoma cases and 31 severe dysplasia and above lesions detected during reexamination were identified, all of which originated from patients with persistent LULs (Pclinical-stage ESCC = .136; Preexamination-detected SDA = .015). CONCLUSION: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.

Differences in clinical manifestations and the fecal microbiome between irritable bowel syndrome and small intestinal bacterial overgrowth.

BACKGROUND: Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share similar abdominal symptoms; however, their differentiation remains controversial. AIMS: To illustrate the differences between the two conditions. METHODS: Patients and healthy controls completed questionnaires and provided stool samples for analysis. RESULTS: IBS presented with the most severe symptoms and was specifically characterized by intense abdominal pain and frequent episodes of diarrhea. Patients with IBS displayed more dysregulated taxonomy within the fecal microbiota than SIBO. Opportunistic pathogens, including Lachnoclostridium, Escherichia-Shigella, and Enterobacter were enriched in the IBS group which contributed to increased bacterial pathogenicity and positively correlated with abdominal pain and bloating, meanwhile, Lachnoclostridium and Escherichia-Shigella were found to be associated with metabolites affiliated to bile acids, alcohols and derivatives. Bacteria enriched in SIBO group correlated with constipation. The bacterial co-occurrence network within the SIBO group was the most intricate. Ruminococcaceae Group were defined as core bacteria in SIBO. Differential metabolites affiliated to androstane steroids and phenylacetic acids were associated with core bacteria. CONCLUSIONS: Our study elucidates the differences between IBS and SIBO in terms of symptoms, microbiota and functions, which provides insights into a better understanding of both diseases and evidence for different treatment strategies.

Construction and validation of serum Metabolic Risk Score for early warning of malignancy in esophagus.

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Dietary factors and patterns in relation to risk of later-onset ulcerative colitis in Chinese: A prospective study of 0.5 million people.

BACKGROUND: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults. AIMS: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese. METHODS: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food. CONCLUSIONS: The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults.

Tunable Interfacial Electric Field-Mediated Cobalt-Doped FeSe/Fe3Se4 Heterostructure for High-Efficiency Potassium Storage.

The interfacial electric field (IEF) in the heterostructure can accelerate electron transport and ion migration, thereby enhancing the electrochemical performance of potassium-ion batteries (PIBs). Nevertheless, the quantification and modulation of the IEF for high-efficiency PIB anodes currently remains a blank slate. Herein, we achieve for the first time the quantification and tuning of IEF via amorphous carbon-coated undifferentiated cobalt-doped FeSe/Fe3Se4 heterostructure (denoted UN-CoFe4Se5/C) for efficient potassium storage. Co doping can increase the IEF in FeSe/Fe3Se4, thereby improving the electron transport, promoting the potassium adsorption capacity, and lowering the diffusion barrier. As expected, the IEF magnitude in UN-CoFe4Se5/C is experimentally quantified as 62.84 mV, which is 3.65 times larger than that of amorphous carbon-coated FeSe/Fe3Se4 heterostructure (Fe4Se5/C). Benefiting from the strong IEF, UN-CoFe4Se5/C as a PIB anode exhibits superior rate capability (145.8 mAh g-1 at 10.0 A g-1) and long cycle lifespan (capacity retention of 95.1 % over 3000 cycles at 1.0 A g-1). Furthermore, this undifferentiated doping strategy can universally regulate the IEF magnitude in CoSe2/Co9Se8 and FeS2/Fe7S8 heterostructures. This work can provide fundamental insights into the design of advanced PIB electrodes.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

A P2/P3 Biphasic Layered Oxide Composite as a High-Energy and Long-Cycle-Life Cathode for Potassium-Ion Batteries.

Layered transition metal oxides are extensively considered as appealing cathode candidates for potassium-ion batteries (PIBs) due to their abundant raw materials and low cost, but their further implementations are limited by slow dynamics and impoverished structural stability. Herein, a layered composite having a P2 and P3 symbiotic structure is designed and synthesized to realize PIBs with large energy density and long-term cycling stability. The unique intergrowth of P2 and P3 phases in the obtained layered oxide is plainly characterized by X-ray diffraction refinement, high-angle annular dark field and annular bright field-scanning transmission electron microscopy at atomic resolution, and Fourier transformation images. The synergistic effect of the two phases of this layered P2/P3 composite is well demonstrated in K+ intercalation/extraction process. The as-prepared layered composite can present a large discharge capacity with the remarkable energy density of 321 Wh kg-1 and also manifest excellent capacity preservation after 600 cycles of K+ uptake/removal.

Genetic associations and potential mediators between psychiatric disorders and irritable bowel syndrome: a Mendelian randomization study with mediation analysis.

Objective: Potential causal associations between psychiatric disorders and irritable bowel syndrome have been demonstrated in observational studies; however, these studies are susceptible to underlying confounding and reverse causation biases. We aimed to assess the causal effects of psychiatric disorders on irritable bowel syndrome (IBS) and the potential mediators from a genetic perspective by conducting a Mendelian randomization (MR) study with mediation analysis. Method: Genetic instruments associated with psychiatric disorders, potential mediators, and IBS were obtained from large-scale genome-wide association studies (GWAS). Three MR methods - the inverse-variance weighted (IVW) method, MR-Egger method, and weighted median method, were used to investigate causal association estimates. Heterogeneity among different genetic instrumental variables (IVs) was assessed using Q tests. Additionally, the MR-PRESSO and MR-Pleiotropy methods were used to verify horizontal pleiotropy and detect outliers that might bias the results, which were removed from further analysis. Consequently, we used MR mediation analysis to investigate potential mediators in the causal associations between psychiatric disorders and IBS. Results: MR provided evidence of the causal effects of genetically predicted broad depression, major depressive disorder (MDD), anxiety disorder, post-traumatic stress disorder (PTSD), and schizophrenia on IBS. The results of MR mediation analysis demonstrated that the reduction in acetate levels mediated 12.6% of the effects of broad depression on IBS; insomnia mediated 16.00%, 16.20%, and 27.14% of the effects of broad depression, MDD, and PTSD on IBS, respectively; and the increase in blood ß-hydroxybutyrate levels mediated 50.76% of the effects of schizophrenia on IBS. Conclusion: Our study confirmed the brain-gut axis involvement and potential modulators in the pathophysiology of psychiatric disorder-induced IBS from a genetic perspective, and suggests potential therapeutic targets for the disrupted brain-gut axis.

Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND & AIMS: The association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure. METHODS: Four databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis. RESULTS: Twenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29-1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08-1.68). This association existed for both Crohn's disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38-2.10) and quinolones (OR, 1.56; 95% CI, 1.37-1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk. CONCLUSIONS: Antibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.

Clinical utility of keratin 14 expression measurement in reflecting the tumor properties and prognosis in patients with renal cell carcinoma: a study with long-term follow-up.

PURPOSE: Keratin 14 (KRT14) is hypothesized to be involved in the pathogenesis of renal cell carcinoma (RCC) based on its tumorigenic role in various cancers and its relationship with the prognosis of other urinary system malignancies. This study aimed to evaluate the correlation of KRT14 with tumor properties and prognosis in RCC patients. METHODS: Data from 180 RCC patients who received tumor resection were retrospectively reviewed. The KRT14 was assessed by immunohistochemistry (IHC) staining in tumor tissues and non-tumor tissues. RESULTS: KRT14 was insufficiently expressed in both tumor and non-tumor tissues, with median (interquartile range) IHC score of 2.0 (0.0-3.4) and 1.0 (0.0-2.0), respectively. While it was relatively higher in tumor versus non-tumor tissues (P < 0.001). Besides, tumor KRT14 was positively correlated with the pathological grade (P = 0.038), tumor size (P = 0.012), T stage (P = 0.006), and TNM stage (P = 0.018). Interestingly, tumor KRT14 high predicted shorter accumulating recurrence-free survival (RFS) (P = 0.003) and accumulating overall survival (OS) (P = 0.001), which was further verified by the multivariate Cox's regression analysis (both P < 0.05). Furthermore, tumor KRT14 high estimated shorter RFS and OS from the Gene Expression Profiling Interactive Analysis and Human Protein ATLAS databases (all P < 0.05). Subgroup analyses indicated that the correlation of tumor KRT14 with accumulating RFS and accumulating OS was more pronounced in RCC patients with better physical status (such as age < 65 years and better eastern cooperative oncology group performance status) and higher tumor stages (such as higher pathological grade). CONCLUSION: High KRT14 in tumor tissue could reflect an advanced tumor features and unsatisfying survival in RCC patients.

Hydroxyl-Decorated Carbon Cloth with High Potassium Affinity Enables Stable Potassium Metal Anodes.

Highly anticipated potassium metal batteries possess abundant potassium reserves and high theoretical capacity but currently suffer from poor cycling stability as a result of dendritic growth and volume expansion. Here, carbon cloths modified with different functional groups treated with ethylene glycol, ethanolamine, and ethylenediamine are designed as 3D hosts, exhibiting different wettability to molten potassium. Among them, the hydroxyl-decorated carbon cloth with a high affinity for potassium can achieve molten potassium perfusion (K@EG-CC) within 3 s. By efficiently inducing the uniform deposition of metal potassium, buffing its volume expansion, and lowering local current density, the developed K@EG-CC anode alleviates the dendrite growth issue. The K@EG-CC||K@EG-CC symmetric battery can be cycled stably for 2100 h and has only a small voltage hysteresis of ≈93 mV at 0.5 mA cm-2 . Moreover, the high-voltage plateau, high energy density, and long cycle life of K metal full batteries can be realized with a low-cost KFeSO4 F@carbon nanotube cathode. This study provides a simple strategy to promote the commercial applications of potassium metal batteries.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and 1H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.

Background/Aims: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients. Methods: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days' colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation. Results: Visceral hypersensitivity induced by IBS-fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations. Conclusions: Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.

KI-Assisted Formation of Spindle-like Prussian White Nanoparticles for High-Performance Potassium-Ion Battery Cathodes.

Prussian white (PW) is considered as a promising cathode material for potassium-ion batteries (KIBs) due to its low cost and high theoretical capacity. However, the high water content and structural defects and the strict synthesis conditions of PW lead to its unsatisfactory cycling performance and low specific capacity, hindering its practical applications. Herein, a template-engaged reduction method is proposed, using MIL-88B(Fe) as a self-template and KI as the reducing agent to prepare K-rich PW with low defects and water content. Furthermore, the hierarchical porous spindle-like morphology can be inherited from the precursor, furnishing sufficient active sites and reducing the ion diffusion path. Consequently, when applied as a KIB cathode material, spindle-like PW (K1.72Fe[Fe(CN)6]0.96·0.342H2O) manifested remarkable potassium storage properties. Notably, a full cell assembled by the spindle-like PW cathode and graphite anode exhibited a large energy density of ∼216.7 Wh kg-1, demonstrating its huge potential for energy storage systems.

Lugol-unstained lesions location in the esophagus affects the detection rate of malignancy: a population-based study.

INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower  = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower  = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower  = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower  = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study.

BACKGROUND & AIMS: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. METHODS: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. RESULTS: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. CONCLUSIONS: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.