Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

FAM83B regulates mitochondrial metabolism and anti-apoptotic activity in pulmonary adenocarcinoma.

Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.

Mesenchymal Stem Cells Attenuates Hirschsprung Disease-Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependewhant Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.

Effect of epigallocatechin-3-gallate modification on the structure and emulsion stability of rice bran protein in the presence of soybean protein isolate.

For improving the emulsion stability of rice bran protein (RBP), RBP was modified by different concentrations of epigallocatechin-3-gallate (EGCG) in the presence of soybean protein isolate (SPI), and RBP-EGCG-SPI conjugate was prepared by alkaline pH-shifting. The results showed that the addition of EGCG led to an increase in the bound phenol content and the flexibility of the secondary structure, a decrease in the free sulfhydryl and disulfide bond content of the RBP-EGCG-SPI conjugate. EGCG covalently bound to RBP and SPI through non-disulfide bonds. When the concentration of EGCG was 10 % (w/v), the emulsifying activity index and emulsion stability index of conjugate reached the maximum value (36.61 m2/g and 255.61 min, respectively), and the conjugate had the best emulsion stability. However, an EGCG concentration above 10 % (w/v) negatively affected the emulsion stability, with increasing particle size due to protein aggregation. Summarily, the modification of EGCG improved the emulsion stability of conjugate by regulating the spatial structure of RBP-EGCG-SPI conjugate. The work provided an important guide to further improve the emulsion stability of RBP.

Intracellular presence of Helicobacter pylori antigen and genes within gastric and vaginal Candida.

BACKGROUND: Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida. METHODS: Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity. RESULTS: A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive. CONCLUSION: In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.

Effects of rice bran rancidity on the interfacial adsorption properties of rice bran protein fibril aggregates and stability of high internal phase Pickering emulsions.

The effects of rice bran rancidity-induced protein oxidation and heating time on the stability of rice bran protein fibril aggregates (RBPFA)-high internal phase Pickering emulsions (HIPPEs) were investigated. The optimal conditions for RBPFA-HIPPEs were 8 mg/mL RBPFA with an oil phase volume fraction of 75 %. Moderate oxidation (rice bran stored for 3 d) and moderate heating (8 h) enhanced the wettability, flexibility, diffusion rate, and adsorption rate of RBPFA, meanwhile, the rheological properties of RBPFA-HIPPEs increased. RBPFA-HIPPEs could be stably stored for 50 d at 25 °C. Moderate oxidized and moderate heated RBPFA-stabilized HIPPEs could remain stable after heat treatment and could be re-prepared after freeze-thaw (3 cycles). Additionally, the stability of RBPFA-HIPPEs was significantly related to the structural characteristics and interfacial properties of RBPFA. Overall, moderate oxidation and moderate heating enhanced the storage, thermal, and freeze-thaw stability of RBPFA-HIPPEs by improving the interfacial properties of RBPFA.

MR Spectroscopy Assessment of Daily Variations of GABA Levels within the Parietal Lobe and Anterior Cingulate Gyrus Regions of Healthy Young Adults.

BACKGROUND: The changes that occur in the gamma-aminobutyric acid (GABA) levels within specific brain regions throughout the day are less clear. PURPOSE: To evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions and explore their association with melatonin (MT) levels, heart rate (HR), and blood pressure. STUDY TYPE: Prospective. SUBJECTS: 26 healthy young adults (15 males and 11 females aged 22-27 years). FIELD STRENGTH/SEQUENCE: 3.0T, T1-weighted imaging, Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. ASSESSMENT: The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. The GABA+, GABA+/Cr were measured at six different time points (1:00, 5:00, 9:00, 13:00, 17:00, and 21:00 hours) using MEGA-PRESS. The blood pressure, HR and sputum MT levels, were also acquired. STATISTICAL TESTS: The one-way repeated-measures analysis of variance (ANOVA) was used to evaluate the GABA, blood pressure, HR, and MT levels throughout the day. A general linear model was used to find the correlation between GABA and blood pressure, HR, and MT. P < 0.05 was statistically significant. RESULTS: Significant variations in GABA+/Cr and GABA+ levels were observed throughout the day within the PL region. The lowest levels were recorded at 9:00 hour (GABA+/Cr: 0.100 ± 0.003，GABA+:1.877 ± 0.051 i.u) and the highest levels were recorded at 21:00 hour (GABA+/Cr: 0.115 ± 0.003, GABA+:2.122 ± 0.052 i.u). The MT levels were positively correlated with GABA+/Cr (r = 0.301) and GABA+ (r = 0.312) within the ACC region. DATA CONCLUSION: GABA+/Cr and GABA+ in ACC are positively correlated with MT. GABA levels in the PL have diurnal differences. These findings may indicate that the body's GABA level change in response to the light-dark cycle. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Reduced miR-513a-5p expression in COPD may regulate airway mucous cell hyperplasia through TFR1-dependent signaling.

Airway mucous cell metaplasia and mucous hypersecretion is one of the key characteristic pathophysiological status of chronic obstructive pulmonary disease (COPD). micro(mi)RNAs are acknowledged as non-encoding RNA molecules playing important roles in gene expression regulation. In this study, we searched the Gene Expression Omnibus (GEO) database for the differentially expressed miRNAs between COPD and non-COPD controls with bioinformatics analysis. Finally, we focused on miR-513a-5p and investigated the potential mechanism by which miR-513a-5p regulates airway mucous hypersecretion and goblet cell metaplasia. A dual-luciferase reporter assay was then showing that miR-513a-5p targeted the 3'-UTR of TFR1 and inhibited its expression in vitro. In vivo transfection demonstrated that TFR1 downregulation partially blocked MUC5AC hypersecretion and goblet cell hyperplasia in COPD model rats. In vitro study, CSE increased the intracellular expression and secretion of MUC5AC by BEAS-2B branchial epithelial cells in the BEAS-2B cell and THP-1 cell coculture system. Coculture with either miR-513a-5p mimic-pretreated or TFR1-deficient THP-1 cells attenuated intracellular MUC5AC expression in BEAS-2B cells exposed to CSE. ELISA demonstrated that transfection of TFR1 siRNA or pretreatment with miR-513a-5p mimic reduced the secretion of inflammatory factors that are responsible for airway goblet cell hyperplasia, such as IL-1ß, IL-13, and IL-17, by THP-1 cells after CSE stimulation. Our findings supported that miR-513a-5p/TFR1 signaling axis might activate macrophages as well as promote airway inflammation and airway mucous cell hyperplasia in COPD.

Bazedoxifene Suppresses the Growth of Osteosarcoma Cells by Inhibiting IL-6 and IL-11/GP130 Signaling Pathway.

Osteosarcoma is the most common primary bone tumor. Using the multiple ligands simultaneous docking method, we found that bazedoxifene could bind to the GP130 D1 domain. We then demonstrated that bazedoxifene can decrease cell viability and cell migration of osteosarcoma cells by inhibiting interleukin 6 (IL-6) and IL-11/GP130 signaling. Consistently, treatment with IL-6 or IL-11 antibody or knockdown of GP130 by siRNA silenced the activation of STAT3, ERK, and AKT. Similarly, recombinant IL-6 and IL-11 proteins antagonized the inhibitory effect of bazedoxifene on osteosarcoma cells. Finally, the combinational treatment of temsirolimus and bazedoxifene synergistically suppressed osteosarcoma development in vitro and in vivo. Our findings suggest that bazedoxifene directly prompts the deactivation of GP130 and inhibits the osteosarcoma progression in vitro and in vivo. Therefore, bazedoxifene could be effectively applied as a therapeutic drug for human osteosarcoma in the future.

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort.

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014-2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.

Development and Validation of a Machine Learning-Based Model Using CT Radiomics for Predicting Immune Checkpoint Inhibitor-related Pneumonitis in Patients With NSCLC Receiving Anti-PD1 Immunotherapy: A Multicenter Retrospective CaseControl Study.

RATIONALE AND OBJECTIVES: This study aimed to develop and evaluate a radiomics-based model combined with clinical and qualitative radiological (semantic feature [SF]) features to predict immune checkpoint inhibitor-related pneumonitis (CIP) in patients with non-small cell lung cancer (NSCLC) treated with programmed cell death protein 1 inhibitors. MATERIALS AND METHODS: This was a multicenter retrospective casecontrol study conducted from January 1, 2018, to December 31, 2022, at three centers. Patients with NSCLC treated with anti-PD1 were enrolled and randomly divided into two groups (7:3): training (n = 95) and validation (n = 39). Logistic regression (LR) and support vector machine (SVM) algorithms were used to transform features into the models. RESULTS: The study comprised 134 participants from three independent centers (male, 114/134, 85%; mean [±standard deviation] age, 63.92 [±7.9] years). The radiomics score (RS) models built based on the LR and SVM algorithms could accurately predict CIP (area under the receiver operating characteristics curve [AUC], 0.860 [0.780, 0.939] and 0.861 [0.781, 0.941], respectively). The AUCs for the RS-clinic-SF combined model were 0.903 (0.839, 0.967) and 0.826 (0.688, 0.964) in the training and validation cohorts, respectively. Decision curve analysis showed that the combined models achieved high clinical net benefit across the majority of the range of reasonable threshold probabilities. CONCLUSION: This study demonstrated that the combined model constructed by the identified features of RS, clinical features, and SF has the potential to precisely predict CIP. The RS-clinic-SF combined model has the potential to be used more widely as a practical tool for the noninvasive prediction of CIP to support individualized treatment planning.

Effects of rice bran rancidity on the release of phenolics and antioxidative properties of rice bran dietary fiber in vitro gastrointestinal digestion products.

Rice bran (RB) as the raw material for rice bran dietary fiber (RBDF) extraction, is rapidly rancidified prior to stabilization. To enhance the RBDF utilization in food industry, effects of RB rancidity (RB was stored for 0, 1, 5, 7, and 10 d) on the bioaccessibility and bioavailability of RBDF-bound phenolics were investigated. With the increase in RB storage time, the RB rancidity degree significantly increased (the acid value of rice bran oil from 5.08 mg KOH/g to 60.59 mg KOH/g), and the endogenous phenolics content in RBDF also increased. Simultaneously, RB rancidity reduced the antioxidant activity of RBDF digestion products during the gastric digestion phase, while RB rancidity increased the antioxidant activity of RBDF digestion products during the intestinal digestion phase. In addition, in vitro gastrointestinal digestion stimulated the release of RBDF-bound phenolics. The released monomeric phenolics (especially ferulic acid and p-coumaric acid) were the major contributors to the increased antioxidant properties of RBDF digestion products. RBDF digestion products could inhibit H2O2-induced oxidative stress and apoptosis of HUVECs. In conclusion, the study found that RB rancidity could improve the antioxidant capacity of RBDF in the small intestine by promoting RB endogenous phenolics bound to RBDF release.

Assessment of neurotransmitter imbalances within the anterior cingulate cortex in women with primary dysmenorrhea: An initial proton magnetic resonance spectroscopy study.

PURPOSE: The neural pathophysiology underlying primary dysmenorrhea (PDM), which leads to poor mode and changes in central pain modulatory systems, remains largely unknown. The objective of this study was to investigate the changes in glutamate/glutamine (Glx) and gamma-aminobutyric acid (GABA+) levels within anterior cingulate cortex (ACC), and their associations with clinical indicators in PDM women. METHODS: Using 3 T proton magnetic resonance spectroscopy (1H-MRS), we acquired and compared ACC-Glx and ACC-GABA+ levels in PDMs (N = 41) and age- and education-matched healthy controls (HCs) (N = 39) during both the menstrual and periovulatory phases, and between menstrual and periovulatory phases within each group. Total creatine (Cr referencing) level was used as an endogenous reference. The correlations of ACC-neurotransmitter levels with clinical characteristics and the correlations of ACC-Glx with ACC-GABA+ levels in the two groups were analyzed. RESULTS: Compared to HCs or the periovulatory phase, PDMs exhibited significantly increased ACC-Glx levels (p < 0.05) during the menstrual phase. Positive correlations between GABA+ and Glx levels (r = 0.385, p = 0.025) were found in PDMs during the menstrual phase. ACC-GABA+ levels were associated with self-rating distress scale (SDS) scores (GABA+/Cr: r = 0.369, p = 0.045) and pain catastrophizing scale (PCS) scores (GABA+/Cr: r = 0.373, p = 0.042) in PDM group in only the menstrual phase. CONCLUSION: Our study represents the first report of ACC-GABA+/Glx imbalances in PDMs during the menstrual phase, which may underlie the mechanisms mediating depression and painful catastrophic symptoms.

Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel.

Background: Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process. Methods: In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor ß1 (TGF-ß1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-ß1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration. Results: Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-ß1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-ß1 and MMP-9. In vitro, mechanical stretch significantly increased TGF-ß1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration. Conclusion: Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Effect of protein oxidation on the emulsion carrier prepared by rice bran protein for improving stability and bioavailability of ß-carotene.

The emulsion carriers which prepared by rice bran protein (RBP) with different oxidation extents were utilized to deliver ß-carotene (BC). The effects of RBP oxidation extent on stability and bioaccessibility of BC in rice bran protein emulsion (RBPE) were investigated by measuring the droplet size, microstructure, digestive stability, cellular antioxidant, and delivery property of BC-RBPE. The results showed that BC-RBPE prepared by moderately oxidized RBP (extracted from rice bran with a storage time of 5 d) presented excellent digestive stability and delivery property during gastrointestinal digestion. The particle size of initial BC-RBPE, BC-RBPE after gastric digestion, and BC-RBPE after intestinal digestion were 509.73, 2149.33, and 997.82 nm, respectively. Compared with free BC suspension, the BC retention after gastric digestion and the BC bioavailability of BC-RBPE prepared by moderately oxidized RBP increased by 23.50% and 27.54%, respectively. In addition, the BC cellular antioxidant activity and BC cellular uptake of BC-RBPE prepared by moderately oxidized RBP were significantly higher than that of free BC-suspension, which increased by 29.63% and 13.84%, respectively. In summary, the study showed that oil-in-water emulsion prepared by moderately oxidized protein is a potential delivery system of BC, which can provide a theoretical basis for improving the utilization of protein by adjusting the extent of protein oxidation.

Worsening Renal Function and Adverse Outcomes in Patients with HFpEF with or without Atrial Fibrillation.

Since worsening renal function (WRF) and atrial fibrillation (AF) often coexist in preserved ejection fraction (HFpEF), we aimed to investigate the effect of WRF on the prognosis of HFpEF patients with and without AF. The study population of this study (n = 1763) was based on the subset of the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). We found that the cumulative probabilities of the primary composite outcome and cardiovascular death were significantly higher in AF patients post-WRF when compared to non-AF patients. In the time-dependent Cox proportional hazard model, WRF was significantly associated with higher risks of adverse outcomes (primary composite outcome: HR = 1.58 (95% CI, 1.19-2.11); all-cause death: HR = 1.50 (95% CI, 1.10-2.06); cardiovascular death: HR, 2.00 (95% CI, 1.34-3.00)) after adjustments for confounding factors at baseline in HFpEF patients with AF, whereas in HFpEF patients without AF, WRF was not significantly associated with any adverse outcome. p for interactions for the primary composite outcome, cardiovascular death, and AF were significant. In conclusion, these findings highlight that WRF was associated with a greater risk of the primary composite outcome, all-cause death, and cardiovascular death in HFpEF patients with AF.

Down-Regulation of HSP by Pd-Cu Nanozymes for NIR Light Triggered Mild-Temperature Photothermal Therapy Against Wound Bacterial Infection: In vitro and in vivo Assessments.

Purpose: We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial's heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy. Methods: We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs. Results: In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria's sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment. Conclusion: The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.

Intracellular presence and genetic relationship of Helicobacter pylori within neonates' fecal yeasts and their mothers' vaginal yeasts.

Helicobacter pylori are transmissible from person to person and among family members. Mother-to-child transmission is the main intrafamilial route of H. pylori transmission. However, how it transmits from mother to child is still being determined. Vaginal yeast often transmits to neonates during delivery. Therefore, H. pylori hosted in yeast might follow the same transmission route. This study aimed to detect intracellular H. pylori in vaginal and fecal yeasts isolates and explore the role of yeast in H. pylori transmission. Yeast was isolated from the mothers' vaginal discharge and neonates' feces and identified by internal transcribed spacer (ITS) sequencing. H. pylori 16S rRNA and antigen were detected in yeast isolates by polymerase chain reaction and direct immunofluorescence assay. Genetic relationships of Candida strains isolated from seven mothers and their corresponding neonates were determined by random amplified polymorphic DNA (RAPD) fingerprinting and ITS alignment. The Candida isolates from four mother-neonate pairs had identical RAPD patterns and highly homologous ITS sequences. The current study showed H. pylori could be sheltered within yeast colonizing the vagina, and fecal yeast from neonates is genetically related to the vaginal yeast from their mothers. Thus, vaginal yeast presents a potential reservoir of H. pylori and plays a vital role in the transmission from mother to neonate.

Exposure to volatile organic compounds is a risk factor for diabetes: A cross-sectional study.

Currently, more studies showed that environmental chemicals were associated with the development of diabetes. However, the effect of volatile organic compounds (VOCs) on diabetes remained uncertain and needed to be studied. This cross-sectional study examined whether exposure to low levels of VOCs was associated with diabetes, insulin resistance (TyG index) and glucose-related indicators (FPG,HbA1c, insulin) in the general population by using the NHANES dataset (2013-2014 and 2015-2016). We analyzed the association between urinary VOC metabolism (mVOCs) and these indicators in 1409 adults by multiple linear regression models or logistic regression models, further Bayesian kernel machine regression (BKMR) models were performed for mixture exposure analysis. The results showed positive associations between multiple mVOCs and diabetes, TyG index, FPG, HbA1c and insulin, respectively. Among them, HPMMA concentration in urine was significantly positively correlated with diabetes and related indicators (TyG index, FPG and HbA1c), and the concentration of CEMA was significantly positively correlated with insulin. The positive association of mVOCs with diabetes and its related indicators was more significant in the female group and in the 40-59 years group. Thus, our study suggested that exposure to VOCs affected insulin resistance and glucose homeostasis, further affecting diabetes levels, which had important public health implications.