Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis.

Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L-arginine-induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up-regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D-lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C-reactive protein. Inhibition of Pck1 by 3-Mercaptopicolinic acid hydrochloride (3-MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3-MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D-lactate, endotoxin, and FITC-Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3-MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3-MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.

Associations of bisphenol A exposure with metabolic syndrome and its components: A systematic review and meta-analysis.

Mounting evidence shows that bisphenol A (BPA) is associated with metabolic risk factors. The aim of this study was to review related epidemiologic studies and conduct a meta-analysis to quantitatively estimate the association between BPA and metabolic syndrome. Four electronic databases were systematically searched to identify suitable articles. A total of 47 published studies were finally included. Two studies involved metabolic syndrome. Of the 17, 17, 14, and 13 studies on the relationship between BPA with abdominal obesity, blood pressure, fasting plasma glucose, and dyslipidemia, 10, 6, 3, and 4 studies were included in the meta-analysis, respectively. The results showed that the risk of abdominal obesity increased with the increase of BPA exposure, especially in the group with higher BPA exposure levels (Quartile 2 vs. Quartile 1, pooled OR = 1.16, 95%CI: 1.01, 1.33; Q3 vs. Q1, pooled OR = 1.31, 95%CI: 1.13, 1.51; Q4 vs. Q1, pooled OR = 1.40, 95%CI: 1.21, 1.61). However, there was no significant correlation between BPA exposure and metabolic syndrome components including hypertension, abnormal fasting plasma glucose, and dyslipidemia. The present study found that BPA exposure is significantly associated with a higher risk of abdominal obesity. However, the relationship between BPA with metabolic syndrome and its other components needs further longitudinal studies to verify.

Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis.

Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high (donor H) and low (donor L) groups according to the diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor H (P < 0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (P < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (P < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.NEW & NOTEWORTHY We demonstrate that donors with high abundance of Bacteroides and Faecalibacterium ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.

Risk stratification in gastric cancer lung metastasis: Utilizing an overall survival nomogram and comparing it with previous staging.

BACKGROUND: Gastric cancer (GC) is prevalent and aggressive, especially when patients have distant lung metastases, which often places patients into advanced stages. By identifying prognostic variables for lung metastasis in GC patients, it may be possible to construct a good prediction model for both overall survival (OS) and the cumulative incidence prediction (CIP) plot of the tumour. AIM: To investigate the predictors of GC with lung metastasis (GCLM) to produce nomograms for OS and generate CIP by using cancer-specific survival (CSS) data. METHODS: Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance, epidemiology, and end results program database. The major observational endpoint was OS; hence, patients were separated into training and validation groups. Correlation analysis determined various connections. Univariate and multivariate Cox analyses validated the independent predictive factors. Nomogram distinction and calibration were performed with the time-dependent area under the curve (AUC) and calibration curves. To evaluate the accuracy and clinical usefulness of the nomograms, decision curve analysis (DCA) was performed. The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer (AJCC) staging system by utilizing Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Finally, the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared. RESULTS: For the purpose of creating the OS nomogram, a CIP plot based on CSS was generated. Cox multivariate regression analysis identified eleven significant prognostic factors (P < 0.05) related to liver metastasis, bone metastasis, primary site, surgery, regional surgery, treatment sequence, chemotherapy, radiotherapy, positive lymph node count, N staging, and time from diagnosis to treatment. It was clear from the DCA (net benefit > 0), time-dependent ROC curve (training/validation set AUC > 0.7), and calibration curve (reliability slope closer to 45 degrees) results that the OS nomogram demonstrated a high level of predictive efficiency. The OS prediction model (New Model AUC = 0.83) also performed much better than the old Cox-AJCC model (AUC difference between the new model and the old model greater than 0) in terms of risk stratification (P < 0.0001) and verification using the IDI and NRI. CONCLUSION: The OS nomogram for GCLM successfully predicts 1- and 3-year OS. Moreover, this approach can help to appropriately classify patients into high-risk and low-risk groups, thereby guiding treatment.

Utilizing Haematococcus pluvialis to simulate animal meat color in high-moisture meat analogues: Texture quality and color stability.

The effect of Haematococcus pluvialis (HP) (0.25∼1.25 %) as a colorant during high moisture extrusion (50 %) on the texture and microstructural properties of soy protein-based high moisture meat analogs (HMMA) was evaluated. Furthermore, the stability of HP-induced meat like color of the HMMA as a function of light exposure, freeze/thawing, frozen storage and cooking temperature and duration was investigated. The addition of HP reduced the elasticity of HMMA but enhanced its hardness, chewiness, and resilience. HP addition at low levels promoted the flexible and disordered regions within the protein secondary structure while excessive HP addition was unfavorable for protein cross-linking. The optimal degree of texturization was achieved with 0.75 % HP. Sensory evaluations revealed that HMMA with 1 %HP had a color similar to fresh beef sirloin, while HMMA with 0.25 % HP had a color closer to fresh pork loin. Light exposure induced the greatest color loss of the meat analogs compared with the cooking and frozen storage. The a* value of HMMA containing 1.25 % HP decreased by 30 % during the 14 days of light exposure. Frozen storage at darkness efficiently preserved the meat-like color of the extrudates. Overall, HP was found as promising colorant for HMMA production but the storage condition of the extrudates should be carefully optimized.

Artificial Skin with Patterned Stripes for Color Camouflage and Thermoregulation.

Chameleons are famous for their quick color changing abilities, and it is commonly assumed that they do this for camouflage. However, recent reports revealed that chameleons also change color for body temperature regulation. Inspired by the structure of the panther chameleon's skin, a stripe-patterned poly(N-isopropylacrylamide) (PNIPAM) and polyacrylamide (PAM) hydrogel film with a laminated structure is fabricated in this work; thus, both camouflage and thermoregulation can be achieved through controlling Vis and NIR light effectively. For the PNIPAM stripe, the upper layer is the native PNIPAM hydrogel and the lower layer is the carbon nanotube-composited PNIPAM hydrogel. Thus, the PNIPAM stripe is capable of reaching 28 °C at a low environmental temperature (12 °C) and a low radiation intensity (20 mW cm-2), while preventing the body temperature from rising by changing to white under a strong radiation intensity (100 mW cm-2). For the PAM stripe, the upper layer combines colloidal photonic crystals and displays a tunable structural color by stretching, and the lower layer is mixed with PNIPAM microgels for thermal regulation. Through the fabrication of multifunctional patterns, the film can achieve both dynamic structural color and thermoregulation by precisely controlling solar radiation absorption, scattering, and reflection. More importantly, in the stripe-patterned system, the shrinkage of the PNIPAM stripes can effectively trigger the elongation of the PAM stripe, which endows the structural color changing process to be self-powered completely. The performances show that the stripe-patterned film may have potential applications in intelligent coatings, especially in areas with large temperature differences during the day such as high plains.

Colonic mucin-2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis.

Mucin-2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC-MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF-α-treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro-inflammatory cytokines (IL-1ß and IL-6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro-inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.

Preparation of fat replacer utilizing gluten and barley ß-glucan and the interaction between them.

BACKGROUND: Fat replacers prepared from polysaccharides and proteins possess functional properties of both polysaccharides and proteins. In this study, an aqueous system of barley ß-glucan (BBG) and gluten was prepared. The interactions between BBG and gluten (with/without extrusion modification) were studied. Triple analysis methods, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and low-field nuclear magnetic resonance (LF-NMR), were utilized to analyze the freezing-thawing and thermal evaporation process, as well as the distribution state of water. Meanwhile, fluorescence microscopic analysis, dynamic rheological analysis and electrophoresis analysis were used to study the structure and rheological properties of the system. RESULTS: The results showed that BBG significantly increased the water-holding capacity of gluten, regardless of extrusion treatment, with the water absorption reaching about 4.8 to 6.4 times of its weight, which was 1 to 2.5 times higher than that without BBG. The triple analysis results suggested that BBG increased the binding capacity of the system to weakly bound water, hindered the aggregation of gluten and reduced the thermal decomposition temperature of the BBG and gluten composite system. After the gluten was extruded and homogenized with the BBG solution, the appearance of the composite system was more uniform and delicate. CONCLUSIONS: In conclusion, BBG increased the water-holding capacity of the BBG and gluten composite system. With these changes, the composite system presented great potential for the preparation of polysaccharide-gluten fat replacer. © 2023 Society of Chemical Industry.

Role of bran particles in the formation of dark spots on fresh wet noodle sheets: what are the dark spots?

BACKGROUND: Dark spots may affect the appearance of fresh noodles during storage, even when made from flour with low ash content. The effect of flour bran content on the degree of dark spot formation in fresh wet noodle sheets (FWNS) is investigated to explain this phenomenon. RESULTS: Confocal laser scanning microscopy (CLSM) observation revealed that the wheat bran particles were responsible for the formation of dark spots on FWNS, with each bran particle core generating a single dark spot. In wheat flours with low ash content, the number of wheat bran particles causing dark spot formation on FWNS was limited, and these particles were not visible to the naked eye until their size exceeded approximately 50 µm. Tropolone, a polyphenol oxidase inhibitor (PubChem CID: 24900578) and dry heating treatment, which inactivates polyphenol oxidase, was found to inhibit or reduce the formation of dark spots. CONCLUSION: Based on these findings, it can be concluded that bran particles, rich in polyphenol oxidase, play a key role in dark spot formation. © 2023 Society of Chemical Industry.

Molecular modification effects on the electrochromic and photochromic properties of diarylethene with intramolecular isomerization behavior.

Diarylethene (DAE) is one of the most widely used functional units for electrochromic or photochromic materials. To better understand the molecular modification effects on the electrochromic and photochromic properties of DAE, two modification strategies, substitution with functional groups or heteroatoms, were investigated theoretically by density functional theory calculations. It is found that red-shifted absorption spectra caused by a decreased highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap and S0 → S1 transition energy during the ring-closing reaction become more significant by adding different functional substituents. In addition, for two isomers, the energy gap and S0 → S1 transition energy decreased by heteroatom substitution of S atoms with O or NH, while they increased by replacing two S atoms with CH2. For intramolecular isomerization, one-electron excitation is the most effective way to trigger the closed-ring (O → C) reaction, while the open-ring (C → O) reaction occurs most readily in the presence of one-electron reduction. Moreover, it is confirmed that substitution with strong electron donating groups (-OCH3/-NH2) or with one O/two CH2 heteroatoms leads to a more favorable closed-ring (O → C) reaction. Functionalized with strong electron-withdrawing groups (-NO2 and -COOH) or one/two NH heteroatom substitutions, the open-ring (C → O) reaction is easier. Our results confirmed that the photochromic and electrochromic properties of DAE can be tuned effectively by molecular modifications, which provides theoretical guidance for the design of new DAE-based photochromic/electrochromic materials.

Electronic structure evolution induced by the charge redistribution during the construction of two-dimensional polymer networks from monomers to crystal frameworks.

Two-dimensional covalent organic frameworks (COFs) are a new type of porous crystalline material constructed by the linkage of organic building units through covalent bonds to produce predetermined structures. Here, the electronic structure evolution induced by the charge redistribution during the construction of two-dimensional polymer networks (sp2c-COF-2 and COF-66) from building units to crystal frameworks is examined theoretically. The calculated results demonstrate that the electronic structure of the framework is controlled by the relative energy level between the frontier orbitals of organic building core and linker units as well as the charge transfer amount between them during the construction of the framework. Moreover, it is observed that a noncoplanar framework becomes more conjugated because the charge transfer amount between core and linker units becomes larger during the construction of 2D frameworks, which leads to a larger charge carrier mobility within the 2D structure of COFs. The charge carrier mobility along the z-direction of the COF crystal is dominated by the interface interaction between COF layers. Thereby, we believed reasonable design or selection of organic building units plays a key role in improving the electronic and optoelectronic properties of such 2D organic frameworks.

[Association between regional fat mass and risk of nonalcoholic fatty liver disease in overweight/obese adults].

OBJECTIVE: To explore the relationship between fat distribution and non-alcoholic fatty liver(NAFLD) in overweight/obese adults. METHODS: This cross-sectional study included 736(190 men and 546 women) 19-56 years old overweight/obese people in Beijing were selected by convenient sampling. Their age and body mass index(BMI) distribution were 36(31-46) years old and 28.0(26.2-30.7), respectively. The body fat mass and regional fat mass were measured by dual energy X-ray absorptiometry(DXA), and Logistic regression model was used to analyze the association between regional fat mass and the risk of NAFLD. RESULTS: The prevalence of NAFLD was 70.0%(515/736) in overweight/obese population. In the multivariate Logistic model, after adjusting for age, gender, BMI, hypertension and body fat mass, waist circumference(WC), thigh fat mass and android fat mass were significantly association with NAFLD risk(P<0.05), but no association was found between arms, trunk and gynoid fat mass and NAFLD risk. There were interactions between thigh fat mass and age(P_(interaction)<0.001) and BMI group(P_(interaction)=0.001). Subgroup analysis showed that thigh fat mass and NAFLD risk were significantly associated in ≤36-year-old(OR=0.62, 95%CI 0.48-0.81), male(OR=0.32, 95%CI 0.16-0.64) and overweight(OR=0.48, 95%CI 0.36-0.64) groups, but in the >36-year-old, female and the obesity group this association was not statistically significant. There was an interaction between trunk fat mass and age group(P_(interaction)=0.009). There was a positive correlation between trunk fat mass and NAFLD risk in >36-year-old group(OR=1.63, 95%CI 1.35-1.97), but no association was found in ≤36-year-old group. In addition, we also found that a significant interaction between gynoid fat mass and BMI group on NAFLD(P_(interaction)<0.001). In overweight, gynoid fat mass was negatively correlated with the risk of NAFLD(OR=0.12, 95% CI 0.06-0.25), but in the obesity group, the association was not statistically significant. There were no statistically significant interactions between WC, arms fat mass and android mass and age, sex and BMI groups. CONCLUSION: WC, android fat mass and thigh fat mass are associated with the risk of NAFLD. Thigh fat mass has a significant interaction with age and BMI group on the risk of NAFLD(only in ≤36-year-old group, male and overweight group a significant protective effect of thigh fat on NAFLD was found, but not in >36-year-old group, female and obesity group). Trunk fat mass had an interaction with age(the association between trunk fat mass and NAFLD was significant in >36-year-old group). Gynoid fat mass and BMI group also have a significant interaction on NAFLD(the detrimental effect of gynoid fat on NAFLD is much more profound in the obesity group).

Characteristics of the enzyme-induced release of bitter peptides from wheat gluten hydrolysates.

Bitter peptides in the enzymatic hydrolysates were prepared and purified from wheat gluten using aqueous ethanol solutions and macroporous resin, which has opened a new road for the extraction and separation of bitter peptides. This report contains the release regularity of bitter peptides and the factors affecting the change of bitter intensity during enzymatic hydrolysis, providing a scientific basis for the research on debitterizing method. In this study, the effects of different degrees of hydrolysis (DH) and enzyme active sites on the bitter peptide content and bitter taste thresholds were discussed. The relationship between amino acid composition, molecular weight distribution, surface hydrophobicity and bitter taste thresholds was extensively researched. The results showed the exposure of hydrophobic amino acids and the bitterness intensity of the hydrolysates increased as the DH increased, and the bitterness of wheat gluten hydrolysates (WGHs) hydrolyzed by Alcalase was stronger than that of Trypsin. According to correlation analysis, the proportion of total hydrophobic amino acid is the first factor that affects the sensory properties of bitter peptide, and the release content of bitter peptides and the content of total bitter amino acids are the second, following by the content of peptide in the molecular weight range of 500-1,000 Da and the surface hydrophobicity. The amino acid sequence of bitter peptides from WGHs were identified and predicted using high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and bioinformatics. It was found that the molecular weight of most of the peptides was below 1,500 Da, and the Q value was higher than 5.86 kJ/mol.

Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis.

OBJECTIVE: To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC). METHODS: The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3 days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-α, IFN-γ, IL-1ß, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay. RESULTS: Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p = 0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-α and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group. CONCLUSION: FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-α, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT02435160&cntry=&state=&city=&dist=.

Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance.

Background: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT. Methods: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed. Results: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = −0.382, p = 0.003) and Nancy index (r = −0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = −0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001). Conclusions: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.

Paneth Cells Protect against Acute Pancreatitis via Modulating Gut Microbiota Dysbiosis.

Acute pancreatitis (AP) is usually accompanied by intestinal failure, but its mechanism is still unclear. In AP patients, the functions of Paneth cells (lysozyme, HD5, Reg3γ, and Wnt3a) decreased. Compared with AP mice, injuries and inflammation of the pancreas and ileum were aggravated in AP mice treated with dithizone (Dith) (Dith+AP mice). Intestinal permeability and bacterial translocation were also increased. 16S rRNA sequencing showed that the gut microbiota of Dith mice and Dith+AP mice exhibited a marked increase in the pathogenic bacterium Helicobacter and a significant decrease in the probiotic bacterium Blautia. Lysozyme gavage in Dith+AP mice effectively alleviated injuries of the pancreas and small intestine. The beneficial effect of lysozyme was associated with a significant increase in the probiotic bacterium Blautia and a virtual absence of the pathogenic bacterium Helicobacter. The severity of AP in antibiotic-treated mice (ABX mice) was significantly aggravated when receiving feces from Dith mice and was markedly alleviated when receiving feces from lysozyme-gavaged mice. In vitro, lysozyme increased the proliferation of enteroids by promoting the activation of the Wnt pathway and Lgr5 expression in intestinal stem cells. IMPORTANCE We demonstrate that AP patients and experimental AP mice exhibited a dysfunction of Paneth cells. Our in vivo research showed that the severity of AP was exacerbated by the long-term dysfunction of Paneth cells, which was associated with gut microbiota disorder. Restoring part of Paneth cell functions through lysozyme supplementation alleviated the severity of AP and gut microbiota dysbiosis. This study provides novel insight into the link of pancreas-gut interactions in the pathogenesis of AP, providing a new direction for the clinical treatment of intestinal complications during AP.

Improving the chemical stability of blue heteroleptic iridium emitter FIrpic in the lowest triplet state through ancillary ligand modification: a theoretical perspective.

With the aim of providing a deeper understanding of the underlying degradation mechanisms associated with the lifetime of blue emitters during the decay process of blue PhOLEDs, quantum chemistry studies were performed to examine the chemical degradation mechanism of common sky blue emitter iridium(III)bis(4,6-di-fluorophenyl)-pyridinato-N,C2')picolinate (FIrpic) and its derivatives with density functional theory (DFT) calculations. For these Ir(III) emitters, the Ir-N1 bond between the ancillary ligand (picolinate) and central iridium will be broken by external light stimuli, which is followed by conversion from the initial emissive metal-to-ligand charge transfer (3MLCT) state to the non-emissive metal centered (3MC) state. The potential energy change for the photo-induced degradation path is then dominated by the energy levels of the 3MT and 3MC states, which are related to the triplet transition energy and the Ir-N1 bond strength, respectively. Thereby, the Ir-N1 bond dissociation in the lowest triplet state will be much harder to proceed if the S0 → T1 transition energy gets more energetically stable or the bond strength gets larger. It is believed that strategic modification of the ancillary ligand, especially by substitution of electron-donating groups at the para position of the pyridyl N atom or extension of the p-electron delocalization, is an effective and easy way to enhance the photochemical stability of the typical blue emitter FIrpic.

Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis.

Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg-1·d-1, po) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1ß, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP.

Inhibition of hexose oxidase on the dark spots in fresh wet noodle sheets: A feasible prevention of dark spots.

Hexose oxidase was a feasible prevention for the dark spots in the fresh wet noodle sheets (FWNS). The chemical mechanism that hexose oxidase recucing the melanins of dark spots was discussed basis on the UPLC-TOF-MS analysis of the polyphenol oxidase (PPO)-catechol system. In the process of PPO browning, hexose oxidase catalyzed the oxidation of o-benzoquinone derivatives and their oligomers, hindering the formation of melanins. Hexose oxidase was efficient in FWNS with low ash content when water addition was 24%~44% or pH range was 4 ~ 7.5. Hexose oxidase could inhubit dark spots in the presence of 10 metal ions. The recommended addition amount was 40 ~ 60 ppm, by which the dark spots could be compolitely inhibited. Hexose oxidase was also suitable for wholewheat and oat FWNS, ΔL6d of wholewheat and oat FWNS were reduced by 4 and 7.98, respectively.

Porous COS@SiO2 Nanocomposites Ameliorate Severe Acute Pancreatitis and Associated Lung Injury by Regulating the Nrf2 Signaling Pathway in Mice.

Severe acute pancreatitis (SAP) is associated with high rates of mortality and morbidity. Chitosan oligosaccharides (COSs) are agents with antioxidant properties. We developed porous COS@SiO2 nanocomposites to study the protective effects and mechanisms of COS nanomedicine for the treatment of acute pancreatitis. Porous COS@SiO2 nanocomposites released COSs slowly under pH control, enabling sustained release and maintaining the drug at a higher concentration. This study aimed to determine whether porous COS@SiO2 nanocomposites ameliorate SAP and associated lung injury. The SAP model was established in male C57BL/6 mice by intraperitoneal injection of caerulein. The expression levels of myeloperoxidase, malondialdehyde, superoxide dismutase, nuclear factor-kappa B (NF-κB), the NOD-like receptor protein 3 (NLRP3) inflammasome, nuclear factor E2-related factor 2 (Nrf2), and inflammatory cytokines were detected, and a histological analysis of mouse pancreatic and lung tissues was performed. In the SAP groups, systemic inflammation and oxidative stress occurred, and pathological damage to the pancreas and lung was obvious. Combined with porous COS@SiO2 nanocomposites before treatment, the systemic inflammatory response was obviously reduced, as were oxidative stress indicators in targeted tissues. It was found that Nrf2 was significantly activated in the COS@SiO2 treatment group, and the expressions of NF-κB and the NLRP3 inflammasome were notably decreased. In addition, this protective effect was significantly weakened when Nrf2 signaling was inhibited by ML385. This demonstrated that porous COS@SiO2 nanocomposites activate the Nrf2 signaling pathway to inhibit oxidative stress and reduce the expression of NF-κB and the NLRP3 inflammasome and the release of inflammatory factors, thus blocking the systemic inflammatory response and ultimately ameliorating SAP and associated lung injury.