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The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1β and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.

Bearing unique redox nature and high oxygen storage capacity, ceria (CeO2) has always been a promising CO oxidation catalyst support for gold (Au) catalysts and the like. Herein, a serial of Au-CeO2-P (P stands for pH value) samples was prepared by a co-precipitation method with the assistance of an alkaline environment and amino groups functionalized ordered mesoporous polymer (OMP-NH2). Afterward, all samples described above were characterized that the Au-CeO2-P catalysts are made of Au-Ce-O solid solution and Au NPs supported on CeO2. It turns out that OMP-NH2 is not just a simple sacrificial template for mesoporous structure, but also plays an important role as an amino source, explaining the presence of rich oxygen vacancies. Due to the concentration of oxygen vacancies in Au-Ce-O solid solution is the key factor for the oxygen mobility of CO oxidation, the catalytic results also demonstrate that the catalytic activity of Au-CeO2-P catalysts is related to the concentration of their oxygen vacancies. Moreover, Au-CeO2-9.6 with a highest concentration of oxygen vacancies (as high as 13.98%) in Au-CeO2-P catalysts exhibits a best catalytic activity (complete conversion at 10 °C).

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

The miR-15a/16 gene cluster is located in human chromosome 13 (13q14.3) and mouse chromosome 14 (14qC3). These genes are involved in cancer development and immune regulation. Our group has previously verified the binding of the 3′-untranslated region of NKG2D gene by miR-16 through dual-luciferase reporter assay. Herein, we found that miR-16 overexpression inhibited the NKG2D expression of CD8+ T cells, and that CD8+ NKG2D+ T cell frequency increased in miR-15/16−/− mice. CD8+ NKG2D+ T cells derived of miR-15/16−/− mice displayed activatory phenotype with enhanced IFN-γ production and cytotoxicity. The transfection of lentivirus containing antago-miR-16 sequences enhanced the NKG2D expression level of CD8+ T cells. However, no significant differences in CD8+ NKG2D+ T cell frequencies existed between wild-type and miR-15/16-transgenic mice because NKG2D was not expressed on the rest CD8+ T cells. When CD8+ T cells of miR-15/16-transgenic mice were treated with IL-2 in vitro, the magnitude of NKG2D expression and activation of CD8+ T cells was lower than that of wild-type mice. miR-15/16−/− mice showed that the exacerbation of colitis induced by dextran sulfate sodium (DSS) with more CD8+ T cells accumulated in inflamed colons, whereas miR-15/16-transgenic mice ameliorated DSS-induced colitis with less infiltration of CD8+ T cells. When NKG2D+ cells were depleted with NKG2D antibody in miR-15/16−/− mice, the aggravated colitis disappeared. All these results demonstrated that NKG2D could be upregulated by decreased miR-16 in CD8+ T cells to mediate inflammation. Thus, gene therapy based on the overexpression of miR-16 in CD8+ T cells can be used for patients with inflammatory diseases.

A facile, efficient and reliable method was designed and established to analyze the plant growth regulators (PGRs) in citrus fruit, based on a simplified dispersive solid-phase extraction (d-SPE) using a shaped zirconium-based metal-organic framework (UiO-66-PDMS bead) as the sorbent. In this method, UiO-66-PDMS beads directly extracted the targets from the homogenized and could be easily separated with a tweezer. It avoided the centrifugation or filtration operation required in normal d-SPE, greatly simplifying the d-SPE process. Moreover, the matrix substances were efficiently removed by this d-SPE process. The method showed good linearities (R

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and lipase in a mouse model of AP induced by caerulein. Moreover, the production of reactive oxygen species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l -arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.

The interaction of the metal and support in copper-ceria oxide catalysts has been proven to have extremely favorable effects on catalytic performance in CO oxidation. Therefore, how to construct more copper-ceria interfaces becomes the key to improve the catalytic activity. Herein, we developed a facile approach to prepare copper-ceria nanosheets with high concentration of interfacial active sites (active copper species sites and oxygen vacancies) using GO as a sacrificial template. Notably, GO was used as an excellent platform to grow precursors of both the Cu and Ce on its surface. Then, transfer them to metal oxides nanosheets by calcination. The CuCe-GO-X catalysts were characterized by SEM, TEM, In situ DRIFT, AFM, XRD, XPS, H2-TPR and Raman spectra and applied in CO oxidation. The results demonstrate that CuCe-GO-600 nanosheets catalyst with about 10 nm thickness shows a higher concentration of oxygen vacancies (7.79%) and active copper species sites (2756 μmol g−1) in the interface of copper-ceria than those of other CuCe-GO-X catalysts. Moreover, CuCe-GO-600 displays a highest catalytic activity (complete conversion at 90 °C with a space velocity of 54,000 mL (h gcat)−1).

A simple, environmentally-friendly and reliable method was developed to simultaneously monitor the residue of methyl 1-naphthalene acetate, parathion-methyl, fenitrothion, bromophos and phenthoate in pomelo by using dispersive solid-phase extraction technique (d-SPE). In this method, these target analytes were captured by MIL-125-NH2 and detected by GC–MS/MS. The key parameters of d-SPE were optimized by the single factor experiment. Under the optimized conditions, a good determination coefficient (R2 > 0.9922) and extraction recoveries (64.7–116.8%) are obtained. The limit of detections (0.03–1.07 ng/g) is lower than the MRLs in citrus fruits established by EU (10–15000 ng/g) and China (10–10000 ng/g). The precisions of intra-day and inter-day are 1.3–8.9% and 3.8–14.9%, respectively. In addition, the sorbent MIL-125-NH2 is stable and can be reused at least eight times. These results prove the established method is efficient and reliable to detect the pesticide residues in pomelo.

The proteasome is involved in the activation of NF-κB and can regulate the progression of inflammatory diseases. However, the role of proteasome in acute pancreatitis (AP) has not been demonstrated. In this study, we first observed that the protein level and activity of proteasome 20S were increased significantly in pancreatic injury tissues after caerulein-induced mild acute pancreatitis (MAP) induction, which was in consistent with the expression of the NF-κB nucleoprotein and positively correlated with the severity of AP. Then, bortezomib, a classical proteasome inhibitor, was used to intervene the progression of MAP in mice. The results showed that bortezomib administration reduced the serum amylase and lipase levels and mitigated histopathological manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the expression of NF-κB p65 nucleoprotein as well as total proteasome 20S protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we found that bortezomib could protect pancreatic acinar cell against necrosis and mitigate the severity of AP in a severe acute pancreatitis model induced by sodium taurocholate hydrate. Taken together, our study for the first time confirmed that the proteasome participated in the pathogenesis of AP and its inhibitor bortezomib could protect against AP in mice.

Introduction Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of algorithms, machine learning (ML) has gradually emerged in the field of disease prediction, assisting doctors in decision-making. Methods A systematic review was conducted using the PubMed, Web of Science, Scopus, and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication time was limited from inception to 29 May 2021. Studies that have used ML to establish predictive tools for AP were eligible for inclusion. Quality assessment of the included studies was conducted in accordance with the IJMEDI checklist. Results In this systematic review, 24 of 2,913 articles, with a total of 8,327 patients and 47 models, were included. The studies could be divided into five categories: 10 studies (42%) reported severity prediction; 10 studies (42%), complication prediction; 3 studies (13%), mortality prediction; 2 studies (8%), recurrence prediction; and 2 studies (8%), surgery timing prediction. ML showed great accuracy in several prediction tasks. However, most of the included studies were retrospective in nature, conducted at a single centre, based on database data, and lacked external validation. According to the IJMEDI checklist and our scoring criteria, two studies were considered to be of high quality. Most studies had an obvious bias in the quality of data preparation, validation, and deployment dimensions. Conclusion In the prediction tasks for AP, ML has shown great potential in assisting decision-making. However, the existing studies still have some deficiencies in the process of model construction. Future studies need to optimize the deficiencies and further evaluate the comparability of the ML systems and model performance, so as to consequently develop high-quality ML-based models that can be used in clinical practice.

Clinical studies have confirmed that indomethacin (Indo) can reduce the incidence and severity of post-endoscopicretrogradecholangio-pancreatography pancreatitis (PEP) effectively. However, the role of Indo on severe acute pancreatitis (SAP) is not clear. In the present study, we aimed to explore the effects of Indo treatment on SAP model induced by caerulein combined with lipopolysaccharide. After intraperitoneal injection of Indo in mice, both the severity of SAP and the serum levels of amylase, lipase, and proinflammatory cytokines were decreased. Furthermore, the mRNA and protein levels of NLRP3 inflammasome pathway (NLRP3,ASC and IL-1β) in pancreatic tissues were down-regulated. In vitro experiments, by isolating the pancreatic acinar cells (PACs) from mice, we found that Indo significantly reduced lactate dehydrogenase(LDH) excretion, increased the cell activity, and inhibited the NLRP3 inflammasome pathway of PACs. Taken together, our data showed that Indo could protect pancreatic acinar cell from injury by inhabiting NLRP3 pathway and decreased the severity of SAP accordingly.

Developing efficient catalysts with high yields of aldol products in the aldol reaction is of great importance and remains a challenge. By a facile route utilizing hydrogen bonding, 1,1,3,3-tetramethylguanidine was successfully loaded on graphene oxide to afford a immobilized catalyst. This immobilized catalyst shows an excellent conversion of 97.3% with a high aldol product selectivity of 92.5% in the aldol reaction of p-nitrobenzaldehyde with acetone, which is superior to the corresponding homogeneous catalyst with a conversion of 97.1% and selectivity of only 59.5% under similar conditions. Furthermore, the immobilized catalyst can be easily recovered and reused without significant loss of the reactivity.

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1- CD4+ NKG2D+ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1- CD4+ NKG2D+ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1- CD4+ NKG2D+ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8+ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1- CD4+ NKG2D+ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1- CD4+ NKG2D+ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1- CD4+ NKG2D+ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1- CD4+ NKG2D+ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.

Two unique discrete cubane-like (COO−)2(H2O)6 anion water clusters in the two solid phase have been observed for the fist time. The two water clusters are remarkably similar and both serve as the building blocks to construct two new 3D hydrogen-bonded architectures. {[Cd(PZA)2(H2O)4]·2H2O}n (1) features a rare (3,4,6)-connected trinodal network with 3,4,6T6 topology, and {[Mn(OPZA)2(H2O)4]·2H2O}n (2) displays a (4,5,6)-connected trinodal network bearing new topology. Moreover, compound 2 exhibits an interesting reversible crystal-to-amorphous transformation upon dehydration and rehydration, while 1 only exhibits crystal-to-crystal transformation during the dehydration.

A highly thermal stable metal–organic framework (MOF), MIL-120, was employed to incorporate low-cost nickel particles by simple impregnate method to obtain heterogeneous catalyst, Ni/MIL-120. The as-synthesized catalysts were evaluated by gas-phase benzene hydrogenation and exhibited excellent catalytic activities in comparison with classic Ni/Al 2 O 3 catalyst. The X-ray diffraction (XRD), H 2 temperature-programmed reduction (H 2 -TPR) and transmission electron microscopic (TEM) results indicated that Ni species were well dispersed on the MOF matrix and the interaction between the Ni species and the MOF-support was weaker than that between the metal species and Al 2 O 3 , which facilitated the catalytic performance of catalyst for benzene hydrogenation.

Employing metal–organic frameworks (MOFs) as precursor, a series of CuO/CeO2 catalysts with well-dispersed copper species were synthesized and applied for preferential CO oxidation in H2-rich stream. The catalyst with 5 wt.% Cu loading calcined at 600 °C for 6 h exhibited an excellent catalytic activity. The high activity of the CuO/CeO2 catalysts indicated that MOF precursor played a key role for improving the dispersion of metal active sites.

A 2D metal-organic framework [Cu2 (BPTC) (Im)4(H2O) (DMF)]n (1) with unsaturated coordinated Cu(II) sites has been prepared under solvothermal condition, and applied to the hydroxylation of phenol after activating. The catalytic results indicate that 1a (the activated 1) exhibits an obvious activity for phenol hydroxylation at 40 °C for 4 h. Compared to the control experiments where the free Cu(II) (from Cu(OAc)2 salt) has been utilized as the catalysts, 1a shows the higher selectivity to diphenols. This suggests that the coordinated environment of unsaturated coordinated Cu(II) sites in the 2D layer play the key role in the phenol hydroxylation.