Synthesis of a molecularly defined single-active site heterogeneous catalyst for selective oxidation of N-heterocycles

Generally, a homogeneous catalyst exhibits good activity and defined active sites but it is difficult to recycle. Meanwhile, a heterogeneous catalyst can easily be reused but its active site is difficult to reveal. It is interesting to bridge the gap between homogeneous and heterogeneous catalysis via controllable construction of a heterogeneous catalyst containing defined active sites. Here, we report that a molecularly defined, single-active site heterogeneous catalyst has been designed and prepared via the oxidative polymerization of maleimide derivatives. These polymaleimide derivatives can be active catalysts for the selective oxidation of heterocyclic compounds to quinoline and indole via the recycling of -C=O and -C-OH groups, which was confirmed by tracing the reaction with GC-MS using maleimide as the catalyst and by FT-IR analysis with polymaleimide as the catalyst. These results might promote the development of heterogeneous catalysts with molecularly defined single active sites exhibiting a comparable activity to homogeneous catalysts

Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR-29 family.

Secreted microRNAs (miRNAs) are novel endocrine factors that play essential pathological and physiological roles. Here, we report that pancreatic β cell-released exosomal miR-29 family members (miR-29s) regulate hepatic insulin sensitivity and control glucose homeostasis. Cultured pancreatic islets were shown to secrete miR-29s in response to high levels of free fatty acids (FFAs) in vitro. In vivo, high levels of FFAs, promoted by either high-fat diet (HFD) feeding (physiopathological) or fasting (physiological), increased the secretion of miR-29s into plasma. Intravenous administration of exosomal miR-29s attenuated insulin sensitivity. The overexpression of miR-29s in the β cells of transgenic (TG) mice promoted the secretion of miR-29s and inhibited the insulin-mediated suppression of glucose output in the liver. We used selective overexpression of traceable heterogenous mutant miR-29s in β cells to confirm that islet-derived exosomal miR-29s target insulin signalling in the liver and blunt hepatic insulin sensitivity. Moreover, in vivo disruption of miR-29s expression in β cells reversed HFD-induced insulin resistance. In vitro experiments demonstrated that isolated exosomes enriched in miR-29s inhibited insulin signalling in the liver and increased hepatic glucose production. These results unveil a novel β cell-derived secretory signal-exosomal miR-29s-and provide insight into the roles of miR-29s in manipulating glucose homeostasis.MRC MD

Distinguishing Tidal Disruption Events from Impostors

Recent claimed detections of tidal disruption events (TDEs) in multi-wavelength data have opened potential new windows into the evolution and properties of otherwise dormant supermassive black holes (SMBHs) in the centres of galaxies. At present, there are several dozen TDE candidates, which share some properties and differ in others. The range in properties is broad enough to overlap other transient types, such as active galactic nuclei (AGN) and supernovae (SNe), which can make TDE classification ambiguous. A further complication is that "TDE signatures" have not been uniformly observed to similar sensitivities or even targeted across all candidates. This chapter reviews those events that are unusual relative to other TDEs, including the possibility of TDEs in pre-existing AGN, and summarises those characteristics thought to best distinguish TDEs from continuously accreting AGN, strongly flaring AGN, SNe, and Gamma-Ray Bursts (GRBs), as well as other potential impostors like stellar collisions, "micro-TDEs," and circumbinary accretion flows. We conclude that multiple observables should be used to classify any one event as a TDE. We also consider the TDE candidate population as a whole, which, for certain host galaxy or SMBH characteristics, is distinguishable statistically from non-TDEs, suggesting that at least some TDE candidates do in fact arise from SMBH-disrupted stars.Comment: 57 pages, 17 figures. Accepted for publication in Springer Space Science Reviews. Chapter in ISSI review "The Tidal Disruption of Stars by Massive Black Holes" vol. 79. Corrected several typos from previous submissio

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT0279955

Quercetin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy by Inhibiting ERK/NF- κ

Background. Hepatic ischemia reperfusion (IR) injury is a common phenomenon in transplantation or trauma. The aim of the present study was to determine the protective effect of quercetin (QE) on hepatic IR injury via the ERK/NF-κB pathway. Methods. Mice were randomized into the sham, IR, QE100 + IR, and QE200 + IR groups. Quercetin was administered intragastrically daily at two doses (100 mg/kg and 200 mg/kg) for 5 days prior to IR injury. The expression levels of liver enzymes, inflammatory cytokines, and other marker proteins were determined at 2, 8, and 24 hours after IR. And they were compared among these groups. Results. Compared with the IR group, the treatment of QE reduced the release of cytokines, leading to inhibition of apoptosis and autophagy via downregulation of the ERK/NF-κB pathway in this model of hepatic IR injury. Conclusion. Apoptosis and autophagy caused by hepatic IR injury were inhibited by QE following a reduction in the release of inflammatory cytokines, and the relationship between the two may be associated with inactivation of the ERK/NF-κB pathway

15-Deoxy- γ

Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM) 1 h before the stimulation with ConA (30 μg/mL). The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity