Scheme 4. Pd-catalyzed enantioselective decarboxylative allylic alkylation. [a] [Pd 2 (dba) 3 ] (3.5 mol %), L2 (8.75 mol %). [b] At 55 8C.Scheme 5. Catalytic enantioselective total synthesis of (À)-aspidospermidine. Reaction conditions: a) HCO 2 H, RT; b) LiAlH 4 , THF, À20 8C, then HCl (2 m); c) K 2 OsO 4 ·2 H 2 O, NMO, THF/H 2 O (1:1), then NaIO 4 ; d) 1,2-ethanedithiol, BF 3 ·Et 2 O, CH 2 Cl 2 ; e) Raney nickel, H 2 , EtOH, 60 8C; f) LiAlH 4 , Et 2 O, reflux; g) Na/NH 3 , THF, À78 8C. NMO = Nmethylmorpholine-N-oxide.
Today, tumor therapy and its therapeutic efficiency evaluation are conducted separately, and current imaging techniques cannot evaluate tumor-therapeutic effects in real time. Therefore, it is of great importance to develop highly efficient theranostic strategies which are able to evaluate their tumor-therapeutic effects in real time. In this work, by rational design of a small molecular near-infrared probe Cys(StBu)-Asp-Glu-Val-Asp-Lys(Cypate)-CBT (Cy-CBT) and using a CBT-Cys click condensation reaction, we facilely prepare an intelligent nanoparticle Cy-CBT-NP which is able to evaluate its photothermal therapy (PTT) efficiency on tumors by fluorescence "Turn-On". Fluorescence of Cy-CBT-NP is quenched and photothermal responsive. Upon caspase 3 (Casp3) cleavage of its DEVD substrates, Cy-CBT-NP disassembles to turn the fluorescence "On", which in turn evaluates the PTT efficiency of the nanoparticle on cells and tumors in real time. We envision that our smart strategy could be applied for PTT and real-time evaluation of the therapeutic efficiency of solid tumors in the near future.
Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.
Background and Aim: Problematic mobile phone use (PMPU) and depression are great public health concerns among adolescents. The aim of this study was to determine the association between PMPU and symptoms of depression, as well as the mediating role of sleep quality. Methods: A total of 4,624 college students participated in this study. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire-9 (PHQ-9) were administered to assess PMPU, sleep quality, and symptoms of depression. Mediation analysis was conducted using PROCESS macro in the SPSS software. Results: Of the participants, 27.5% were classified as PMPU, 44.9% exhibited symptoms of depression, and 15.6% reported sleep problems. Compared with those without PMPU, those with PMPU exhibited higher rates of sleep problems and depressive symptoms. The mediation analysis further revealed partial mediation effects of sleep quality on the association between PMPU and depression. Conclusions: This study demonstrated that PMPU was associated with mental health in college students, and sleep quality played a mediating role in this relationship. Our findings highlight the critical role of early intervention for depression with a focus on those with PMPU and, more specifically, on those with sleep problems.
Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus nephritis (LN) and induce infiltrating inflammatory cells in kidney in animal models. Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-inflammatory effects. Monocyte chemoattractant protein-1(MCP-1) is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP-1 protein expression with LPS are poorly understood. Expression of MCP-1 was examined by western blot and enzyme-linked immunosorbent assay, respectively. The activity of nuclear factor (NF)-kappaB was measured by western blot. These mice have uncontrolled proliferation of T cells, an impaired response to T cell mitogen and produce autoantibodies against nuclear antigens, including DNA. We found that after LPS treatment for 14 weeks, LPS increased MCP-1 protein expression in kidney, which was significantly suppressed by antioxidant PDTC. The expression of NF-κB, pERK, pJNK and MCP-1 were increased, pp38 expression was decreased significantly, concomitantly with sera anti-dsDNA, MCP-1 and the acceleration of severity of autoimmune kidney injury. LPS induce markedly neutrophil infiltration in the glomerulus, especially around the mesangial region. PDTC reduced the number of infiltrating inflammatory cells and severity of kidney injury via inhibiting NF-κB and p38 MAPK activity. They also markedly prevented LPS-induced pJNK and MCP-1. Therefore, MCP-1 may be responsible for the recruitment and activation of leukocytes in diseased kidneys in female MRL/lpr mice. In this study, the long-term administration of PDTC had impacts on the prevention of end-stage organ damage induced by LPS treated. We demonstrated that PDTC inhibited LPS-induced monocyte migration and attenuated LPS-induced p38 MAPK activation. Based on these data we infer that PDTC inhibits LPS-induced MCP-1 expression, secretion and function through inhibition of NF-κB and p38 MAPK activity. Our study suggests that MAPK is an important therapeutic target of monocyte recruitment and accumulation within the glomerulus in inflammatory renal disease. These results suggest that PDTC protects against kidney inflammation of SLE at least in part via NF-κB and MAPK signaling pathways induction, and that inhibitory action on anti-dsDNA may be associated with the protective mechanism of PDTC. In summary, PDTC pretreatment attenuates LPS-induced kidney injury in female MRL/lpr mice through regulating NF-κB and MAPK signaling pathways. Our results indicate that LPS induces MCP-1 mainly through activating NF-κB and its downstream MAPK, and that such effect was inhibited by PDTC, suggesting the efficacy of PDTC in preventing kidney fibrosis in lupus-prone mice. Therefore, appropriate inhibition of NF-κB activation may attenuate the kidney injury in lupus-prone mice.
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