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Increasing evidence shows a close relationship between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Recently, glucagon-like peptide-1 (GLP-1), a gut incretin hormone, has become a well-established treatment for T2DM and is likely to be involved in treating cognitive impairment. In this mini review, the similarities between AD and T2DM are summarised with the main focus on GLP-1-based therapeutics in AD.

Primary cutaneous anaplastic large-cell lymphoma (pC-ALCL) is distinguished from systemic anaplastic large-cell lymphoma (S-ALCL) with cutaneous involvement. Although pC-ALCL is a unique entity with different genetics, clinical characteristics, and prognosis, its causes are unknown. Herein, we report the case of a Chinese woman with a 4-month history of a gradually enlarged ulcerative mass in her right forearm following an unidentified insect bite. Biopsy revealed an extensive infiltrate with patches of large anaplastic lymphoid cells. These cells were immunohistochemically positive for CD45, CD30, and TIA-1 and negative for CD2, CD3, CD4, CD5, CD20, CD7, CD8, and ALK-1. DUSP22-IRF4 rearrangement was detected; on the other hand, TP63 rearrangement was not observed by fluorescence in situ hybridization (FISH). No Epstein-Barr virus-encoded small RNAs (EBERs) were detected by ISH. Rearrangement of monoclonal TCR gene was found using BIOMED-2 polymerase chain reaction. No abnormality was found on the subsequent positron emission tomography-computed tomography (PET-CT) scan. After five cycles of cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP) chemotherapy, the patient achieved complete remission. This is the first report of a unique pC-ALCL with DUSP22-IRF4 rearrangement following an insect bite other than S-ALCL involving the skin.

Emerging evidence indicates extensive oxidative stress is a consequence of obesity which impairs bone formation. Glutathione peroxidase 7 (GPX7) is a conserved endoplasmic reticulum (ER) retention protein, lacking of which causes accumulation of reactive oxygen species (ROS) and promotes adipogenesis. Since the imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cell (BMSC) leads to severe bone diseases such as osteoporosis, it is critical to investigate the potential protective role of Gpx7 in osteogenesis. Here, we provide evidence that deficiency of Gpx7 reduces osteogenesis, but increases adipogenesis in both human BMSCs (hBMSCs) and mouse mesenchymal stem cell line. Interestingly, further studies indicate this defect can be alleviated by the ER stress antagonist, but not the ROS inhibitor, unveiling an unexpected finding that, unlike adipogenesis, lacking of Gpx7 inhibits osteogenesis mediating by induced ER stress instead of enhanced ROS. Furthermore, the mTOR signalling pathway is found down‐regulation during osteogenic differentiation in Gpx7‐deficient condition, which can be rescued by relief of ER stress. Taken together, for the first time we identify a novel function of Gpx7 in BMSCs’ osteogenic differentiation and indicate that Gpx7 may protect against osteoporotic deficits in humans through ER stress and mTOR pathway interplay.

Purpose Hepatocellular carcinoma (HCC) is a common malignant cancer and the third leading cause of death worldwide. The molecular mechanism of HCC remains unclear. Recent studies have demonstrated that the ubiquitin‐proteasome system (UPS) is associated with HCC. Ubqln2, a member of the UPS, is abnormally expressed in HCC. However, whether Ubqln2 is associated with HCC prognosis remains unknown. Patients and Methods We analyzed the associations between overall survival and various risk factors in 355 HCC tissue samples obtained from the Cancer Genomic Atlas (TCGA) database at the mRNA level and in 166 HCC tissue samples from Southwest Hospital at the protein level. qRCR was used to determinate Ubqln2 expression in cancer and noncancerous tissues. The association between Ubqln2 and Ki‐67 was analyzed by immunohistochemistry. The association between Ubqln2 expression and survival was analyzed using Kaplan‐Meier curve and Cox proportional hazards models. A nomogram was used to predict the impact of Ubqln2 on prognosis. Mutated genes were analyzed to determine the potential mechanism. Results Ubqln2 highly expressed in HCC tissues. The Ubqln2 mRNA level had significant relations with UICC tumor stage (P = .022), UICC stage (P = .034) and resection potential (P = .017). Concordantly, the Ubqln2 protein was closely associated with tumor size (P = .005), UICC stage (P = .012), and recurrence (P = .009). Ubqln2 was highly expressed in HCC and positively associated with poor survival. The nomogram precisely predicted the prognosis of HCC patients with high or low Ubqln2 expression. A genomic waterfall plot suggested that Ubqln2 expression was closely associated with mutated CTNNB1. Conclusion Our findings reveal that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1., Ubqln2 is abnormally expressed in HCC but its role remains unknown. Here, we reported that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1.

It has been shown that long noncoding RNAs (lncRNAs) are involved in the carcinogenesis of multiple cancers. However, the roles of lncRNAs in gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) remain elusive. In the present study, we found that lncNEN885 was markedly decreased in human gastric NEN samples compared to adjacent normal tissues by transcriptome sequencing. Functionally, silencing or overexpression of lncNEN885 could not obviously affect cell proliferation or apoptosis in BON‐1 or LCC‐18 cells but could affect cell migration and invasion as well as wound‐healing rates. Furthermore, dysregulation of lncNEN885 affected these biological functions by activating epithelial‐mesenchymal transition through increased expression of Snail, vimentin, and N‐cadherin as well as decreased E‐cadherin levels in BON‐1 and LCC‐18 cells. Silencing of lncNEN885 could dramatically increase the phosphorylation of glycogen synthase kinase‐3β and decrease the expression of adenomatous polyposis coli and Axin, with the subsequent accumulation of β‐catenin. Taken together, dysregulation of lncNEN885 can regulate cell migration and invasion by activating epithelial‐mesenchymal transition process partially through canonical Wnt/β‐catenin signaling in GEP‐NEN cells, which may be a novel biomarker for the metastasis of GEP‐NENs.

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. A process that involves the generation of N-centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional-group tolerance.

Background To study the antidiabetic effects and mechanisms of the fenugreek extracts in streptozotocin (STZ)‐induced type 2 diabetic (T2DM) mice fed a high‐fat diet (HFD). Methods We established C57BL/6J mice model of T2DM using HFD‐fed and STZ‐induced method. Then, the mice were administered with two types of fenugreek extracts (E1, flavonoid and E2, stilbene glycoside) for 4 weeks and the effects on fasting blood glucose (FBG), weight, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and pathological indexes were investigated. Results Administration of fenugreek extracts decreased the FBG level compared with that of the model group. Comparatively, the high‐dose E2 decreased the FBG more significantly than the other treatments did. Both extracts showed an obvious antioxidant effect by increasing serum SOD and CAT activities and decreasing the MDA content. Furthermore, the high‐dose E1 showed a significant difference (P

Details of a biogenetically inspired strategy that led to the synthesis of the hetidine-type C20-diterpenoid alkaloid skeleton are reported in this paper. Key steps of our synthesis include a C—H oxidation to convert the atisine-type core to the ajaconine skeleton, as well as an aza-Prins cyclization that establishes the hetidine alkaloid skeleton. An unexpected heptacyclic framework bearing a unique tricyclo[3.3.1.02,7]nonane moiety has been obtained during our studies, which may represent a new type of C20-diterpenoid alkaloids yet to be discovered.

The asymmetric total syntheses of a group of structurally complex Kopsia alkaloids, (-)-kopsine, (-)-isokopsine, (+)-methyl chanofruticosinate, (-)-fruticosine, and (-)-kopsanone, has been achieved. The key strategies for the construction of the molecular complexity in the targets included an asymmetric Tsuji-Trost rearrangement to set the first quaternary carbon center at C20, an intramolecular cyclopropanation by diazo decomposition to install the second and third quaternary carbon centers at C2 and C7, respectively, and a SmI2 -promoted acyloin condensation to assemble the isokopsine core. A radical decarboxylation of an isokopsine-type intermediate results in a thermodynamic partial rearrangement to give N-decarbomethoxyisokopsine and N-decarbomethoxykopsine, two key intermediates for the syntheses of Kopsia alkaloids with different subtype core structures.

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine (2, atisine type) and gymnandine (4, denudatine type). The synthesis features a biogenetically inspired strategy that relies on C-H oxidation, aza-pinacol coupling, and aza-Prins cyclization as key steps.

The incorporation of nitrogen atoms into policyclic diterpenes has led to one of the most fascinating group of natural products with cage-like structures: diterpenoid alkaloids. Their singular architectural features and significant bioactivities made them highly pursued targets amongst the synthetic community over decades. A total of seven types of diterpenoid alkaloid molecules have been synthesized thus far, and the research in this area experienced a new climax in the past five years. With a brief overview and summary of the historic achievements, this Focus Review particularly covers the recent, post-2010 advances in the field of diterpenoid alkaloid synthesis, highlighting the utilization of innovative synthetic methods and strategies. Despite numerous achievements, there are still a number of such alkaloids with different and unique structural types waiting to be accomplished, implying that the pursuit is far from ending.

The square-planar diimine platinum(II) complex Pt(BpyC≡CSiMe3)(C≡CC6H5)2 (1, BpyC≡CSiMe3 = 4-[(2-trimethylsilyl)ethynyl]-2,2′-bipyridine) was prepared and characterized. In the solid state, 1 shows unusual reversible thermochromic and mechanochromic properties. When crystalline 1·2(CHCl3) is heated or ground, the bright yellow emission centered at ca. 544 (576, sh) nm changes to 722 nm, which corresponds to a thermo- and mechanochromic response redshift of ca. 146–178 nm. Once the heated or ground samples were exposed to organic vapors, they reverted to the original crystalline state, and the luminescence changed from red to yellow. The conversion between a triplet metal-to-ligand charge transfer/ligand-to-ligand charge transfer (3MLCT/3LLCT) emission state and a triplet metal–metal-to-ligand charge transfer (3MMLCT) state is the reason for the luminescence change.

Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated the effect of LPS on antigen-stimulated mast cell degranulation and the underlying mechanisms. We found that LPS enhanced degranulation in RBL-2H3 cells and mouse peritoneal mast cells upon FceRI activation, in a dose- and time-dependent manner. Parallel to the alteration of degranulation, LPS increased FceRI-activated Ca(2+) mobilization, as well as Ca(2+) entry through store-operated calcium channels (SOCs) evoked by thapsigargin. Blocking Ca(2+) entry through SOCs completely abolished LPS enhancement of mast cell degranulation. Consistent with functional alteration of SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major subunits of SOCs, in a time-dependent manner. In addition, LPS increased the mRNA level of Toll-like receptor 4 (TLR4) in a time-dependent manner. Blocking TLR4 with Cli-095 inhibited LPS, increasing transcription and expression of SOC subunits. Concomitantly, the effect of LPS enhancement of Ca(2+) mobilization and mast cell degranulation was largely reduced by Cli-095. Administration of LPS (1 μg) in vivo aggravated airway hyperreactivity and inflammatory reactions in allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage fluid were increased by LPS treatment. In addition, Ca(2+) mobilization was enhanced in peritoneal mast cells isolated from LPS-treated asthmatic mice. Taken together, these results imply that LPS enhances mast cell degranulation, which potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide increases Ca(2+) entry through SOCs by upregulating transcription and expression of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in enhancement of mast cell degranulation upon antigen stimulation.

The incorporation of nitrogen atoms into policyclic diterpenes has led to one of the most fascinating group of natural products with cage-like structures: diterpenoid alkaloids. Their singular architectural features and significant bioactivities made them highly pursued targets amongst the synthetic community over decades. A total of seven types of diterpenoid alkaloid molecules have been synthesized thus far, and the research in this area experienced a new climax in the past five years. With a brief overview and summary of the historic achievements, this Focus Review particularly covers the recent, post-2010 advances in the field of diterpenoid alkaloid synthesis, highlighting the utilization of innovative synthetic methods and strategies. Despite numerous achievements, there are still a number of such alkaloids with different and unique structural types waiting to be accomplished, implying that the pursuit is far from ending.

Three new C20-diterpenoid alkaloids, along with twenty-two known alkaloids, were isolated from the whole herbs of Delphinium tatsienense. The new alkaloids include a vakognavine-type C20-diterpenoid alkaloid, designated as tatsienenseine A (1), and two hetisine-type C20-diterpenoid alkaloids, designated as tatsienenseines B (2) and C (3). Their structures were elucidated by IR, HR-ESI-MS, 1D- and 2D-NMR analyses.

Further investigation on the roots of Aconitum piepunense led to the isolation of a novel bis-diterpenoid alkaloid designated as piepunine (1). Its structure was established by extensive interpretation of its 1D- and 2D-NMR data, high-resolution ESI-MS, and IR spectra. Piepunine represents the first example of an atisine–denudatine-type bis-diterpenoid alkaloids.

Further phytochemical investigation of the roots of Aconitum hemsleyanum var. circinatum resulted in the isolation of three new aconitine-type C19-diterpenoid alkaloids, hemsleyanines E–G (1–3, resp.). The structures of these new alkaloids were elucidated on the basis of spectral data including 2D-NMR.

One new C19-diterpenoid alkaloid, named liangshantine (1), and three new C20-diterpenoid alkaloids, liangshansines A–C (2–4, resp.), as well as eight known compounds, were isolated from the roots of Aconitum liangshanicum. The structures of these new alkaloids were elucidated by spectroscopic methods.

Trichocarpinine (1), the first hetidine–hetisine type bisditerpenoid alkaloid, was isolated from the whole herbs of Aconitum tanguticum var. trichocarpum. Its structure was determined by a combination of spectroscopic techniques, including HR-ESI-MS and 1D- and 2D-NMR experiments. Its plausible biogenetic pathway was proposed as well (Scheme).

Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.

Marine organisms represent an abundant sources of bioactive natural products with unique chemical structure. Pimarane diterpenes are a structurally diverse family of natural products with various biological activities and pharmacological properties. A prolific source of new marine-derived pimarane diterpenes have attracted considerable interest because of their unique structural diversity and varied biological activities, including antimicrobial, antitumor, and antiproliferative activities. This review provides a comprehensive overview of the structures, names, bioactivities, and references of 80 marine-derived pimarane-type natural products for the first time.

The increasing demands for new lead compounds in pharmaceutical and agrochemical industries have driven scientists to search for new bioactive natural products. Marine microorganisms are rich sources of novel, bioactive secondary metabolites, and have attracted much attention of chemists, pharmacologists, and molecular biologists. This mini-review mainly focuses on macrolactins, a group of 24-membered lactone marine natural products, aiming at giving an overview on their sources, structures, biological activities, as well as their potential medical applications.

Three new cytochalasins Z24 (I), Z25 (II), and Z26 (III) are isolated along with the known compound, scoparasin B.

The secondary structures of porcine brain Cu4Zn3-metallothionein (MT)-III and Cd5Zn2MT-I, Cd5Zn2MT-II, and Zn7MT-I from rabbit livers in the solid state are investigated by Fourier transform IR spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman). The Cu4Zn3MT-III contains 26–28% β-turns and half-turns, 13–14% 310-helices, 47–49% random coils, and 11–12% β-extended chains. The structural comparison of porcine brain Cu4Zn3MT-III with rabbit liver Cd5Zn2MT-I (II) and Zn7MT-I shows that the contents of the random coil structure are obviously increased. The results indicate that the insert of an acidic hexapeptide in the α domain of Cu4Zn3MT-III possibly forms an α helix. However, because the bands assigned to the α-helix and random coil structures are overlapped in the spectra, the content of random coil structures in Cu4Zn3MT-III is therefore higher than those in Cd5Zn2MT-I, Cd5Zn2MT-II, and Zn7MT-I. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 65: 81–88, 2002

The ocean is a capacious area with the most abundant biological resources on the earth. The particularity of the marine ecological environment (high pressure, high salt, and hypoxia) makes the marine species survival competition fiercely, forcing many marine organisms in the process of life to produce a great deal of secondary metabolites with special structures and biological activities. In this article, 118 natural products which were isolated from four kinds of marine organisms, sponges, algae, soft corals and fungus, showing PTP1B inhibitory activity were summarized from 2010 to 2016, which may become the leading compounds towards treating Diabetes mellitus (DM). What's more, we briefly summarized the structure-activity relationship of PTP1B inhibitors.

The research conceptualizes workgroup emotional climate (WEC) and workgroup emotional labor as contrasting types of emotional exchange within teams, with the former defined as team-member directed emotional exchanges and the latter as the outward directed emotional exchanges required to enact one's role. Data were obtained from a sample of 840 workgroup members from 148 workgroups in China. Results showed that positive WEC is a source of group efficacy with positive consequences for workgroup performance. The findings also lend support to the idea that people have limited emotional resources and thus, while a positive WEC improves group performance, this relationship is weakened as workgroup emotional labor increases. The study identifies two types of emotional exchanges characterizing a workgroup and enriches understanding of team emotional dynamics. Team leaders need to recognize the value of WEC and the workgroup emotional labor requirements and try to induce more positive WEC to facilitate team performance.

An efficient three-step synthesis of nonenolide (V), a lactose with coconut-like and rancid odour, is given.

Two new alkaloids, wattisines A and B, are isolated along with three known alkaloids from the roots of the title species.

One new C19-diterpenoid alkaloid, named liangshantine (1), and three new C20-diterpenoid alkaloids, liangshansines A–C (2–4, resp.), as well as eight known compounds, were isolated from the roots of Aconitum liangshanicum. The structures of these new alkaloids were elucidated by spectroscopic methods.

Further phytochemical investigation of the roots of Aconitum hemsleyanum var. circinatum resulted in the isolation of three new aconitine-type C19-diterpenoid alkaloids, hemsleyanines E–G (1–3, resp.). The structures of these new alkaloids were elucidated on the basis of spectral data including 2D-NMR.

The increasing demands for new lead compounds in pharmaceutical and agrochemical industries have driven scientists to search for new bioactive natural products. Marine microorganisms are rich sources of novel, bioactive secondary metabolites, and have attracted much attention of chemists, pharmacologists, and molecular biologists. This mini-review mainly focuses on macrolactins, a group of 24-membered lactone marine natural products, aiming at giving an overview on their sources, structures, biological activities, as well as their potential medical applications.

Treatment of compounds 2 and 5, both from the C19-diterpenoid alkaloid deltaline 1, with 5% NaOH methanol (room temperature, 16 h) and NaOH-N,N-dimethylformamide (reflux, 10 h) led to the two novel skeletal rearrangement products 4 (90%) and 6 (62%), respectively, involving Wagner–Meerwein rearrangement and Grob fragmentation. Their structures were fully characteristized based on 2D NMR and HR-MS data.