Regioselective Dehydrogenative Reverse Prenylation of Indoles with 2-Methyl-2-butene.

Bulk chemical 2-methyl-2-butene, one of the main C5 distillates of the petrochemical industry, has scarcely been utilized directly in synthesizing high-value-added fine chemicals. Herein, we use 2-methyl-2-butene as the starting material to develop a palladium-catalyzed highly site- and regio-selective C-3 dehydrogenation reverse prenylation of indoles. This synthetic method features mild reaction conditions, a broad substrate scope, atom- and step-economies.

Designed bacteria based on natural pbr operons for detecting and detoxifying environmental lead: A mini-review.

Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Asymmetric Total Syntheses of Hypoestin A, Albolic Acid, and Ceroplastol II.

The first asymmetric total synthesis of bioactive diterpenoid hypoestin A with an unprecedented [5-8-5-3] tetracyclic skeleton is accomplished in 15 steps from commercially available (R)-limonene. Furthermore, the second asymmetric total syntheses of sesterterpenoids albolic acid and ceroplastol II in 21 steps are also reported. The synthetically challenging and highly functionalized [X-8-5] (X = 5 or 7) tricarbocyclic ring systems found in hypoestin A, albolic acid, ceroplastol II, and schindilactone A, as well as other natural products, are efficiently and directly constructed via a unique intramolecular Pauson-Khand reaction of an allene-yne. This work represents the first reported use of the Pauson-Khand reaction to access synthetically challenging eight-membered-ring systems in natural product synthesis.

Se-(Fluoromethyl) Benzenesulfonoselenoates: Shelf-Stable, Easily Available Reagents for Monofluoromethylselenolation.

A new class of electrophilic monofluoromethylselenolation reagents, Se-(fluoromethyl) benzenesulfonoselenoates, has been developed. They can be readily prepared from sodium benzenesulfinates, Se powder and ClCFH2 in one step under mild reaction conditions. Se-(fluoromethyl) benzenesulfonoselenoates are efficient electrophilic monofluoromethylselenolation reagents for a wide range of nucleophiles including indole, 6-azaindole, pyrrole, thiophene, electron-rich arene, aryl boronic acid and alkyne. The monofluoromethylselenolation approach features mild and environmentally friendly reaction conditions, good tolerance of various functional groups, and broad substrate scope.

Synthesis of Acyl Hydrazides via a Radical Chemistry of Azocarboxylic tert-Butyl Esters.

A new chemistry of azo compounds, that is, addition of free radicals generated in situ to access various acyl hydrazides, has been developed. The protocol provides a novel strategy for the synthesis of valuable acyl hydrazides. The transformation features mild reaction conditions, good tolerance of functional groups, and a broad substrate scope. In view of the importance of acyl hydrazides in functional materials and medicinal chemistry, this approach would find broad applications.

Switchable, Reagent-Controlled C(sp3)-H Selective Iodination and Acetoxylation of 8-Methylquinolines.

An efficient Pd-catalyzed C(sp3)-H selective iodination of 8-methylquinolines is reported herein for the first time. Because of the versatility of organic iodides, the method offers a facile access to various C8-substituted quinolines. By slightly switching the reaction conditions, an efficient C(sp3)-H acetoxylation of 8-methylquinolines has also been enabled. Both approaches feature mild reaction conditions, good tolerance of functional groups, and a broad substrate scope.

Co-ordination between leaf biomechanical resistance and hydraulic safety across 30 sub-tropical woody species.

BACKGROUND AND AIMS: Leaf biomechanical resistance protects leaves from biotic and abiotic damage. Previous studies have revealed that enhancing leaf biomechanical resistance is costly for plant species and leads to an increase in leaf drought tolerance. We thus predicted that there is a functional correlation between leaf hydraulic safety and biomechanical characteristics. METHODS: We measured leaf morphological and anatomical traits, pressure-volume parameters, maximum leaf hydraulic conductance (Kleaf-max), leaf water potential at 50 % loss of hydraulic conductance (P50leaf), leaf hydraulic safety margin (SMleaf), and leaf force to tear (Ft) and punch (Fp) of 30 co-occurring woody species in a sub-tropical evergreen broadleaved forest. Linear regression analysis was performed to examine the relationships between biomechanical resistance and other leaf hydraulic traits. KEY RESULTS: We found that higher Ft and Fp values were significantly associated with a lower (more negative) P50leaf and a larger SMleaf, thereby confirming the correlation between leaf biomechanical resistance and hydraulic safety. However, leaf biomechanical resistance showed no correlation with Kleaf-max, although it was significantly and negatively correlated with leaf outside-xylem hydraulic conductance. In addition, we also found that there was a significant correlation between biomechanical resistance and the modulus of elasticity by excluding an outlier. CONCLUSIONS: The findings of this study reveal leaf biomechanical-hydraulic safety correlation in sub-tropical woody species.

Synthesis of Aporphine Analogues via Palladium-Catalyzed Intramolecular Aryl-Aryl Dehydrogenative Coupling.

Reported herein is an intramolecular dehydrogenative coupling of two inert aryl C-H bonds for the synthesis of aporphine analogues. The process represents a novel tool for the preparation of aporphines via palladiun-catalyzed C-H bond activation. The present reaction is compatible with various functional groups, and the coupling products have been further applied for the synthesis of natural products aporphine and zenkerine.

Photocatalyzed Csp3-Csp3 cross-dehydrogenative coupling of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones.

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones, the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst is low and the oxidant is inexpensive and less toxic.

Synthesis of trifluoromethylthioesters from aldehydes via a visible light-promoted radical process.

We report herein an efficient, economical, and scalable trifluoromethylthiolation of aldehydes to generate trifluoromethylthioesters via a visible light-promoted radical process. The transformation features cheap reagents, simple operation, a broad substrate scope, and especially no metal involved in the reaction. Trifluoromethylthiolations of several complex aldehyde-containing bioactive compounds have been realized; thus the approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and bioactive molecules, and should have many applications in medicinal chemistry.

Iodine-catalyzed guanylation of amines with N,N'-di-Boc-thiourea.

Herein, we report that iodine-catalyzed guanylation of primary amines can be accomplished with N,N'-di-Boc-thiourea and TBHP to afford the corresponding guanidines in 40-99% yields. Oxidation of the HI byproduct by TBHP eliminates the need for an extra base to prevent the protonation of substrates and makes the reaction especially useful for both electronically and sterically deactivated primary anilines.

Intraosseous schwannoma of the mobile spine: a report of twenty cases.

PURPOSE: To clarify the clinical features, surgical strategies, and outcomes of intraosseous schwannoma (IOS) of the mobile spine. METHODS: We retrospectively reviewed patients with primary benign spinal schwannoma who underwent surgery in our orthopedic department. RESULTS: A total of 101 patients with primary benign schwannoma located in the mobile spine underwent surgery in our orthopedic department from 2005 to 2015. Twenty-five patients presented with aggressive features. Twenty patients were regularly followed up, twelve with lesions in the cervical spine, six with lesions in the thoracic region, and two with lesions in the lumbar spine. Preoperative CT-guided biopsy was performed in fourteen cases; the accuracy of diagnosis was 100%, and IOS is not histologically different from conventional schwannoma. The computed tomography (CT) scan revealed expansile and osteolytic bone destruction in all these cases, with six patients having pathological fracture. On T2-weighted magnetic resonance imaging, the lobulated schwannomas showed heterogeneous signal intensity and significant heterogeneous enhancement on post-contrast images. Gross total resection was performed in seventeen patients and subtotal resection in three. Tumor-involved nerve roots resection were documented to decrease local recurrence in fourteen cases. The visual analog scale score decreased from 5.66 ± 1.79 preoperatively to 1.16 ± 1.77 at the final follow-up. No local recurrence was noticed at the final follow-up. CONCLUSION: CT-guided biopsy is effective for the preoperative diagnosis of spinal IOS. Total resection is the optimal treatment for IOS, whereas subtotal resection could be an alternative choice for high-risk cases. These slides can be retrieved under electronic supplementary material.

[Galectin3 Regulates Transforming Growth Factor-ß-induced Epithelial-mesenchymal].

Objective To explore the role of Galectin3 in transforming growth factor-ß(TGF-ß)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Methods Galectin3 was over-expressed in an A549 cell line. EMT was induced in lung cancer A549 cells by adding TGF-ß. The expressions of Galectin3,E-cadherin,and vimentin were determined by Western blot. The protein expression of E-cadherin and the morphological changes of the cells were detected by immunofluorescence. Cellular proliferation was analyzed with cell counting kit-8,and the cellular migration and invasion was measured by scratches healing and Transwell assay,respectively.Results When only Galectin3 was over-expressed in A549 cell line,the expression levels of EMT-related proteins such as E-cadherin and vimentin were not changed,and the abilities of cellular proliferation,invasion,and migration were not changed either. When the EMT was induced by TGF-ß in A549 cells,the E-cadherin expression was down-regulated and the vimentin expression was up-regulated in A549 cells with Galectin3 over-expression. There was no significant change in cellular proliferation,whereas the abilities of cellular invasion and migration were enhanced.Conclusion The TGF-ß-induced EMT in A549 cells can be enhanced by Galectin3.

Synthesis of Difluoromethylthioesters from Aldehydes.

Difluoromethylthioester compounds are yet another important kind of organofluorine compound and are reported here for the first time. They can be efficiently synthesized from various aldehydes. The synthetic method features mild reaction conditions, good tolerance of functional groups, broad substrate scope, and importantly, no metal is involved in the reaction. The approach has the potential to become an important tool for the late-stage functionalization of advanced synthetic intermediates, and should have many applications in medicinal chemistry.

Integrin αvß1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or ß1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and ß1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvß1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV.

Intertwined Order and Holography: The Case of Parity Breaking Pair Density Waves.

We present a minimal bottom-up extension of the Chern-Simons bulk action for holographic translational symmetry breaking that naturally gives rise to pair density waves. We construct stationary inhomogeneous black hole solutions in which both the U(1) symmetry and spatially translational symmetry are spontaneously broken at a finite temperature and charge density. This novel solution provides a dual description of a superconducting phase intertwined with charge, current, and parity orders.

Double 1,4-addition of (thio)salicylamides/thiosalicylic acids with propiolate derivatives: a direct, general synthesis of diverse heterocyclic scaffolds.

A simple and practical ring-closure procedure to prepare a range of diverse heterocycles has been developed. In this transformation, a variety of substituted (thio)salicylamides and thiosalicylic acids undergo a double 1,4-addition reaction with propiolate derivatives in the presence of an inorganic base (K3PO4), as a result benzothiazinones, benzoxazinones and benzoxathiinones were prepared in good to excellent yields, respectively, even in gram scales. In addition, further transformation towards more complex structures and oxicam drug analogues has also been successfully carried out.

Promoter methylation and expression of CDH1 and susceptibility and prognosis of eyelid squamous cell carcinoma.

Eyelid skin tumors are the most frequent type of cancer in ophthalmology. And, eyelid squamous cell carcinoma (SCC) accounts for a large part of it. CDH1 encodes E-cadherin, a glycoprotein that plays an important part in cell-cell interaction. Loss of CDH1 function was suspected to be associated with tumorigenesis. Methylation of CDH1 promotors can alter the expression of its protein and is also considered as a contributor to various cancers. In this study, CDH1 methylation and expression profile as well as prognosis of 38 cases of eyelid SCC and the corresponding adjacent tissues were analyzed to clarify the role of CDH1 methylation in SCC carcinogenesis and prognosis. Methylation was detected by PCR, and CDH1 expression was evaluated by immunohistochemistry. We observed that CDH1 methylation is significantly correlated with decreased CDH1 protein expression in eyelid SCC patients. Patients with methylation and low expression of CDH1 are significantly associated with advanced and aggressive phenotypes. Therefore, CDH1 methylation and CDH1 expression are both independent prognostic factors for prognosis of eyelid SCC patients.

Molecular and pathogenicity characterization of Gallid herpesvirus 2 newly isolated in China from 2009 to 2013.

During the course of our continuous surveillance of Gallid herpesvirus 2 (GaHV-2), 44 isolates were obtained from GaHV-2-positive chickens of different flocks in China from 2009 to 2013. The meq gene, considered as a major GaHV-2 oncogene, was sequenced and was found to contain an open reading frame of 1020 nucleotides encoding a 339 amino acid (aa) polypeptide in all isolates. Compared with the GaHV-2 GA strain, the meq genes in 15.9 % (7/44) of the isolates analyzed in this study contained an aa substitution mutation at position 88 (A to T) of which is the first report. The main characteristics of Chinese GaHV-2 isolates meq genes included the substitutions K77E, D80Y, V115A, T139A, P176R, and P217A, and the aa substitution frequency at positions 139 and 176 showed an increase. To test the pathogenicity of the isolates, a pathogenicity study and a vaccination-challenge test were performed on three selected isolates (ZY/1203, WC/1203, and WC/1110) and reference strain GA. The results showed that the three isolates induced gross Marek's disease (MD) lesions in 95.0-100 % cases, which was a higher rate than that obtained for strain GA (82.4 %). Three isolates induced mortality in 10-21.1 % of specific-pathogen-free chickens, which was similar to results with strain GA (23.5 %). The commercially available CVI988 vaccine induced lower protective indices (PIs) against ZY/1203 (82.4) and WC/1110 (83.3) as compared to those against WC/1203 (100) and GA (100). These results showed an evolving trend in the meq genes of the isolates; three isolates exhibited higher morbidity as compared to the reference strain and the vaccine induced lower PIs against two isolates as compared to that against the reference strain.