Search

Withanolides are a group of naturally occurring C 28 steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of O -functional groups has enabled various natural alterations to both the carbocyclic skeleton and the side chain. Consequently, these molecules have intricate structural features that lead to their highly varied display of biological activities including anticancer, anti-inflammatory, and immunomodulating properties. Despite being intriguing leads for further discovery research, synthetic access to the withanolides remains highly challenging-compounds for current biological research are mainly isolated from plants, often inefficiently. Here, we report the divergent synthesis of 11 withanolides in 12 to 20 steps, enabled by a gram-scale route and a series of late-stage functionalizations, most notably a bioinspired photooxygenation-allylic hydroperoxide rearrangement sequence. This approach enables further biological research disconnected from a reliance on minute quantities of the parent natural products or their simple derivatives.

Einstein-Podolsky-Rosen (EPR) steering is commonly shared among multiple observers by utilizing unsharp measurements. Nevertheless, their usage is restricted to local measurements and does not encompass all nonlocal measurement-based cases. In this work, a method for finding beneficial local measurement settings has been expanded to include nonlocal measurement cases. This method is applicable for any bipartite state and offers benefits even in scenarios with a high number of measurement settings. Using the Greenberger-Horne-Zeilinger state as an illustration, we show that employing unsharp nonlocal measurements can activate the phenomenon of steering sharing in contrast to using local measurements. Furthermore, our findings demonstrate that nonlocal measurements with unequal strength possess a greater activation capability compared to those with equal strength. Our activation method generates fresh concepts for conservation and recycling quantum resources., (© 2024. The Author(s).)

An increased interest to expand three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared with their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) centre to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange chemistry has enabled the development of the enantiopure bifunctional S(VI) transfer reagent t-BuSF to overcome current synthetic limitations. Here, we disclose a reagent platform that serves as a chiral sulfur fluorine exchange template for the rapid asymmetric synthesis of over 70 sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiomeric excess and good overall yields. Furthermore, the practical utility of the bifunctional S(VI) transfer reagent was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogues., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans -dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to β-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac) 3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee)., (© 2023 Wiley-VCH GmbH.)

Objective: This study aims at assessing the potential benefits of observation of monocyte-to-albumin ratio (MAR) and neutrophil percentage-to-hemoglobin ratio (NPHR) in the detection of non-small cell lung cancer (NSCLC)., Methods: This study retrospectively involved 195 NSCLC patients and 204 healthy volunteers. The correlations between the clinicopathological characteristics of NSCLC and the two ratios including MAR and NPHR were assessed. The diagnostic efficiency of NSCLC patients by MAR and NPHR, alone or in combination with carcinoembryonic antigen (CEA), was assessed by receiver operating characteristic (ROC) curve. The risk factors for NSCLC were analyzed with binary logistic regression., Results: Compared to healthy controls, the levels of MAR and NPHR in NSCLC patients were elevated. MAR and NPHR were related to clinicopathologic characteristics and increased significantly along with the progression of NSCLC. The area under the curve (AUC) for 95% confidence interval (95% CI) of MAR and NPHR in the diagnosis of NSCLC was 0.812 (0.769-0.854) and 0.724 (0.675-0.774), respectively. The combination of MAR, NPHR, and CEA achieved the highest diagnostic utility compared to each individually or combined markers (AUC, 0.86; 95% CI, 0.824-0.896; sensitivity, 72.8%; specificity, 87.3%). Further analysis showed that MAR combined with NPHR presented the potential to detect early-stage (IA-IIB) NSCLC (AUC, 0.794; 95% CI, 0.743-0.845; sensitivity, 55.1%; specificity, 87.7%). The result indicated that MAR and NPHR might be risk factors for NSCLC., Conclusion: MAR and NPHR could be novel and effective auxiliary indexes in the detection of NSCLC, especially when combined with CEA., Competing Interests: The authors did not report any exist potential conflict of interest associate with this study., (© 2023 Zhao et al.)

SNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16 INK4A -independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer., (© 2023. The Author(s).)

The present study aimed to evaluate the potential of the monocyte to red blood cell count ratio (MRR), the neutrophil to red blood cell count ratio (NRR), the lymphocyte to red blood cell count ratio (LRR) and the product of lymphocyte count and albumin concentration (LA) for the diagnosis of lung cancer. The cases of 216 patients with newly diagnosed lung cancer and 184 healthy volunteers were retrospectively analysed. The MRR and NRR were found to be higher in patients with lung cancer compared with those in healthy controls, while the LRR and LA were lower. The receiver operating characteristic curve analysis revealed that of the four markers, the MRR and LA yielded a higher area under the curve (AUC) (MRR: AUC, 0.810; 95% CI, 0.768-0.847; and LA: AUC, 0.721; 95% CI, 0.674-0.764). The combination of MRR, LA, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) achieved the highest diagnostic value when compared with other single or combined markers (AUC, 0.882; 95% CI, 0.846-0.912; sensitivity, 81.9%; specificity, 81.0%). As the disease progressed, the MRR tended to increase, while LA exhibited a decreasing trend. Binary logistic regression analysis revealed an increase in the MRR, as well as in CEA and CYFRA21-1 concentrations, and a decrease in the LA, which could all be possible risk factors for lung cancer. Differences in the MRR and LA between patients with early stage (IA-IIIA) lung cancer and healthy controls were observed. Further analysis revealed that the MRR also exhibited the potential to detect early stage (IA-IIIA) lung cancer in the model. The present findings demonstrated that the MRR and LA may be used as auxiliary biomarkers for the diagnosis of lung cancer and could partly indicate disease progression., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Chen et al.)

In order to comprehensively and systematically analyze the reasons why antioxidant inhibitors can scavenge free radicals in coal and inhibit coal spontaneous combustion, this paper studies the effects of VC, TBHQ, EGCG and BHT on coal spontaneous combustion by means of coal spontaneous combustion characteristics experiments and quantum chemical simulation methods. The low-temperature oxidation characteristics of coal were studied through temperature-programmed experiments. The results showed that the CO emission of coal samples with antioxidants was significantly lower than that of raw coal. At 170 °C, the maximum decrease was 37.74%. Fourier infrared test showed that compared with the coal samples without antioxidant treatment, the adsorption strength of hydroxyl structure and oxygen-containing functional groups of the treated coal samples was significantly reduced. The area percentages of hydroxyl and methylene changed significantly, decreased by 7.14% and 6.46%, respectively. Subsequently, molecular models of four antioxidants were constructed using quantum chemical theory, and their Mulliken charges, BDE values ​and frontier orbitals were calculated according to density functional theory (DFT), and the active sites and inhibition mechanisms of antioxidants were discussed. The results showed that H 9 of VC, H 33 of EGCG, H 1 of TBHQ and H 40 of BHT all had strong ability to scavenge oxygen-containing free radicals, and their order of strength was TBHQ > BHT > EGCG > VC. Antioxidant inhibitors mainly reduce the number of active free radicals by removing the peroxide groups in the initial stage of the coal oxygen reaction, and remove the hydroxyl groups to prevent the further spontaneous combustion of coal and inhibit the low temperature oxidation process of coal., (© 2022. The Author(s).)

Synthetic lethality is a genetic interaction that results in cell death when two genetic deficiencies co-occur but not when either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic-lethal interactions by virtue of their redundant functions. Here, we demonstrate a paralog-based synthetic lethality by targeting vaccinia-related kinase 1 (VRK1) in glioblastoma (GBM) deficient of VRK2, which is silenced by promoter methylation in approximately two thirds of GBM. Genetic knockdown of VRK1 in VRK2-null or VRK2-methylated cells resulted in decreased activity of the downstream substrate barrier to autointegration factor (BAF), a regulator of post-mitotic nuclear envelope formation. Reduced BAF activity following VRK1 knockdown caused nuclear lobulation, blebbing, and micronucleation, which subsequently resulted in G2-M arrest and DNA damage. The VRK1-VRK2 synthetic-lethal interaction was dependent on VRK1 kinase activity and was rescued by ectopic expression of VRK2. In VRK2-methylated GBM cell line-derived xenograft and patient-derived xenograft models, knockdown of VRK1 led to robust tumor growth inhibition. These results indicate that inhibiting VRK1 kinase activity could be a viable therapeutic strategy in VRK2-methylated GBM., Significance: A paralog synthetic-lethal interaction between VRK1 and VRK2 sensitizes VRK2-methylated glioblastoma to perturbation of VRK1 kinase activity, supporting VRK1 as a drug discovery target in this disease., (©2022 The Authors; Published by the American Association for Cancer Research.)

Six new halogenated butenolides, tongalides A-C ( 1 - 3 ) and their acetylated congeners ( 4 - 6 ), were isolated from an extract of the Antarctic rhodophyte Delisea sp. that displayed significant antibiotic activity. The structures of the compounds were determined by analysis of data acquired by spectroscopic and spectrometric techniques including NMR, HRESIMS, optical rotation, and X-ray diffraction studies. The newly isolated compounds were assayed for antibacterial activity, but exhibited no growth inhibition of ESKAPE pathogens. The extract bioactivity was attributed to the previously reported Z -acetoxyfimbrolide A also isolated from the extract, providing further evidence that the exocyclic double bond is essential to the antibacterial activity of the structurally related fimbrolide class of metabolite.

Chirality is one of the most important intrinsic properties of (supra)molecules. In this study, we obtained enantiomeric metallo-supramolecular octahedra without using any chiral sources. Such cages were self-assembled by prochiral trispyridine ligand L based on a C 3h truxene core and Cu II salts. Crystallization of the cages with BF 4 - as counterions afforded racemate crystals; while crystallizations of cages with ClO 4 - and OTf - as counterions resulted in conglomerates with spontaneous resolution. Three types of chirality were observed in each cage, including planar chirality of the truxene core, axial chirality from the pyridyl and truxene moieties, and propeller chirality of the pyridyl-Cu II coordination sites. The cages reported here are among the largest discrete synthetic metallo-supramolecules ever reported with chiral self-sorting behavior. Remarkably, the chiral cages exhibited very slow racemization even at low concentrations, suggesting their high stability in solution., (© 2022 Wiley-VCH GmbH.)

Mind wandering has been argued to be beneficial for breaking through mental impasses, which leads to better creative performance upon a second attempt (i.e., the incubation effect). However, the evidence is inconsistent. Different from the propensity for mind wandering that has been the focus of past studies, in this study we further examined the role of diversity (i.e., non-repetitiveness of mind wandering respective to its content) and types of mind wandering along the dimensions of intentionality and awareness during incubation when engaging in a 0-back task (a mind wandering-prone condition) and a focused-breathing practice (a mindfulness-induced condition). We proposed that diversity rather than the propensity for mind wandering was crucial for post-incubation divergent creativity and that mindfulness induction would be a more effective way to elicit the incubation effect because it should result in fewer but more diverse mind-wandering incidents than engaging in a mind wandering-prone task. We conducted an experiment with a between-participant variable (incubation tasks: mind wandering-prone, mindfulness-induced, and no incubation). As predicted, the mindfulness-induced group (N = 30) outperformed the control group (N = 31) on flexibility for the unusual uses task measuring divergent thinking after incubation, but the mind wandering-prone group (N = 29) did not outperform the control group. In addition, the diversity of mind wandering and the tendency toward intentional mind wandering predicted the magnitude of incubation effects on flexibility and originality, respectively. Theoretical and practical implications are discussed., Competing Interests: The authors have declared that no competing interests exist.

A new class of stable four-coordinated benzotriazole-borane compounds was developed via gold-catalyzed alkyne hydroboration. The application of polymeric (BH 2 CN) n reagent gave the formation of cyano-amine-boranes (CAB) complexes with less basic N-heterocyclic amines and anilines. Various new CABs were investigated in catalytic hydroboration to synthesize N-B cycles. The 1,2,3-benzotriazoles were identified as the only feasible N-source, giving the four coordinated borane N-B cycles (BTAB) in excellent yields (up to 90%) with good functional group tolerability. This new class of polycyclic N-B compounds showed excellent stability toward acid, base, high temperature, and photo-irradiation. The facile synthesis, excellent stability, strong and tunable fluorescence emission make BTAB interesting new fluorescent probes for future chemical and biological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In nature as well as life systems, the presence of asymmetrical and dissymmetrical structures with specific functions is extremely common. However, the construction of metallo-supramolecular assemblies based on dissymmetrical ligands still remains a considerable challenge for avoiding the generation of unexpected isomers with similar thermodynamic stabilities, especially for three-dimensional supramolecular structures. In this study, a strategy for the conformational control of metallo-supramolecular cages via the enhancement of ligand dissymmetry was proposed. Four dissymmetrical ditopic ligands were designed and synthesized. By increasing the dissymmetry of length or angle, conformations of assemblies were precisely controlled to form discrete cis-Pd n L 2n molecular cages., (© 2021 Wiley-VCH GmbH.)

Biomimetic metal-organic frameworks have attracted great attention as they can be used as bio-inspired models, allowing us to gain important insights into how large biological molecules function as catalysts. In this work, we report the synthesis and utilization of such a metal-metalloporphyrin framework (MMPF) that is constructed from a custom-designed ligand as an efficient halogen bond donor catalyst for Diels-Alder reactions under ambient conditions. The implementation of fabricated halogen bonding capsule as binding pocket with high-density C-Br bonds enabled the use of halogen bonding to facilitate organic transformations in their three-dimensional cavities. Through combined experimental and computational studies, we showed that the substrate molecules diffuse through the pores of the MMPF, establishing a host-guest system via the C-Br⋅⋅⋅π interaction. The formation of halogen bonds is a plausible explanation for the observed boosted catalytic efficiency in Diels-Alder reactions. Moreover, the unique capability of MMPF highlights new opportunities in using artificial non-covalent binding pockets as highly tunable and selective catalytic materials., (© 2021 Wiley-VCH GmbH.)

Extending the structural hierarchy and complexity through small-molecular self-assembly is a powerful way to obtain large discrete, functional molecular architecture. A hydrogen-bonded supramolecular organic framework (H S OF) with nanometer-size pores is constructed in a solid state with simple guanosine-monomer self-assembly. To extend the hierarchy of the G-quartet self-assembly to a higher order thanthatofthetraditionalG-quadruplex,H-bondacceptorsontheC-8 position of guanosine are introduced to establish inter-quadruplex linkage via H bonding to N(2)-H B from the neighboring G-quartet. After screening different C-8 substitution groups and various synthesis conditions, H S OF-G1a' is obtained by solvent evaporation under diluted condition. Single-crystal X-ray structure reveals that cubic repeating units formed by G 8 are the supermolecule secondary building block (SBU) with large pores (d=34A). To our knowledge, this is the first G-quartet self-assembly with an organized structure beyond cylindrical G-quadruplexes., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

A helical metal-organic framework was prepared by using a conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups were applied to introduce atropic repulsion, thereby allowing the formation of extended frameworks for the first time. With this new ligand design, a helical-shaped MOF with significantly improved air and moisture stability was successfully prepared, thus providing a new strategy for ligand design toward porous material constructions., (© 2021 Wiley-VCH GmbH.)

Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water., (© 2021 Wiley-VCH GmbH.)

Systematic investigations were performed with various substituted groups at C8 purine and ribose. A series of isoG analogs, C8-phenyl substituted isoG were synthesized and applied for Cs + coordination. The structural proximity between purine and ribose limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, deoxy isoG derivative with modification on ribose ( tert -butyldimethylsilyl ether) was applied to assemble with the Cs + cation. Critical solvent (CDCl 3 and CD 3 CN) and anion (BPh 4 - , BARF - , and PF 6 - ) effects were revealed, leading to the controllable formation of various stable isoG pentaplexes, including singly charged decamer, doubly charged decamer, and 15-mer, etc. Finally, the X-ray crystal structure of [isoG 20 Cs 3 ] 3+ (BARF - ) 3 was successfully obtained, which is the first example of multiple-layer deoxy isoG binding with the Cs + cation, providing solid evidence of this new isoG ionophore beyond two-layer sandwich self-assembly., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here we report the first example of alkyne trifunctionalization through simultaneous construction of C-C, C-O, and C-N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl-gold nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both electrophiles (N source) and oxidants (C source). Vinyl-gold(III) intermediates were revealed as effective nucleophiles toward diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature or 40 °C).

Purpose: To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells., Methods: The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the combination of PYM with anti-PD-1 antibody. The ELISA kits were used to quantify the ICD related ATP and HMGB1 levels. The Transwell assay was conducted to determine the chemotaxis ability of THP-1 cell in vitro. The flow cytometry was used to measure reactive oxygen species level and analyze the ratio of immune cell subsets., Results: PYM induced ICD in murine 4T1 breast cancer and B16 melanoma cells and increased the release of nucleic acid fragments that may further promote the monocytic chemotaxis. In the 4T1 murine breast cancer model, PYM alone, anti-PD-1 antibody alone, and their combination suppressed tumor growth by 66.3%, 16.1% and 77.6%, respectively. PYM markedly enhanced the therapeutic efficacy of anti-PD-1 antibody against 4T1 breast cancer. The calculated CDI (coefficient of drug interaction) indicated synergistic effect. Evaluated by graphic analysis, the nucleated cells intensity in the femur bone marrow remained unchanged. Histopathological observations revealed no noticeable toxico-pathological changes in the lung and various organs, indicating that the PYM and anti-PD-1 antibody combination exerted enhanced efficacy at well-tolerated dosage level. By the combination treatment, a panel of immunological changes emerged. The ratio of CD3 + cells, NK cells and NKT cells increased and Tregs decreased in peripheral blood. The DCs increased in the spleen. Prominent changes occurred in tumor infiltrating lymphocytes. The ratio of CD8 + cells increased, while that of CD4 + cells decreased; however, the ratio of CD3 + cells remained unchanged, implying that certain immunological responses emerged in the tumor microenvironment. PYM alone could also increase CD8 + cells and reduce CD4 + cells in tumor infiltrating lymphocytes., Conclusions: The studies indicate that PYM, as an ICD inducer with mild myelosuppression effect, may enhance the therapeutic efficacy of anti-PD-1 antibody in association with tumor infiltrating CD8 + T cell augmentation.

Porous materials with open metal sites have been investigated to separate various gas mixtures. However, open metal sites show the limitation in the separation of some challenging gas mixtures, such as C 2 H 2 /CO 2 . Herein, we propose a new type of ultra-strong C 2 H 2 nano-trap based on multiple binding interactions to efficiently capture C 2 H 2 molecules and separate C 2 H 2 /CO 2 mixture. The ultra-strong acetylene nano-trap shows a benchmark Q st of 79.1 kJ mol -1 for C 2 H 2 , a record high pure C 2 H 2 uptake of 2.54 mmol g -1 at 1×10 -2  bar, and the highest C 2 H 2 /CO 2 selectivity (53.6), making it as a new benchmark material for the capture of C 2 H 2 and the separation of C 2 H 2 /CO 2 . The locations of C 2 H 2 molecules within the MOF-based nanotrap have been visualized by the in situ single-crystal X-ray diffraction studies, which also identify the multiple binding sites accountable for the strong interactions with C 2 H 2 ., (© 2021 Wiley-VCH GmbH.)

Extended tetratopic benzoic acid ligands with "orthogonal-twisted-arms" conformations were designed and synthesized for the construction of new MOF structures (OTA-MOF). Upon coordination with Cd 2+ and Cu 2+ cations, two well-defined new MOFs were prepared. X-ray single crystal structures were successfully obtained, demonstrating the formation of a new topology (4,4,4-c). The OTA2-MOF-Cu gave moderate stability in organic solvents and good gas sorption ability toward CO 2 . This new MOF showed superior catalytic reactivity toward the epoxide-CO 2 cycloaddition, giving >50 folds yield enhancement over the controlled reaction without MOF. It is expected that this new ligand design, porous structure, and excellent CO 2 catalytic reactivity will make OTA-MOF promising new materials for applications in catalysis and separation., (© 2020 Wiley-VCH GmbH.)

The separation of xylene isomers (para-, meta-, orth-) remains a great challenge in the petrochemical industry due to their similar molecular structure and physical properties. Porous materials with sensitive nanospace and selective binding sites for discriminating the subtle structural difference of isomers are urgently needed. Here, we demonstrate the adaptively molecular discrimination of xylene isomers by employing a NbOF 5 2- -pillared metal-organic framework (NbOFFIVE-bpy-Ni, also referred to as ZU-61) with rotational anionic sites. Single crystal X-ray diffraction studies indicate that ZU-61 with guest-responsive nanospace/sites can adapt the shape of specific isomers through geometric deformation and/or the rotation of fluorine atoms in anionic sites, thereby enabling ZU-61 to effectively differentiate xylene isomers through multiple C-H···F interactions. ZU-61 exhibited both high meta-xylene uptake capacity (3.4 mmol g -1 ) and meta-xylene/para-xylene separation selectivity (2.9, obtained from breakthrough curves), as well as a favorable separation sequence as confirmed by breakthrough experiments: para-xylene elute first with high-purity (≥99.9%), then meta-xylene, and orth-xylene. Such a remarkable performance of ZU-61 can be attributed to the type anionic binding sites together with its guest-response properties.

To offset the environmental impact of platinum-group element (PGE) mining, recycling techniques are being explored. Porous organic polymers (POPs) have shown significant promise owing to their selectivity and ability to withstand harsh conditions. A series of pyridine-based POP nanotraps, POP-Py, POP-pNH 2 -Py, and POP-oNH 2 -Py, have been designed and systematically explored for the capture of palladium, one of the most utilized PGEs. All of the POP nanotraps demonstrated record uptakes and rapid capture, with the amino group shown to be vital in improving performance. Further testing on the POP nanotrap regeneration and selectivity found that POP-oNH 2 -Py outperformed POP-pNH 2 -Py. Single-crystal X-ray analysis indicated that POP-oNH 2 -Py provided a stronger complex compared to POP-pNH 2 -Py owing to the intramolecular hydrogen bonding between the amino group and coordinated chlorine molecules. These results demonstrate how slight modifications to adsorbents can maximize their performance., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An electrochemical approach in promoting directed C-H alkynylation with terminal alkyne via iridium catalysis is reported. This work employed anodic oxidation of Ir(III) intermediate (characterized by X-ray crystallography) to promote reductive elimination, giving the desired coupling products in good yields (up to 95%) without the addition of any other external oxidants. This transformation is suitable for various directing groups with H 2 as the only by-product, which warrants a high atom economy and practical oxidative C-C bond formation under mild conditions., Competing Interests: The authors claim no competing financial interest.

A synergistic gold/iron catalytic system was developed for sequential alkyne hydration and vinyl gold addition to aldehydes or ketones. Fe(acac) 3 was identified as an essential co-catalyst in preventing vinyl gold protodeauration and facilitating nucleophilic additions. Effective C-C bond formation was achieved under mild conditions (r.t.) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). Extending reaction scope to intramolecular fashion achieved successful macrocyclization (16-31 ring sizes) with excellent yields (up to 90%, gram-scale) without extended dilution (0.2 M), which highlighted the great potential of this new crossed-aldol strategy in challenging target molecule synthesis., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

A donor/acceptor diazo activation strategy, processing via condensation using diazonium salts without the addition of any other catalysts or reagents, is reported. The diazenium intermediate was found to undergo cyclization to give indazoles in excellent yields. Alternatively, in the presence of nitriles, substituted 1,2,4-triazoles were obtained in good to excellent yields. This interesting diazenium route provides a new approach to achieve complex heterocycle synthesis under mild conditions.

In this report, we describe the synthesis of two porphyrin-containing Pt(II) supramolecular assemblies via coordination-driven self-assembly. X-ray crystallographic analysis on one assembly reveals that the metalla-assembly formation imposes large interchromophore distances, leading to a higher 1 O 2 generation efficiency, relative to the corresponding small molecular precursors. The metalla-assemblies were examined as photosensitizers for photodynamic therapy as the potential reduction of the unfavorable self-aggregation phenomenon. In vivo and in vitro investigations demonstrate that the metalla-assemblies exhibit enhanced anticancer activity with minimal dose requirement and side effects comparable to the small molecule precursors. Thus, our work demonstrates that self-assembly provides a promising methodology for enhancing the therapeutic effectiveness of anticancer agents.

Gold-catalyzed alkyne and allene diselenations were developed. Excellent regioselectivity (trans) and good to excellent yields were achieved (up to 98 % with 2 % catalyst loading) with a wide range of substrates. Mechanistic investigation revealed the formation of a vinyl gold(I) intermediate followed by an intermolecular selenium cation migration, suggesting that a gold(I/III) redox process was successfully implemented under mild conditions., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, for the first time, we present the successful synthesis of a novel two-dimensional corrole-based covalent organic framework (COF) by reacting the unusual approximately T-shaped 5,10,15-tris(p-aminophenyl)corrole H 3 TPAPC with terephthalaldehyde, which adopts desymmetrized hcb topology and consists of a staggered AB stacking structure with elliptical pores. The resultant corrole-based COF, TPAPC-COF, exhibits high crystallinity and excellent chemical stability. The combination of extended π-conjugated backbone and interlayer noncovalent π-π interactions endows TPAPC-COF with excellent absorption capability in the entire visible-light and even near-infrared regions. Moreover, this work suggests the promise of TPAPC-COF as a new class of photoactive material for efficient singlet-oxygen generation with potential photodynamic therapy application as demonstrated by in vitro anticancer studies., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Previous studies have demonstrated the diagnostic value of glucose transporter 1 (GLUT-1) to distinguish malignant mesothelioma (MM) from reactive mesothelial cells (RMC), but the results are inconsistent. The purpose of this meta-analysis is to investigate the diagnostic accuracy of GLUT-1 in distinguishing MM from RMC. Methods: A systematical search was conducted until May 2019 in PubMed, Medline, Embase and the Cochrane Library. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess the quality of the eligible studies. The Stata15 and Review Manager5.3 software programmes were used to perform the meta-analysis. Results: A total of 24 studies, including 969 MM patients and 1080 RMC individuals were explored in the meta-analysis. The summary assessments revealed that the pooled sensitivity was 0.73 (95% CI, 0.62-0.81) and the pooled specificity was 0.95 (95% CI, 0.91-0.98). The area under the summary ROC curve (AUC) was 0.93 (95% CI: 0.91-0.95). Conclusions: GLUT-1 is highly accurate to distinguish MM from RMC.

Due to the high oxidation potential between Au I and Au III , gold redox catalysis requires at least stoichiometric amounts of a strong oxidant. We herein report the first example of an electrochemical approach in promoting gold-catalyzed oxidative coupling of terminal alkynes. Oxidation of Au I to Au III was successfully achieved through anode oxidation, which enabled facile access to either symmetrical or unsymmetrical conjugated diynes through homo-coupling or cross-coupling. This report extends the reaction scope of this transformation to substrates that are not compatible with strong chemical oxidants and potentiates the versatility of gold redox chemistry through the utilization of electrochemical oxidative conditions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The corrole unit from the porphyrinoid family represents one of the most important ligands in the field of coordination chemistry, which creates a unique environment allowing for the observation of unusual electronic states of bound metal cations and has shown great promise in various applications. Nevertheless, studies that directly and systematically introduce these motifs in porous crystalline materials for targeting further functionalizations are still lacking. Herein, we report for the first time the construction of two robust corrole-based metal-organic frameworks (MOFs), M 6 (μ 3 -O) 4 (μ 3 -OH) 4 (OH) 3 (H 2 O) 3 (H 3 TCPC) 3 (M = Zr for Corrole-MOF-1 and M = Hf for Corrole-MOF-2 , H 3 TCPC = 5,10,15-tris( p -carboxylphenyl)corrole), which are assembled by a custom-designed C 2 ν -symmetric corrolic tricarboxylate ligand and the unprecedented D 3 d -symmetric 9-connected Zr 6 /Hf 6 clusters. The resultant frameworks feature a rare (3,9)-connected gfy net and exhibit high chemical stability in aqueous solutions within a wide range of pH values. Furthermore, we successfully prepared the cationic Corrole-MOF-1(Fe) from the iron corrole ligand, which can serve as an efficient heterogeneous catalyst for [4 + 2] hetero-Diels-Alder reactions between unactivated aldehydes and a simple diene, outperforming both the homogeneous counterpart and the porphyrinic MOF counterpart.

Precise control of the outer-sphere environment around the active sites of heterogeneous catalysts to modulate the catalytic outcomes has long been a challenge. Here, we demonstrate how this can be fulfilled by encapsulating catalytic components into supramolecular capsules, used as building blocks for materials synthesis, whereby the microenvironment of each active site is tuned by the assembled wall. Specifically, using a cationic template equipped with a polymerizable functionality, anionic ligands can be encapsulated by ion pair-directed supramolecular assembly, followed by construction into porous frameworks. The hydrophilic ionic wall enables reactions to be achieved in water that usually requires organic solvents and also facilitates the enrichment of the substrate into the hydrophobic pocket, leading to superior catalytic performances as demonstrated by the industrially relevant hydroformylation. Remarkably, the formation of the supramolecular assembly and catalyst encapsulation further engenders reaction selectivity, which reaches an even greater extent after construction of the porous framework.

Previously, we reported that N-2-aryl triazoles (NATs) exhibited good fluorescence activity in the UV/blue light range. In an effort to achieve biocompetitive NAT fluorophores with green/yellow emission, a new class of 4-keto-2-(4'-N,N-diphenyl)-phenyl triazoles were designed and synthesized. Herein, we present our study on these novel fluorophores which demonstrated excellent luminescence emission both in solution (Φ up to 96%) and in the solid state (Φ up to 43%). Furthermore, these new compounds showed aggregation-induced emission (AIE) properties and reversible mechanochromic luminescence properties, which suggested their potential applications in chemical and materials science.

With the objective of investigating the characteristics influencing high-risk sexual behaviours in elderly men (60-74 years of age) in Chongqing, China, a total of 1433 healthy elderly men with sexual intercourse frequencies of one to six times/month who were willing to participate in the questionnaires were studied at four hospitals. We measured serum testosterone levels and performed follow-ups every six months, with a total of 1128 elderly men followed up after two years. We also investigated socio-economic and demographic characteristics (age, education, income, location, marital status and number of marriages), types of sexual partners, age differences with fixed sexual partners, frequency of sexual intercourse, combined basic age-related diseases, sexually transmitted infections (STIs) education, elderly self-care ability and high-risk sexual behaviours (frequency of sexual intercourse and number of sexual partners) using questionnaires. We analysed the influencing factors of high-risk sexual behaviours in elderly men using a univariate analysis, multivariate logistic regression analysis, BP neural network prediction and cluster analysis. Finally, we found that serum total testosterone, age, types of sexual partners, age differences with fixed partners and frequency of sexual intercourse are five factors that influence high-risk sexual behaviours in elderly men.

Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.

Silver nanowires with high yield, uniform size and high aspect ratio were successfully synthesized by a simple and effective polyol method under low temperature and quiescent conditions, adopting CuCl2·2H2O as the nucleation control agent for the first time. The synthesized silver nanowires were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Vis diffuse reflectance spectroscopy (DRS). The results indicate that the silver nanowires were composed of face-centered cubic structure of pure metallic silver with high crystallinity. And the silver nanowires have an average length of 80~100 μm and an average diameter of 40~80 nm. Thus, the aspect ratio of the nanowires was greater than 1000. In addition, the influence on the morphology and structure of the silver nanowires were investigated for reaction temperature, mole ratio of PVP:AgNO3, molecular weight of PVP and mole ratio of control agent CuCl2 · 2H2O:AgNO3. Finally, the optimum reaction condition were obtained for the preparation of the silver nanowires with high aspect ratio.

The present study examines how a person's working memory capacity (WMC) and awareness of change in context influences modulating inhibitory control. Context was manipulated by changing the predictive validity of a prime to a following target (i.e., the proportion of prime repetition) across three phases in a single-prime negative priming task. The prime was a distractor for the following target when the proportion was 25% (in the first and third phases) and a useful cue when the proportion rose to 75% (in the second phase). Participants' WMCs were measured and whether they were aware of the change of the prime-repetition proportion was determined in interviews at the end of the experiment. We found that when the stimulus-onset asynchrony (SOA) was short (Experiment 1), participants aware of the change of prime-repetition proportion showed a null negative priming effect when the contingency increased from 25% to 75%, and then rebooted the effect when it decreased back to 25%, thus indicating an ability to modulate inhibitory control as context varied. In contrast, the unaware participants kept inhibiting primes all the time. When SOA was long (Experiment 2), participants with awareness even showed a positive priming effect when the prime-repetition proportion increased. Surprisingly, participants' WMCs did not matter except for the conscious strategy used in the long-SOA condition. This is the first study simultaneously investigating how WMC and awareness can affect people's ability to modulate inhibitory control and reveals that awareness plays a more direct role in such modulation than does WMC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Overexpression of EGFR and MMP-2 plays an essential role in the initiation and progression of non-small-cell lung carcinoma (NSCLC). In this study, a novel format of EGFR/MMP-2 bi-targeted fusion protein Ec-LDP-TIMP2 and its enediyne-integrated analogue Ec-LDP(AE)-TIMP2 have been prepared by genetic engineering and molecular reconstitution. The Ec-LDP(AE)-TIMP2 comprises endogenous inhibitor of matrix metalloproteinase 2 (TIMP2), EGF-derived oligopeptide (Ec), lidamycin apoprotein (LDP), and the extremely potent cytotoxic enediyne (AE). By tissue microarray, Ec-LDP-TIMP2 showed high binding intensity and selectivity to human NSCLC specimens as compared with the matched non-cancerous tissues. By in vivo imaging, Ec-LDP-TIMP2 displayed prominent tumor-specific distribution in human NSCLC H460 xenograft. Particularly, Ec-LDP(AE)-TIMP2 inhibited tumor growth of H460 xenograft in athymic mice more striking. At doses of 0.2 and 0.4mg/kg, Ec-LDP(AE)-TIMP2 suppressed tumor growth by 74% and 89%, respectively. No histopathological changes were found in various organs of treated animals, suggesting that the effective dosage was tolerated. In summary, the ligand-based and enediyne-integrated fusion protein displaying extremely potent cytotoxicity might be highly effective for NSCLC therapy and useful as a carrier for drug delivery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Two novel cyclic hexapeptides designated actinosynneptides A (1) and B (2), together with three tryptophan containing diketopiperazines, namely cyclo(L-Trp-L-Trp) (3), cyclo(L-Trp-N-MeL-Trp) (4), and cyclo(N-MeL-Trp-N-MeL-Trp) (5), were isolated from the culture of the genetically engineered strain HGF052::asm18 derived from Actinosynnema pretiosum ATCC31565. Their structures were elucidated on the basis of spectroscopic analyses and single-crystal X-ray diffractions. Compound 1 is the first example of 3-amino-6-hydroxy-2-piperidone-containing cyclic peptides, and 1 and 2 showed moderate cytotoxic activities against HeLa and PC3 cell lines.

A convenient synthetic method for the construction of morpholine derivatives from easily available aziridines and propargyl alcohols has been successfully developed. A tandem nucleophilic ring-opening of aziridine/6-exo-dig cyclization/double bond isomerization sequence was achieved by using a single gold(i) catalyst under mild conditions. The gold(i) catalyst served as a π acid and also a σ acid to realize the dual activation of both reactants in this reaction. The obtained unsaturated morpholine products could be easily hydrogenated to achieve target morpholine derivatives with good diastereoselectivities in high yields.

In this study, the complete mitochondrial genome sequence of bearded pig, Sus barbatus, with the total length of 16,480 bp, is determined for the first time. This mitogenome harbors 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region (D-loop). The overall base composition is A (34.80%), C (26.07%), G (13.12%), and T (26.01%), so the slight A-T bias (60.81%) was detected. Most of the genes are distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes. To obtain the phylogenetic relationship of the Cetartiodactyla, 11 mitochondrial genomes were used for phylogenetic analysis. The mitochondrial genome of S. barbatus presented here will contribute to a better understanding of the population genetics.

The short-term training effects on various executive functions (EFs) by a movement-based contemplative practice (MBCP) are examined. Three aspects of EFs (working memory capacity, inhibition, switching) are assessed before and after a month-long 12-h training period using Body-Mind Axial Awareness (BMAA) principles that Confucius followers have practiced for more than 2000years. A mindfulness-based practice (Chan-meditation) and a waiting-list control group served as contrast groups. Our results showed that the BMAA group performed better on the task that measured working memory capacity than did the Chan-meditation and the waiting-list groups after training. In addition, the Chan-meditation groups outperformed the control group on attentional switching, a novel finding for this kind of practice. Our findings not only show a new effect of short-term MBCPs on EFs, but also indicate movement-based and mindfulness-based contemplative practices might benefit development of various aspects of EFs in different ways., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To investigate the possible contribution of GDNF in matrix-degrading, cell-adhesion during perineural invasion (PNI) of salivary adenoid cystic carcinoma (ACC)., Methods: Totally 42 ACCs and 5 normal salivary tissues were included in the present study．Immunohistochemical staining SP method was used to detect the expression of GDNF,MMP-9,NF-κB,integrin β1 in ACC specimens and normal salivary tissues. Statistical analysis was performed using SPSS16.0 software package. RESULTS：GDNF was strongly expressed in ACC tumor cells and nerve fibers adjacent to ACC tumor cells. NF-κB, MMP-9, integrin β1 were positively expressed in ACC cell cytoplasm, integrin β1 was also found in ACC cell membrane, and NF-κB in nuclei occasionally. The positive expression rate was 69.05%（29/42）,66.67%（28/42）,61.90%（26/42）, respectively. The differences between the expression of NF-κB, MMP-9, integrinβ1 in PNI group and non-PNI group were significant (P=0.005,P=0.011,P=0.001, respectively). Expression of NF-κB, MMP-9, integrin β1 was correlated to that of GDNF(r=0.443, P=0.003; r=0.401, P=0.009; r=0.535, P=0.000, respectively). Expression of MMP-9 and integrin β1 was positively correlated to that of NF-κB(r=0.501, P=0.001; r=0.429, P=0.005). Expression of MMP-9 was correlated positively to that of integrin β1 (r=0.381, P=0.013). CONCLUSIONS：GDNF may increase the matrix-degrading and cell-adhesion of ACC in the process of PNI. NF-κB, MMP-9 and integrin β1 involve in ACC cells invading nerves.

Quantum phase transition is one of the most interesting aspects in quantum many-body systems. Recently, geometric quantum discord has been introduced to signature the critical behavior of various quantum systems. However, it is well-known that topological quantum phase transition can not be described by the conventional Landau's symmetry breaking theory, and thus it is unknown that whether previous study can be applicable in this case. Here, we study the topological quantum phase transition in Kitaev's 1D p-wave spinless quantum wire model in terms of its ground state geometric quantum discord. The derivative of geometric quantum discord is nonanalytic at the critical point, in both zero temperature and finite temperature cases. The scaling behavior and the universality are verified numerically. Therefore, our results clearly show that all the key ingredients of the topological phase transition can be captured by the nearest neighbor and long-range geometric quantum discord.