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The introduction of thianthrene as a linchpin has proven to be a versatile strategy for the C-H functionalization of aromatic compounds, featuring a broad scope and fast diversification. The synthesis of aryl thianthrenium salts has displayed an unusually high para regioselectivity, notably superior to those observed in halogenation or borylation reactions for various substrates. We report an experimental and computational study on the mechanism of aromatic C-H thianthrenation reactions, with an emphasis on the elucidation of the reactive species and the nature of the exquisite site selectivity. Mechanisms involving a direct attack of arene to the isolated O-trifluoracetylthianthrene S-oxide (TT+-TFA) or to the thianthrene dication (TT2+) via electron transfer under acidic conditions are identified. A reversible interconversion of the different Wheland-type intermediates before a subsequent, irreversible deprotonation is proposed to be responsible for the exceptional para selectivity of the reaction.

A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and tert-butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs. With cyclohexanes, the relative importance of HAT from C-1 decreases on going from methyl- and phenylcyclohexane to ethyl-, isopropyl-, and tert-butylcyclohexane. Deactivation is also observed at C-2 with site-selectivity that progressively shifts to C-3 and C-4 with increasing substituent steric bulk. The site-selectivities observed in the corresponding oxidations promoted by ethyl(trifluoromethyl)dioxirane support this mechanistic picture. Comparison of these results with those obtained previously for C-H bond azidation and functionalizations promoted by the PINO radical of phenyl and tert-butylcyclohexane, together with new calculations, provides a mechanistic framework for understanding C-H bond functionalization of cycloalkanes. The nature of the HAT reagent, C-H bond strengths, and torsional effects are important determinants of site-selectivity, with the latter effects that play a major role in the reactions of oxygen-centered HAT reagents with monosubstituted cyclohexanes.

While synthetic chemistry has experienced substantial development in the past century, challenges still remain to fully satisfy the needs in drug development. A bias in sampling linear and disc-shaped molecules in drug discovery over spherical ones has existed due to the lack of efficient access to the latter chemical space. Specifically, efficient strategies to synthesize tetraarylmethanes, a unique family of spherical molecules, has remained scarce. In particular, there has been essentially no efficient asymmetric synthesis of chiral tetraarylmethanes due to the overwhelming steric congestion and challenging stereocontrol encountered in assembly of the all-aryl-substituted quaternary stereocentre. Here we disclose an efficient catalytic synthesis of chiral tetraarylmethanes with high enantioselectivity via a stereoconvergent formal nucleophilic substitution reaction. Control experiments and density functional theory calculations provided strong support on hydrogen bonding interactions as the key elements to successful stereocontrol. The obtained enantioenriched products showed impressive preliminary anticancer activities. Tetraarylmethanes display special properties due to their spherical nature and are applied in various areas, but strategies for their asymmetric production are lacking. Now, their enantioselective synthesis is reported and in vitro studies indicate their potential as anticancer agents.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic-co-glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage in vivo. In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs via cytotoxicity assays in vitro and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs in vitro. In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.

The critical issue in nanoscale medicine delivery systems is the targeted efficiency to guarantee the maximum accumulation of nanodrugs in tumors to exert better therapeutic action. In this study, we adopted an active and potent strategy based on mesenchymal stem cells (MSCs) certified with excellent tumor-tropism ability to load and ship MnO2@Ce6 nanoparticles into a tumor site. Notably, under the premise of the negligible cellular toxicity of MnO2@Ce6 on MSCs, its considerable uptake by MSCs enabled this nanoplatform (MnO2@Ce6-MSCs) to distribute increasingly inside the tumor. Briefly, a Ce6 photosensitizer was bound to MnO2 nanospheres by physical adsorption, improving its own stability in blood circulation. Furthermore, the delivered MnO2@Ce6 could modulate the tumor microenvironment (TME) by high sensitivity to excess hydrogen protons (H+) and H2O2. Thus, O2 generated by these reactions served as an abundant source for 1O2 conversion under a 633 nm laser exposure, which overcame the crucial bottleneck of the unfavorable hypoxia condition in TME for photodynamic therapy (PDT). In addition, MnO2 decomposed into Mn2+, which was represented by high T1 relaxivity in magnetic resonance imaging (MRI). The Mn2+ was finally removed rapidly from the body by liver metabolism and kidney filtration. These results endowed the original nanoplatform with striking potential for MSC-guided, Ce6-converted, MRI-monitored PDT for further innovation of a clinical cancer diagnosis-treatment agent.

Despite the enormous developments of asymmetric catalysis, the basis for asymmetric induction is largely limited to spatial interaction between substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between aryl and heteroaryl groups without a directing group or electronic manipulation. Here we address this challenge by a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With the versatile 2-indole imine methide as platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that, while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

In physiological processes, hypochlorous acid can regulate in vitro signaling molecules as one kind of reactive oxygen species (ROS). Serious diseases, such as cardiovascular disorders, neurodegene...

Chiral tetrahydrothiophenes and tetrahydroselenophenes are highly useful structural units. Described here is a new catalytic asymmetric approach for their synthesis. With a suitable chiral Brønsted acid catalyst, an oxetane desymmetrization by a well-positioned internal sulfur or selenium nucleophile proceeded efficiently to generate all-carbon quaternary stereocenters with excellent enantioselectivities. Taming the sulfur and selenium nucleophile in the form of a thioester and selenoester, respectively, is crucial to the success of this work. This approach also allows the facile synthesis of chiral tetrahydrothiopyrans. Mechanistic studies, including DFT calculations, suggested an intramolecular acyl-transfer pathway. Utilities of the chiral products are also demonstrated.

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control., Catalytic asymmetric dearomatization is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. Here the authors show an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition.

Filamentous fungi identification by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been challenging due to the lack of simple and rapid protein extraction methods and insufficient species coverage in the database. In this study, we created two rapid protein extraction methods for filamentous fungi: a one-step zirconia-silica beads method (ZSB) and a focused-ultrasonication method (FUS). The identification accuracy of two methods were evaluated with the VITEK MS, as well as number of spectra peaks and signal-to-noise ratio (S/N) with M-Discover 100 MALDI-TOF MS compared to the routine method. The better method was applied to build a filamentous fungi in-house spectra library for the M-Discover 100 MS, and then another one and routine method were performed in parallel to verify the accuracy and commonality of the in-house library. Using the two optimized methods, the dedicated operating time before MALDI-TOF MS analysis was reduced from 30 min to 7 (ZSB) or 5 (FUS) min per sample, with only a few seconds added for each additional strain. And both two methods identified isolates from most mold types equal to or better than the routine method, and the total correct identification rate using VITEK MS was 79.67, 76.42, and 76.42%, respectively. On the other hand, the two rapid methods generally achieved higher maximum and minimum S/N ratios with these isolates tested as compared to the routine method. Besides, the ZSB method produced overall mean of maximum and minimum S/N ratio higher than that by FUS. An in-house library of M-Discover MS was successfully built from 135 isolates from 42 species belonging to 18 genera using the ZSB method. Analysis of 467 isolates resulted in 97.22% correctly identified isolates to the species level by the ZSB method versus 95.50% by the routine method. The two novel methods are time- and cost-effective and allow efficient identification of filamentous fungi while providing a simplified procedure to build an in-house library. Thus, more clinical laboratories may consider adopting MALDI-TOF MS for filamentous fungi identification in the future.

Hydrogen sulfide (H2S) is a kind of gaseous signal molecule in many physiological processes. In order to detect H2S, a novel “turn on” fluorescent probe 6,12-dihydroxyperylene-1,7-dione (DPD) was designed and synthesized. The probe DPD is fluorescence silence, while the addition of H2S induces an obvious green fluorescence with an obvious color change from dark blue to yellow-green. The probe shows excellent selectivity, fast response (2.5 min) and linear curve (0–90 μM) in wide effective pH range (4–10). Competition experiments are also revealed in corresponding studies and the detection limit is 3.6 μM. The response mechanism is proved to be the reduction of the probe by H2S, which is confirmed by 1H NMR. Furthermore, through the fluorescence turn-on signal toward H2S in Hela cells, probe DPD was successfully applied to monitor H2S in living Hela cells.

Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.

We developed a versatile and modular method for cytosolic protein delivery through metal ion-induced co-assembly of gold nanoclusters and proteins into supramolecular assemblies. The versatility and high efficiency of this strategy to assemble and deliver various proteins into living cells were demonstrated. Importantly, the activity of proteins was maintained during the delivery. This modular approach provides an exciting and promising new nano-platform for cytosolic protein delivery.

This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes. Additionally, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.

O‐GlcNAcylation catalysed by O‐GlcNAc transferase (OGT) is a reversible post‐translational modification. O‐GlcNAcylation participates in transcription, epigenetic regulation, and intracellular signalling. Dysregulation of O‐GlcNAcylation in response to high glucose or OGT expression has been implicated in metabolic diseases and cancer. However, the underlying mechanisms by which OGT regulates hepatoma development remain largely unknown. Here, we employed the lentiviral shRNA‐based system to knockdown OGT to analyse the contribution of OGT in hepatoma cell proliferation and stem‐like cell potential. The sphere‐forming assay and western blot analysis of stem‐related gene expression were used to evaluate stem‐like cell potential of hepatoma cell. We found that the level of total O‐GlcNAcylation or OGT protein was increased in hepatocellular carcinoma. OGT activated stem‐like cell potential in hepatoma through eukaryotic initiation factor 4E (eIF4E) which bound to stem‐related gene Sox2 5'‐untranslated region. O‐GlcNAcylation of eIF4E at threonine 168 and threonine 177 protected it from degradation through proteasome pathway. Expression of eIF4E in hepatoma was determined by immunostaining in 232 HCC patients, and Kaplan‐Meier survival analysis was used to determine the correlation of eIF4E expression with prognosis. High glucose promoted stem‐like cell potential of hepatoma cell through OGT‐eIF4E axis. Collectively, our findings indicate that OGT promotes the stem‐like cell potential of hepatoma cell through O‐GlcNAcylation of eIF4E. These results provide a mechanism of HCC development and a cue between the pathogenesis of HCC and high glucose condition.

We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α-CH2 Bpin-substituted crotylboronate. Chiral phosphoric acid (S)-A-catalyzed asymmetric allyl addition with the reagent gave Z-anti-homoallylic alcohols with excellent enantioselectivities and Z-selectivities. When the enantiomeric acid catalyst (R)-A was utilized, the stereoselectivity was completely reversed and E-anti-homoallylic alcohols were obtained with high E-selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.

Fe isotopes have been applied to the petrogenesis of ore deposits. However, the behavior of iron isotopes in the mineralization of porphyry-skarn deposits is still poorly understood. In this study, we report the Fe isotopes of ore mineral separations (magnetite, pyrite, chalcopyrite and pyrrhotite) from two different skarn deposits, i.e., the Tonglvshan Cu-Fe skarn deposit developed in an oxidized hydrothermal system and the Anqing Cu skarn deposit developed in a reduced hydrothermal system. In both deposits, the Fe isotopes of calculated equilibrium fluids are lighter than those of the intrusions responsible for the skarn and porphyry mineralization, corroborating the “light-Fe fluid” hypothesis. Interestingly, chalcopyrite in the oxidized-Tonglvshan skarn deposit has lighter Fe than chalcopyrite in the reduced-Anqing skarn deposit, which is best understood as the result of the prior precipitation of magnetite (heavy Fe) from the ore fluid in the oxidized-Tonglvshan systems and the prior precipitation of pyrrhotite (light Fe) from the ore fluid in the reduced-Anqing system. The δ56Fe for pyrite shows an inverse correlation with δ56Fe of magnetite in the Tonglvshan. In both deposits, the Fe isotope fractionation between chalcopyrite and pyrite is offset from the equilibrium line at 350 °C and lies between the FeS-chalcopyrite equilibrium line and pyrite-chalcopyrite equilibrium line at 350 °C. These observations are consistent with the FeS pathway towards pyrite formation. That is, Fe isotopes fractionation during pyrite formation depends on a path from the initial FeS-fluid equilibrium towards the pyrite-fluid equilibrium due to the increasing extent of Fe isotopic exchange with fluids. This finding, together with the data from other deposits, allows us to propose that the pathway effect of pyrite formation in the Porphyry-skarn deposit mineralization is the dominant mechanism that controls Fe isotope characteristics.

The development of α,α-disubstituted crotylboronate reagents is reported. Chiral Bronsted acid-catalyzed asymmetric aldehyde addition with the developed E-crotylboron reagent gave (E)-anti-1,2-oxaborinan-3-enes with excellent enantioselectivities and E-selectivities. With BF3·OEt2 catalysis, the stereoselectivity is reversed, and (Z)-δ-boryl-anti-homoallylic alcohols are obtained with excellent Z-selectivities from the same E-crotylboron reagent. The Z-crotylboron reagent also participates in BF3·OEt2-catalyzed crotylation to furnish (Z)-δ-boryl-syn-homoallylic alcohols with good Z-selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Bronsted acid-catalyzed asymmetric allylation. Stereochemical models for BF3·OEt2-catalyzed reactions are proposed to rationalize the Z-selective allyl additions. These reactions generate highly valuable homoallylic alcohol products with a stereodefined trisubstituted alkene unit. The synthetic utility is further demonstrated by the total syntheses of salinipyrones A and B.

Injection of urethral bulking agents is a low-risk, minimally invasive surgical procedure to treat stress urinary incontinence (SUI). In this study, we developed a promising injectable bulking agent comprising extracellular matrix fragments of adipose-derived stem cell sheets (ADSC ECM) and investigated its effectiveness in urethral bulking therapy. The structural integrity and proteins of ADSC sheet ECM were well retained in decellularized ADSC ECM fragments. To locate transplanted ADSC ECM fragments, they were labeled with ultrasmall super-paramagnetic iron oxide nanoparticles, which enabled in vivo monitoring after implantation in a SUI rat model for up to 4 weeks. When ADSC ECM fragments were injected into the rat urethra, they became fully integrated with the surrounding tissue within 1 week. Four weeks after transplantation, host cells had regenerated within the ADSC ECM fragment injection area. Moreover, new smooth muscle tissue had formed around the ADSC ECM fragments, as confirmed by positive staining of myosin. These results indicate that injection of ECM fragments may be a promising minimally invasive approach for treating SUI.

Geochemical and iron isotopic compositions of magnetite, ilmenite and pyrite separates from the Fe Ti oxide ores hosted in the Damiao anorthosite-type Fe Ti ore deposit were analyzed to investigate sub-solidus cooling history of the titanomagnetite. The Fe Ti oxides form two series of solid solutions, namely, ulvospinel-magnetite (Usp-Mtss) and hematite-ilmenite (Hem-Ilmss) solid solutions. The magnetite separates have 14–27 mol% ulvospinel, while the ilmenite separates have 5–8 mol% hematite. Major element compositions of the mineral separates suggest that the ilmenites were mainly exsolved from the Usp-Mtss by oxidation of ulvospinel in the temperature range of ~820–600 °C and experienced inter-oxide re-equilibration with the magnetites. Associated with the exsolution is the substantial inter-mineral iron isotope fractionation. The magnetite separates are characterized by high δ57Fe (+0.27 − +0.65‰), whereas the ilmenite separates have lower δ57Fe (−0.65 to −0.28‰). Two types of pyrite are petrographically observed, each of which has a distinctive iron isotope fingerprint. Type I pyrite (pyriteI) with higher δ57Fe (δ57Fe = +0.63 − +0.95‰) is consistent with magmatic origin, and type II pyrite (pyriteII) with lower δ57Fe (δ57Fe = −0.90 to −0.11‰) was likely to have precipitated from fluids. Iron isotopic fingerprints of the pyriteI probably indicate variations of oxygen fugacity, whereas those of the pyriteII may result from fluid activities. The iron isotopic fractionation between the magnetite and ilmenite is the net result of sub-solidus processes (including ulvospinel oxidation and inter-oxide re-equilibration) without needing varying oxygen fugacity albeit its presence. Although varying composition of magnetite-ilmenite pairs reflects variations of oxygen fugacity, inter-oxide iron isotopic fractionation does not.

Organic mobilizing agents have been advocated for phytoremediation of heavy metals contaminated soils, while the effects of application period of such agents remain unclear. A pot experiment was conducted, with two composited organic agents (oxalic acid or citric acid + dissolved organic fertilizer (OA + DOF and CA + DOF)) and four application periods (seeding, jointing, flag leaf and heading stages) of sorghum (Sorghum bicolor L.), to investigate their impacts on Cd bioavailability in soil. Results indicated that application of the two composited agents increased soil dissolved organic carbon (DOC) and DTPA extractable Cd by 7.31–49.13%, Cd contents in roots and shoots by 21.49–72.10%, bioaccumulation factor (BCF) and translocation factor (TF) of shoots by 4.44–71.99%, while reduced soil pH by 0.25–0.53 units, respectively. Most of these indices increased with the application periods, and largely peaked with their application during the flag leaf to heading stages. Meanwhile, the maximum sorghum biomass (132.84 g pot−1) and Cd bioaccumulation quantity (BCQ, 0.71 mg pot−1) in shoots were obtained for the CA + DOF applied at the heading. The DTPA extractable Cd was closely related to soil pH and DOC. Similar close relationships were observed between the Cd contents in shoots and soil DTPA extractable Cd, pH and DOC. The BCQ of Cd was positively related to the shoots biomass rather than their Cd contents. Therefore, the sorghum combined with the CA + DOF may be advocated as an alternative phytoremediation mode in Cd-contaminated soils, and the mobilizing agent should be primarily applied at the heading stage.

We report a dual function asymmetric catalysis by a chiral phosphoric acid catalyst that controls both enantioselective addition of an achiral α-vinyl allylboronate to aldehydes and pseudo-axial orientation of the α-vinyl group in the transition state. The reaction produces dienyl homoallylic alcohols with high Z-selectivities and enantioselectivities. Computational studies revealed that minimization of steric interactions between the alkyl groups of the diol on boron and the chiral phosphoric acid catalyst influence the orientation of α-vinyl substituent of the allylboronate reagent to occupy a pseudo-axial position in the transition state.

Objective: Gecko active components (GACs), extracted from the powder of whole Gecko, have been reported to be effective against esophageal squamous cell carcinoma (ESCC). Endoplasmic reticulum stress (ERs) has been regarded as an important cause for pathogenesis of esophageal squamous cell carcinoma (ESCC). In this paper, we aimed to study the effect of GACS on apoptosis of human esophageal carcinoma KYSE150 cells and to analyze the underlying signaling pathway. Methods: MTT assay was used to detect the viability of KYSE150 cells, and Flow cytometry was applied to detect reactive oxygen species (ROS), calcium generation, and the level of mitochondrial membrane potential (MMP). Western blot analysis was applied to observe the expression of apoptosis-related proteins and endoplasmic reticulum stress (ERs)-related proteins in KYSE150 cells. Results: The results showed that GACs inhibited KYSE150 cell vitality in a dose- and time-dependent manner. Not only that, GACs could up-regulated ERs-related and apoptosis-related proteins expression, and the content of ROS and calcium were significantly increased, and also, the level of MMP was significantly decreased. Conclusion: The results of this report suggested that induction of apoptosis occurs through the ERs dependent signaling pathways.

Gecko (Gekko japonicus) extracts have been used in traditional Chinese medicine for many years. It has been proven that the gecko polypeptide mixture (GPM) extracted from gecko can inhibit the growth of multiple types of tumor cells. In order to investigate the possible anti-tumor molecular mechanisms of GPM, we used RNA-seq technology to identify the differentially expressed genes (DEGs) of human hepatocellular carcinoma (HCC) HepG2 cells treated with or without GPM. MTT assay was used to detect the viability of HepG2 cells. DAPI fluorescence staining was performed to observe morphological changes in the nuclei of HepG2 cells. Western blot analysis was applied to observe the expressions of apoptosis-related and endoplasmic reticulum stress (ERS)-related proteins in HepG2 cells. Flow cytometry assay was performed to detect the apoptosis and reactive oxygen species (ROS) in HepG2 cells. Our results showed that GPM inhibited HepG2 cells proliferation and induced the apoptosis of HepG2 cells. RNA-seq analysis suggested that the ER-nucleus signaling pathway involved in the anti-cancer molecular mechanism of GPM. Therefore, GPM may induce apoptosis in HepG2 cells via the ERs pathway.

The trifluoromethyl group (CF3) is a very important functional group. The mechanism of transition metal catalyzed trifluoromethylation has received considerable attention in recent years. In this work, the detailed mechanism of the copper-catalyzed oxytrifluoromethylation of allylamines with CO2 was investigated by density functional theory (DFT) calculations. Differing from the previous Cu(I)–Cu(III) catalytic cycle, the results show that the reaction proceeds through a Cu(I)–Cu(II) catalytic cycle. Deprotonation of allylamines initially occurs with the assistance of a copper catalyst followed by CO2 insertion. In the presence of Togni reagent II, the copper(I) carboxylate species can then be oxidized to the copper(II) dicarboxylate intermediate along with the formation of a free trifluoromethyl radical, which then attacks the alkene moiety to generate the electrophilic addition diradical adduct. The spiro ring is constructed by a carboxylate-delivered radical–radical cross-coupling procedure. In addition, the calculated global electrophilicity shows that the copper(III) intermediate cannot be generated from the combination of the electron deficient copper center and the electrophilic trifluoromethyl radical. Frontier molecular orbital analysis indicates that the Togni reagent II is activated by neutral Cu(I) rather than the cationic Cu(I) species. The origin of the diastereoselectivity can be mainly attributed to the repulsion between the trifluoromethyl group and the carbonyl moiety.

Density functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.

Density functional theory method N12 was used to study the mechanism of the [Ir(cod)OH]2/Xyl–MeO–BIPHEP-catalyzed para-selective C–H borylation reaction. The results revealed that the use of a bulky diphosphine ligand such as Xyl–MeO–BIPHEP was unfavorable for the previously proposed iridium(III)/iridium(V) catalytic cycle because it resulted in considerable steric repulsion in the hepta-coordinated iridium(V) intermediate. Inspired by this steric effect, we have proposed a novel iridium(I)-/iridium(III)-based catalytic cycle for this transformation and shown that it can be used to account for the experimental results. The iridium(I)/iridium(III) catalytic cycle induced by this steric effect consists of several steps, including (i) the oxidative addition of the C–H bond of the substrate to an active iridium(I) boryl complex; (ii) the reductive elimination of a C–B bond; (iii) the oxidative addition of B2pin2 to an iridium(I) hydride complex; and (iv) the reductive elimination of a B–H bond. Notably, the c...

Inductively coupled plasma mass spectrometry (ICP-MS) is the most commonly used technique to determine the abundances of trace elements in a wide range of geological materials. However, incomplete sample digestion, isobaric interferences and instrumental drift remain obvious problems that must be overcome in order to obtain precise and accurate results. For this reason, we have done many experiments and developed a set of simple, cost-effective and practical methods widely applicable for precise and rapid determination of trace element abundances in geological materials using ICP-MS. Commonly used high-pressure digestion technique is indeed effective in decomposing refractory phases, but this inevitably produces fluoride complexes that create new problems. We demonstrate that the fluoride complexes formed during high-pressure digestion can be readily re-dissolved using high-pressure vessel at 190 °C for only 2 h for 50 mg sample. In the case of isobaric interferences, although oxide (e.g., MO+/M+) and hydroxide (e.g., MOH+/M+) productivity is variable between runs, the (MO+/M+)/(CeO+/Ce+) and (MOH+/M+)/(CeO+/Ce+) ratios remain constant, making isobaric interference correction for all other elements of interest straightforward, for which we provide an easy-to-use off-line procedure. We also show that mass-time-intensity drift curve is smooth as recognized previously, for which the correction can be readily done by analyzing a quality-control (QC) solution and using off-line Excel VBA procedure without internal standards. With these methods, we can produce data in reasonable agreement with recommended values of international rock reference standards with a relative error of 60% of time (e.g., 60 h).

The density functional theory (DFT) method M06-L was used to study the general mechanism of palladium-catalyzed C–S bond formation reactions. Our theoretical calculations revealed that this type of reaction starts with a palladium-assisted metalation–deprotonation step. Oxidative addition of the sulfur source affords a thiolate–palladium(IV) intermediate, and subsequent reductive elimination generates the new C–S bond. A final protonation regenerates the active palladium(II) catalyst and releases the product. Our proposed mechanism could be applied to a series of palladium-catalyzed C–S bond formation reactions used for the construction of dibenzothiophene derivatives. The rate-limiting step of the catalytic cycle is oxidative addition to yield the thiolate–palladium(IV) intermediate. In contrast, formation of a sulfonium intermediate is unfavourable. In addition, the effect of substituents on the rate-determining step was studied with Hammett plots. Our calculations showed that incorporation of electron-withdrawing groups at the 4-position and electron-donating groups at the 15 and 16-positions would promote intramolecular oxidative addition of thioethers to palladium.

Many studies have shown that the average iron (Fe) isotope compositions of mantle-derived rocks, mantle peridotite and model mantle are close to those of chondrites. Therefore, it is considered that chondrite values represent the bulk Earth Fe isotope composition. However, this is a brave assumption because nearly 90% of Fe of the Earth is in the core, where its Fe isotope composition is unknown, but it is required to construct bulk Earth Fe isotope composition. We approach the problem by assuming that the Earth’s core separation can be approximated in terms of the Sudbury-type Ni-Cu sulfide mineralization, where sulfide-saturated mafic magmas segregate into immiscible sulfide liquid and silicate liquid. Their density/buoyancy controlled stratification and solidification produced net-textured ores above massive ores and below disseminated ores. The coexisting sulfide minerals (pyrrhotite (Po) &gt, pentlandite (Pn) &gt, chalcopyrite (Cp)) and silicate minerals (olivine (Ol) &gt, orthopyroxene (Opx) &gt, clinopyroxene (Cpx)) are expected to hold messages on Fe isotope fractionation between the two liquids before their solidification. We studied the net-textured ores of the Sudbury-type Jinchuan Ni-Cu sulfide deposit. The sulfide minerals show varying δ56Fe values (−1.37–−0.74‰ (Po) &lt, 0.09–0.56‰ (Cp) &lt, 0.53–1.05‰ (Pn)), but silicate minerals (Ol, Opx, and Cpx) have δ56Fe values close to chondrites (δ56Fe = −0.01 ± 0.01‰). The heavy δ56Fe value (0.52–0.60‰) of serpentines may reflect Fe isotopes exchange with the coexisting pyrrhotite with light δ56Fe. We obtained an equilibrium fractionation factor of Δ56Fesilicate-sulfide ≈ 0.51‰ between reconstructed silicate liquid (δ56Fe ≈ 0.21‰) and sulfide liquid (δ56Fe ≈ −0.30‰), or Δ56Fesilicate-sulfide ≈ 0.36‰ between the weighted mean bulk-silicate minerals (δ56Fe[0.70ol,0.25opx,0.05cpx] = 0.06‰) with weighted mean bulk-sulfide minerals (δ56Fe ≈ −0.30‰). Our study indicates that significant Fe isotope fractionation does take place between silicate and sulfide liquids during the Sudbury-type sulfide mineralization. We hypothesize that significant iron isotope fractionation must have taken place during core–mantle segregation, and the bulk Earth may have lighter Fe isotope composition than chondrites although Fe isotope analysis on experimental sulfide-silicate liquids produced under the varying mantle depth conditions is needed to test our results. We advocate the importance of further research on the subject. Given the close Fe-Ni association in the magmatic mineralization and the majority of the Earth’s Ni is also in the core, we infer that Ni isotope fractionation must also have taken place during the core separation that needs attention.

Element doping has been proved to be a useful method to correct for the mass bias fractionation when analyzing iron isotope compositions. We present a systematic re-assessment on how the doped nickel may affect the iron isotope analysis in this study by carrying out several experiments. We find three important factors that can affect the analytical results, including the Ni:Fe ratio in the analyte solutions, the match of the Ni:Fe ratio between the unknown sample and standard solutions, and the match of the Fe concentration between the sample and standard solutions. Thus, caution is required when adding Ni to the analyte Fe solutions before analysis. Using our method, the δ56Fe and δ57Fe values of the USGS standards W-2a, BHVO-2, BCR-2, AGV-2 and GSP-2 are consistent with the recommended literature values, and the long-term (one year) external reproducibility is better than 0.03 and 0.05‰ (2SD) for δ56Fe and δ57Fe, respectively. Therefore, the analytical method established in our laboratory is a method of choice for high quantity Fe isotope data in geological materials.

Both theoretical and experimental studies were performed to explore the mechanism, regioselectivity, and enantioselectivity of phosphine-catalyzed [3 + 2] annulation between allenoates and acrylate or imine. Using density functional theory computations, we predicted that the enantioselective determining step is the nucleophilic addition of acrylate or imine to the catalyst-activated allenoate. In the key step, we proposed two hydrogen bonding interaction models (intermolecular H-bond model and intramolecular H-bond model). For acrylate substrates, the reaction proceeds via the intramolecular H-bond model and the strong noncovalent interactions between the 2-naphthyl ester moiety lead to the re-face attack pathway being more favorable. For imine substrates, the intermolecular H-bond model operates. In the annulation process, the bulky n-propyl oriented toward a crowded, sterically demanding environment plays a significant role in asymmetric induction. The theoretical calculation results agreed with experimental observations, and these results provide valuable insight into catalyst design and understanding of mechanisms of related reactions.

Due to the large area of Cd-contaminated paddy soils worldwide, low-cost measures to reduce the accumulation of Cd in rice plant are necessary. A field experiment was therefore conducted to investigate the reducing effect of lime combined with foliar applications of Zn (ZnSO4) or Fe (EDTA·Na2Fe) on Cd concentrations in brown rice on a Cd-contaminated paddy soil. The results indicated that liming alone or in combination with foliar sprays of Zn or Fe increased the soil pH by 0.27–0.63 units. However, limited effects of lime or lime combined with foliar applications of Zn/Fe on soil DTPA-extractable Cd, rice grain and rice straw biomass were observed. Liming alone significantly reduced the Cd concentration in brown rice and rice straw by 31.8% and 42.3%, respectively. The Cd concentrations in brown rice decreased by 25.5% and 65.4% and in rice straw by 53.0% and 68.1% after liming combined with foliar applications of Fe and Zn, respectively. In contrast, liming combined with foliar spraying of Fe significantly increased the transfer ratio of Cd from the rice straw to the grain. As a low-cost technique, lime application combined with foliar application of ZnSO4 could be recommended for the remediation of Cd-contaminated paddy soils.

Background: Viscum coloratum (Komar) Nakai, known as Hujisheng in china, has been widely used as a herb medicine to treat a variety of diseases, including cardiovascular diseases, cancer, hypertension, hepatitis and hemorrhage. Objective: The aim was to investigate pharmacokinetic interactions among co existing ingredients in V. coloratum after intravenous administration of three different preparations (four monomer solutions, the mixture of them and Viscum coloratum extracts) to rats. Materials and Methods: After protein precipitation pretreatment with plasma samples, high performance liquid chromatographic methods were developed and applied to quantitatively determinate the four components [syringin (Syri), homoeriodictyol 7 O -β- D glycoside (Hedt III), homoeriodictyol 7 O -β- D apiose (1 → 2)-β- D glycoside (Hedt II) and homoeriodictyol 7 O -β- D apiosiyl (1 → 5)-β- D apiosyl (1 → 2)-β- D glycoside (Hedt I)].The pharmacokinetic parameters (Area under the curve [AUC (0-t) ], AUC (0-∞) , t 1/2 ) were calculated using DAS 2.1 software (Chinese Pharmacological Society,Shanghai,China) and compared statistically by One way analysis of variance using SPSS software (18.0, Chicago, IL, USA) with P Results: Good linearities were achieved in the measured concentration range with R 2 it0.9920. Precision, accuracy and extraction recovery were all within the acceptable range. For Syri, there was a significant difference only on t 1/2 among three treatment groups. For Hedt I, Hedt II and Hedt III, three flavonoid glycosides, the change of AUC (0- t ) , AUC (0-∞) and t 1/2 were markedly distinctive and even converse. Conclusion: Complex, extensive pharmacokinetic interactions were observed among these components in V. coloratum . They were mutually influenced by the in vivo absorption, distribution, metabolism and elimination. The result suggested traditional Chinese medicine was a complicated system, and we should take a scientific and dialectic view in the research and development processes.

The research was conducted to investigate the accumulation, distribution and availability of Cd in paddy soil and their relation to Cd in rice plants under 30-year fertilization regimes. Six treatments were involved in the study: control without fertilization (CK), chemical fertilizer (NPK), high nitrogen chemical fertilizer (HN), rice straw incorporation (ST), low and high dosage of manure fertilizer (LM and HM). Total and DTPA extractable concentration of Cd (T-Cd and DTPA-Cd) in bulk soils (20 cm topsoil), profiles (0-60 cm) and aggregates (2, 1-2, 0.5-1, 0.25-0.5, 0.053-0.25 and 0.053 mm) were investigated. The Cd concentration in relevant rice plant (roots, stems, leaves, husks and grains) were also analyzed. Manure fertilizers caused T-Cd accumulation in bulk soil with a significant increase of 36.2% in LM and 81.2% in HM. Similar impacts of manure fertilizers were observed in DTPA-Cd in the bulk soil. Further, the HM generated a further accumulation in deeper soil layers, presenting a remarkable increase of T-Cd (28.3%-225%) in 10-40 cm and DTPA-Cd (116%-158%) in 10-30 cm profiles. Moreover, the continuous application of manure fertilizers enhanced the availability of Cd in all aggregate size classes with an increase of 17.3%-87.8% in DTPA-Cd. Organic fertilizers (LM, HM and ST) heightened the content of Cd (38.0%-152%) in all parts of rice plant. The accumulation of Cd in rice plants was directly affected by fertilization regimes and Cd availability in the 10-20 cm soil layers and 0.25-0.5 mm aggregates. In conclusion, long-term application of manures resulted in increasing availability of Cd in aggregates and in topsoil and subsoil layers, which accordingly enhanced the accumulation of Cd in rice plants.

A new fluorescent prestaining method for gel-separated glycoproteins in 1D and 2D SDS-PAGE was developed by using dansylhydrazine in this study. The prestained gels could be easily imaged after electrophoresis without any time-consuming steps needed for poststains. As low as 4-8 ng glycoproteins (transferrin, α1-acid glycoprotein) could be selectively detected, which is comparable to that of Pro-Q Emerald 488, one of the most commonly used glycoprotein stain. In addition, a subsequent study of deglycosylation, glycoprotein affinity isolation, and LC-MS/MS analysis was performed to confirm the specificity of the newly developed method.

An improved periodate/Schiff's base based fluorescent stain with dansylhydrazine (DH) for glycoproteins in 1D and 2D SDS-PAGE was described. Down to 4-8 ng of glycoproteins can be selectively detected within 2 h, which is approximately 16-fold higher than that of original protocol, but similar to that of Pro-Q Emerald 488 stain (Invitrogen, Carlsbad, USA). Furthermore, subsequent study of deglycosylation, glycoprotein affinity isolation, and LC-MS/MS analysis were performed to confirm the specificity of the improved method. As a result, improved DH stain may provide a new choice for selective, economic, MS compatible, and convenient visualization of gel-separated glycoproteins.

As a non-covalent fluorescence probe, in this study, salicylaldehyde azine (SA) was introduced as a sensitive fluorescence-based dye for detecting proteins both in 1-D and 2-D polyacrylamide electrophoresis gels. Down to 0.2 ng of single protein band could be detected within 1 h, which similars to that of glutaraldehyde (GA)-silver stain, but approximately four times higher than that of SYPRO Ruby fluorescent stain. Furthermore, comparative analysis of the MS compatibility of SA stain with SYPRO Ruby stain indicated that SA stain is compatible with the downstream of protein identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, the probable mechanism of the SA stain was investigated by molecular docking. The results demonstrated that the interaction between SA and protein was mainly contributed by hydrogen bonding and hydrophobic forces.

Two air-stable N-heterocyclic carbene (NHC) adducts of cyclopalladated ferrocenylpyridine containing chloride or iodide anions 2–3 have been easily prepared from the bridge-splitting reaction of the palladacyclic dimer 1 and anion exchange reaction, respectively. They were characterized by elemental analysis, IR, 1H, and 13C NMR. Additionally, the structures of these complexes were determined by single-crystal X-ray analysis. These adducts have been successfully applied to the coupling of terminal alkynes with arylboronic acids under atmospheric conditions.

We have successfully developed a series of novel and modular ferrorence-based amino-phosphine-alcohol (f-Amphol) ligands, and applied them to iridium-catalyzed asymmetric hydrogenation of various simple ketones to afford the corresponding chiral alcohols with excellent enantioselectivities and conversions (98-99.9 % ee, >99 % conversion, turnover number up to 200 000). Control experiments and density functional theory (DFT) calculations have shown that the hydroxyl group of our f-Amphol ligands played a key role in this asymmetric hydrogenation.

A series of tridentate ferrocene aminophosphoxazoline ligands like APX is synthesized and successfully applied to the asymmetric hydrogenation of ketones.

A series of modular and rich electronic tridentate ferrocene aminophosphoxazoline ligands (f-amphox) have been successfully developed and used in iridium-catalytic asymmetric hydrogenation of simple ketones to afford corresponding enantiomerically enriched alcohols under mild conditions with superb activities and excellent enantioselectivities (up to 1 000 000 TON, almost all products up to >99% ee, full conversion). The resulting chiral alcohols and their derivatives are important intermediates in pharmaceuticals.

A novel cadmium metal-organic coordination polymer, namely Cd(atda)(3-abpt)(H2O)·2H2O (H2atda = (4-amino-1,2,4-triazole-3,5-diyldithio) diacetic acid, 3-abpt = 4-amino-3,5-bis(3-pyridyl)-1,2,4-triazole)), has been obtained under hydrothermal conditions by the reaction of cadmium salts with two kinds of organic ligands, characterized by single-crystal X-ray diffraction analysis, elemental analysis, and thermogravimetric analysis. Structural analysis reveals that complex possesses a 2D honeycomb network. Additionally, the complex show strong fluorescence in solid state at room temperature.

N-4,6-dimethyl-2-pyrimidinylimidazole 1 and its hydroxyethyl derivative 1-(2-hydroxyethyl)-3-(4,6-dimethyl-2-pyrimidinyl)imidazolium chloride 2 have been synthesized and characterized. The attempted synthesis of bis(N-heterocyclic carbene)palladium complexes via the direct reaction of 2 with Pd(OAc)2 results in the unexpected formation of a bis(N-arylimidazole) palladium complex 3. Additionally, the analogous bis(N-methylimidazole) palladium complex 4 has also been synthesized by the above method. Compounds 1–4 were characterized by elemental analysis, IR, and 1H NMR. Additionally, their crystal structures have been determined by X-ray diffraction. Complexes 3 and 4 were found to be efficient catalysts for the Suzuki reaction.

Two new N-heterocyclic carbene (NHC)-phosphine palladium(II) complexes Pd(IMeo)PPh3I2 1 and Pd(IMeo) P(C6H4-p-Me)3I2 2 (IMeo = 1,3-di-4-methoxyphenyl- imidazolin-2-ylidene) have been easily prepared from the reaction of the corresponding iodide-bridged NHC dimer with phosphine ligands in high yields. Complexes 1 and 2 were characterized by elemental analysis, IR, 1H NMR, ESI-MS and single-crystal X-ray analysis. Complex 1 adopts a trans geometry in the solid state, while 2 is cis. The common features of the structures of these complexes are intermolecular C H⋯I and C H⋯O hydrogen bonds. These complexes were found to be efficient catalysts for the Suzuki reaction of aryl bromides.

Two triphenylphosphine (PPh3)-cyclometallated iridium(III) pyrimidine complexes Ir(NDMP)2PPh3Cl 1 and Ir(NDMP)(PPh3)2Cl2 2 (NDMP = 2-(2-naphthyl)-4,6- dimethyl-pyrimidine) were synthesized and characterized by NMR, IR, ESI-MS, and elemental analysis. Additionally, their detailed structures have been determined by X-ray single-crystal diffraction. The complex 1 was a PPh3-biscyclometalated Ir(III) complex, while 2 was a PPh3-monocyclometalated Ir(III) complex. These complexes were found to be efficient catalysts for α-alkylation of ketones with alcohols.

Two novel anthracene derivatives 2-tert-butyl-9,10-bis(2-biphenyl) anthracene (TBBPA) and 2-tert-butyl-9,10-bis[2-(1-naphthyl)phenyl]anthracene (TBNPA) were synthesized and characterized. The quantum chemical calculations show that TBBPA and TBNPA have highly non-coplanar structures. Both the two anthracene derivatives exhibit deep-blue emission with high fluorescence quantum yields. The electrochemical properties and energy levels of the two compounds were investigated by cyclic voltammetry. The non-doped devices based on the two anthracene derivatives exhibit low turn-on voltage and stable deep-blue emission with high efficiency (external quantum efficiency of about 3.0%). The Commission Internationale de l'Eclairage (CIE) coordinates (0.15, 0.07) of the devices are very close to the National Television System Committee (NTSC) blue standard. The comprehensive performances of the devices are comparable to the best of the non-doped deep-blue OLEDs with a CIE coordinate of y < 0.10.