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We herein demonstrate superparamagnetic [Fe.sub.3][O.sub.4] nanoparticles coated with nitrilotriacetic acid derivative (NTA) that can bind with different immobilized metal ions are capable of probing diverse target species. Immobilized Ni(II) on the surfaces of the NTA-magnetic nanoparticles have the capability of selectively trapping histidine (His)-tagged proteins such as a mutated streptopain tagged with 6 x His, i.e., C192S (MW ~42 kDa), from cell lysates. Enrichment was achieved by vigorously mixing the sample solution and the nanoparticles by pipetting in and out of a sample vial for only 30 s. After enrichment, the probe-target species could be readily isolated by magnetic separation. We also characterized the proteins enriched on the affinity probes using on-probe tryptic digestion under microwave irradiation for only 2 min, followed by matrix-assisted laser desorption/ionization mass spectrometry analysis. Using this enrichment and tryptic digestion, the target species can be rapidly enriched and characterized, reducing the time required for carrying out the complete analysis to less than 10 min. Furthermore, when either Zr(IV) or Ga (III) ions are immobilized on the surfaces of the NTA-magnetic nanoparticles, the nanoparticles have the capability of selectively enriching phosphorylated peptides from tryptic digests of [alpha]-, [beta]-caseins, and diluted milk. The detection limit for the tryptic digests of [alpha]- and [beta]-caseins is ~50 fmol.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides a straightforward means to differentiate microorganism species based on mass spectral fingerprinting. The pathogen cell concentration in an infected sample, however, is generally lower than that capable of being detected directly by MALDI-MS. Furthermore, the presence of proteins or metabolites in biological fluids always causes unavoidable interference for the identification of microorganism species. Vancomycin, which binds to D-Ala-D-Ala moieties on the cell walls of Gram-positive bacteria and, therefore, inhibits peptidoglycan synthesis, is one of the most potent antibiotics. Thus, we have employed vancomycin-modified magnetic nanoparticles as affinity probes to selectively trap Gram-positive pathogens from sample solutions; i.e., these bacteria can be isolated from sample solutions by applying a magnetic field. The isolated cells could then be characterized by MALDI-MS. This approach effectively reduces the interference of protein and metabolite signals in the mass spectra of Gram-positive bacteria because vancomycin has such high specificity for the D-Ala-D-Ala units of the cell walls. The lowest cell concentration we detected for both Staphylococcus saprophyticus and Staphylococcus aureus in a urine sample (3 mL) was ~7 x [10.sup.4] cfu/mL.

In this paper, we report a method for fabricating biofunctionalized nanoparticles by attaching human immunoglobulin (IgG) onto their surfaces through either electrostatic interactions or covalent binding. We found that these IgG-presenting nanoparticles can bind selectively to the cell walls of pathogens that contain IgG-binding sites based on the investigation of transmission electron microscopy images. Our results demonstrate that such Au--IgG nanoparticles may serve as useful nanoscale probes for exploring the interactions between IgG and pathogens. Furthermore, the IgG-presenting magnetic nanoparticles have been employed as effective affinity probes for selectively concentrating traces of target bacteria from sample solutions. The trapped bacteria were then characterized by using matrix-assisted laser desorption/ionization mass spectrometry. The lowest cell concentration we detected for both Staphylococcus saprophyticus and Staphylococcus aureus in aqueous sample solutions (0.5 mL) was ~3 x [10.sup.5] cfu/mL, while the detectable cell concentration for S. saprophyticus in a urine sample was ~3 x [10.sup.7] cfu/mL.

MALDI mass spectrometry is used widely in various fields because it has the characteristics of speed, ease of use, high sensitivity, and wide detectable mass range, but suppression effects between analyte molecules and interference from the sample matrix frequently arise during MALDI analysis. The suppression effects can be avoided if target species are isolated from complicated matrix solutions in advance. Herein, we proposed a novel method for achieving such a goal. We describe a strategy that uses gold nanoparticles to capture charged species from a sample solution. Generally, ionic agents, such as anionic or cationic stabilizers, encapsulate gold nanoparticles to prevent their aggregation in solution. These charged stabilizers at the surface of the gold particles are capable of attracting oppositely charged species from a sample solution through electrostatic interactions. We have employed this concept to develop nanoparticle-based probes that selectively trap and concentrate target species in sample solutions. Additionally, to readily isolate them from solution after attracting their target species, we used gold nanoparticles that are adhered to the surface of magnetic particles through S--Au bonding. A magnet can then be employed to isolate the Au@magnetic particles from the solution. The species trapped by the isolated particles were then characterized by MALDI MS after a simple washing. We demonstrate that Au@magnetic particles having negatively charged surfaces are suitable probes for selectively trapping positively charged proteins from aqueous solutions. In addition, we have employed Au@magnetic particle-based probes successfully to concentrate low amounts of peptide residues from the tryptic digest products of cytochrome c ([10.sup.-7] M).

This work presents a novel method for direct desorption/ ionization of analytes from sol--gel-derived film. 2,5-Dihydroxy benzoic acid (DHB), a common MALDI matrix, was incorporated into a sol--gel polymeric structure. The sol--gel-derived DHB thin film can assist the mass analysis of analytes by laser desorption/ionization, with a matrix interference-free background in the mass spectra. The sol--gel-derived film can function as an energy absorber during laser irradiation because it contains DHB molecules. Furthermore, laser irradiation with normal laser power (70-110 [micro]J) is not likely to generate any background ions from this sol--gel-DHB derived film. The samples were prepared straightforwardly. After a thin film was formed on a Parafilm membrane from the sol--gel-derived DHB solution coating, the sample solution was directly added to the top of the film, for laser desorption/ionization mass analysis. The analyte signals were homogeneously obtained on the sol--gel-derived DHB film. Experimental results show that the optimum concentrations of DHB incorporated in the sol--gel solution were between 7500 ppm and 10 000 ppm, providing a matrix interference-free background. Analytes, including small proteins, peptides, amino acids, and small organics, were used to demonstrate the effectiveness of the proposed method. However, a higher laser power (> 110 [micro]J) than normal was required to desorb small proteins from the sol--gel-derived DHB film. Therefore, a few matrix ions desorbed from the thin film were generated during laser irradiation. The detection limit for both small molecules and proteins, using this sol--gel-assisted laser desorption/ionization (SGALDI) mass spectrometry (MS), was as low as 81 fmol. However, a mass spectrometer with cutoff-mass selection could detect 8.1 fmol of cytochrome c. The largest analyte observed by the SGALDI-MS in this study was myoglobin.

Redoxbehavior of Fe(I) complexes bearing a PNP-pincer-type phosphaalkeneligand, 2,6-bis[1-phenyl-2-(2,4,6-tri-tert-butylphenyl)-2-phosphaethenyl]pyridine(BPEP-Ph), is reported. The four-coordinate Fe(I) complex [FeBr(BPEP-Ph)](1) readily reacts with 1 equiv of tBuNC in toluene at −35 °C to give [FeBr(tBuNC)(BPEP-Ph)] (2) with a 17e configuration. Complex 2is fairly stable in neat benzene at room temperature, butsmoothly undergoes disproportionation in the presence of added tBuNC to afford the Fe(0) complex [Fe(tBuNC)2(BPEP-Ph)] (3) and the Fe(II) complex[FeBr2(tBuNC)4] (4) along with free BPEP-Ph. The single-crystal X-ray diffraction studiesof 3and 4reveal distorted trigonal bipyramidaland square pyramidal arrangements around Fe, respectively. The yieldof 3increases up to 50%/2when 2 equivof tBuNC is added to the system. A disproportionationprocess involving a 19e intermediate is proposed. [ABSTRACT FROM AUTHOR]

Cesium carbonate promoted direct amidation of unactivated esters with amino alcohols was developed without the use of transition-metal catalysts and coupling reagents. This method enabled the synthesis of several serine-containing oligopeptides and benzamide derivatives with yields up to 90%. The methodology proceeds under mild reaction conditions and exhibits no racemization for most naturally occurring amino acid substrates. The reaction demonstrates good compatibility with primary alkyl and benzyl esters and broad tolerance for a range of amino acid substrates with nonpolar and protected side chains. The hydroxy group on the amine nucleophile was found to be critical for the reaction to be successful. A likely mechanism involving cesium coordination to the substrates enabling the subsequent proximity-driven acyl transfer was proposed. The practicality of this approach was demonstrated in the preparation of a biologically active nicotinamide derivative in a reasonable yield.

In an integrated circuit, signal propagation loss is proportional to the frequency, dissipation factor ( D f ), and square root of dielectric constant ( D k ). The loss becomes obvious as we move to high-frequency communication. Therefore, a polymer having low D k and D f is critical for copper-clad laminates at higher frequencies. For this purpose, a 4-vinylbenzyl ether phenoxy-2,3,5,6-tetrafluorophenylene-terminated OPE (VT-OPE) resin was synthesized and its properties were compared with the thermoset of commercial OPE-2St resin. The thermoset of VT-OPE shows a higher T g (242 vs 229 °C), a relatively high cross-linking density (1.59 vs 1.41 mmole cm -3 ), a lower coefficient of thermal expansion (55 vs 76 ppm/°C), better dielectric characteristic at 10 GHz ( D k values of 2.58 vs 2.75, D f values of 0.005 vs 0.006), lower water absorption (0.135 vs 0.312 wt %), and better flame retardancy (UL-94 VTM-0 vs VTM-1 with dropping seriously) than the thermoset of OPE-2St. To verify the practicability of VT-OPE for copper-clad laminate, a laboratory process was also performed to prepare a copper-clad laminate, which shows a high peeling strength with copper foil (5.5 lb/in), high thermal reliability with a solder dipping test at 288 °C (>600 s), and the time for delamination of the laminate in thermal mechanical analysis (TMA) at 288 °C is over 60 min., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

T lymphocyte infiltration with immunotherapy potentially suppresses most devastating brain tumors. However, local immune privilege and tumor heterogeneity usually limit the penetration of immune cells and therapeutic agents into brain tumors, leading to tumor recurrence after treatment. Here, a rabies virus glycoprotein (RVG)-camouflaged gold yarnball (RVG@GY) that can boost the targeting efficiency at a brain tumor via dual hierarchy- and RVG-mediated spinal cord transportation, facilitating the decrease of tumor heterogeneity for T cell infiltration, is developed. Upon magnetoelectric irradiation, the electron current generated on the GYs activates the electrolytic penetration of palbociclib-loaded dendrimer (Den[Pb]) deep into tumors. In addition, the high-density GYs at brain tumors also induces the disruption of cell-cell interactions and T cell infiltration. The integration of the electrolytic effects and T cell infiltration promoted by drug-loaded RVG@GYs deep in the brain tumor elicits sufficient T cell numbers and effectively prolongs the survival rate of mice with orthotopic brain tumors.

Organic-inorganic hybrid halide perovskites (OIHPs) with inherent mixed ionic-electronic conduction ability have been proposed as promising candidates for memristors with unique optoelectronic characteristics. Despite the great achievements toward understanding the working mechanism and exploring their functionality as water-sensitive materials, the humidity effect on the resistive switching (RS) characteristics still remains to be studied. This study investigates the humidity effect on the RS characteristics of Au/CH 3 NH 3 PbI 3 /FTO memristor. The memristor works well at moderate relative humidity (RH, <75%) and degrades rapidly at higher RH of 90%. An obvious decrease in low resistance states on increasing the RH level is observed, which could be attributed to water-induced reduction of the iodide migration barrier. Raman and X-ray diffraction analyses indicate that the migration barrier reduction possibly originated from the weakening of the Pb-I bond caused by the intercalation of water molecules into the crystal lattice. The humidity-sensitive RS characteristics of the memristor could extend the scope of OIHP application for sensing and security applications and also prompt researchers to pay attention to the humidity effect on memristor devices with OIHPs.

Platinum telluride (PtTe 2 ) has garnered significant research enthusiasm owing to its unique characteristics. However, large-scale synthesis of PtTe 2 toward potential photoelectric and photovoltaic application has not been explored yet. Herein, we report direct tellurization of Pt nanofilms to synthesize large-area PtTe 2 films and the influence of growth conditions on the morphology of PtTe 2 . Electrical analysis reveals that the as-grown PtTe 2 films exhibit typical semimetallic behavior, which is in agreement with the results of first-principles density functional theory (DFT) simulation. Moreover, the combination of multilayered PtTe 2 and Si results in the formation of a PtTe 2 /Si heterojunction, exhibiting an obvious rectifying effect. Moreover, the PtTe 2 -based photodetector displays a broadband photoresponse to incident radiation in the range of 200-1650 nm, with the maximum photoresponse at a wavelength of ∼980 nm. The R and D * of the PtTe 2 -based photodetector are found to be 0.406 A W -1 and 3.62 × 10 12 Jones, respectively. In addition, the external quantum efficiency is as high as 32.1%. On the other hand, the response time of τ rise and τ fall is estimated to be 7.51 and 36.7 μs, respectively. Finally, an image sensor composed of a 8 × 8 PtTe 2 -based photodetector array was fabricated, which can record five near-infrared (NIR) images under 980 nm with a satisfying resolution. The result demonstrates that the as-prepared PtTe 2 material will be useful for application in NIR optoelectronics.

Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as the preferred choice for the treatment of atrial fibrillation (AF). The establishment of a therapeutic range to minimize bleeding and thrombosis is important for personalized treatment of NOACs. The importance of dried blood spots (DBSs) has increased in medical care. An efficient and effective DBS analytical method could facilitate the concentration management of NOACs. The postcolumn infused internal standard (PCI-IS) method was applied to estimate spot volume and quantify dabigatran, rivaroxaban, and apixaban concentrations on DBS cards. The extraction solvent contented 0.1% formic acid and 70% ACN with a successive extraction procedure. Paired DBS and plasma samples from patients undergoing NOAC therapy ( n = 269) were used to calculate conversion factors. [ 13 C 6 ]-Rivaroxaban was selected as the PCI-IS. The quantification accuracy for the three NOACs was within 88.9-104.3%. The RSDs of the repeatability and intermediate precision were below 10%. The obtained conversion factors of DBS to plasma concentrations of dabigatran, apixaban, and rivaroxaban were 1.81, 1.59, and 1.31, respectively. Bland-Altman analysis showed that the % differences between predicted and measured plasma concentrations were within a bias of ±20%. The result showed that PCI-IS was an accurate and efficient LC-MS/MS method to simultaneously estimate blood volume and NOAC concentrations on DBS cards. The stability results revealed that the DBS sampling strategy could improve compound stability. The developed method offers a new strategy for the therapeutic drug monitoring of NOACs and may improve the safe use of these drugs.

Metal oxides have attracted substantial attention over the years and are commonly used in the semiconductor industry because of their excellent physical and chemical properties. Among the various metal oxides, cuprous oxide (Cu 2 O) is regarded as a promising material. It is inexpensive, earth-abundant, and nontoxic; therefore, it can be used in catalysis, sensors, solar cells, and p-type semiconductors. However, the redox reaction of Cu 2 O is still uncertain. The size, morphology, and structure of Cu 2 O strongly influence its properties. In this work, we developed a new synthesis method of Cu 2 O that involves reducing the precursor by an electron beam without reducing agent. The growth process of Cu 2 O nanocubes was observed via in situ liquid cell transmission electron microscopy (in situ LCTEM). The nucleation kinetics, oscillating growth behavior, and redox reaction of the Cu 2 O nanocubes in the liquid phase were systematically studied. Cu 2 O exhibited a round shape at the beginning and transformed into a cubic shape afterward. Interestingly, the Cu 2 O nanocubes grew clearly under long-term observation; however, their diameters increased and fluctuated during the short-term observation. The electron beam not only stimulated the solution to reduce the nanocubes but also caused electron radiation effect to the nanocubes. During the Cu 2 O growth and dissolution, the cubic shape evolved with specific planes in the {100} family. Our direct observation sheds light on the preparation of Cu 2 O by a reduction method, extending the study of reaction kinetics and providing a new way to synthesize metal oxides.

To explore the regulatory factor of light quality affecting exopolysaccharide (EPS) production, transcriptome analysis of Nostoc flagelliforme cells exposed to red light (R), blue light (B), and mixed light (B/R = 15:7) (BR) with white fluorescent light as control was performed. The differentially expressed genes mainly enriched in carbohydrate metabolism and energy metabolism. Significant enrichment in the oxidation-reduction process and energy metabolism indicated that intracellular redox homeostasis was disrupted. An assay of reactive oxygen species (ROS) and malondialdehyde contents demonstrated light quality induced oxidative stress. To illustrate the relationship between ROS level and EPS accumulation, the effects of the exogenous addition of ROS scavenger N-acetyl cysteine and inducer H 2 O 2 on the oxidation-reduction level and EPS production were compared. The results revealed that light quality regulated EPS biosynthesis via the intracellular ROS level directly other than oxidative stress. Understanding such relationships might provide guidance for efficient EPS production to regulate the intracellular redox level.

Olefin cross-metathesis (CM) is a viable reaction for the modification of alkene-containing proteins. Although allyl sulfide or selenide side-chain motifs in proteins can critically enhance the rate of CM reactions, no efficient method for their site-selective genetic incorporation into proteins has been reported to date. Here, through the systematic evaluation of olefin-bearing unnatural amino acids for their metabolic incorporation, we have discovered S-allylhomocysteine (Ahc) as a genetically encodable Met analogue that is not only processed by translational cellular machinery but also a privileged CM substrate residue in proteins. In this way, Ahc was used for efficient Met codon reassignment in a Met-auxotrophic strain of E. coli (B834 (DE3)) as well as metabolic labeling of protein in human cells and was reactive toward CM in several representative proteins. This expands the use of CM in the toolkit for "tag-and-modify" functionalization of proteins.

Directed assembly of loosely, Na + -bound, oxidovanadate-centered quartets of C 4 -symmetry from tailor-made chiral N-salicylidene-vanadyl(V) complexes, for the first time, allows for highly efficient Ba 2+ - or Hg 2+ -specific detection (by 51 V NMR and VCD), transport (forming a unique helical capsule or a capped square planar complex, respectively), and green recovery from an aqueous phase containing 4 different alkaline earth ions or from at least 10 different metal ions of similar size and charge capacity into the CHCl 3 layer without interference from oxa- or oxophilic ions like Mg 2+ , Ca 2+ , Cu 2+ , Cd 2+ , and Pb 2+ .

Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains. A new ELP nanoparticle (ISR) was synthesized that includes the canonical integrin-targeting ligand (Arg-Gly-Asp, RGD). FSI and ISR mixed in a 1:1 molar ratio coassemble into bifunctional nanoparticles containing both the FKBP domain for Rapa loading and the RGD ligand for integrin binding. Coassembled nanoparticles were evaluated for bifunctionality by performing in vitro cell-binding and drug-retention assays and in vivo MDA-MB-468 breast tumor regression and tumor-accumulation studies. The bifunctional nanoparticle demonstrated superior cell target binding and similar drug retention to FSI; however, it enhanced the formulation potency, such that tumor growth was suppressed at a 3-fold lower dose compared to an untargeted FSI-Rapa control. This data suggests that ELP-mediated scaffolds are useful tools for generating multifunctional nanomedicines with potential activity in cancer.

We report the synthesis, characterization, and photovoltaic properties of four ruthenium complexes (CI101, CBTR, CB111, and CB108) having various N-heterocyclic carbene ancillary ligands, pyridine-imidazole, -benzimidazole, -dithienobenzimidazole, and -phenanthroimidazole, respectively. These complexes were designed to investigate the effect of extended conjugation ordained from ring fusion on the power conversion efficiencies of the solar cells. The device sensitized by CB108, the pyridine-phenanthroimidazole conjugated complex, showed an improved efficiency (9.89%) compared to those of pyridine-benzimidazole conjugated system (CBTR, 9.72%) and the parent unfused ring system (CI101, 6.24%). Surprisingly, the sulfur-incorporated pyridine-dithienobenzimidazole system (CB111, 9.24%) exhibited a little lower efficiency than that of N719 (9.41%). The enhanced photovoltaic performance of CB108 was mainly attributed to the increase in electron lifetime and diffusion length confirmed by the electrochemical impedance spectroscopy.

Bacteria cell walls contain many repeating glycan structures, such as peptidoglycans, lipopolysaccharides, teichoic acids, and capsular polysaccharides. Their synthesis starts in the cytosol, and they are constructed from a glycan lipid carrier, undecaprenyl phosphate (C 55 P), which is essential for cell growth and survival. The lipid derivative undecaprenol (C 55 OH) is predominant in many Gram-positive bacteria but has not been detected in Gram-negative bacteria; its origin and role have thus remained unknown. Recently, a homologue of diacylglycerol kinase (DgkA) in Escherichia coli (E. coli) was demonstrated to be an undecaprenol kinase (UK) in the Gram-positive bacterium Streptococcus mutans (S. mutans). In this study, we found that S. mutans UK was not only an undecaprenol kinase but also a Mg-ADP-dependent undecaprenyl phosphate phosphatase (UpP), catalyzing the hydrolysis of C 55 P to C 55 OH and a free inorganic phosphate. Furthermore, the naturally undetectable C 55 OH was observed in E. coli cells expressing S. mutans dgkA, supporting the phosphatase activity of UK/UpP in vivo. These two activities were indispensable to each other and utilized identical essential residues binding to their substrates, suggesting that both activities share the same active site and might involve a direct phosphoryl transfer mechanism. This study revealed a unique membrane enzyme displaying bifunctional activities determined by substrate binding and C 55 OH production. The reciprocal conversion of C 55 P and the undecaprenol pool efficiently regulate cell wall synthesis, especially in Gram-positive bacteria.

The first chiral Brønsted acid-catalyzed asymmetric cascade allylboration/oxo-Michael reaction between o-formyl chalcones and allylboronate has been successfully discovered, which afforded chiral 1,3-disubstituted 1,3-dihydroisobenzofurans with a yield, diastereoselective ratio (dr) and enantioselective excess (ee) up to 94%, 2.5:1, and 98%, respectively. In addition, 2,3-dienylboronic pinacol ester was also applied into this cascade reaction with good catalytic results.

A radical-mediated approach has been introduced for the C-S bond activation of arylalkenyl sulfides. The protocol provides an efficient approach for the generation of various alkenes including alkenyl silanes, sulfones, phosphine oxides, and nitroolefins. In most cases, these radical substitutions are performed under metal-free conditions with stereospecificity.

A newly developed aqueous system with acid and phosphide was introduced in which odorless and stable sodium arylsulfinates can in situ generate arylsulfenyl radicals. These radicals have high reactivity to react with alkynes, alkenes, and H-phosphine oxides for the synthesis of alkyl and alkenyl sulfides and phosphonothioates. The control experiments and quantum calculations are also performed to gain insights into the generation mechanism of arylsulfenyl radicals. Notably, the chemistry is free of thiol odors, organic solvents, and metals.

Transition-metal-free radical access to 1,4-benzothiazine derivatives from o-aminobenzenethiols is disclosed. This procedure is available for various ketones including α,β-unsaturated, cyclic, linear, and fluoroalkyl ketones to generate a number of 1,4-benzothiazines, which exist in numerous bioactive and natural molecules, rendering this protocol attractive to both synthetic and medicinal chemistry.

The effect of a ligand on the electron deficiency and Lewis acidity of the Cp*-substituted boron dication has been investigated experimentally and theoretically. In addition to the reported IMes- and N-heterocyclic olefin (NHO)-stabilized boron dications, the related cyclic alkylamino carbene (CAAC)-coordinated boron mono- and dications have also been synthesized and structurally characterized. An electrochemical study of dications [3a-3c] 2+ confirms the higher electron deficiency of the dicationic system than the related boron monocations. Moreover, the presence of a π-acidic CAAC ligand is critical for realizing stable radical species generated from the chemical reduction of boron cations. The nature of the axial ligand also significantly affects the selectivity of the hydride addition reaction of boron dications. While bulky superhydride reacts with [3a-3c] 2+ in the same manner to give the cyclic boreniums, [BH 4 ] - attacks three different electrophilic sites of boron dications: the sp 2 carbon of Cp* of the IMes-coordinated system ([3a] 2+ ), the central boron atom of the NHO-stabilized analogue ([3b] 2+ ), and the ylidene carbon of the CAAC-containing boron dication ([3c] 2+ ).

α,α-Difluorodiaroylmethane can be used as a nucleophilic difluoromethylation reagent for generating α-thioaryl-α,α-difluoroacetophenones (Ar(1)COCF2SAr) and difluoromethylthiolated arenes (ArSCF2H) under transition-metal-free conditions. The reaction selectivity is mainly dependent on temperature. The method has also been extended to the synthesis of α-thioaryl-α-monofluoroacetophenones using α-monofluorodibenzoylmethane. Moreover, the benzoyl cation derived from α,α-difluorodibenzoylmethane can react with nucleophiles to afford the desired products in a one-pot process.

A newly developed regio- and stereoselective radical addition of alkyne under metal-free conidtions has been disclosed. This chemistry, in which odorless sodium arenesulfinates in place of thiols are used as the sulfur reagent, provides an efficient, one-pot approach for the generation of β-iodoalkenyl sulfides, which can be easily further functionalized to derive various alkenes and alkynyl sulfides rendering this methodology attractive to both synthetic and medicinal chemistry.

Enterovirus 71 (EV71) is a human enterovirus that has seriously affected the Asia-Pacific area for the past two decades. EV71 infection can result in mild hand-foot-and-mouth disease and herpangina and may occasionally lead to severe neurological complications in children. However, the specific biological processes that become altered during EV71 infection remain unclear. To further explore host responses upon EV71 infection, we identified proteins differentially expressed in EV71-infected human glioblastoma SF268 cells using isobaric mass tag (iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Network analysis of proteins altered in cells infected with EV71 revealed that the changed biological processes are related to protein and ion transport, regulation of protein degradation, and homeostatic processes. We confirmed that the levels of NEDD4L and PSMF1 were increased and reduced, respectively, in EV71-infected cells compared to mock-infected control cells. To determine the physiological relevance of our findings, we investigated the consequences of EV71 infection in cells with NEDD4L or PSMF1 depletion. We found that the depletion of NEDD4L significantly reduced the replication of EV71, whereas PSMF1 knockdown enhanced EV71 replication. Collectively, our findings provide the first evidence of proteome-wide dysregulation by EV71 infection and suggest a novel role for the host protein NEDD4L in the replication of this virus.

A high-fat diet contributes to the etiology of metabolic diseases. As the liver plays a crucial role in metabolism, an insight into the hepatic proteomics will help to illustrate the physiological effect of a high-fat diet. Fourteen nine-week old male Syrian hamsters were maintained on either control (C) or high-fat (HF) diets (0.2% cholesterol +22% fat) for 8 weeks. Hamsters were chosen because they show close similarity to human lipid metabolism. At the end of study, blood and livers were collected for analysis. Liver proteins were fractionated by electrophoresis, digested by trypsin, and then separated by label-free nano-LC/MS/MS. The TurboSequest algorithm was used to identify the peptide sequences against the hamster database in Universal Proteins Resource Knowledgebase (UniProt). The results indicate that 1191 hepatic proteins were identified and 135 of them were expressed differentially in the high-fat group (p < 0.05). Some of these 135 proteins that involve in metabolic diseases were further validated by Western blotting. The animals maintained on the high-fat diet had significantly (p < 0.05) higher serum triglyceride, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and uric acid. Animals consuming a high-fat diet also had significantly (p < 0.05) more accumulation of triglyceride and cholesterol in livers. Xanthine dehydrogenase (XDH), which plays an important role in uric acid synthesis, was up-regulated by the high-fat diet (p < 0.05). The α-subunit of hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (HADHA), which catalyzes the second and third reactions of β-oxidation, was down-regulated by the high-fat diet (p < 0.05). Aconitate hydratase 2 (ACO2), which catalyzes the conversion of citrate to isocitrate in TCA cycle, was down-regulated in animals of the high-fat group (p < 0.05). Inflammatory markers annexin A3 (ANXA3) and annexin A5 (ANXA5) were up-regulated by the high-fat diet (p < 0.05). Moreover, enzymes involved in the urea cycle were suppressed by high-fat diet, including carbamoyl phosphate synthase 1 (CPS1), ornithine transcarbamoylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and arginase 1 (ARG 1). Post-translational modifications (PTM) of ANXA3, ANXA5, and XDH were also analyzed. A set of differentially expressed proteins were identified as molecular markers for elucidating the pathological mechanism of high-fat diet.