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A bacterial galactokinase (ScGalK) phosphorylates xylose to xylose 1-phosphate, and allows xylose recycling via a simple UDP-xylose 'salvage pathway', which significantly reduces cofactor requirements compared to the known pentose phosphate pathway.

ConspectusElectron-deficient boron-based catalysts with metal-free but metallomimetic characteristics provide a versatile platform for chemical transformations. However, their catalytic performance is usually lower than that of the corresponding metal-based catalysts. Furthermore, many elaborate organoboron compounds are produced via time-consuming multistep syntheses with low yields, presenting a formidable challenge for large-scale applications of these catalysts. Given this context, the development of organoboron catalysts with the combined advantages of high efficiency and easy preparation is of critical importance.Therefore, we envisioned that the construction of a dynamic Lewis multicore system (DLMCS) by integrating the Lewis acidic boron center(s) and a Lewis basic ammonium salt in one molecule would be particularly efficient for on-demand applications because of the intramolecular synergistic effect. This Account summarizes our recent efforts in developing modular organoboron catalysts with unprecedented activities for several chemical transformations. A series of mono-, di-, tri-, and tetranuclear organoboron catalysts was readily designed and prepared in nearly quantitative yields over two steps using commercially available feedstocks. Notably, these catalysts can be modularly tailored by fine control over the electrophilic property of the Lewis acidic boron center(s), electronic and steric effects of the electropositive ammonium cation, linker length between the boron center and the ammonium cation, the number of boron centers, and the nucleophilic anion. This modular design allows systematic manipulation of the reactivity and efficacy of the catalysts, thus optimizing suitable catalysts for versatile chemical transformations. These include the coupling of CO2 and epoxides, copolymerization of CO2 and epoxides, ring-opening polymerization (ROP) of epoxides, and ring-opening copolymerization (ROCOP) of epoxides and cyclic anhydrides.The utilization of mononuclear organoboron catalysts provided a turnover frequency of 11050 h-1 for the CO2/propylene oxide coupling reaction, an unprecedented efficiency of 5.0 kg of polymer/g of catalyst for the copolymerization of CO2 and cyclohexene oxide, and a record-breaking catalytic efficiency of 7.4 kg of polymer/g of catalyst for the ROCOP of epoxides with cyclic anhydrides. A turnover number of 56500 was observed at a catalyst loading of 10 ppm for the ROP of epoxides using the dinuclear catalysts. The tetranuclear organoboron catalysts realized the previously intractable task of the copolymerization of CO2 and epichlorohydrin, producing poly(chloropropylene carbonate) with the highest molecular weight of 36.5 kg/mol reported to date.Furthermore, the study revealed that the interaction between the dynamic Lewis multicore, that is, the intramolecular synergistic effect between the boron center(s) and the quaternary ammonium salt, plays a key role in mediating the catalytic activity and selectivity. This was based on investigations of the crystal structures of the catalysts, key intermediates, reaction kinetics, and density functional theory calculations. The modular tactics for the construction of organoboron catalysts presented in this Account should inspire more advanced catalyst designs.

Aliphatic polyethers are one of the most widely used polymers, whose synthesis is largely dependent on metallic compounds. Recent development of organocatalysts may break the limits of this long-standing field and infuse vitality into polyether production. In this Synpacts article, the recent advances of organocatalysts for polyether production is introduced in aspects of catalytic performance and mechanism. Moreover, attentions are paid to the latest contributions of bifunctional organoboron catalysts which can be prepared with high yields from cost-effective raw materials in two facile reactions and show excellent performance in the polyether production with remarkable catalytic efficiency, controllability on molecular weight, and explicit polymerization mechanism. Based on these advances, it is envisioned that new discoveries using organocatalysts will continue in the foreseeable future.1 Introduction2 Challenges in Metallic Catalysts3 Previous Advances in Organocatalysts4 Recent Contributions of Bifunctional Organoboron Catalysts5 Conclusion

Poly(cyclopentene carbonate) (PCPC) produced by copolymerization of CO

The copolymerization of carbon dioxide (CO2) and epoxides to produce aliphatic polycarbonates is a burgeoning technology for the large-scale utilization of CO2 and degradable polymeric materials. Even with the wealth of advancements achieved over the past 50 years on this green technology, many challenges remain, including the use of metal-containing catalysts for polymerization, the removal of the chromatic metal residue after polymerization, and the limited practicable epoxides, especially for those containing electron-withdrawing groups. Herein, we provide kinds of pinwheel-shaped tetranuclear organoboron catalysts for epichlorohydrin/CO2 copolymerization with >99% polymer selectivity and quantitative CO2 uptake (>99% carbonate linkages) under mild conditions (25-40 °C, 25 bar of CO2). The produced poly(chloropropylene carbonate) has the highest molecular weight of 36.5 kg/mol and glass transition temperature of 45.4 °C reported to date. The energy difference (ΔEa = 60.7 kJ/mol) between the cyclic carbonate and polycarbonate sheds light on the robust performance of our metal-free catalyst. Control experiments and density functional theory (DFT) calculations revealed a cyclically sequential copolymerization mechanism. The metal-free feature, high catalytic performance under mild conditions, and no trouble with chromaticity for the produced polymers imply that our catalysts are practical candidates to advance the CO2-based polycarbonates.

A hierarchical multichannel polydopamine (HMPDA) nanoparticle with ample chondroitin sulfate (CS) is fabricated via modification of the silane coupling agent (APTES), followed by grafting CS on the unique bicontinuous open channels of HMPDA through amidation reaction. The obtained nanoparticles with both mesopores and macropores, abbreviated as HMPDA-A-CS15, possess a total pore volume of 0.3398 cm3 g-1, and a large surface area up to 69.10 m2 g-1. The as-prepared HMPDA-A-CS15 exhibits significantly enhanced selectivity for the separation of LDL, which is attributed to the specific recognition effect of CS for LDL. Furthermore, the unique large open channels endow the HMPDA-A-CS15 nanoparticles with a gratifying sorption capacity (1015.2 mg g-1) for LDL adsorption. The captured LDL can be stripped using 0.5% (v/v) ammonia solution with the advantage of easy atomization in downstream mass spectrometry (MS) analyses, and a recovery of 71.7% is achieved. Moreover, HMPDA-A-CS15 is further employed in the enrichment of LDL, which can be separated from the complex serum of simulated hypercholesterolemia patients with a favorable adsorption performance, as illustrated by the SDS-PAGE technique.

Background: Hepatocellular carcinoma (HCC) presents a common malignant tumor worldwide. Although kinectin 1 (KTN1) is the most frequently identified antigen in HCC tissues, the detailed roles of KTN1 in HCC remain unknown. This study seeks to clarify the expression status and clinical value of KTN1 in HCC and to explore the complicated biological functions of KTN1 and its underlying mechanisms. Methods: In-house reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of KTN1 in HCC tissues. External gene microarrays and RNA-sequencing datasets were downloaded to confirm the expression patterns of KTN1. The prognostic ability of KTN1 in HCC was assessed by a Kaplan-Meier curve and a hazard ratio forest plot. The CRISPR/Cas9 gene-editing system was used to knock out KTN1 in Huh7 cells, which was verified by PCR-Sanger sequencing and western blotting. Assays of cell migration, invasion, viability, cell cycle, and apoptosis were conducted to explore the biological functions. RNA sequencing was performed to quantitatively analyze the functional deregulation in KTN1-knockout cells compared to Huh7-wild-type cells. Upregulated genes that co-expressed with KTN1 were identified from HCC tissues and were functionally annotated. Results: KTN1 expression was increased in HCC tissues (standardized mean difference [SMD] = 0.20 [0.04, 0.37]). High KTN1 expression was significantly correlated with poorer prognosis of HCC patients, and KTN1 may be an independent risk factor for HCC (pooled HRs = 1.31 [1.05, 1.64]). After KTN1-knockout, the viability, migration, and invasion ability of HCC cells were inhibited. The proportion of HCC cells in the G0-G1 phases increased after KTN1 knockout, which also elevated the apoptosis rates in HCC cells. Several cascades, including innate immune response, chemical carcinogenesis, and positive regulation of transcription by RNA polymerase II, were dramatically changed after KTN1 knockout. KTN1 primarily participated in the cell cycle, DNA replication, and microRNAs in cancer pathways in HCC tissues. Conclusion: Upregulation of KTN1 served as a promising prognosticator in HCC patients. KTN1 promotes the occurrence and deterioration of HCC by mediating cell survival, migration, invasion, cell cycle activation, and apoptotic inhibition. KTN1 may be a therapeutic target in HCC patients.

A series of highly active organoboron catalysts for the coupling of CO2 and epoxides with the advantages of scalable preparation, thermostability, and recyclability is reported. The metal-free catalysts show high reactivity towards a wide scope of cyclic carbonates (14 examples) and can withstand a high temperature up to 150 °C. Compared with the current metal-free catalytic systems that use mol % catalyst loading, the catalytic capacity of the catalyst described herein can be enhanced by three orders of magnitude (epoxide/cat.=200 000/1, mole ratio) in the presence of a cocatalyst. This feature greatly narrows the gap between metal-free catalysts and state-of-the-art metallic systems. An intramolecular cooperative mechanism is proposed and certified on the basis of investigations on crystal structures, structure-performance relationships, kinetic studies, and key reaction intermediates.

The utilization of carbon dioxide (CO2) as a monomer for copolymerization with three-membered cyclic ethers, also known as oxiranes or epoxides, has received much renewed interest due to the need for degradable polymeric materials derived from renewable resources. Since the early discovery of the catalytic coupling of CO2 and oxiranes to afford polycarbonates, the area has progressed significantly over the 50 succeeding years. Herein, we describe the currently well-established catalyzed copolymerization process of oxiranes and carbon dioxide utilizing homogeneous metal catalysts. Pertinent to the commercial success of this process is the presence of rapid and reversible chain-transfer reactions that occur in the presence of protic impurities or additives leading to the formation of macropolyols. The focus of this review is to summarize the various synthetic strategies for the production of designer block copolymers for various applications in material science and biomedicine.

This manuscript describes a kind of bifunctional organocatalyst with unprecedented reactivity for the synthesis of polyethers via ring-opening polymerization (ROP) of epoxides under mild conditions. The bifunctional catalyst incorporates two 9-borabicyclo[3.3.1]nonane centers on the two ends as Lewis acidic sites for epoxide activation and a quaternary ammonium halide in the middle as the initiating site. The catalyst could be easily prepared in two steps from commercially available stocks on up to kilogram scale with ≈100 % yield. The organoboron catalyst mediated ROP of epoxides displays living behavior with low catalyst loading (5 ppm) and enables the synthesis of polyethers with molecular weights of over a million grams per mole (>106  g mol-1 ). Based on the investigations on crystal structure of catalyst, MALDI-TOF, and 11 B NMR spectroscopy, an intramolecular ammonium cation assisted SN 2 mechanism is proposed and verified by DFT calculations.

Objective To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). Methods Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer‐generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. Results A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437). Conclusion Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

The metallic catalyst-dominated alternating copolymerization of CO2 and epoxides has flourished for 50 years; however, the involved multistep preparation of the catalysts and the necessity to remov...

The functionalization of glycosides with ionic compounds such as ionic liquids provides enhanced polarity for the labelled glycans thanks to the presence of a permanent positive charge. The chemical derivatisation of glycans with ionic liquids constitutes an emerging strategy to boost the detection sensitivity in MS applications. This allows the straightforward monitoring and detection of the presence of labelled glycans in complex matrices and in those cases where very limited amounts of material were available such as in biological samples and chemoenzymatic reactions. The use of ionic liquid based derivatisation agents can be further exploited for the labelling of live cells via metabolic oligosaccharide engineering for the detection of cancer biomarkers and for the tuning of live cells-surface properties with implications in cancer prognosis and progression. In this mini-review we summarise the latest development of the ionic liquid based derivatisation agents in glycoscience focussing on their use for sensitive MS applications.

A novel imidazolium derivative (GITag) shows superior ionisation and consequently allows increased mass spectrometric detection capabilities of oligosaccharides and N-glycans. Here we demonstrate that human serum samples can be directly labelled by GITag on a MALDI target plate, abrogating prevalently required sample pretreatment or clean-up steps.

A novel imidazolium derivative (GITag) shows superior ionisation and consequently allows increased mass spectrometric detection capabilities of oligosaccharides and N-glycans. Here we demonstrate that human serum samples can be directly labelled by GITag on a MALDI target plate, abrogating prevalently required sample pretreatment or clean-up steps., A novel imidazolium derivative (GITag) shows superior ionisation and therefore allows increased mass spectrometric detection capabilities, herein demonstrated by directly labelling human serum N-glycans without sample pretreatment or cleanup steps.

Producing polyesters with high molecular weight (Mn ) through ring-opening copolymerization (ROCOP) of epoxides with cyclic anhydrides remains a major challenge. Herein, we communicate a metal-free, highly active, and high thermoresistance system for the ROCOP of epoxides with cyclic anhydrides to prepare polyesters (13 examples). The organoboron catalysts can endure a reaction temperature as high as 180 °C for the ROCOP of cyclohexane oxide (CHO) with phthalic anhydride (PA) without the observation of any side reactions. The average Mn of the produced poly(CHO-alt-PA) climbed to 94.5 kDa with low polydispersity (Ð=1.19). Furthermore, an unprecedented turnover number of 9900, equivalent to an efficiency of 7.4 kg of polyester/g of catalyst, was achieved at a feed ratio of CHO/PA/catalyst=20000:10000:1 at 150 °C. Kinetic studies, crystal structure analysis, 11 B NMR spectra, and DFT calculations provided mechanistic justification for the effectiveness of the catalyst system.

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

The copolymerization of carbon dioxide (CO

A salt-responsive nanoplatform is constructed through a simple tactic by tethering zwitterionic nanohydrogels (NGs) on a carboxylated silica (SiO2-COOH) framework. Chondroitin sulfate (CS), with a ...

Background: Hepatocellular carcinoma (HCC) presents a common malignant tumor worldwide. Although kinectin 1 (KTN1) is the most frequently identified antigen in HCC tissues, the detailed roles of KTN1 in HCC remain unknown. This study seeks to clarify the expression status and clinical value of KTN1 in HCC and to explore the complicated biological functions of KTN1 and its underlying mechanisms. Methods: In-house reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of KTN1 in HCC tissues. External gene microarrays and RNA-sequencing datasets were downloaded to confirm the expression patterns of KTN1. The prognostic ability of KTN1 in HCC was assessed by a Kaplan-Meier curve and a hazard ratio forest plot. The CRISPR/Cas9 gene-editing system was used to knock out KTN1 in Huh7 cells, which was verified by PCR-Sanger sequencing and western blotting. Assays of cell migration, invasion, viability, cell cycle, and apoptosis were conducted to explore the biological functions. RNA sequencing was performed to quantitatively analyze the functional deregulation in KTN1-knockout cells compared to Huh7-wild-type cells. Upregulated genes that co-expressed with KTN1 were identified from HCC tissues and were functionally annotated. Results: KTN1 expression was increased in HCC tissues (standardized mean difference [SMD] = 0.20 [0.04, 0.37]). High KTN1 expression was significantly correlated with poorer prognosis of HCC patients, and KTN1 may be an independent risk factor for HCC (pooled HRs = 1.31 [1.05, 1.64]). After KTN1-knockout, the viability, migration, and invasion ability of HCC cells were inhibited. The proportion of HCC cells in the G0-G1 phases increased after KTN1 knockout, which also elevated the apoptosis rates in HCC cells. Several cascades, including innate immune response, chemical carcinogenesis, and positive regulation of transcription by RNA polymerase II, were dramatically changed after KTN1 knockout. KTN1 primarily participated in the cell cycle, DNA replication, and microRNAs in cancer pathways in HCC tissues. Conclusion: Upregulation of KTN1 served as a promising prognosticator in HCC patients. KTN1 promotes the occurrence and deterioration of HCC by mediating cell survival, migration, invasion, cell cycle activation, and apoptotic inhibition. KTN1 may be a therapeutic target in HCC patients.

Zr-based metal-organic framework, UiO-66-NH2, provides favorable adsorption capacity to phosphoproteins, however, it exhibits obvious nonspecific adsorption to other proteins. In the present work, we report a facile strategy to reduce the nonspecific adsorption of nonphosphoproteins by modifying UiO-66-NH2 with imidazolium ionic liquids (ILs). With respect to bare UiO-66-NH2, the modified counterpart, UiO@IL, exhibits much improved selectivity to phosphoproteins while maintains comparable adsorption performance. The surface of UiO@IL presents a strong hydrophilicity due to the modification of ILs. Hydrophobic and electrostatic interaction between the absorbent and nonphosphoprotein is significantly reduced. In addition, the interaction between imidazole group of ILs moiety and phosphate group in phosphoprotein ensures the favorable adsorption capacity of UiO@IL for phosphoproteins. Anionic moieties of ILs, i.e., Cl−, Br−, BF4−, CF3SO3−, play negligible effect in the adsorption process. As a representative, phosphoprotein β-casein (β-ca) is selectively enriched at a mass ratio of BSA:β-ca = 100:1. UiO@IL was further applied for the selective enrichment of phosphoprotein in milk.

A series of highly active organoboron catalysts for the coupling of CO

The metallic catalyst-dominated alternating copolymerization of CO

The development of solvent-free, metal-free, recyclable organic catalysts is required for the current chemical fixation of carbon dioxide converted into cyclic carbonates. With the goal of reducing the cost, time, and energy consumption for the coupling reaction of CO

A ratiometric fluorescent probe (RIL) for imaging lysosomal HOCl was prepared, which was designed based on the imidazo[1,5-a]pyridine-rhodamine platform. The probe’s selectivity was excellent, and the detection was not affected by other analytes. Probe RIL responded to HOCl rapidly with a low detection limit of 27 nM. For the biological application, RIL performed well in detecting endogenous HOCl in RAW264.7 cells. Furthermore, the probe could target lysosomes and monitor lysosomal HOCl changes due to the introduction of morpholine moiety, which was identified as a lysosome-targeting group. We believe that RIL had significant potential as a practical molecular tool for HOCl-related research in lysosomes.

Construction of block copolymers is a practical method for modifying the properties of CO2-based polycarbonates (CO2-PCs) in order to meet specific needs. Herein, we report a well-defined single-site β-diiminate zinc complex 1 equipped with the capacities of coordination copolymerization of CO2/epoxide and reversible addition–fragmentation chain transfer (RAFT) polymerization of vinyl monomers. Complex 1 is specifically designed to possess a 3-(benzylthiocarbonothioylthio)propionate (BSTP) initiating group, which enables the controlled ring-opening copolymerization of epoxides and CO2, leaving a polycarbonate with BSTP functional group at the end of the chain. The end-capped BSTP allows direct chain extension via living RAFT polymerization, thus providing a robust method to construct various CO2-based block copolymers in one pot via a tandem catalysis strategy. The structure of 1 is established by single-crystal X-ray diffraction as well as 1H and 13C NMR. By utilizing 1, a wide range of CO2-based block c...

The coupling of epoxides and carbon dioxide to polycarbonates (CO2–PCs) has been the subject of intense research for nearly half a century. Although tremendous progress has been achieved, their aliphatic characteristics and lack of functionalities of CO2–PCs limit the scope of their application in high value-added and functional materials. In this article, the first CO2-based polycarbonate with the ability to autonomously self-heal is constructed via a one-pot synthetic strategy. The key to the success of the synthetic strategy is efficient tandem three different catalytic reactions, i.e., hydrolysis of epoxides, immortal copolymerization of CO2/epoxides, and thiol–ene click reactions in a one-pot process. Based on the standard tensile testing, these CO2-based materials show robust self-healing properties, where the extensibility, maximal strength, and Young’s modulus of the specimens can almost entirely recover to their original value under ambient temperature. Our studies demonstrate that the self-heali...

Immortal copolymerization of epoxides/CO2 using macro-chain-transfer agent (macro-CTA) is a useful method to prepare CO2-based block copolymers for manufacturing high value-added materials. Despite a variety of CO2-based block copolymers that have been reported using distinct macro-CTAs, issues including catalytic activity and blocking efficiency for the immortal polymerization remain superficially understood. Here, we systematically studied the reaction activity and blocking efficiency by using various macro-CTAs (including PPG, PEG, and PS) in the presence of two classical catalyst systems ((BDI)ZnOAc and SalenCoTFA/PPN-TFA). By analysis of the gel permeation chromatograms via mathematical deconvolution, it comes to a conclusion that the size, nature, and ratio of [macro-CTA]/[Cat.] strongly influence the catalytic activity of the reaction and blocking efficiency for the resultant block copolymers. Thin film self-assembly of PS/PPC block copolymers was investigated, and the results were analyzed by SEM ...

A modified coaxial electrospraying process, which was characterized by the use of pure solvent as a sheath working fluid, was developed for the continuous and robust generation of medicated nanoparticles. Tamoxifen citrate (TAM) was encapsulated in zein, a plant protein. The influences of the key parameter shell-to-core fluid flow rate on the electrospraying processes and on the resulting protein-based composite particles were investigated in detail. Scanning electron microscopy images revealed that compared with particles prepared via the traditional single-fluid process, TAM-loaded zein particles prepared via the modified coaxial process were rounder with smaller diameters, narrower smaller size distribution, and more compact inner structures. Owing to the reinforced secondary interactions between TAM and zein, all the particles were similarly amorphous composites, as verified by their X-ray patterns and attenuated total reflectance–Fourier transform infrared spectra. The medicated nanoparticles synthesized via the coaxial process exhibited a better drug sustained-release profile than those synthesized via the traditional single-fluid process, with a smaller initial burst release, longer release period, and shorter tailing-off stage. The microformation mechanisms of the electrosprayed particles and their drug sustained-release mechanisms were suggested. By altering the traditional concept of electrospraying, the modified coaxial electrospraying method developed in this study provides a powerful new process for the generation of nanoparticles with novel structures and functions.