Transition‐metal‐catalyzed C‐alkylation of ketones and secondary alcohols, with alcohols, avoids use of organometallic or environmentally unfriendly alkylating agents by means of borrowing hydrogen ...(BH) or hydrogen autotransfer (HA) activation of the alcohol substrates. Water is formed as the only by‐product, thus making the BH process atom‐economical and environmentally benign. Diverse homogeneous and heterogeneous transition‐metal catalysts, ketones, and alcohols can be used for this transformation, thus rendering the BH process promising for replacing those procedures that use traditional alkylating agents. This Minireview summarizes the advances during the last five years in transition‐metal‐catalyzed BH α‐alkylation of ketones, and β‐alkylation of secondary alcohols with alcohols. A discussion on the application of the BH strategy for C−C bond formation is included.
Something borrowed: The major advances during the past five years in transition‐metal‐catalyzed borrowing‐hydrogen (BH) alkylation of ketones, secondary alcohols, and related compounds with alcohols are summarized. Water is formed as the only by‐product, thus making the BH process atom‐economical and environmentally benign.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•A novel chitinase gene from Paenicibacillus barengoltzii was cloned and expressed.•The recombinant chitinase was purified and biochemically characterized.•The hydrolysis properties of chitinase on ...chitin materials were evaluated.•The chitinase hydrolyzed colloidal chitin to yield mainly N-acetyl chitobiose.•The enzyme has great potential in N-acetyl chitobiose production.
A novel chitinase gene (PbChi70) from a marine bacterium Paenicibacillus barengoltzii was cloned and functionally expressed in Escherichia coli. The recombinant enzyme (PbChi70) was purified to homogeneity with a recovery yield of 51.9%. The molecular mass of purified enzyme was estimated to be 70.0kDa by SDS–PAGE. PbChi70 displayed maximal activity at pH 5.5 and 55°C, respectively. It exhibited strict substrate specificity for colloidal chitin, glycol chitin, powdery chitin, and N-acetyl chitooligosaccharides with degrees of polymerization above three. The enzyme exhibited an endo-type cleavage pattern and hydrolyzed colloidal chitin to yield mainly (GlcNAc)2. Furthermore, colloidal chitin was hydrolyzed by PbChi70 to produce 21.6mgmL−1 (GlcNAc)2 with the highest conversion yield of 89.5% (w/w). (GlcNAc)2 was further separated by an active charcoal column with a purity of 99% and a final yield of 61%. The unique enzymatic properties of the chitinase may make it a good candidate for (GlcNAc)2 production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The complex geometry of rotating machines makes the flows strongly affected by rotation and curvature, which are challenging for turbulence modeling. During the development of CFD, large amount of ...turbulence models appeared and hence make the user hard to decide which one to choose. The present paper presents a coherent review of the various approaches proposed in the recent literatures on this topic. First, the influence of the rotation and curvature is reviewed and concluded. Then, the basic concepts of RANS and LES are introduced to facilitate the description of the models and each method is classified into several types. A variety of models are then described and assessed either by the results in the literatures or by own results, with special concentration on the application to rotating machines. Finally, a brief introduction to the hybrid RANS/LES is made and assessed, together with the recommendation for the selection of the models. The aim of the review is to provide information on the advantages and limitations of related models and make it easier for the user to choose an appropriate model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
If a centrifugal impeller is in deep stall, it requires a large amount of additional energy to break free. As such, it is crucial to study the prediction method of impeller stall and establish its ...relationship with force and torque. This study employs a computational fluid dynamics numerical simulation method to analyze the flow field within the impeller of a centrifugal pump, while monitoring the changes in hydraulic torque of the blades. By examining the impeller’s internal flow field characteristics and external (energy performance) characteristics curves under different working conditions, the stall process was classified into three stages: germination, transition and stabilization. The evolution of stall cells under different stall stages was also analyzed. We utilized time-frequency conversion and analysis to extract characteristic parameters from instantaneous hydraulic torque results generated under different working conditions. A more effective model for predicting impeller stall stages was built by virtue of support vector machine algorithm. The proposed model exhibits improved feasibility and effectiveness in comparison to traditional prediction methods. It is expected to have significant implications for stable operation monitoring and safety protection of centrifugal pumps.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A comprehensive analysis of the molecular mechanism underlying colorectal tumor evaluated the development of colorectal cancer (CRC) and proposed targeting small molecular inhibitors. Nonetheless, ...the adoptive resistance of these therapies remains a challenge with respect to achieving an effective clinical response. Thus, identifying the molecular mechanisms guiding CRC growth is essential. The results of The Cancer Genome Atlas (TCGA) dataset analysis demonstrated a critical role of signal transducer and activator of transcription 3 (STAT3) pathway in tumor immune suppression via modulation of the recruitment of Treg cells and M2 type tumor-associated macrophages. The in vivo experiments elucidate that targeting STAT3 pathways markedly reduce the proportions of TAMs and Tregs by inhibiting tumor progression. These findings revealed crosstalk between Treg cells and M2 macrophages, proving a potential therapeutic strategy for CRC therapy. Combinatorial treatment with STAT3 inhibitor and programmed death 1 (PD-1) antibody therapy effectively prevents CRC tumor growth in a mouse model with high anti-tumor immunity. In summary, targeting STAT3 disrupts the interaction between Treg cells and M2 macrophages and improves the anti-tumor response in CRC, thereby offering a promising strategy to treat patients with CRC.
Currently, the biological understanding of Crohn's disease (CD) remains limited. PANoptosis is a revolutionary form of cell death reported to participate in numerous diseases, including CD. In our ...study, we aimed to uncover the roles of PANoptosis in CD. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified by overlapping PANoptosis-related genes and differentially expressed genes between CD and normal samples in a combined microarray dataset. Three machine learning algorithms were adopted to detect hub DE-PRGs. To stratify the heterogeneity within CD patients, nonnegative matrix factorization clustering was conducted. In terms of immune landscape analysis, the "ssGSEA" method was applied. qRT-PCR was performed to examine the expression levels of the hub DE-PRGs in CD patients and colitis model mice. Ten hub DE-PRGs with satisfactory diagnostic performance were identified and validated: CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1 and XBP1. These genes displayed significant associations with certain immune cell types and CD-related genes. We also constructed gene‒microRNA, gene‒transcription factor and drug‒gene interaction networks. CD samples were classified into two PANoptosis patterns according to the expression levels of the hub DE-PRGs. Our results suggest that PANoptosis plays a nonnegligible role in CD by modulating the immune system and interacting with CD-related genes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Less than 20% of melanoma patients respond to programmed cell death-1 (PD-1) blockade immunotherapies. Thus, it is crucial to understand the dynamic changes in the tumor microenvironment (TME) after ...PD-1 blockade, for developing immunotherapy efficacy.
A genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells, and B16-F10 melanoma mice were used as models. The cellular and molecular characteristics and mechanisms of Treg cells in melanoma were assessed by performing gene expression studies, immunohistochemistry, RNA sequencing, and flow cytometry.
Here, we evaluate the countenance of T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and various immunosuppressive factors within tumor-infiltrated Treg cells after treatment with anti-PD-1 or the indicator transduction and activator of transcription 3 (STAT3) inhibitors. Increased expression of Tim-3 is markedly observed within the tissues of the PD-1 blockade resistance of melanoma patients. Targeting STAT3 significantly boosts the response of resistant-PD-1 therapy within the melanoma mouse model. Mechanistically, the manifestation of STAT3 decreases the expression of Tim-3 and various cytokines in the purified Treg cells from individual PBMCs and the murine melanoma model, limiting the immunosuppression of Treg cells.
Our findings indicate that Tim-3 expression on Treg cells within the TME is STAT3-dependent, providing support to STAT3 as a target and enhancing the immunotherapy for patients suffering from melanoma.
Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis, and it has a good therapeutic effect on ischemic stroke. We sought to ...explore the therapeutic effects of THSWD on pyroptosis in rats with middle cerebral artery occlusion-reperfusion (MCAO/R).
MCAO/R model of rats were established by suture-occluded method. MCAO/R rats were randomly divided into five groups, which were model group, nimodipine group, THSWD high, medium and low dose group (18, 9, and 4.5 g/kg, respectively), rats of sham group without thread embolus. All rats were treated by intragastric administration for 7 days. We detected the level of inflammatory factors. NLRP3 and Caspase-1 were detected by immunofluorescence. Western blot was used to detect NLRP3, Caspase-1, ASC, and GSDMD in penumbra. Also, the expression of TXNIP, HMGB1, toll-like receptors (TLR4), NF-κB, and MAPK were detected.
THSWD treatment improved the behavioral function and brain pathological damage. These results showed that the levels of TNF-α, TGF-β, IL-2, IL-6, IL-1β, and IL-18 were significantly reduced in THSWD treatment groups. THSWD could significantly decrease the expression levels of NLRP3, Caspase-1, Caspase-1 p10, ASC, TXNIP, GSDMD, HMGB1, TLR4/NFκB, p38 MAPK, and JNK in penumbra.
Our results showed that THSWD could reduce the activation level of NLRP3 inflammatory corpuscle, down-regulate GSDMD, and inhibit pyroptosis in MCAO/R rats. These may be affected by inhibiting HMGB1/TLR4/NFκB, MAPK signaling pathways.
A general and efficient method for the synthesis of pronucleotide (ProTide) 5′-phosphoramidate monoesters is reported. This method consists of a highly stereoselective 5′-phosphorylation mediated by ...dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing 3′-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.
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IJS, KILJ, NUK, PNG, UL, UM
1 Departments of Anesthesiology, 2 Neurobiology and Anatomy, 3 Physiology, and 4 Chemistry, University of Utah, Salt Lake City, Utah; and 5 College of Pharmacy, Seoul National University, Seoul, ...Korea
Submitted 13 December 2007;
accepted in final form 27 May 2008
The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.
Address for reprint requests and other correspondence: A. R. Light, Department of Anethesiology and Neurobiology and Anatomy, 3C444 SOM, University of Utah School of Medicine, 30N. 1900E., Salt Lake City, UT 84132-2304 (E-mail: alan.light{at}hsc.utah.edu )
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