Catalytic Asymmetric Amino Acid and Its Derivatives by Chiral Aldehyde Catalysis

Amine acid transformation is an important chemical process in biological systems. As a well-developed and acknowledged tool, chiral aldehyde catalysis provides good catalytic activation and stereoselective control abilities in the asymmetric reaction of N-unprotected amino acid esters and amino acid esters analogs, in which the key to success is the design of the catalysts derived from chiral BINOL aldehyde, which is based on the face control of enolate intermediates. In this review, one of the co-catalytic systems that combined with a transition metal to form a multiplex catalytic system and the well-established multiplex stereocenters of chiral aldehyde catalysis have been reviewed. Finally, a novel organocatalysis is prospected

Learner conceptions of biological processes in a content and language integrated learning context

In science education, learner conceptions concern how students interpret and understand scientific issues. Recent research into learner conceptions acknowledges students’ knowledge, experiences, language, and resources that demonstrate scientific reasoning rather than their misunderstanding. In this study, we follow a functional approach to learner conceptions and explore the functions of language in constructing and representing students’ interpretations of scientific knowledge. The major theoretical framework guiding this research is the thematic pattern analysis theory (Lemke, 1990), which views scientific phenomena as the patterning of semantic relations (i.e., the relation between scientific concepts and its function). We aim to examine the emergence of learner conceptions and potential factors informing student thematic patterning of scientific issues. This study (research ethics reference number: 20200122) is situated in an undergraduate biology course that employed Content Language Integrated Learning (CLIL) in which equal emphasis was given on learning biological concepts and learning the languaging (i.e., appropriately using the thematic patterns) of the concepts. We focus on one written assignment in which students were asked to reason about the mechanism of Antidiuretic Hormone (ADH) in water transport in the scenario of water intoxification from extensive exercise and water consumption. The primary data included students’ written responses, question prompts, and marking schemes. Other textual data including textbooks, PowerPoint slides, and teacher notes were consulted to have a contextualized understanding of students’ responses. Preliminary analysis revealed a basic thematic pattern embedded in most students’ responses: EXERCISE (condition) --\u3e SWEATING (result/condition) --\u3e WATER LOSS (result/condition) --\u3e WATER CONSUMPTION (result/condition). We also identified different thematic patterns of student conceptions along each aspect of the basic pattern. To explore factors informing learner conceptions, we then compared the thematic patterns of students’ responses and the model answer, which helped demonstrate how implicit and conflicting thematic patterns incorporated in instructional materials may hamper students’ understanding of scientific concepts. For example, the notion of water may contain an implicit semantic relation of hyponym, i.e., water (subordinate term) as a specific type of molecule (superordinate category) composed of atoms; however, students may draw from their everyday experience and view water as a free-flowing substance. This study thus calls for biology teachers’ attention to the patterning of scientific representations. It also provides implications for science education in general and stimulates science teachers’ thinking in their language use in teaching scientific concepts. Works cited Lemke, J. (1990). Talking science: Language, learning, and values. Ablex Publishing Corporation. Tang, K. S. (2020). Discourse strategies for science teaching and learning: Research and practice. Routledge

Determination of bupropion hydrochloride in rat plasma by LC-MS/MS and Its application to pharmacokinetic study

A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for quantitation of bupropion hydrochloride in rat plasma using triazolam as an internal standard. Chromatographic separation was achieved on a SB-C18 column at 30 °C, with 50: 50 (v/v) acetonitrile-0.1 % formic acid in water as mobile phase. The flow rate was 0.3 mL/min. The determination of bupropion was performed in MRM mode, m/z 239.9 → 183.7 for bupropion and m/z 343.0 → 308.0 for triazolam (IS) and positive ion electrospray ionization interface. Calibration curve was linear over range of 1.2 to 480 ng/mL. The intra- and inter-run relative standard deviations of the assay were less than 10 %. The mean absolute recoveries determined at the concentrations of 2.4, 48 and 360 ng/mLwere 91.00%, 92.06%, 91.71%, respectively. The validated method is successfully used to analyze the drug in samples of rat plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

CpG Oligodeoxynucleotides Enhance the Efficacy of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes by Modifying the Th1 Polarization and Local Infiltration of Th17 Cells

Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs) was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8+ T cells and CD8+ T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs

Determination of bupropion hydrochloride in rat plasma by LC-MS/MS and Its application to pharmacokinetic study

A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for quantitation of bupropion hydrochloride in rat plasma using triazolam as an internal standard. Chromatographic separation was achieved on a SB-C18 column at 30 °C, with 50: 50 (v/v) acetonitrile-0.1 % formic acid in water as mobile phase. The flow rate was 0.3 mL/min. The determination of bupropion was performed in MRM mode, m/z 239.9 → 183.7 for bupropion and m/z 343.0 → 308.0 for triazolam (IS) and positive ion electrospray ionization interface. Calibration curve was linear over range of 1.2 to 480 ng/mL. The intra- and inter-run relative standard deviations of the assay were less than 10 %. The mean absolute recoveries determined at the concentrations of 2.4, 48 and 360 ng/mLwere 91.00%, 92.06%, 91.71%, respectively. The validated method is successfully used to analyze the drug in samples of rat plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Characterization of the soybean KRP gene family reveals a key role for GmKRP2a in root development

Kip-related proteins (KRPs), as inhibitory proteins of cyclin-dependent kinases, are involved in the growth and development of plants by regulating the activity of the CYC-CDK complex to control cell cycle progression. The KRP gene family has been identified in several plants, and several KRP proteins from Arabidopsis thaliana have been functionally characterized. However, there is little research on KRP genes in soybean, which is an economically important crop. In this study, we identified nine GmKRP genes in the Glycine max genome using HMM modeling and BLASTP searches. Protein subcellular localization and conserved motif analysis showed soybean KRP proteins located in the nucleus, and the C-terminal protein sequence was highly conserved. By investigating the expression patterns in various tissues, we found that all GmKRPs exhibited transcript abundance, while several showed tissue-specific expression patterns. By analyzing the promoter region, we found that light, low temperature, an anaerobic environment, and hormones-related cis-elements were abundant. In addition, we performed a co-expression analysis of the GmKRP gene family, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) set enrichment analysis. The co-expressing genes were mainly involved in RNA synthesis and modification and energy metabolism. Furthermore, the GmKRP2a gene, a member of the soybean KRP family, was cloned for further functional analysis. GmKRP2a is located in the nucleus and participates in root development by regulating cell cycle progression. RNA-seq results indicated that GmKRP2a is involved in cell cycle regulation through ribosome regulation, cell expansion, hormone response, stress response, and plant pathogen response pathways. To our knowledge, this is the first study to identify and characterize the KRP gene family in soybean

Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models

Background Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in each of these cell types. Some genes show brain-specific DS-DM, while others show stronger DS-DM in T cells. Both 5-methyl-cytosine and 5-hydroxy-methyl-cytosine contribute to the DS-DM. Thirty percent of genes with DS-DM in adult brain cells also show DS-DM in fetal brains, indicating early onset of these epigenetic changes, and we find early maturation of methylation patterns in DS brain and lymphocytes. Some, but not all, of the DS-DM genes show differential expression. DS-DM preferentially affected CpGs in or near specific transcription factor binding sites (TFBSs), implicating a mechanism involving altered TFBS occupancy. Methyl-seq of brain DNA from mouse models with sub-chromosomal duplications mimicking DS reveals partial but significant overlaps with human DS-DM and shows that multiple chromosome 21 genes contribute to the downstream epigenetic effects. Conclusions These data point to novel biological mechanisms in DS and have general implications for trans effects of chromosomal duplications and aneuploidies on epigenetic patterning