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关键词： Hirshfeld surface   acetamide   crystal structure   imidazolidine   phenytoin analog  

摘要： The title phenytoin analog 2-(2,5-dioxo-4,4-di­phenyl­imidazolidin-1-yl)-N-(4-fluoro­phen­yl)acetamide, C₂₃H₁₈FN₃O₃, was synthesized by alkyl­ation of phenytoin with 2-chloro-N-(4-fluoro­phen­yl)acetamide under phase-transfer catalysis conditions and crystallized as colorless blocks in the monoclinic space group P2₁/c. In the mol­ecular structure, the imidazolidine ring shows a slight departure from planarity, adopting a twist conformation, while the two phenyl substituents are markedly inclined to the mean plane of the heterocyclic ring. The N-substituted 4-fluoro­phenyl­acetamide fragment projects away from the imidazolidine core, with its conformation partly consolidated by an intra­molecular C—H⋯O contact. In the crystal packing, pairs of inversion-related mol­ecules are linked through N—H⋯O hydrogen bonds to form dimers, which are further connected by additional N—H⋯O inter­actions into layers extending parallel to the bc plane. These layers stack along the a-axis direction through normal van der Waals contacts. Hirshfeld surface analysis was used to qu­antify the inter­molecular inter­actions, showing that H⋯H contacts give the largest contribution to the crystal packing, followed by C⋯H/H⋯C and O⋯H/H⋯O contacts, the latter being associated with the classical N—H⋯O hydrogen bonds. F⋯H/H⋯F inter­actions also contribute to the packing, mainly through contacts between adjacent mol­ecular layers.

关键词： Catalysis  

摘要： Permanganate-mediated oxidative cyclisation of 1,5-dienes under chiral phase transfer catalysis (CPTC) conditions provides 2,5-dihydroxyalkyl substituted tetrahydrofurans (THF-diols) wherein four new C–O bonds are established with excellent control of relative and absolute stereochemistry. Structurally complex THF-containing motifs found in a host of bioactive natural products are accessible by oxidative transformation of simple dienes, which is exemplified by formal syntheses of cis-solamin A. Electron-withdrawing ester or ketone groups in the substrates – conjugated to one alkene of the 1,5-diene system – direct the initial manganation reaction to the electron-deficient alkene, which proceeds with enantiofacial selectivity in the presence of the CPTC. Cinchona alkaloid scaffolds are a convenient platform for chiral quaternary ammoniums with short synthetic routes to anthracenylmethyl and 3,5-bis(trifluoromethylbenzyl) CPTC derivatives realising enantioselectivities up to 89–94% ee for structurally distinct 1,5-diene systems using a readily-available and inexpensive oxidant. DFT calculations provide significant new mechanistic insight into the permanganate-mediated reaction supporting the involvement of a protonated Mn(v) glycolate in THF ring-formation through enhanced electrophilicity of the metal oxo intermediate. Furthermore, calculations identify the interplay between dipole-driven electrostatic stabilisation and cooperative noncovalent interactions in the transition state complex for manganation in the first reaction step, leading to the observed facial selectivity in this powerful synthetic reaction.

摘要： Purpose: Chimeric antigen receptor (CAR) T-cell therapy has been a breakthrough in many hematologic malignancies, but success in relapsed/refractory (R/R) acute myeloid leukemia (AML) has been limited due to underwhelming response rates and high on-target/off-tumor toxicity. This phase 1 dose-escalation trial evaluated the safety and efficacy of KITE-222, an autologous CAR T-cell therapy that recognizes C-type lectin-like molecule 1 (CLL-1 predominantly expressed on myeloid cells but absent on normal hematopoietic stem cells and other tissues.Patients and Methods: Patients with R/R AML (>= 50 kg) received a single intravenous infusion of 3 & times;107 (cohort 1 1 & times;108 (cohort 2 or 3 & times;108 (cohort 3) KITE-222 CAR+ T cells. The primary endpoint was the incidence of dose-limiting toxicities (DLT). Key secondary endpoints included overall remission rate, incidence of adverse events (AE and pharmacokinetics/pharmacodynamics.Results: Twelve patients received KITE-222. One patient in cohort 3, who was the only patient to receive two courses of lymphodepleting chemotherapy, experienced a DLT (prolonged grade 4 neutropenia/thrombocytopenia) but achieved a best response of morphologic leukemia-free state on day 14 following infusion (confirmed on day 44). All patients experienced grade >= 3 AEs, none had grade >= 3 cytokine release syndrome, and one had grade >= 3 immune effector cell-associated neurotoxicity syndrome. Clinically meaningful responses were lacking across dose levels despite detectable CAR T-cell expansion. Although two of five cohort 3 patients with clear expansion had near-complete depletion of CLL-1+ bone marrow blasts after infusion, CLL-1- blasts persisted, and reductions in total blasts were not observed.Conclusions: Despite successful manufacturing and acceptable safety, KITE-222 lacked preliminary efficacy, warranting future studies that address CLL-1 heterogeneity and focus on improving in vivo expansion and antitumor activity.

关键词： 1   25dihydroxyvitamin D   DEQAS   analytical variation   uncertainty   vitamin D  

摘要： The Vitamin D External Quality Assessment Scheme (DEQAS) evaluates participants’ performance of analytical methods for vitamin D metabolites, including 1,25dihydroxyvitamin D (1,25(OH)₂D), by distributing samples globally on a quarterly basis. In this review an assessment of the performance of current 1,25(OH)₂D methods is presented. Data submitted by scheme participants for the 2024/25 DEQAS distribution cycle was analysed and trends between assays were compared. The four distributions across the 2024/25 DEQAS cycle covered a wide concentration range, challenging participants to report results across the full reference interval. Analytical performance is improving; however, variation persists between the major method groups. Participation in an accuracy-based scheme is considered the gold standard, but there is currently no reference measurement procedure available for 1,25(OH)₂D. Participant performance is therefore assessed against the Method Laboratory Trimmed Mean (MLTM). To evaluate the validity of this approach, measurement uncertainty was calculated for each method and for the All Laboratory Trimmed Mean (ALTM) across all of the distributions of the 2024/25 cycle. Calculated measurement uncertainty fell within the limits of acceptability (less than 30% of standard deviation) for the ALTM, and for the MTLM of DiaSorin Liaison XL group. For method groups with fewer participants, the uncertainty of the MLTM as a target value fell outside the limits of acceptability, confirming that the ALTM offers a more robust target value. This finding supports the use of the ALTM for assessing participants’ performance, with acceptable performance being defined as the ALTM ± 30%, in at least 80% of distributed samples. This performance target represents what can be achieved with the current ‘state of the art’ of methods for 1,25(OH)₂D measurement.

关键词： Alzheimer’s disease   soluble Aβoligomers   glutamate transporter 1   ceftriaxone   hippocampal synaptic plasticity   long-term potentiation   mitochondria   presynaptic  

摘要： In Alzheimer’s disease,perturbations of glutamate neurotransmission lead to synaptic dysfunction and synapse loss.Several studies have used glutamate transport inhibitors to demonstrate that soluble oligomers of amyloid-β induce synaptic dysfunction by interrupting glutamate uptake mediated by glutamate transporter 1,the major glutamate transporter in the brain.The cellular targets of the synaptic effects of soluble amyloid-β oligomers,including the nature of any interaction with glutamate transporter 1,remain ill-defined.We have generated a conditional glutamate transporter 1 knockout mouse to investigate cell-type specific functions of glutamate transporter 1.Field excitatory postsynaptic potentials were examined in the CA1 region of mouse hippocampal slices.We confirmed that hippocampal long-term potentiation impairment is induced by both soluble Aβ oligomers and glutamate uptake inhibitors.Amyloid-β oligomers,including those isolated directly from the cortex of patients with Alzheimer’s disease,failed to inhibit hippocampal long-term potentiation in neuronal glutamate transporter 1 but not astrocytic glutamate transporter 1 knockout mice.The masking or occlusion of the effect of soluble Aβ oligomers by knockout of glutamate transporter 1 in neurons suggests that the metabolic or signaling consequences of knockout of glutamate transporter 1 in neurons and oAβ inhibition of synaptic plasticity show epistasis and thus share a similar molecular pathway.To extend these observations,we tested the effects of other types of manipulation of glutamate homeostasis on synaptic plasticity and the pathophysiology of soluble Aβ oligomers.Ceftriaxone,which upregulates glutamate transporter 1 levels,among other effects,prevented the impairment of long-term potentiation by soluble Aβ oligomers.Collectively,our findings suggest that the effects of amyloid-β on synaptic function are highly dependent on glutamate reuptake homeostasis and that the disruption of synaptic function by s

关键词： 职业教育   1+X证书   教学方法   课程改革  

摘要： 高职院校现有课程体系、师资队伍建设等与宠物行业人才市场需求不完全匹配,“1+X”证书制度的实施和普及,对高职的人才培养提出新的要求,本文旨在探讨如何在“1+X”证书制度下对宠物美容与护理课程进行改革。采用模块化、实践性强、行业导向性强的课程设置,以培养学生的实际操作技能和行业素养为目标,经过课程改革与实践,学生的学习积极性和实践能力得到显著提升,学生对宠物行业有了更深入的了解和认识,就业竞争力也得到增强。

关键词： V(V)   淋溶   生物炭   Shewanella oneidensis MR-1   土壤柱  

摘要： 针对土壤中高毒性､高迁移性的五价钒(V(V))污染所带来的环境风险,本研究探讨了利用生物炭负载Shewanella oneidensis MR-1修复V(V)污染土壤的可行性与作用机理.土壤柱淋溶试验表明,微生物接种量和环境pH值是影响V(V)还原的关键因素.初始接种量1.0×10^(8)cells/mL､pH值中性条件下,V(V)的还原固定效果最佳,淋出液中V(V)浓度显著降低;酸性条件则会抑制微生物活性,导致V(V)淋溶加剧.研究发现生物炭作为微生物载体具有明显优势,其多孔结构为S.oneidensis MR-1提供了稳定的微环境,有效减少菌体流失.负载微生物后,土壤中钒的形态由易迁移的可还原态(含量从45.86%降至20.58%)显著转化为稳定的残渣态(由40.54%增加至59.83%).扫描电镜(SEM)显示生物炭的孔隙结构为S.oneidensis MR-1提供了稳定的附着位点,促进了微生物与土壤中钒的相互作用.傅里叶变换红外光谱(FTIR)分析证实,S.oneidensis MR-1促进了羟基､羧基及含硫官能团的形成与转化,这些官能团共同参与了V(V)的生物还原与固定.三维荧光光谱(3D-EEM)分析表明,生物炭负载S.oneidensis MR-1能显著增强胞外聚合物(EPS)中色氨酸和芳香族蛋白的生成,揭示生物炭为微生物提供了有利的生长环境并增强其活性.研究结果表明,将S.oneidensis MR-1固定于生物炭上可显著降低土壤钒的淋溶迁移,为钒污染场地修复提供理论依据和技术支撑.

关键词： 5月份   出口量   出口金额   充气橡胶轮胎  

摘要： 82万吨5月份,我国橡胶轮胎出口82万吨,同比(下同)下降4.9%;出口金额135.94亿元,下降10.4%。其中,新的充气橡胶轮胎出口量为79万吨,下降5.0%;出口金额130.18亿元,下降10.6%。5884万条按条数计算,5月份,新的充气橡胶轮胎出口5884万条,下降4.8%。403万吨1―5月,我国橡胶轮胎累计出口403万吨,增长3.5%;出口金额约为674.08亿元,下降2.4%。其中,新的充气橡胶轮胎累计出口387万吨,增长3.3%;出口金额为646亿元,下降2.5%。