Selective

选择性
  • 文章类型: Journal Article
    C-C单键的选择性硼氢化在化学工业中提出了基本挑战。以前,仅使用贵金属Ir和Rh的催化系统,与N-和P-配体结合,可以做到这一点,确保键裂解和选择性。与此形成鲜明对比的是,我们发现了一种用于C-C单键硼氢化的前所未有的通用无过渡金属系统。该方法不含过渡金属和配体,并且在化学和区域选择性方面超越了过渡金属系统,基材多功能性,或收益率。此外,我们的系统容忍各种官能团,如Ar-X(X=卤化物),杂环,酮,酯类,酰胺,硝基,腈,和C=C双键,它们通常在过渡金属的存在下容易发生硼氢化。因此,具有不同结构和功能的不同范围的γ-硼酸化胺已经容易地获得。实验机理研究,密度泛函理论(DFT),和内在键轨道(IBO)计算揭示了氢硼烷促进的C-C键裂解和氢化物转移反应途径。酰胺的羰基抑制游离N-H和氢硼烷之间的脱氢。酰胺的氮上的孤对电子促进环丙烷中C-C键的裂解。
    Selective hydroboration of C-C single bonds presents a fundamental challenge in the chemical industry. Previously, only catalytic systems utilizing precious metals Ir and Rh, in conjunction with N- and P- ligands, could achieve this, ensuring bond cleavage and selectivity. In sharp contrast, we discovered an unprecedented and general transition-metal-free system for the hydroboration of C-C single bonds. This methodology is transition-metal and ligand-free and surpasses the transition-metal systems regarding chemo- and regioselectivities, substrate versatility, or yields. In addition, our system tolerates various functional groups such as Ar-X (X = halides), heterocyclic rings, ketones, esters, amides, nitro, nitriles, and C=C double bonds, which are typically susceptible to hydroboration in the presence of transition metals. As a result, a diverse range of γ-boronated amines with varied structures and functions has been readily obtained. Experimental mechanistic studies, density functional theory (DFT), and intrinsic bond orbital (IBO) calculations unveiled a hydroborane-promoted C-C bond cleavage and hydride-shift reaction pathway. The carbonyl group of the amide suppresses dehydrogenation between the free N-H and hydroborane. The lone pair on the nitrogen of the amide facilitates the cleavage of C-C bonds in cyclopropanes.
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  • 文章类型: Journal Article
    作为一种有毒的挥发性有机污染物(TVOC),甲醛对微生物有毒性作用,从而抑制了甲醛废水处理的生化过程。因此,甲醛的选择性降解对实现高效、低成本的甲醛废水处理具有重要意义。本研讨构建了非均相Fe-ZSM-5/H2O2Fenton体系以选择性降解目标化合物。通过将Fe3+固定在ZSM-5分子筛的表面,成功制备了Fe-ZSM-5。XRD,BET和FT-IR光谱研究表明Fe-ZSM-5主要由微孔组成。研究了不同变量对甲醛选择性非均相Fenton降解性能的影响。在优化的Fenton系统中360分钟后,与葡萄糖相比,甲醛降解率为93.7%,甲醛选择性为98.2%。值得注意的是,所得到的选择性Fenton氧化体系具有广泛的pH适用性,从3.0到10.0。此外,Fe-ZSM-5在五个连续循环中使用,而甲醛降解效率没有显著下降。活性氧物质清除剂的使用表明羟基自由基是负责降解甲醛的主要活性物质。此外,该系统在高浓度甲醛的情况下获得了巨大的降解性能,降解效率达95.0%以上。
    As a toxic Volatile Organic Pollutant (TVOC), formaldehyde has a toxic effect on microorganisms, consequently inhibiting the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance in achieving high-efficiency and low-cost formaldehyde wastewater treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system f or the selective degradation of target compounds. By immobilizing Fe3+ onto the surface of a ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies showed that Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde-selective heterogeneous Fenton degradation performance were studied. The 93.7% formaldehyde degradation and 98.2% selectivity of formaldehyde compared with glucose were demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability, from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in five consecutive cycles without a significant drop in formaldehyde degradation efficiency. The use of reactive oxygen species scavengers indicated that the hydroxyl radical was the primary active species responsible for degrading formaldehyde. Furthermore, great degradation performance was acquired with high concentrations of formaldehyde for this system, and the degradation efficiency was more than 95.0%.
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  • 文章类型: Journal Article
    半纤维素可以通过酸预处理选择性地去除。在这项研究中,采用硫酸铝预处理辅助的稀硫酸实现了半纤维素的选择性去除。最佳预处理条件为160°C,1.5wt%硫酸铝,0.7wt%稀硫酸,和40分钟。组分分析结果表明,半纤维素和木质素的去除率分别达到98.05%和9.01%,分别,这表明硫酸铝预处理辅助稀硫酸可以高选择性地去除半纤维素。结构特征(SEM,FTIR,BET,TGA,和XRD)表明预处理改变了粗糙度,结晶度孔径,和玉米秸秆的官能团,有利于提高酶解效率。本研究为半纤维素的高选择性分离提供了一种新的途径,从而为其随后的高价值利用提供了新的见解。
    Hemicellulose can be selectively removed by acid pretreatment. In this study, selective removal of hemicellulose was achieved using dilute sulfuric acid assisted by aluminum sulfate pretreatment. The optimal pretreatment conditions were 160 °C, 1.5 wt% aluminum sulfate, 0.7 wt% dilute sulfuric acid, and 40 min. A component analysis showed that the removal rate of hemicellulose and lignin reached 98.05% and 9.01%, respectively, which indicated that hemicellulose was removed with high selectivity by dilute sulfuric acid assisted by aluminum sulfate pretreatment. Structural characterizations (SEM, FTIR, BET, TGA, and XRD) showed that pretreatment changed the roughness, crystallinity, pore size, and functional groups of corn straw, which was beneficial to improve the efficiency of enzymatic hydrolysis. This study provides a new approach for the high-selectivity separation of hemicellulose, thereby offering novel insights for its subsequent high-value utilization.
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  • 文章类型: Journal Article
    硬化蛋白是一种分泌型糖蛋白,主要在骨细胞中表达,通过拮抗Wnt/β-catenin信号通路抑制骨形成,和硬化蛋白的loop3区域最近被发现作为骨合成代谢治疗的一个新的治疗靶点而不增加心血管风险。在这里,我们使用基于结构的虚拟筛选来搜索选择性靶向硬化蛋白loop的小分子抑制剂3.一种新型天然产物命中ZINC4228235(THFA)被鉴定为硬化蛋白环3选择性抑制剂,其针对硬化蛋白环3的Kd值为42.43nM。使用分子建模指导的修饰对THFA进行简化和推导,从而发现了一种有效的环3选择性小分子抑制剂,化合物(4-(3-乙酰氨基丙-1-炔-1-基)苯甲酰基)甘氨酸(AACA),与命中的THFA相比具有改善的结合亲和力(Kd=15.4nM)。进一步的体外实验表明,化合物AACA可以减弱转染的硬化素对Wnt信号和骨形成的抑制作用。这些结果使AACA成为开发抗骨质疏松症药物而不增加心血管风险的潜在候选者。
    Sclerostin is a secreted glycoprotein that expresses predominantly in osteocytes and inhibits bone formation by antagonizing the Wnt/β-catenin signaling pathway, and the loop3 region of sclerostin has recently discovered as a novel therapeutic target for bone anabolic treatment without increasing cardiovascular risk. Herein, we used a structural based virtual screening to search for small molecular inhibitors selectively targeting sclerostin loop3. A novel natural product hit ZINC4228235 (THFA) was identified as the sclerostin loop3-selective inhibitor with a Kd value of 42.43 nM against sclerostin loop3. The simplification and derivation of THFA using molecular modeling-guided modification allowed the discovery of an effective and loop3-selective small molecular inhibitor, compound (4-(3-acetamidoprop-1-yn-1-yl)benzoyl)glycine (AACA), with improved binding affinity (Kd = 15.4 nM) compared to the hit THFA. Further in-vitro experiment revealed that compound AACA could attenuate the suppressive effect of transfected sclerostin on Wnt signaling and bone formation. These results make AACA as a potential candidate for development of anti-osteoporosis agents without increasing cardiovascular risk.
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  • 文章类型: Journal Article
    生物炭材料已显示出广阔的催化应用潜力。然而,在电容去离子技术(CDI)系统中使用这些材料去除重金属仍然面临着巨大的挑战,因为它们的比容量和去除能力低。这里,报道了锌掺杂对生物炭界面/本体电化学的综合调控,这表明从渗滤液中Pb2的高可再生容量(20mgg-1)和出色的选择性电容去除能力(SCR)。与K+(8%)相比,Pb2+的SCR效率高达99%,Na+(13%),和Cd2+(37%)。这项工作证明了生物炭上掺杂的Zn可以与水分解产生的OH-结合形成M─OH键,有利于提高比容量。重要的是,也可以通过调节Zn的含量来优化双层电容和伪电容之间的关系,导致重金属的去除能力不同。因此,这项工作提供了对电荷存储动力学的见解,这为为更广泛的环境应用设计和优化生物炭电极提供了有价值的指南。
    Biochar materials have shown great potential for broad catalytic application. However, using these materials in the capacitive deionization technology (CDI) system for heavy metal removal still faces a significant challenge due to their low specific capacity and removal capability. Here, a comprehensive regulation on the interfacial/bulk electrochemistry of biochar by Zn doping is reported, which suggests a high renewable capacity (20 mg g-1) and outstanding selective capacitive removal ability (SCR) of Pb2+ from leachate. The SCR efficiency of Pb2+ is as high as 99% compared to K+ (8%), Na+ (13%), and Cd2+ (37%). This work proves that the doped Zn on the biochar can combine with OH- generated by water splitting to form M─OH bonds, which is beneficial for improving the specific capacity. Significantly, the relationship between double-layer capacitance and pseudo-capacitance can also be optimized by regulating the content of Zn, leading to different removal abilities of heavy metals. Therefore, this work offers insights into charge-storage kinetics, which provide valuable guidelines for designing and optimizing the biochar electrode for broader environmental applications.
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  • 文章类型: Journal Article
    背景:胃静脉曲张破裂出血是左侧门静脉高压症(LSPH)的主要表现之一。出血是致命的,需要安全有效的干预措施。
    目的:评估改良内镜超声(EUS)引导的选择性N-丁基-2-氰基丙烯酸酯(NBC)注射治疗LSPH胃底静脉曲张出血的临床安全性和有效性。
    方法:对LSPH致胃底静脉曲张破裂出血患者进行回顾性观察研究。进行了术前EUS评估。根据NBC注射技术将注册患者分为改良组和常规组。NBC注射技术的最终选择取决于患者的偏好和临床状况。技术和临床成功率,操作时间,NBC剂量,围手术期并发症,术后住院时间,并分析了再出血率,分别。
    结果:共纳入27例患者。两组之间在基线特征方面没有观察到统计学上的显着差异。与常规组患者相比,改良组患者的NBC剂量显著减少(2.0±0.6mLvs3.1±1.0mL;P=0.004),内镜手术时间增加(71.9±11.9minvs22.5±6.7min;P<0.001).同时,两组在技术和临床成功率上无显著差异,围手术期并发症,术后住院时间,和复发性出血率。
    结论:改良EUS引导的选择性NBC注射证明了LSPH引起的胃底静脉曲张出血的安全性和有效性,具有减少注射剂量和无辐射风险的优点。缺点是时间消耗和技术挑战。
    BACKGROUND: Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension (LSPH). The hemorrhage is fatal and requires safe and effective interventions.
    OBJECTIVE: To evaluate the clinical safety and efficacy of modified endoscopic ultrasound (EUS)-guided selective N-butyl-2-cyanoacrylate (NBC) injections for gastric variceal hemorrhage in LSPH.
    METHODS: A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted. Preoperative EUS evaluations were performed. Enrolled patients were divided into modified and conventional groups according to the NBC injection technique. The final selection of NBC injection technique depended on the patients\' preferences and clinical status. The technical and clinical success rates, operation time, NBC doses, perioperative complications, postoperative hospital stay, and recurrent bleeding rates were analyzed, respectively.
    RESULTS: A total of 27 patients were enrolled. No statistically significant differences were observed between the two groups regarding baseline characteristics. In comparison to patients in the conventional group, patients in the modified group demonstrated significantly reduced NBC doses (2.0 ± 0.6 mL vs 3.1 ± 1.0 mL; P = 0.004) and increased endoscopic operation time (71.9 ± 11.9 min vs 22.5 ± 6.7 min; P < 0.001). Meanwhile, the two groups had no significant difference in the technical and clinical success rates, perioperative complications, postoperative hospital stay, and recurrent bleeding rates.
    CONCLUSIONS: Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage, with advantages of reduced injection dose and no radiation risk. Drawbacks were time consumption and technical challenge.
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  • 文章类型: Journal Article
    商用氢气(H2)传感器在高温下运行,这增加了功率消耗并由于H2的易燃性质而带来安全风险。这里,使用旋涂和印刷方法制造聚合物-贵金属-金属氧化物膜,以实现高灵敏度,低电压操作,宽操作浓度,和室温下近单选择性H2传感器。具有优化的Pd纳米颗粒和SnO2厚度的H2传感器在室温和2%H2下显示出16,623的极高响应,响应时间为6s,恢复时间为5s。同时,印刷柔性传感器表现出优异的灵敏度,在2%H2下的响应为2300。在室温下优异的传感性能是由于最佳的SnO2厚度,对应于德拜长度以及由Pd催化剂的优化覆盖率引起的氧气和H2溢出。此外,利用WO3和SnO2薄膜的多重结构制备了一种新型的双信号传感器,这证明了同时的电导和透射率,即,颜色变化。这项工作提供了一种有效的策略来开发健壮的,灵活,透明,和持久的H2传感器通过基于聚合物-金属-金属氧化物纳米结构的大面积印刷工艺。
    Commercial hydrogen (H2) sensors operate at high temperatures, which increases power consumption and poses a safety risk owing to the flammable nature of H2. Here, a polymer-noble metal-metal oxide film is fabricated using the spin-coating and printing methods to realize a highly sensitive, low-voltage operation, wide-operating-concentration, and near-monoselective H2 sensor at room temperature. The H2 sensors with an optimized thickness of Pd nanoparticles and SnO2 showed an extremely high response of 16,623 with a response time of 6 s and a recovery time of 5 s at room temperature and 2% H2. At the same time, printed flexible sensors demonstrate excellent sensitivity, with a response of 2300 at 2% H2. The excellent sensing performance at room temperature is due to the optimal SnO2 thickness, corresponding to the Debye length and the oxygen and H2 spillover caused by the optimized coverage of the Pd catalyst. Furthermore, multistructures of WO3 and SnO2 films are used to fabricate a new type of dual-signal sensor, which demonstrated simultaneous conductance and transmittance, i.e., color change. This work provides an effective strategy to develop robust, flexible, transparent, and long-lasting H2 sensors through large-area printing processes based on polymer-metal-metal oxide nanostructures.
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  • 文章类型: Journal Article
    随着各行业超低排放稳步推进,非常规污染物的管理逐渐受到关注。对许多不同的工艺和设备产生负面影响的这种非常规污染物是氯化氢(HCl)。虽然在处理工业废气和合成气方面具有很强的优势和潜力,钙和钠基碱性粉末去除HCl的工艺技术尚未得到深入研究。综述了反应因素对钙和钠基吸附剂脱氯的影响,包括温度,颗粒大小,水的形式。介绍了用于捕获氯化氢的钠和钙基吸附剂的最新进展,对比了各种吸附剂的脱氯能力。在低温范围内,钠基吸附剂比钙基吸附剂具有更强的脱氯效果。固体吸附剂和气体之间的表面化学反应和产物层扩散是至关重要的机理。同时,考虑了SO2和CO2与HCl的竞争行为对脱氯性能的影响。还提供和讨论了选择性去除氯化氢的机理和必要性,并指出了今后的研究方向,为今后的工业实际应用提供理论依据和技术参考。
    With the steady progress of ultra-low emissions in various industries, the management of unconventional pollutants is gradually attracting attention. A such unconventional pollutant that negatively affects many different processes and pieces of equipment is hydrogen chloride (HCl). Although it has strong advantages and potential in the treatment of industrial waste gas and synthesis gas, the process technology of removing HCl by calcium- and sodium-based alkaline powder has not yet been thoroughly studied. The impact of reaction factors on the dechlorination of calcium- and sodium-based sorbents is reviewed, including temperature, particle size, and water form. The most recent developments in sodium- and calcium-based sorbents for capturing hydrogen chloride were presented, and the dechlorination capabilities of various sorbents were contrasted. In the low-temperature range, sodium-based sorbents had a stronger dechlorination impact than calcium-based sorbents. Surface chemical reactions and product layer diffusion between solid sorbents and gases are crucial mechanisms. Meanwhile, the effect of the competitive behavior of SO2 and CO2 with HCl on the dechlorination performance has been taken into account. The mechanism and necessity of selective hydrogen chloride removal are also provided and discussed, and future research directions are pointed out to provide the theoretical basis and technical reference for future industrial practical applications.
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  • 文章类型: Journal Article
    蛋白激酶构成激酶家族中最大的一组,遗传改变导致的蛋白激酶的突变和易位与许多疾病的发病机理密切相关。Bruton’s酪氨酸激酶(BTK)是蛋白激酶中的一员,在B细胞的发育和功能中起着举足轻重的作用。BTK属于酪氨酸TEC家族。BTK的异常激活与B细胞淋巴瘤的发病密切相关。因此,BTK一直是治疗血液系统恶性肿瘤的关键靶标。迄今为止,两代小分子共价不可逆BTK抑制剂已被用于治疗恶性B细胞肿瘤,并在迄今难治性疾病中表现出临床疗效。然而,这些药物是共价BTK抑制剂,这不可避免地导致长期使用后的耐药性,导致患者耐受性差。第三代非共价BTK抑制剂Pirtobrutinib已获得在美国上市的批准,从而规避C481突变引起的耐药性。目前,提高安全性和耐受性是开发新型BTK抑制剂的首要问题.本文系统地总结了最近发现的共价和非共价BTK抑制剂,并根据其结构对它们进行了分类。本文还详细讨论了绑定模式,结构特征,药理活性,每种结构类型中典型化合物的优点和局限性,为更安全的发展提供有价值的参考和见解,在未来的研究中更有效、更有针对性的BTK抑制剂。
    Protein kinases constitute the largest group within the kinase family, and mutations and translocations of protein kinases due to genetic alterations are intimately linked to the pathogenesis of numerous diseases. Bruton\'s tyrosine kinase (BTK) is a member of the protein kinases and plays a pivotal role in the development and function of B cells. BTK belongs to the tyrosine TEC family. The aberrant activation of BTK is closely associated with the pathogenesis of B-cell lymphoma. Consequently, BTK has always been a critical target for treating hematological malignancies. To date, two generations of small-molecule covalent irreversible BTK inhibitors have been employed to treat malignant B-cell tumors, and have exhibited clinical efficacy in hitherto refractory diseases. However, these drugs are covalent BTK inhibitors, which inevitably lead to drug resistance after prolonged use, resulting in poor tolerance in patients. The third-generation non-covalent BTK inhibitor Pirtobrutinib has obtained approval for marketing in the United States, thereby circumventing drug resistance caused by C481 mutation. Currently, enhancing safety and tolerance constitutes the primary issue in developing novel BTK inhibitors. This article systematically summarizes recently discovered covalent and non-covalent BTK inhibitors and classifies them according to their structures. This article also provides a detailed discussion of binding modes, structural features, pharmacological activities, advantages and limitations of typical compounds within each structure type, providing valuable references and insights for developing safer, more effective and more targeted BTK inhibitors in future studies.
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  • 文章类型: Journal Article
    端粒3'-突出端有可能形成称为多聚G-四链体(G4s)的高阶结构,它可能主要存在于端粒中,代表了开发副作用少的抗癌剂的有吸引力的药物靶标。然而,通过随机筛选仅发现了少数选择性结合多聚体G4s的分子,这意味着很大的改进空间。在这项研究中,我们提出了一种可行的策略来设计对多聚G4s具有可能选择性的小分子配体,然后通过将三唑环连接到喹喔啉骨架上合成了多芳基化合物的集中文库。其中,QTR-3被确定为最有希望的选择性配体,可以在G4-G4界面结合,从而稳定多聚G4s并诱导端粒区的DNA损伤,从而导致细胞周期停滞和细胞凋亡。值得注意的是,QTR-3对乳腺癌细胞对正常乳腺细胞有更显著的抑制作用。
    The telomeric 3\'-overhang had potential to form into higher-order structures termed multimeric G-quadruplexes (G4s), which may mainly exist in telomeres, representing an attractive drug target for development of anticancer agents with few side effects. However, only a few molecules that selectively bind to multimeric G4s have been found by random screening, which means a lot of room for improvement. In this study, we raised a feasible strategy to design small-molecule ligands with possible selectivity to multimeric G4s, and then synthesized a focused library of multi-aryl compounds by attaching triazole rings to the quinoxaline skeleton. Among them, QTR-3 was identified as the most promising selective ligand that may bind at the G4-G4 interface, which accordingly stabilized multimeric G4s and induced DNA damage in telomeric region, thereby leading to cell cycle arrest and apoptosis. Notably, QTR-3 showed more significant inhibition on breast cancer cells against normal mammary cells.
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