Cell membrane receptors are pivotal targets in precise therapeutics, yet their ubiquitous expression across tissues remains a fundamental barrier to achieving cell-specific intervention. To overcome the limitations of conventional monotargeting approaches, we developed a light-gated DNA nanoclaw machine (L-DNM) that integrates high-specificity recognition, spatiotemporally controlled therapy, and real-time monitoring of molecular activation within a unified nanoplatform. The L-DNM employed a multivalent targeting mechanism directed against a triple-marker signature, epithelial cell adhesion molecule (EpCAM), MUC1, and nucleolin (NCL), achieving exceptional targeting accuracy toward MCF-7 human breast cancer cells even in heterogeneous environments. Its novel photocleavable aptamer design ensures that the Met-inhibiting function remains biologically inert until activated by UV irradiation. This strategy enables precise spatiotemporal control over receptor tyrosine kinase (RTK) inhibition with minimal off-target effects. Furthermore, the system couples therapeutic activation with instantaneous electrochemiluminescence (ECL) reporting, transforming molecular recognition events into quantifiable signals with high signal-to-noise ratio in complex matrices. By unifying multiplexed targeting, light-gated activation, and self-reporting capability, the L-DNM platform represents a transformative shift from conventional therapeutics to adaptive, intelligent theranostic systems.
Baicalin (BA), a key flavonoid isolated from Scutellariae Radix (SR), possesses diverse pharmacological activities encompassing anticancer, anti-inflammatory, and hepatoprotective effects. In order to achieve rapid separation and enrichment of BA from complex matrix samples, core-shell magnetic molecularly imprinted polymers (MMIPs) were fabricated using BA as the template molecule and Fe3O4 nanoparticles as the magnetic core. Subsequently, key preparation parameters, including the ratio of functional monomers to cross-linking agents, imprinting time, and the dosage of BA were systematically optimized. Under the optimized conditions, the prepared MMIPs exhibited rapid binding kinetics and a remarkable maximum adsorption capacity of 18.21 mg/g, accompanied by an imprinting factor (IF) of 3.919. Furthermore, the developed MMIPs were successfully employed for the selective extraction and determination of BA from SR. Specifically, the average recoveries of BA at three spiked concentrations (5.00, 11.20, and 20.00 µg/mL) were 107.0%, 92.7%, and 105.2%, respectively, with corresponding relative standard deviations (RSDs) of 5.31%, 1.65%, and 3.28% (n = 3). Overall, this work provides a novel and efficient adsorbent for trace flavonoids enrichment from complex herbal samples, offering a promising pretreatment strategy for active ingredient analysis in traditional Chinese medicine research.
A novel dimeric eudesmanoid possessing a rare cyclobutane ring from Chloranthus multistachys, named bimultistanolide C (1), is a sesquiterpene dimer, which is two monomers linked together through a cyclobutane ring, possibly generated through [2+2] cycloaddition. The structure of the new compound was characterized by means of spectroscopic methods including 1D, 2D NMR, and HR-ESI-MS.
Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.
Enzyme-catalyzed micro/nanomotors exhibit significant promise in drug delivery and sensing due to the exceptional biocompatibility, adaptability, and capacity to employ endogenous fuels. Nevertheless, the flow field generated by the catalytic reaction of enzymes exposed to the outside may considerably impair the recognition ability of surface-connected functional components, such as aptamers. Here, advantage is taken of cell membrane coating technology to create biomimetic micromotors that selectively distributed glucose oxidase (GOx) and employ aggregation-induced emission sensing to quickly capture and visualize circulating tumor cells (CTCs). Once the cell membrane selectively filters glucose, the flow field created by GOx is restricted within the intramembrane cavity. This design produces the required driving force while reducing interference on the exterior surface recognition function. By spatially segregating functional components, these biomimetic micromotors achieve CTCs collection in less than a min, enable real-time in situ detection. The proposed strategy demonstrates the potential of spatially segregated biomimetic micromotors for rapid CTCs enrichment and real-time sensing, which may inspire further development of multifunctional platforms in liquid biopsy applications.
Biosensing technologies have demonstrated significant potential in exploring the binding of drugs to receptor tyrosine kinases (RTKs). As a typical transmembrane receptor, there are still several shortcomings in the utilization of the intracellular kinase domain of RTKs, the primary action site of small-molecule inhibitors, resulting in insufficient binding and unclear action sites, which impair the efficiency and accuracy of biosensing. Herein, using epidermal growth factor receptor (EGFR) as an example, we reported a biosensing platform based on cell membrane camouflage technology for evaluating drugs binding to the intracellular kinase domain of EGFR. The azide-functionalized cell membranes modified through glucose metabolism were reverse-coated onto alkyne-functionalized magnetic nanoparticles via bioorthogonal reaction (CMRMNPs), therefore effectively exposing the intracellular kinase domain of EGFR without damage. To construct the biosensing platform, a small-molecule fluorescent probe derived from the gefitinib pharmacophore (GN probe) was further synthesized and incubated with CMRMNPs. This strategy facilitated the efficient localization of the GN probe within the intracellular kinase domain of EGFR. Ultimately, this approach was successfully implemented to evaluate the binding of three inhibitors with EGFR. This study provides a viable strategy for constructing biomimetic biosensors with a defined cell membrane orientation and offers novel insights and methodologies for the study of drug binding with the intracellular kinase regions of RTKs.
Quality control and clarifying ingredients are the foundation of pharmacodynamic material basis research. Pedicularis decora Franch. (P. decora) is clinically used to treat Alzheimer's disease and exerts significant antioxidative, anti-inflammatory and neuroprotective effects. However, there is little systematic research on the extraction and composition and the current research on P. decora focused on the quality control and extraction with aucubin as only quality marker. It reported that Iridoid glycosides (IGs) and phenylpropanoid glycosides (PeGs), which are characteristic components of the Pedicularis species, have been reported to have various anti-Alzheimer's activity. This study focused on the extraction and rapid qualitative analysis of IGs and PeGs in P. decora. First, HPLC-UV method was established to detect five IGs and PeGs analytes simultaneously and assess the effect of the extraction technology. Then, the G1-entropy method with the Box-Behnken response surface design methodology was used to optimized extraction technology. The optimum conditions were determined to be reflux with 55% methanol aqueous solutions, at 75 degree celsius for 50 min. Finally, by establishing UPLC-Q/TOF-MS, 15 IGs and 15 PeGs in P. decora were rapidly identified and characterized for the first time. The results will provide a reverence of a higher quality standard and the pharmacodynamic material basis research. [GRAPHICS] .
Taibai ginseng (roots of Pedicularis decora Franch.) has been reported to possess anti-Alzheimer's disease (anti-AD) activity and can be potentially used for treating AD. However, the chemical constituents of taibai ginseng have not yet been elucidated because of the paucity of relevant studies, which hinders further research on the pharmacological mechanism and utilization of taibai ginseng. In this study, a rapid and efficient method for comprehensively analyzing the chemical constituents of taibai ginseng was established for the first time. We used ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry in combination with the UNIFI data-processing platform to automatically characterize and identify the chemical profile of taibai ginseng. As a result, more than 76 compounds were detected, and their structures were characterized. These compounds include 24 iridoid glycosides, 24 phenylethanol glycosides, 15 terpenoids, and 13 other components. More than fifty of these compounds from taibai ginseng were reported for the first time. Our results provide a reference for the quality control of taibai ginseng and establish a higher quality standard for pharmacodynamic research. Appropriate modification of the method reported herein can enable its use for the screening and characterization of taibai ginseng and other compounds from the Pedicularis genus.
Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make tumor cells more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy is promising in meeting the challenge of detecting heterogeneous CTCs due to its inherent antiadhesive properties, it is still limited by the reduction or loss of expression of known markers. Bioorthogonal glycol-metabolic engineering is expected to break down this barrier by feeding the cells with sugar derivatives with a unique functional group to establish artificial targets on the surface of tumor cells. Herein, an engineered leukocyte biomimetic colorimetric sensor was accordingly fabricated for high-efficient detection of heterogeneous CTCs. Compared with conventional leukocyte membrane coating, the sensor could covalently bound to the heterogeneous CTCs models fed with Ac(4)ManNAz in vitro through the synergy of bioorthogonal chemistry and metabolic glycoengineering, ignoring the phenotypic changes of heterogeneous CTCs. Meanwhile, a sandwich structure composed of leukocyte biomimetic layer/CTCs/MoS2 nanosheet was formed for visual detection of HeLa cells as low as 10 cells mL(-1). Overall, this approach can overcome the dependence of conventional cell membrane biomimetic technology on specific cell phenotypes and provide a new viewpoint to highly efficiently detect heterogeneous CTCs.
The alkaloid ingredients were considered to be responsible for the diverse pharmacological activities of the medicinal plant Tabernaemontana corymbosa (Roxb. ex Wall.). In the current finding, the systematic phytochemical investigation on T. corymbosa have been achieved. One new indole alkaloid tabercorympyline A (1) along with seven known indoles (2-8) were isolated from T. corymobsa. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. Tabercorympyline A (1) possessed the indole skeleton with rare N-containing nine membered ring. Chemical information network was used to comprehensively discover the clues for the glioma therapeutic leads from T. corymbosa alkaloids (TA). Inspired by chemical information network analysis, all the isolated compounds have been further validated their anti glioma activities in glioma cell line U251. Interestingly, the compounds 2, 3, 5, and 6 exhibited significant inhibitory effects on glioma cells in vitro. Molecular docking was ultimately used to indicate possible binding performance and mechanism between active compounds (2-3) and the core targets. This study sequentially assembled chemical information and network analysis, phytochemistry, molecular docking, and in vitro activity validation to comprehensively explore the effective compounds, related targets, and potential mechanisms of TA therapy for glioma.
Three previously undescribed 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, (5S,6R,7S,8S)-8-chloro-5-ethoxy-6,7-dihydroxy-2-[2-(4'-methoxyphenyl)ethyl]-5,6,7,8-tetrahydrochromone (1), (5R,6S,7R,8R)-8-chloro-5-ethoxy-6,7-dihydroxy-2-(2- phenylethyl)-5,6,7,8-tetrahydrochromone (2), (5S,6R,7S,8R)-5,8-dichloro-6,7- dihydroxy-2-[2-(4'-methoxyphenyl)ethyl]-5,6,7,8-tetrahydrochromone (3), and 28 known analogues (4-31) were isolated from the stems of Aquilaria sinensis. Their structures were characterized by the spectroscopic methods, and the absolute configuration was resolved by circular dichroism (CD) spectroscopy. Bioactivity evaluation indicated that compounds 3-8 had significant inhibition effect in the production of NO in an inflammatory cell model with relatively lower IC50 values of 5.54, 11.44, 3.68, 7.15, 10.26 and 13.04 μM, respectively, compared to the positive control indomethacin (IC50 = 23.03 μM).
This paper analyzes the policy changes related to paper evaluation and their impact and challenges to subject analysis services, and studies the Wuhan University Library as an example to summarize its transformational practices on researching response and practical exploration. In the new era, university libraries should play a role in the macro-evaluation of school, assisting in the selection of representative works, strengthening frontier tracking, supporting the development of the school’s journals,and building a school-level paper center.
Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1–2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.
针对近年来太湖水体中长孢藻(Dolichospermum,曾用名鱼腥藻Anabaena)比例增加的趋势,本文研究了2005-2019年太湖春季不同湖区长孢藻生物量的长期变化趋势和空间差异,探究了冬、春季气象条件(气温、日照时长、风速、降雨量)和营养盐(总氮、总磷)水平对其的影响.结果表明,2005-2019年太湖监测数据显示春季长孢藻生物量有比较明显的升高现象,主要发生在竺山湖富营养程度较高的区域,其次是湖心区、梅梁湾和南部湖区.偏最小二乘路径建模(PLS-PM)结果表明,不同湖区长孢藻生物量变化的主要驱动因素存在差异.在湖心区,春季长孢藻的生物量主要受冬季气候条件(气温、风速、日照时长)的影响,其次受春季营养盐和春季气候条件的影响.在梅梁湾、竺山湖和南部湖区,春季长孢藻的生物量主要受春季气候条件的影响.在梅梁湾和竺山湖,春季风速、日照时长是春季长孢藻生物量的显著影响因子;在南部湖区,春季长孢藻生物量的主要驱动因素是春季的日照时长和春季气温.本研究从长时间序列角度,对太湖固氮蓝藻的时空分布特征和影响因素开展了研究,为太湖不同湖区开展针对性的藻类水华防控和富营养化治理提供理论基础.
Chromatographically pure galactosylceramide I3-sulfate (cerebroside sulfate (CBS)) containing palmitic acid or D-2-hydroxypalmitic acid has been prepared by the acylation of galactosylsphingosine I3-sulfate obtained from the saponification of bovine brain sulfatides. Optically pure D-2-hydroxypalmitic acid was obtained by adapting literature methods for the synthesis of the racemic acid and its resolution. The thermotropic behavior of the two synthetic CBSs were compared to each other and to the corresponding components in natural CBS, obtained by fractionation of bovine brain sulfatides, in order to determine the contribution of the hydroxy fatty acid to intermolecular hydrogen bonding between molecules of the lipid. The gel to liquid crystalline phase transition temperature (Tc) of the hydroxy fatty acid (HFA) synthetic form is 53.2 degrees C, 3 degrees higher than that of the non-hydroxy fatty acid (NFA) form at low concentrations of Na+ or K+. A similar difference was found for the HFA and NFA forms of natural CBS. The enthalpy of the NFA synthetic form is 8.5 kcal/mol, about 30% greater than that of the HFA form. The difference in Tc between the NFA and HFA forms is abolished as the Na+ or K+ concentration increases but the difference in enthalpy persists. Increasing cation concentration, over the range 0.01-2 M, increases Tc more than for an acidic phospholipid, phosphatidylglycerol, probably due to increased intermolecular hydrogen bonding as the charged sulfate is shielded. K+ causes a 3-4 degrees C greater increase in Tc relative to that produced by Na+ while K+ and Na+ have similar effects on phosphatidylglycerol.
着生藻类一般生长位置相对稳定,其群落分布主要受环境因素的影响,同时,着生藻类还是重要的水环境指示生物.本研究对鄱阳湖丰水期5个典型湖区(主航道、西部湿地、南矶湿地、撮箕湖和东南湖汊)着生藻类的群落结构特征进行调查,包括生物量、优势种及生物多样性,分析影响着生藻类群落区域分布的环境因子,以期为鄱阳湖水环境保护和水资源合理利用提供基础资料.结果表明:鄱阳湖着生藻类群落以硅藻、绿藻和蓝藻为主;鄱阳湖着生藻类总生物量有着明显的区域差异:主航道区域的生物量相对最高,平均为419 mg/m2;其次是东南湖汊,平均为322 mg/m2;南矶湿地和西部湿地分别为172和52 mg/m2;而撮箕湖的总生物量相对最低,为9 mg/m2.主航道的着生藻类优势种群为绿藻和硅藻,西部湿地、南矶湿地、撮箕湖和东南湖汊4个区域的优势种群为硅藻.冗余分析结果显示鄱阳湖丰水期着生藻类群落分布与总磷、电导率、pH值、总氮、硝态氮和悬浮物等理化因子关系较为密切.鄱阳湖主航道与长江连通,水体流速高;西部湿地、南矶湿地、撮箕湖和东南湖汊为季节性连通湖泊,丰水季节与主湖区水体连为一体,枯水季节独立蓄水.5个湖区的区域差异是导致其着生藻类群落结构差异的重要原因之一.着生藻类的多样性指数分析表明鄱阳湖水体处于中度污染状态.
目的 研究白毛七乙酸乙酯萃取部位的化学成分.方法 运用硅胶柱色谱、Sephadex LH-20柱色谱和反相HPLC法等方法对白毛七乙酸乙酯萃取部位的化学成分进行分离纯化,通过波谱技术结合化合物的理化性质对分离得到的化合物进行结构鉴定.结果 从白毛七乙酸乙酯萃取部位分离得到8个化合物,分别鉴定为:2′-羟基-4,4′,6′-三甲氧基查尔酮(1);2′-羟基-4,3′,4′,6′-四甲氧基查尔酮(2);球松素(3);5α,8α-环二氧-(22E,24R)麦角甾-6,22-二烯-3β-醇(4);5α-豆甾烷-3,6-二酮(5);xanthoxyol(6);(+)-松脂素-4-O-β-D-吡喃葡萄糖苷(7);望春玉兰素C(8).结论 化合物2~8均为首次从该植物中分离得到.
可视化分析是文献计量分析中较为重要的一种.在进行可视化分析时,数据清洗工作至关重要,但目前的可视化分析软件一般不具备数据清洗功能,即使具备,也无法实现批量化的快速清洗.文章以石墨烯领域的WOS文献题录数据可视化分析为对象,探索了利用OpenRefine的聚类功能,对题录中的重要信息进行聚类,形成软件可识别的规范术语文件,进行可视化的方法,验证了该方法用于文献情报挖掘中可视化分析的优越性.研究结果表明,利用OpenRefine聚类功能可以高效地对文献题录重要信息进行处理,机构合作网络中,重复节点减少了9%;关键词共现网络中,词频最大可增加742次,明显减少了重复节点,提高了可视化分析的准确性和情报挖掘的效率.
Highly specific novel glycopeptide-based fluorescent molecularly imprinting polymers (g-FMIPs) were constructed to recognize and determine the target glycoprotein in complex biological samples. The glycopeptide of ovalbumin (OVA), with the unique structural characteristics of glycan and peptide, and potential application in improving the specificity recognition of g-FMIPs, was selected as the template molecule. The nitrogen-doped graphene quantum dots (N-GQDs) were introduced for fluorescence response. The obtained g-FMIPs possessed rapid binding kinetics and high adsorption capacity. Notably, the g-FMIPs exhibited remarkable selectivity and sensitivity with a high imprinting factor of 6.57, good linearity of 0.625 − 5.00 μM, and limit of detection of 0.208 μM. After treatment with g-FMIPs, the concentration of OVA in eluted solution was 1.07 μM. The obtained recoveries at 1.43 μM, 2.86 μM, and 4.29 μM spiked concentrations were 97.2%, 93.5%, and 101%, respectively, and the relative standard deviations were 2.6%, 4.2%, and 1.1%, respectively. In summary, the proposed strategy will expand the MIPs construction method and its application prospects in precision recognition and sensitive detection of trace glycoproteins from complex biosamples.
Two new dinor-eudesmane sesquiterpenoids, named multistalin A (1), and multistalin B (2), together with three sesquiterpene glycosides (3-5), and a norlabdane-type diterpene (6) were isolated from the root extract of Chloranthus multistachys Pei. Their structures were elucidated on the basis of spectroscopic analysis including 1D, 2D NMR techniques and HR-ESI-MS. In addition, the cytotoxicity activities of the isolated compounds against selected cancer cells (Hela and A-549) were evaluated by MTT assay.