Achieving highly selective recognition of structurally similar substrates in water has been, and still remains, challenging. Herein, we report highly selective recognition of adenosine (A) and its analogs by using a hybridtube (HT) with endo-functionalized cavity. Fluorescence titration data and density-functional theory calculations reveal that the macrocycle's hydrophobic cavity and its internal hydrogen-bonding sites are crucial for attaining this high binding selectivity to A and its analogs. Decreasing the number of hydrophilic hydroxyl groups on the ribose ring while increasing the number of hydrophobic methyl groups on the purine ring can significantly enhance the hydrophobic effect between host and guest, thereby strengthening the binding affinity. Furthermore, different hydrogen bond acceptors on the guest can greatly affect host-guest binding, leading to a substantial enhancement in binding selectivity (A/dA up to 61.7-fold). Based on the high binding selectivity of HT, a substrate-selective fluorescent supramolecular tandem assay was developed for real-time and continuous monitoring of the enzyme activity of adenosine deaminase (ADA). Finally, we demonstrated the potential of this tandem assay for inhibitor screening, which holds significant implications for drug design and medical diagnostics.

Iron ion (Fe3+) is crucial for both biological organisms and the environment, and iron dyshomeostasis can lead to a variety of diseases and environmental issues. Therefore, the detection of Fe3+ is of significant importance across various fields. For this purpose, through the co-assembly of water-soluble tetralactam macrocycle H and 1,1,2,2tetraphenylethylene (TPE), we prepared a new type of tetralactam macrocycle based aggregation-induced emission dots (AIE-dots), namely TPE@H. TPE@H exhibitted good water-solubility and allowed the waterinsoluble TPE to aggregate and exhibit strong fluorescence emission in water. Furthermore, the fluorescence of TPE@H could be quenched by Fe3+ through the inner filter effect, making TPE@H a potential "turn-off" fluorescent probe for Fe3+ detection. TPE@H exhibited a limit of detection as low as 1 mu M with high selectivity, and also retained good detection performance in domestic water, human serum, and even drugs, indicating its great potential for biological and environmental monitoring of Fe3+. This study not only provides a green and efficient method for detecting Fe3+, but also expands the approach for application of water-insoluble dyes in the aqueous environment.

As significant synthetic antibacterial agents, the residues of fluoroquinolones antibiotics (FQs) affect food safety and public health through bioaccumulation. However, it remains challenging for accurate sensing and discrimination of FQs due to their high complexity and multivariate nature. In this work, deep learning-assisted accurate sensing and discrimination of FQs was realized based on fluorescent terbium-doped carbon dots (TbCDs) nanosensor. The Tb-CDs showed a ratiometric fluorescence response to FQs due to the combined inner filter effect and the antenna effect. Variation in the concentrations and species of FQs causes significant and distinct fluorescence intensity changes of Tb-CDs at 427 nm and 549 nm. Six important FQs could be detected and discriminated through the principal component analysis even at a low concentration. With the assistance of deep learning, the more accurate quantitative analysis of six FQs by the single Tb-CDs nanosensor was realized, especially at low concentration. This machine learning-assisted analysis method provides a new way for accurate sensing and discrimination of FQs in food samples.

Succinylcholine (SC) is a widely used depolarizing muscle relaxant, but improper use can lead to arrhythmias and, in severe cases, pose a life-threatening risk. Additionally, some criminals exploit SC for illicit activities. Therefore, rapid SC detection is paramount for clinical practice and public safety. Currently, however, limited methods are available for the rapid detection of SC. A fluorescent indicator displacement assay sensor based on molecular recognition of an amide naphthotube was developed. This sensor enabled the rapid fluorescent detection of SC through competitive binding between SC and methylene blue with the amide naphthotube. The sensor exhibited exceptional sensitivity with a detection limit as low as 1.1 mu mol/ L and a detection range of 1.1 similar to 60 mu mol/L, coupled with outstanding selectivity and robust stability. Furthermore, this sensor accurately determined SC levels in biological samples such as serum. In summary, this research provides a new solution for the rapid and accurate sensing of SC in complex matrices and offers new insights for the swift identification and detection of toxins.

Rationale: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. Methods: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. Results: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K-a = 1.89x107 M-1) and decamethonium (K-a = 1.01x107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. Conclusion: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.

The rise of multidrug-resistant (MDR) bacteria poses a substantial challenge in clinical settings, particularly with the increasing prevalence of ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) as critical MDR bacteria. These ESKAPE pathogens have the capability to undermine antibiotic treatments, leading to a high incidence of drug resistance. However, the development of efficient antibacterial agents against ESKAPE pathogens is still in the bottleneck. Herein, the first example of antibacterial carbon dots against ESKAPE pathogens was reported. Onion powder-based carbon dots were melted with poly(hexamethylene biguanide) hydrochloride (PHMB) to obtain guanidinium-functionalized carbon dots (GCDs), which exhibited satisfactory antibacterial activity against all the tested bacteria, including both Gram-positive and Gram-negative bacteria, and even ESKAPE pathogens. The efficient antibacterial ability of GCDs derives from the rupture of the bacterial cell membrane and elevated ROS levels. Safety assessments revealed that GCDs neither trigger detectable drug resistance nor exhibit any cytotoxic effects. Furthermore, GCDs effectively promoted wound healing without observable adverse reactions of mixed MDR bacteria-infected wounds in rats. The GCDs also showed excellent long-term stability. These findings indicate that GCDs hold promise as an efficient antibacterial agent for the treatment of MDR strain-caused clinical infected-wound healing.

Recently, carbon dots (CDs) as newly developed carbon-based nanomaterials due to advantages such as excellent photostability and easy surface functionalization have generated wide application prospects in fields such as biological imaging and chemical sensing. The multicolor emission carbon dots (M-CDs) were acquired through the selection of different carbon source precursors, change of synthesis conditions and synthesis environment. Therefore, the aim of this review is to summarize the latest research progress in polychromatic CDs from the perspectives of synthesis strategies, luminescent mechanisms, luminescent properties and applications. This review focuses on how to prepare MCDs by changing raw materials and synthesis conditions such as reaction temperature, synthesis time, synthesis pH, and synthesis solvent. This review also presents the optical properties of MCDs, concentration effects, solvent effects, pH effects, elemental doping, and surface passivation on them, as well as their creative applications in the field of sensing applications. It is anticipated that this review will serve as a guide for the development of multifunctional M-CDs and inspire future research on controllable design and preparation of M-CDs.

The development of novel lysosome-targetable fluorescence (FL) probes for visualizing intracellular HClO is of great significance for better exploring the function of HClO in pathophysiological processes. In this work, bromine-doped carbon dots (Br-CDs) were prepared using bromothymol blue as the precursor by a facile hydrothermal method. Br-CDs were covalently conjugated with N-aminomorpholine (AM) to afford the AM-functionalized Br-CDs (Br-CDs-AM) as a lysosome-targetable nanoprobe for subcellular organelle-specific HClO monitoring. The as-prepared Br-CDs-AM exhibits pH stability, strong resistance to photobleaching, superior long-term fluorescence stability (12 weeks), high sensitivity (19.3 nM), ultrarapid response (8 s), extremely low cytotoxicity, and outstanding biocompatibility. These favorable features enable the nanoprobe to be used primarily for the location tracking of lysosomes and to rapidly visualize endogenous and exogenous HClO in live cells. Thus, the study provides a new pathway to design nanoprobes based on Br-CDs-AM for subcellular organelle-specific imaging and for elucidating the complex biological functions of HClO.

目的 研究丙戊酸钠对严重烫伤合并海水浸泡延迟补液模型大鼠心脑损伤的保护作用.方法 将大鼠按照随机数字表法分为烫伤+延迟补液组(S组)、烫伤+海水浸泡+延迟补液组(SS组)、烫伤+海水浸泡+丙戊酸钠+延迟补液组(SSV组),每组60只.所有大鼠采用沸水水浴法建立35％总体表面积Ⅲ度烫伤模型.SS组和SSV组大鼠烫伤后立即浸泡于人工海水中(30 min),其中SSV组出水后即刻皮下注射丙戊酸钠300 mg/kg.各组烫伤后2 h按1/2 Parkland公式于30 min内静脉输入乳酸钠林格注射液进行延迟补液.记录大鼠死亡时间,计算各组大鼠平均生存时间和24 h生存率;分别于烫伤前和烫伤后0、2、5 h检测大鼠的平均动脉压(MAP)、心率(HR)、呼吸频率(RR)、直肠温度(RT)、动脉血pH、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、实际碳酸氢根(HCO3-)、肌酸激酶同工酶(CK-MB)、神经元烯醇化酶(NSE);观察大鼠心脏、脑组织病理变化.结果 SS组大鼠24 h生存率(55％)较S组(90％)显著降低,而SSV组大鼠24 h生存率(75％)较SS组显著升高(P<0.05);与S组比较,SS组大鼠烫伤后0、2、5 h的MAP、RT、HR、pH、PaO2、HCO3-显著降低而CK-MB、NSE水平显著升高,烫伤后2、5 h的PaCO2显著升高,烫伤后0、2 h的RR显著降低(P<0.05);与SS组比较,SSV组大鼠在烫伤后2、5 h的MAP、RT、HR、pH、PaO2、HCO3-显著升高而PaCO2和CK-MB、NSE水平显著降低,烫伤后2 h的RR显著升高(P<0.05).在烫伤后2、5 h,SS组大鼠心脏、脑组织损伤程度较S组明显加重;SSV组大鼠心脏、脑组织病理损伤程度较SS组明显减轻.结论 严重烫伤大鼠合并海水浸泡后,皮下注射丙戊酸钠能保护大鼠心脑功能,改善生命体征和血气指标,延长其存活时间,提高其生存率.

本文概述了化学毒物毒剂洗消剂和洗消技术的种类、特点、洗消原理,以及在环境、人员等不同洗消对象中的应用,简介了当前光催化、等离子体、高温高压射流等洗消技术,以及不同剂型洗消剂和纳米复合材料、智能织物等材料在洗消技术中的应用特点,展望洗消剂、洗消技术发展前景.

本文结合新型冠状病毒肺炎疫情防控中化学消毒剂的应用,概述了精确消毒用药的意义,提出了精确消毒需掌握用药时机、消毒剂选择、施药方式、施药部位、施药频率、施药浓度等十个方面影响消毒效果和安全的因素,即精准用药十要素.提高化学消毒的科学性,以防过度防疫和防疫不足.

A water-soluble tetralactam macrocycle with 2,6-diethoxynaphthalene groups as side walls is able to strongly bind riboflavin (K-a >10(7) M-1) in water through hydrogen bonding and the hydrophobic effect. The encapsulated riboflavin can be stabilized by the host against photo-degradation under UV-vis irradiation, which may be harnessed to extend the shelf life of riboflavin.

Streptavidin has applied to many areas including detection, purification, labeling, crosslinking and immobilization resulting in a high demand on its production. In this study, we report a method for preparation of recombinant core streptavidin (cSAV) protein using highperformance hydrophobic interaction chromatography (HPHIC). Firstly the cSAV was successfully cloned and expressed in Escherichia coli as inclusion bodies. A bifunctional stationary phase mainly working as HIC mode accompanied by weak anion exchange chromatography (WAX) was prepared using β-phenylethylamine (PEA) as a ligand. The denatured cSAV was then refolded and simultaneously purified by PEA hydrophobic interaction chromatography (PEA-HIC). The mass recovery and purity of cSAV by single-step were 30.2% and 98%, respectively. The bioactivity was determined to be 13.2 U/mg by biotin binding capacity assay. This method provides a new possibility for fast separation with simultaneous renaturation of cSAV.

目的 比较3种内毒素活性定量检测方法在乳品中的应用情况.方法 采用2种传统东方鲎(Tachypleus amebocyte lysate,TAL)试验(动态浊度法/动态显色法)和1种便携式内毒素检测仪(portable test system,PTS)对牛奶、酸奶和奶粉产品内毒素活性进行检测,评估3种方法在乳品内毒素活性检测中的应用情况.结果 3种方法用于乳品内毒素活性检测的加标回收率为50％～200％,符合药典要求.对比动态浊度法,动态显色法检测乳品内毒素活性的加标回收率范围更加接近100％.PTS方法的内毒素活性检测值分别与2种传统TAL试验的检测值有较好的线性关系.结论 3种方法均适用于乳品内毒素活性的检测,但动态显色法更加适合乳品内毒素的检测.

目的 建立一种定量检测果汁细菌内毒素活性的方法,准确评估果汁潜在的内毒素污染风险.方法 采用动态显色法东方鲎(Tachypleus amebocyte lysate,TAL)试验对常见的4种果汁(橙汁、桃汁、苹果汁和葡萄汁)细菌内毒素活性进行检测,对果汁样品中的干扰因素进行识别与排除,最后使用抗增液排除β-葡聚糖等类似物质带来的假阳性结果.结果 市售果汁(n=36)的细菌内毒素活性范围为＜0.2～209.5 EU/mL,自榨果汁(n=12)的细菌内毒素活性范围为＜0.4～4.2 EU/mL,加标回收率范围均在50％～200％之间,符合药典要求.结论 动态显色法TAL试验适用于常见的4种果汁(橙汁、桃汁、苹果汁和葡萄汁)细菌内毒素活性的检测,为果汁的健康风险评价和卫生监管提供参考.

目的 评价3种常用化学消毒剂对脂环酸芽孢杆菌芽孢的杀灭效果.方法 采用悬液定量杀菌试验方法,对3种化学消毒剂杀灭脂环酸芽孢杆菌芽孢的效果进行观察.结果 有效氯浓度为5000 mg/L的次氯酸钠作用30 min,对脂环酸芽孢杆菌芽孢的杀灭对数值为2.94;二氧化氯浓度为40 mg/L作用1.5 min,对脂环酸芽孢杆菌芽孢的杀灭对数值为>5.00;过氧化氢浓度为30 g/L作用15 min,对脂环酸芽孢杆菌芽孢的杀灭对数值为>5.00.结论 本研究中的3种化学消毒剂,在设计条件下以二氧化氯杀灭脂环酸芽孢杆菌芽孢的效果最好.

OBJECTIVESedentary lifestyle and over‐nutrition are the underlying driving forces behind the development of metabolic diseases, particularly diabetes, dyslipidemia, obesity, etc. Physical inactivity reduced proportion of oxidative muscle fibers, and is associated with these metabolic dysfunctions. PPARβ/δ is the targeted nuclear receptor directly responsible for reprogramming the fiber‐specific contractile, links muscle fiber type to energy metabolism. PPARα activation contributes to hepatic fatty acid oxidation and lipid metabolism. Here we tested if moderate PPARα/β activation is a feasible substitute therapeutic strategy to sedentary lifestyle related metabolic disorders.METHODSWe used a combination of virtual docking, SPR‐based binding, luciferase reporter and target gene transcriptional assays to analyze the interaction mode, affinity and agonistic activity of F3SM to PPAR in vitro, respectively. With reference to exercise, the impact of F3SM on muscle endurance and strength were comparatively studied in normal mice. Serum metabolomics study was used to analyse the overall metabolic alterations. And the insulin sensitizing and anti‐dyslipidemia effects of F3SM were examined in high‐diet‐induced (HFD) obesity mice.RESULTSF3SM interacted with PPARα/β‐LBD, showed specific binding with PPARα/β, displayed potent PPARδ agonism (EC50 1.37 ± 0.33nM) and accompanied by a relative weaker PPARα agonism (EC50 75.18 ± 1.88nM), but without PPARγ activation. Target gene expression assay confirmed transcriptional activation of PPARα and PPARβ by F3SM respectively in the target tissues. Similar to exercise training, F3SM enhanced the running capability of normal mice in a dose‐dependent manner and increased the proportion of oxidative skeletal muscle fibers. Correspondingly, F3SM treated muscle was also confirmed to be fatigue‐resistant. Furthermore, serum fatty acid metabolism and whole serum metabolism disclosed the levels of intermediate metabolites and key enzymes in fatty acid oxidation pathways were increased following F3SM treatment. Thus serum unsaturated fatty acid levels, especially polyunsaturated fatty acids were raised. More importantly, F3SM indeed was capable of ameliorating glucose intolerance and hyperlipidemia in the HFD mice. In consistent with this, F3SM significantly promoted the uptake of fatty acids into hepatocytes in a dose‐dependent and insulin‐independent manner.CONCLUSIONSDual PPARα/β activation by F3SM increases the proportion of oxidative muscle fibres and switches the energy source to enhanced utilization of fatty acids. Moderate PPARα/β activation could replicate the metabolic benefits of exercise training and may be a promising strategy in combating sedentary lifestyle related metabolic diseases.Support or Funding InformationNational Science and Technology Major Project(2012ZX09301‐003), National Natural Science Foundation of China (81430090, 81773790)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mammalian neural stem cells (NSCs) are not only responsible for normal development of the central nervous system (CNS), but also participate in brain homeostasis and repair, thus hold promising clinical potentials in the treatment of neurodegenerative diseases and trauma. However the molecular networks regulating the stemness and differentiation of NSCs have not been fully understood. In this study, we show that Tweety-homolog 1 (Ttyh1), a five-pass transmembrane protein specifically expressed in mouse brain, is involved in maintaining stemness of murine NSCs. Blocking or activating Notch signal led to downregulation and upregulation of Ttyh1 in cultured NSCs, respectively, suggesting that Ttyh1 is under the control of Notch signaling. Knockdown of Ttyh1 in cultured NSCs resulted in a transient increase in the number and size of neurospheres, followed by a decrease of stemness as manifested by compromised neurosphere formation, downregulated stem cell markers, and increased neuronal differentiation. We generated Ttyh1 knockout mice by deleting its exon 4 using the CRISPR-Cas9 technology. Surprisingly, in contrast to a previous report, Ttyh1 knockout did not result in embryonic lethality. NSCs derived from Ttyh1 knockout mice phenocopied NSCs transfected with Ttyh1 siRNA. Immunofluorescence showed that loss of Ttyh1 leads to the increase of neurogenesis in adult mice. Taken together, these findings indicate that Ttyh1, which is likely downstream to Notch signaling, plays an important role in regulating NSCs.

目的 了解我国北方地区黑龙江、北京、内蒙古和西藏4省份自备井水质状况,为加强自备井水的卫生监督和管理提供依据.方法 对我国北方地区4省份233个自备井,按照《生活饮用水标准检验方法》(GB/T 5750-2006)进行采样,检测感官性状、化学、细菌学和毒理学共27项水质指标,并进行卫生学评价.结果 我国北方地区4省份自备井水总不合格率为52.36％.4省份的水质差异性大.黑龙江自备井的超标指标主要是浑浊度、肉眼可见物、锰、砷和硝酸盐;北京自备井的超标指标主要是硝酸盐和微生物;内蒙古自备井的超标指标主要是硫酸盐和氟化物;西藏自备井的超标指标则是锌和氯化物.结论 根据地域区别和水质特征,加强自备井水源管理、消毒和水质净化,保证居民饮用水安全.