Dual-functional cellulase-mediated gold nanoclusters for ascorbic acid detection and fluorescence bacterial imaging.

Protein-protected metal nanomaterials are becoming the most promising fluorescent nanomaterials for biosensing, bioimaging, and therapeutic applications due to their obvious fluorescent molecular properties, favorable biocompatibility and excellent physicochemical properties. Herein, we pioneeringly prepared a cellulase protected fluorescent gold nanoclusters (Cel-Au NCs) exhibiting red fluorescence under the excitation wavelength of 560 nm via a facile and green one-step method. Based on the fluorescence turn-off mechanism, the Cel-Au NCs were used as a biosensor for specificity determination of ascorbic acid (AA) at the emission of 680 nm, which exhibited satisfactory linearity over the range of 10-400 µM and the detection limit of 2.5 µM. Further, the actual sample application of the Au NCs was successfully established by evaluating AA in serum with good recoveries of 98.76%-104.83%. Additionally, the bacteria, including gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), were obviously stained by Cel-Au NCs with strong red emission. Thereby, as dual-functional nanoclusters, the prepared Cel-Au NCs have been proven to be an excellent fluorescent bioprobe for the detection of AA and bacterial labeling in medical diagnosis and human health maintenance.

Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC50 = 4.58 ± 0.24 µM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 µM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization.

Correction: Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

[This corrects the article DOI: 10.1039/D1MD00306B.].

Excellent catalytic properties of luminescent Cu@Cu2S nanozymes and their antibacterial applications.

Luminescent Cu@Cu2S nanozymes have been prepared by a one-pot method, displaying high peroxidase-like and oxidase-like activity. Fluorescence images show that these nanozymes adhere to the surface of the bacterial cell and scanning electron microscopy reveals that the nanomaterials cause folding and collapse of the bacterial surface, resulting in bacterial death.

Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives.

Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents' discovery.

Flash nanoprecipitation of ultra-small semiconducting polymer dots with size tunability.

Small-sized semiconducting polymer dots (Pdots) provide better tissue and subcellular penetration while minimizing unspecific interactions, and make the fast clearance of Pdots from human bodies possible by urinary excretion. We employ a powerful and scalable technology, flash nanoprecipitation, to prepare Pdots with small sizes (hydrodynamic diameters ∼10 nm).

Reduction of falling number in soft white spring wheat caused by an increased proportion of spherical B-type starch granules.

A low falling number (FN) in wheat indicates high α-amylase activity associated with poor end-use quality. We hypothesize starch - the substrate of α-amylase, can directly influence hot flour pasting properties and its susceptibility to α-amylase, which further affects viscosity. We examined the structural characteristics of starch in three soft white spring wheat cultivars grown in Idaho in 2013 (normal FN year) and 2014 (low FN year with pre-harvest rains). Our data surprisingly show that starch in some low FN wheat was not significantly degraded by α-amylase but had developmental changes with an increased proportion of B-type wheat starch. We reconstituted wheat starch and verified that starch with an increase of B-granules has a relatively low viscosity and high susceptibility to wheat α-amylase, which further facilitates the decrease of viscosity. The influence of starch structure and starch-enzyme interaction must be considered while developing a solution to the low FN issue.

Impacts of Starch and the Interactions Between Starch and Other Macromolecules on Wheat Falling Number.

Wheat with a low falling number (FN) has been particularly prevalent in recent years and has resulted in a loss of more than $140 million in a single year in the wheat industry in the Pacific Northwest of the United States. FN measurement is a standard method for the evaluation of grain α-amylase activity, and a low FN indicates a reduction in hot wholemeal paste viscosity due to sprouting damage. Recent studies show that a low FN may result from a developmental change of starch and adverse effects of non-α-amylase macromolecules on wheat. In this review, we describe the principles of FN measurement and the relationship between FN and α-amylase. We also discuss the isozymes, locations, and inhibitors of wheat α-amylase. The effects of various aspects of starch, which is the substrate of α-amylase, on wheat FN are also discussed, including starch structural characteristics (for example, starch granule architecture), starch susceptibility to α-amylase, and the interaction between starch and nonstarch macromolecules (for example, lipids). Studies on the effects of planting environments (for example, temperature) and agronomic practices (for example, irrigation and fertilization) on both starch paste viscosity and FN are also reviewed. This paper highlights the importance of considering the impacts of starch and the interactions of starch and other macromolecules, including wheat α-amylase, on wheat FN, which is important for developing strategies to solve the low FN problem.

Graphene quantum dots: Highly active bifunctional nanoprobes for nonenzymatic photoluminescence detection of hydroquinone.

In this paper, a simple and sensitive photoluminescence method is developed for the hydroquinone quantitation by using graphene quantum dots which simultaneously serve as a peroxidase-mimicking catalyst and a photoluminescence indicator. In the presence of dissolved oxygen, graphene quantum dots with intrinsic peroxidase-mimicking catalytic activity can catalyze the oxidation of hydroquinone to produce p-benzoquinone, an intermediate, which can efficiently quench graphene quantum dots' photoluminescence. Based on this effect, a novel fluorescent platform is proposed for the sensing of hydroquinone, and the detection limit of 5 nM is found.

Fluorescent blood glucose monitor by hemin-functionalized graphene quantum dots based sensing system.

In the present work, a highly sensitive and specific fluorescent biosensor for blood glucose monitoring is developed based on hemin-functionalized graphene quantum dots (GQDs) and glucose oxidase (GOx) system. The GQDs which are simply prepared by pyrolyzing citric acid exhibit strong fluorescence and good water-solubility. Due to the noncovalent assembly between hemin and GQDs, the addition of hemin can make hydrogen peroxide (H2O2) to destroy the passivated surface of GQDs, leading to significant fluorescence quenching of GQDs. Based on this effect, a novel fluorescent platform is proposed for the sensing of glucose. Under the optimized conditions, the linear range of glucose is from 9 to 300µM, and the limit of detection is 0.1µM. As unique properties of GQDs, the proposed biosensor is green, simple, cost-efficient, and it is successfully applied to the determination of glucose in human serum. In addition, the proposed method provides a new pathway to further design the biosensors based on the assembly of GQDs with hemin for detection of biomolecules.

An ultrasensitive chemiluminescent immunosensor for the detection of human leptin using hemin/G-quadruplex DNAzymes-assembled signal amplifier.

In this work, we reported a sensitive chemiluminescent immunosensor for the detection of human leptin by using hemin/G-quadruplex DNAzymes to amplify detection signal. In this sensing system, the primary antibody (anti-human leptin) was firstly bound to the 96-well plates, and human leptin and biotinylated secondary antibody were successively combined to form sandwich-type immune complex through specific interactions. Then streptavidin labeled with hemin/G-quadruplex DNAzymes was assembled to the sandwich-type immunocomplex by streptavidin-biotin interaction. The DNAzymes exhibited an excellent catalytic activity to the chemiluminescent reaction of luminol with hydrogen peroxide in strong alkaline solution, leading to significant enhancement in response signal. Under the optimum conditions, the proposed immunosensor showed high sensitivity and selectivity with a low detection limit of 1.9 pg mL(-1) and a wide linear response range of human leptin from 10 to 1000 pg mL(-1). The immunosensor was used to detect human leptin in serum, and the results were in good agreement with the data obtained by conventional ELISA method.

Effect of zibushenjing fang on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency: a mechanistic study.

OBJECTIVE: To investigate the effects of Zibushenjing Fang (formula for tonifying the kidney essence) on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency. METHODS: Fifty male Kunming mice were randomly divided into five groups: normal group, model group, Jinkuishenqi Wan group, Zibushenjing Fang high dose group, and Zibushenjing Fang low dose group, with 10 mice in each group. The model of kidney essence insufficiency syndrome was established in all the mice except the normal group by using a cat to threaten the mice and by swimming until exhaustion daily which lasted about 21 days. Mice in the model group were administered 20 mL/ kg(-1) x d(-1) of normal saline intragastrically. The Jinkuishenqi Wan group was given 2.7 g/kg(-1) x d(-1) of a solution of Jinkuishenqi Wan. The Zibushenjing Fang high dose group was given 20 g/kg(-1) x d(-1) and the Zibushenjing Fang low dose group was given 10 g/kg(-1) x d(-1) of a solution of Zibushenjing Fang. The general condition of all the groups was observed, including the quantity of food and water intake, swimming time, length of femur, and weight of the femur and musculus quadriceps femoris. The total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and methane dicarboxylic aldehyde (MDA) activities in the brain tissues were detected. RESULTS: Zibushenjing Fang could improve the manifestation of kidney essence insufficiency, increase the quantity of food and water intake, swimming time, femur length, and femur and musculus quadriceps femoris weight. It could also regulate the activities of T-SOD, GSH-Px, and MDA in brain tissue. CONCLUSION: Zibushenjing Fang may play an important role in treating kidney essence insufficiency syndrome by promoting body development and improving brain tissue antioxidation.

Simultaneous determination of glucose, fructose and lactose in food samples using a continuous-flow chemiluminescence method with the aid of artificial neural networks.

In this study, a simple continuous-flow chemiluminescence (CL) system was developed for simultaneous determination of glucose, fructose and lactose in ternary mixtures of reducing sugars without previous separation. This method was based on the different kinetics of the individual sugars in the oxidation reaction with potassium ferricyanide. The known luminol-K(3)Fe(CN)(6) CL system was used to measure the kinetic data of the system. The CL intensity was measured and recorded every second from 1 to 300 s. The data obtained were processed chemometrically using an artificial neural network. The relative standard errors of prediction for three analytes were <5%. The proposed method was successfully applied to the simultaneous determination of the three sugars in some food samples.

Simultaneous determination of three organophosphorus pesticides residues in vegetables using continuous-flow chemiluminescence with artificial neural network calibration.

In this article, a continuous-flow chemiluminescence (CL) system with artificial neural network calibration is proposed for simultaneous determination of three organophosphorus pesiticides residues. This method is based on the fact that organophosphorus pesticides can be decomposed into orthophosphate with potassium peroxodisulphate as oxidant under ultraviolet radiation and that the decomposing kinetic characteristics of the organophosphorus pesticides with different molecular structure are significantly different. The produced orthophosphate can react with molybdate and vanadate to form the vanadomolybdophosphoric heteropoly acid, which can oxidize luminol to produce intense CL emission. The CL intensity of the solution was measured and recorded every 2s in the range of 0-250s. The obtained data were processed chemometrically by use of a three-layered feed-forward artificial neural network trained by back-propagation learning algorithm, in which input node, hidden node and output nodes were 65, 21 and 3, respectively. The proposed multi-residue analysis method was successfully applied to the simultaneous determination of the three organophosphorus pesticides residue in some vegetables samples.

Simultaneous determination of rifampicin and isoniazid by continuous-flow chemiluminescence with artificial neural network calibration.

In this paper a continuous-flow chemiluminescence (CL) system with artificial neural network calibration is proposed for simultaneous determination of rifampicin and isoniazid. This method is based on the different kinetic spectra of the analytes in their CL reaction with alkaline N-bromosuccinimide as oxidant. The CL intensity was measured and recorded every second from 1 to 300 s. The data obtained were processed chemometrically by use of an artificial neural network. The experimental calibration set was 20 sample solutions. The relative standard errors of prediction for both analytes were approximately 5%. The proposed method was successfully applied to the simultaneous determination of rifampicin and isoniazid in a combined pharmaceutical formulation.