Metabolic profiling of milk thistle different organs using UPLC-TQD-MS/MS coupled to multivariate analysis in relation to their selective antiviral potential.

INTRODUCTION: Silybum marianum commonly known as milk thistle is one of the most imperative medicinal plants due to its remarkable pharmacological activities. Lately, the antiviral activities of S. marianum extract have been studied and it showed effectiveness against many viruses. OBJECTIVE: Although most previous studies were concerned mainly with silymarin content of the fruit, the present study provides comprehensive comparative evaluation of S. marianum different organs' chemical profiles using UPLC-MS/MS coupled to chemometrics to unravel potentially selective antiviral compounds against human coronavirus (HCoV-229E). METHODOLOGY: UPLC-ESI-TQD-MS/MS analysis was utilized to establish metabolic fingerprints for S. marianum organs namely fruits, roots, stems and seeds. Multivariate analysis, using OPLS-DA and HCA-heat map was applied to explore the main discriminatory phytoconstituents between organs. Selective virucidal activity of organs extracts against coronavirus (HCoV-229E) was evaluated for the first time using cytopathic effect (CPE) inhibition assay. Correlation coefficient analysis was implemented for detection of potential constituents having virucidal activity. RESULTS: UPLC-MS/MS analysis resulted in 87 identified metabolites belonging to different classes. OPLS-DA revealed in-between class discrimination between milk thistle organs proving their significantly different metabolic profiles. The results of CPE assay showed that all tested organ samples exhibited dose dependent inhibitory activity in nanomolar range. Correlation analysis disclosed that caffeic acid-O-hexoside, gadoleic and linolenic acids were the most potentially selective antiviral phytoconstituents. CONCLUSION: This study valorizes the importance of different S. marianum organs as wealthy sources of selective and effective antiviral candidates. This approach can be extended to unravel potentially active constituents from complex plant matrices.

Testing the effect of semi-transparent spectrally selective thin film photovoltaics for agrivoltaic application: A multi-experimental and multi-specific approach.

The integration of photovoltaic technologies within the agricultural framework, known as agrivoltaics, emerges as a promising and sustainable solution to meet the growing global demands for energy and food production. This innovative technology enables the simultaneous utilization of sunlight for both photovoltaics (PV) and photosynthesis. A key challenge in agrivoltaic research involves identifying technologies applicable to a wide range of plant species and diverse geographic regions. To address this challenge, we adopt a multi-experimental and multi-species approach to assess the viability of semi-transparent, spectrally selective thin-film silicon PV technology. Our findings demonstrate compatibility with crop production in controlled environments for both plants and algae. Notably, selective thin-film PV exhibits the potential to enhance crop yields and serves as a photo-protectant. We observe that plant and algal growth increases beneath the selective PV film when supplemented with appropriate diffuse light in the growth environment. Conversely, in situations where light intensity exceeds optimal levels for plant growth, the selective PV film provides a photo-protective effect. These results suggest potential supplementary benefits of employing this technology in regions characterized by excessive light irradiation, where it can contribute to healthy plant growth.

Structural design of La2(CO3)3 loaded magnetic biochar for selective removal of phosphorus from wastewater.

High levels of phosphorus released into the environment can cause eutrophication issues in wastewater, therefore discharge concentrations of such element are regulated in many countries. This study addresses the pressing need for effective phosphorus removal methods by developing a novel La2(CO3)3 and MnFe2O4 loaded biochar composite (LMB). A remarkable adsorption capacity towards the three forms of phosphorus from wastewater, including phosphate, phosphite, and etidronic acid monohydrate (as a representative of organic phosphorus), was exhibited by LMB (88.20, 16.35, and 15.95 mg g-1, respectively). The high saturation magnetization value (50.17 emu g-1) highlighted the easy separability and recyclability of the adsorbent. The adsorption process was well described by the Langmuir isotherm model and the pseudo-second-order kinetic model, which mainly involved chemisorption. Characterization results confirm the effective loading of La2(CO3)3 with ligand exchange and electrostatic attraction identified as the primary mechanisms. Importantly, the LMB demonstrated exceptional selectivity for phosphorus in wastewater samples containing various substances, exhibiting minimal interference from competing ions (Cl-, NO3-, SO42-, and CO32-). These findings enhance the understanding of LMB's application in efficient wastewater phosphorus removal. Holding significant promise in wastewater remediation, the LMB acts as an effective adsorbent, contributing substantially to the prevention and control of various types of phosphorus pollutants, thereby mitigating wastewater eutrophication.

Highly selective photoelectrochemical CO2 reduction by crystal phase-modulated nanocrystals without parasitic absorption.

Photoelectrochemical (PEC) carbon dioxide (CO2) reduction (CO2R) holds the potential to reduce the costs of solar fuel production by integrating CO2 utilization and light harvesting within one integrated device. However, the CO2R selectivity on the photocathode is limited by the lack of catalytic active sites and competition with the hydrogen evolution reaction. On the other hand, serious parasitic light absorption occurs on the front-side-illuminated photocathode due to the poor light transmittance of CO2R cocatalyst films, resulting in extremely low photocurrent density at the CO2R equilibrium potential. This paper describes the design and fabrication of a photocathode consisting of crystal phase-modulated Ag nanocrystal cocatalysts integrated on illumination-reaction decoupled heterojunction silicon (Si) substrate for the selective and efficient conversion of CO2. Ag nanocrystals containing unconventional hexagonal close-packed phases accelerate the charge transfer process in CO2R reaction, exhibiting excellent catalytic performance. Heterojunction Si substrate decouples light absorption from the CO2R catalyst layer, preventing the parasitic light absorption. The obtained photocathode exhibits a carbon monoxide (CO) Faradaic efficiency (FE) higher than 90% in a wide potential range, with the maximum FE reaching up to 97.4% at -0.2 V vs. reversible hydrogen electrode. At the CO2/CO equilibrium potential, a CO partial photocurrent density of -2.7 mA cm-2 with a CO FE of 96.5% is achieved in 0.1 M KHCO3 electrolyte on this photocathode, surpassing the expensive benchmark Au-based PEC CO2R system.

A novel deep eutectic solvent modified magnetic covalent organic framework for the selective separation and determination of trace copper ion in medicinal plants and environmental samples.

BACKGROUND: Pretreatment techniques should be introduced before metal ion determination because there is very low content of heavy metals in Chinese medicinal plants and environmental samples. Magnetic dispersive micro solid phase extraction (MDMSPE) has been widely used for the separation and adsorption of heavy metal pollutants in medicinal plants and environmental samples. However, the majority of MDMSPE adsorbents have certain drawbacks, including low selectivity, poor anti-interference ability, and small adsorption capacity. Therefore, modifying currently available adsorption materials has gained attention in research. RESULTS: In this study, a novel adsorbent MCOF-DES based on a magnetic covalent organic framework (MCOF) modified by a new deep eutectic solvent (DES) was synthesized for the first time and used as an adsorbent of MDMSPE. The MDMSPE was combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for selective separation, enrichment, and accurate determination of trace copper ion (Cu2+) in medicinal plants and environmental samples. Various characterization results show the successful preparation of new MCOF-DES. Under the optimal conditions, the enrichment factor (EF) of Cu2+ was 30, the limit of detection (LOD) was 0.16 µg L-1, and the limit of quantitation (LOQ) was 0.54 µg L-1. The results for the determination of Cu2+ were highly consistent with those of inductively coupled plasma mass spectrometry (ICP-MS), which verified the accuracy and reliability of the method. SIGNIFICANCE: The established method based on a new adsorption material MCOF-DES has achieved the selective separation and determination of trace Cu2+ in medicinal and edible homologous medicinal materials (Phyllanthus emblica Linn.) and environmental samples (soil and water), which provides a promising, selective, and sensitive approach for the determination of trace Cu2+ in other real samples.

One-step synthesis of phytic acid-assisted hydrochar boost selective sorption and in situ passivation of lanthanum.

The rare earth metal element lanthanum (La) possesses carcinogenic, genotoxic, and accumulative properties, necessitating urgent development of an efficient and cost-effective method to remove La. However, current sorbents still encounter challenges such as poor selectivity, low sorption capacity, and high production costs. This study therefore proposes a promising solution: the creation of phytic acid-assisted sludge hydrochars (P-SHCs) to eliminate La from water and soil environments. This method harnesses phytic acid's exceptional binding ability and the economical hydrothermal carbonization process. P-SHCs exhibit robust sorption affinity, fast sorption kinetics, and excellent sorption selectivity for La when compared with pristine hydrochars (SHCs). This advantage arises from the remarkable binding ability of phosphate functional groups (polyphosphates) on P-SHCs, forming P-O-La complexes. Moreover, P-SHCs demonstrate sustained sorption efficiency across at least five cycles, with a slight decrease attributed to the loss of phosphorus species and mass during recycling. Furthermore, P-SHCs demonstrated superior economic feasibility, with a higher estimated cost-benefit ratio than that of other sorbents. Our study further validates the exceptional passivation capability of P-SHCs, showcasing relative stabilization efficiency ranging from 37.6 % to 79.6 % for La contamination. Additionally, acting as soil passivation agents, P-SHCs foster the enrichment of specific soil microorganisms such as Actinobacteria and Proteobacteria, capable of solubilizing phosphorus and resisting heavy metals. These findings present novel ideas and technical support for employing P-SHCs in combatting environmental pollution stemming from rare earth metals.

Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Preparation of novel polyvinyl alcohol-carbon nanotubes containing imidazolyl ionic liquid/chitosan hydrogel for highly efficient uranium extraction from seawater.

A novel polyvinyl alcohol-carbon nanotube containing an imidazolyl ionic liquid/chitosan composite hydrogel (termed CBCS) was prepared for highly selective uranium adsorption from seawater. The results show that CBCS has good adsorption properties for uranium within the pH range of 5.0-8.0. Kinetics and thermodynamics experiments show that the theoretical maximum adsorption capacity of CBCS to U(VI) is 496.049 mg/g (288 K, pH = 6.0), indicating a spontaneous exothermic reaction. Mechanism analysis shows that the hydroxyl group, amino group, and CN bond on the surface of CBCS directly participate in uranium adsorption and that the dense pores on the surface of CBCS play an important role in uranium adsorption. The competitive adsorption experiment shows that CBCS has excellent uranium adsorption selectivity. In addition, CBCS exhibits good reusability. After five adsorption-desorption cycles, the uranium adsorption rate of CBCS can still reach >98 %. Hence, CBCS has excellent potential for uranium extraction from seawater.

Emerging electro-driven technologies for phosphorus enrichment and recovery from wastewater: A review.

The recovery of phosphorus from wastewater is a critical step in addressing the scarcity of phosphorus resources. Electro-driven technologies for phosphorus enrichment have gathered significant attention due to their inherent advantages, such as mild operating conditions, absence of secondary pollution, and potential integration with other technologies. This study presents a comprehensive review of recent advancements in the field of phosphorus enrichment, with a specific focus on capacitive deionization and electrodialysis technologies. It highlights the underlying principles and effectiveness of electro-driven techniques for phosphorus enrichment while systematically comparing energy consumption, enrichment rate, and concentration factor among different technologies. Furthermore, the study provides a thorough analysis of the capacity of various technologies to selectively enrich phosphorus and proposes several methods and strategies to enhance selectivity. These insights offer valuable guidance for advancing the future development of electrochemical techniques with enhanced efficiency and effectiveness in phosphorus enrichment from wastewater.

A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms.

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Enhanced formaldehyde oxidation over MnO2 and doped manganese-based catalysts: Experimental and theoretical Insights into mechanism and performance.

Thermal catalytic degradation of formaldehyde (HCHO) over manganese-based catalysts is garnering significant attention. In this study, both theoretical simulations and experimental methods were employed to elucidate the primary reaction pathways of HCHO on the MnO2(110) surface. Specifically, the effects of doping MnO2 with elements such as Fe, Ce, Ni, Co, and Cu on the HCHO oxidation properties were evaluated. Advanced characterization techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), and X-ray photoelectron spectroscopy (XPS), were employed to discern the physical properties and chemical states of the active components on the catalyst surface. The comprehensive oxidation pathway of HCHO on the MnO2(110) surface includes O2 adsorption and dissociation, HCHO adsorption and dehydrogenation, CO2 desorption, H2O formation and desorption, oxygen vacancy supplementation, and other elementary reactions. The pivotal rate-determining step was identified as the hydrogen migration process, characterized by an energy barrier of 234.19 kJ mol-1. Notably, HCHOO and *CHOO emerged as crucial intermediates during the reaction. Among the doped catalysts, Fe-doped MnO2 outperformed its counterparts doped with Ce, Ni, Co, and Cu. The optimal degradation rate and selectivity were achieved at a molar ratio of Fe: Mn = 0.1. The superior performance of the Fe-doped MnO2 can be ascribed to its large specific surface area, conducive pore structure for HCHO molecular transport, rich surface-adsorbed oxygen species, and a significant presence of oxygen vacancies.

Insights into Leishmania donovani potassium channel family and their biological functions.

Leishmania donovani is the causative organism for visceral leishmaniasis. Although this parasite was discovered over a century ago, nothing is known about role of potassium channels in L. donovani. Potassium channels are known for their crucial roles in cellular functions in other organisms. Recently the presence of a calcium-activated potassium channel in L. donovani was reported which prompted us to look for other proteins which could be potassium channels and to investigate their possible physiological roles. Twenty sequences were identified in L. donovani genome and subjected to estimation of physio-chemical properties, motif analysis, localization prediction and transmembrane domain analysis. Structural predictions were also done. The channels were majorly α-helical and predominantly localized in cell membrane and lysosomes. The signature selectivity filter of potassium channel was present in all the sequences. In addition to the conventional potassium channel activity, they were associated with gene ontology terms for mitotic cell cycle, cell death, modulation by virus of host process, cell motility etc. The entire study indicates the presence of potassium channel families in L. donovani which may have involvement in several cellular pathways. Further investigations on these putative potassium channels are needed to elucidate their roles in Leishmania. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03692-y.

Ratiometric sensing interface for glutathione determination based on electro-polymerized copper-coordinated molecularly imprinted layer supported on silver/porous carbon hybrid.

A novel molecularly imprinted ratiometric-based sensor was designed for highly selective and ultrasensitive electrochemical detection of glutathione (GSH). The sensor consists of porous carbon co-doped with nitrogen and sulfur formed on the surface of graphite electrode (N, S@PC/GE). Silver nanoparticles (Ag) were grown on the surface of N, S@PC/GE to improve the conductivity/surface area of the sensor and represent an internal reference signal for ratiometric response. The monomer (pyrrole-4-carboxylic acid, Py-COOH) was electro-polymerized on the surface of Ag/N, S@PC/GE in the presence of Cu (II) to form Cu-MIP@Ag/N, S@PC/GE. Addition of GSH decreased the signal of Ag at 0.18 V (oxidation of Ag) due to coordination complexation, while the signal response at 0.83 V (oxidation of Ag-GSH complex) was increased. Under optimum conditions, the ratio response (IGSH/IAg) was increased with increasing the concentration of GSH in the range of 0.01-500 nM with a detection limit (S/N = 3) of 0.003 nM. The electrochemical sensor exhibits many advantages including low LOD, high selectivity, good reproducibility, and satisfactory stability. The sensor was successfully applied to determine GSH in dietary supplements and human serum samples with recoveries % ranged from 97.4 to 101.8% and relative standard deviation % (RSD %) did not exceed 3.8%. This research paper introduces new information for the construction of molecular imprinted ratiometric-based electrochemical sensors for highly selective and sensitive detection of (bio) molecules.

Anti-tumor effects of novel alkannin derivatives with potent selectivity on comprehensive analysis.

BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.

Development of an Efficient FRET-Based Ratiometric Uranium Biosensor.

The dispersion of uranium in the environment can pose a problem for the health of humans and other living organisms. It is therefore important to monitor the bioavailable and hence toxic fraction of uranium in the environment, but no efficient measurement methods exist for this. Our study aims to fill this gap by developing a genetically encoded FRET-based ratiometric uranium biosensor. This biosensor was constructed by grafting two fluorescent proteins to both ends of calmodulin, a protein that binds four calcium ions. By modifying the metal-binding sites and the fluorescent proteins, several versions of the biosensor were generated and characterized in vitro. The best combination results in a biosensor that is affine and selective for uranium compared to metals such as calcium or other environmental compounds (sodium, magnesium, chlorine). It has a good dynamic range and should be robust to environmental conditions. In addition, its detection limit is below the uranium limit concentration in drinking water defined by the World Health Organization. This genetically encoded biosensor is a promising tool to develop a uranium whole-cell biosensor. This would make it possible to monitor the bioavailable fraction of uranium in the environment, even in calcium-rich waters.

LUMO-Mediated Se and HOMO-Mediated Te Nanozymes for Selective Redox Biocatalysis.

Selenium (Se) and tellurium (Te) nanomaterials with novel chain-like structures have attracted widespread interest owing to their intriguing properties. Unfortunately, the still-unclear catalytic mechanisms have severely limited the development of biocatalytic performance. In this work, we developed chitosan-coated Se nanozymes with a 23-fold higher antioxidative activity than Trolox and bovine serum albumin coated Te nanozymes with stronger prooxidative biocatalytic effects. Based on density functional theory calculations, we first propose that the Se nanozyme with Se/Se2- active centers favored reactive oxygen species (ROS) clearance via a LUMO-mediated mechanism, while the Te nanozyme with Te/Te4+ active centers promoted ROS production through a HOMO-mediated mechanism. Furthermore, biological experiments confirmed that the survival rate of γ-irritated mice treated with the Se nanozyme was maintained at 100% for 30 days by inhibiting oxidation. However, the Te nanozyme had the opposite biological effect via promoting radiation oxidation. The present work provides a new strategy for improving the catalytic activities of Se and Te nanozymes.

Smart pH- and Temperature-Sensitive Micelles Based on Chitosan Grafted with Fatty Acids to Increase the Efficiency and Selectivity of Doxorubicin and Its Adjuvant Regarding the Tumor Cells.

The main factors that determine the low effectiveness of chemotherapy are the low target bioavailability of antitumor drugs and the efflux process. In attempts to overcome this problem, several approaches are proposed here. Firstly, the development of polymeric micellar systems based on chitosan grafted by fatty acids (different types to optimize their properties), which, on the one hand, increase the solubility and bioavailability of cytostatics and, on the other hand, effectively interact with tumor cells due to the polycationic properties of chitosan, allowing for more effective penetration of cytostatic drugs into the cells. Secondly, the use of adjuvants-synergists of cytostatics (such as eugenol) included in the same micellar formulation-that selectively enhance the accumulation and retention of cytostatics in the tumor cells. pH- and temperature-sensitive polymeric micelles developed show high entrapment efficiency for both cytostatics and eugenol (EG) >60% and release the drug in a prolonged manner for 40 h in a weakly acidic medium corresponding to the microenvironment of tumors. In a slightly alkaline environment, the drug circulates longer (more than 60 h). The thermal sensitivity of micelles is realized due to an increase in the molecular mobility of chitosan, which undergoes a phase transition at 32-37 °C. The effect of the cytostatic drug doxorubicin (Dox) on cancerous A549 cells and model healthy cells of human embryonic renal epithelium (HEK293T) was studied by FTIR spectroscopy and fluorescence microscopy. Micellar Dox penetrates into cancer cells 2-3 times more efficiently when using EG adjuvant, which inhibits efflux, as demonstrated by a significant increase in the ratio of intra- and extracellular concentrations of the cytostatic. However, here it is worth remembering about healthy cells that they should not be damaged: according to changes in the FTIR and fluorescence spectra, the penetration of Dox into HEK293T when using micelles in combination with EG is reduced by 20-30% compared to a simple cytostatic. Thus, experimental developments of combined micellar cytostatic drugs have been proposed to increase the effectiveness of cancer treatment and overcome multiple drug resistance.

Structures of L-proline trans-hydroxylase reveal the catalytic specificity and provide deeper insight into AKG-dependent hydroxylation.

L-Proline hydroxylase is a member of the non-heme Fe2+/α-ketoglutarate (AKG)-dependent hydroxylase family that catalyzes the reaction from L-proline to hydroxy-L-proline, which is widely used in drug synthesis, biochemistry, food supplementation and cosmetic industries. Here, the first crystal structure of L-proline trans-hydroxylase and its complexes with substrate and product are reported, which reveal the structural basis of trans-cis proline hydroxylation selectivity. Structure comparison with other AKG-dependent hydroxylases identifies conserved amino acid residues, which may serve as signatures of in-line or off-line AKG binding modes in the AKG-dependent enzyme family.

Development of Yin-Yang ligand for cannabinoid receptors.

Cannabinoid receptors (CBs), including CB1 and CB2, are the key components of a lipid signaling endocannabinoid system (ECS). Development of synthetic cannabinoids has been attractive to modulate ECS functions. CB1 and CB2 are structurally closely related subtypes but with distinct functions. While most efforts focus on the development of selective ligands for single subtype to circumvent the undesired off-target effect, Yin-Yang ligands with opposite pharmacological activities simultaneously on two subtypes, offer unique therapeutic potential. Herein we report the development of a new Yin-Yang ligand which functions as an antagonist for CB1 and concurrently an agonist for CB2. We found that in the pyrazole-cored scaffold, the arm of N1-phenyl group could be a switch, modification of which yielded various ligands with distinct activities. As such, the ortho-morpholine substitution exerted the desired Yin-Yang bifunctionality which, based on the docking study and molecular dynamic simulation, was proposed to be resulted from the hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. Our results demonstrated the feasibility of structure guided ligand evolution for challenging Yin-Yang ligand.

Poly(amidoxime)-graft-magnetic chitosan for highly efficient and selective uranium extraction from seawater.

Adsorbents with highly efficient and selective recovery performance towards uranium are significantly demanded for the sustainable nuclear power production. Herein, poly(amidoxime)-graft-magnetic chitosan (P(AO)-g-MC) was synthesized through functionalizing magnetic chitosan with polyacrylonitrile followed by amidoximation process. Under magnetic field, P(AO)-g-MC can be separated from the solution in 10 s. Owing to the strong affinity of high-density amidoxime groups towards uranium, P(AO)-g-MC showed remarkable adsorption capacity, rapid kinetics and good regeneration performance in uranium spiked aqueous solution. Notably, the 7-day uranium adsorption capacity of P(AO)-g-MC from natural seawater in column mode was up to 5.14 mg/g, 12 times that of vanadium. The excellent uranium uptake performance over vanadium originated from the strong coordination by N and O in amidoxime groups according to theoretical simulation. The advantages of easy separating and high selectivity make P(AO)-g-MC a very potential uranium adsorbent in natural seawater.