Enantioselective Labeling of Zebrafish for D-Phenylalanine Based on Graphene-Based Nanoplatform.

Enantioselective labeling of important bioactive molecules in complex biological environments by artificial receptors has drawn great interest. From both the slight difference of enantiomers' physicochemical properties and inherently complexity in living organism point of view, it is still a contemporary challenge for preparing practical chiral device that could be employed in the model animal due to diverse biological interference. Herein, we introduce γ-cyclodextrin onto graphene oxide for fabricating γ-cyclodextrin and graphene oxide assemblies, which provided an efficient nanoplatform for chiral labelling of D-phenylalanine with higher chiral discrimination ratio of KD/KL = 8.21. Significantly, the chiral fluorescence quenching effect of this γ-CD-GO nanoplatform for D-phenylalanine enantiomer in zebrafish was 7.0-fold higher than L-isomer, which exhibiting real promise for producing practical enantio-differentiating graphene-based systems in a complex biological sample.

Recent Advances of Cell Membrane Coated Nanoparticles in Treating Cardiovascular Disorders.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.

Research on the Node Importance of a Weighted Network Based on the K-Order Propagation Number Algorithm.

To describe both the global and local characteristics of a network more comprehensively, we propose the weighted K-order propagation number (WKPN) algorithm to extract the disease propagation based on the network topology to evaluate the node importance. Each node is set as the source of infection, and the total number of infected nodes is defined as the K-order propagation number after experiencing the propagation time K. The simulation of the symmetric network with bridge nodes indicated that the WKPN algorithm was more effective for evaluation of the algorithm features. A deliberate attack strategy, which indicated an attack on the network according to the node importance from high to low, was employed to evaluate the WKPN algorithm in real networks. Compared with the other methods tested, the results demonstrate the applicability and advancement that a lower number of nodes, with a higher importance calculated by the K-order propagation number algorithm, has to achieve full damage to the network structure.

Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical-Structured Fiber Device for Overcoming Cancer Multidrug Resistance.

Multiple drug resistance (MDR) of cancer cells is a major cause of chemotherapy failure. It is currently a great challenge to develop a direct and effective strategy for continuously inhibiting the P-glycoprotein (P-gp) drug pump of MDR tumor cells, thus enhancing the intracellular concentration of the therapeutic agent for effectively killing MDR tumor cells. Here, a new implantable hierarchical-structured ultrafine fiber device is developed via a microfluidic-electrospinning technology for localized codelivery of doxorubicin (DOX) and apatinib (AP). An extremely high encapsulation efficiency of ≈99% for the dual drugs is achieved through this strategy. The release of the loaded dual drugs can be controlled in a programmable release model with a rapid release of the micelles, while AP is slowly released. The sustained release of AP can continuously inhibit the P-gp drug pump of MDR tumor cells, increasing the intracellular DOX accumulation. The in vivo DOX biodistribution displays that the DOX accumulation in the tumor tissues achieves 17.82% after implanting the fiber device for 72 h, which is 6.36-fold higher than that of the intravenously injected DOX. Importantly, the fiber device shows an excellent antitumor effect on MDR tumor-bearing mice with low systemic toxicity.

Construction of a Switchable Nanochannel for Protein Transport via a Pillar[5]arene-Based Host-Guest System.

Modulating protein selective translocation is a significant process, which has great potential for mimicking and understanding complex biological activities. As such, how to construct a nanochannel that can accomplish well gating protein transport is vital and challenge. Herein, inspired by nature, we presented a robust strategy to construct a switchable nanochannel by introducing a pH responsive binary host-guest system into a nanochannel. Benefiting from the novel design of the pillar[5]arene as gatekeeper, the functional nanochannel can well facilitate histone transport. Under pH regulation, the host-guest assembled nanochannel is capable of switching "on" and "off" to manipulate the histone translocation process. This study exemplifies the importance of molecular switch mediated protein transport in this process and provides a new theoretical model for biological research, which will open a new avenue for better understanding of some physiological and pathological behaviors.

Sky Detection in Hazy Image.

Sky detection plays an essential role in various computer vision applications. Most existing sky detection approaches, being trained on ideal dataset, may lose efficacy when facing unfavorable conditions like the effects of weather and lighting conditions. In this paper, a novel algorithm for sky detection in hazy images is proposed from the perspective of probing the density of haze. We address the problem by an image segmentation and a region-level classification. To characterize the sky of hazy scenes, we unprecedentedly introduce several haze-relevant features that reflect the perceptual hazy density and the scene depth. Based on these features, the sky is separated by two imbalance SVM classifiers and a similarity measurement. Moreover, a sky dataset (named HazySky) with 500 annotated hazy images is built for model training and performance evaluation. To evaluate the performance of our method, we conducted extensive experiments both on our HazySky dataset and the SkyFinder dataset. The results demonstrate that our method performs better on the detection accuracy than previous methods, not only under hazy scenes, but also under other weather conditions.

Robust Scale Adaptive Tracking by Combining Correlation Filters with Sequential Monte Carlo.

A robust and efficient object tracking algorithm is required in a variety of computer vision applications. Although various modern trackers have impressive performance, some challenges such as occlusion and target scale variation are still intractable, especially in the complex scenarios. This paper proposes a robust scale adaptive tracking algorithm to predict target scale by a sequential Monte Carlo method and determine the target location by the correlation filter simultaneously. By analyzing the response map of the target region, the completeness of the target can be measured by the peak-to-sidelobe rate (PSR), i.e., the lower the PSR, the more likely the target is being occluded. A strict template update strategy is designed to accommodate the appearance change and avoid template corruption. If the occlusion occurs, a retained scheme is allowed and the tracker refrains from drifting away. Additionally, the feature integration is incorporated to guarantee the robustness of the proposed approach. The experimental results show that our method outperforms other state-of-the-art trackers in terms of both the distance precision and overlap precision on the publicly available TB-50 dataset.

Macroscopic Responsive Liquid Quantum Dots Constructed via Pillar[5]arene-Based Host-Guest Interactions.

Liquid quantum dots (QDs) have been used as a fluorescent films sensor. Constructing a macroscopic, responsive, liquid QD system for lysine (Lys) is a challenging task. To achieve a selective macroscopic response towards Lys, herein we present a new strategy for integrating host-guest chemistry into a liquid QD system. Water-soluble pillar[5]arene WP5 was designed and synthesized as a host. WP5 was introduced onto the surface of PEG1810-modified QDs by host-guest interactions to obtain liquid WP5-1810-QDs. The interaction between WP5 and Lys is stronger than that between WP5 and PEG-1810, causing WP5 to be released from the 1810-QDs surface in the presence of Lys, resulting in macroscopic fluorescence quenching. This smart material shows promise in amino acid sensing and separation.

Lost Food and Associated Phosphorus Footprint: Evidence from China.

The environmental impacts of excessive phosphorus emissions (PE) have been widely discussed in recent years. This study aims to calculate and evaluate the phosphorus footprint (PF) of food thrown away in Chinese universities. Based on a nationwide survey involving 9192 university students from 29 provinces and 29 universities in China, the result reveals that the PF generated by food waste in Chinese university canteens was 3.209 Kt in 2018. Furthermore, it is found that meal satisfaction, gender, regional economic level, dietary culture, and years of education all have significant impacts on lost food PF. Our findings emphasize the importance of reducing food waste in university canteens, which plays a crucial role in ensuring food security and environmental protection.

Coumarin-furo[2,3-d]pyrimidone hybrid molecules targeting human liver cancer cells: synthesis, anticancer effect, EGFR inhibition and molecular docking studies.

The design, synthesis and investigation of antitumor activities of some coumarin-furo[2,3-d]pyrimidone hybrid molecules are reported. In vitro, HepG2 cells were used to investigate the cytotoxicity of 6a-n and 10a-n. The results demonstrated that coupling a furopyrimidone scaffold with coumarin through a hydrazide linker can effectively improve their synergistic anticancer activity. The coumarin-furo[2,3-d]pyrimidone combination 10a exhibited significant inhibitory activity against HepG2 cells with IC50 = 7.72 ± 1.56 µM, which is better than those of gefitinib and sorafenib. It is worth mentioning that the coumarin-furo[2,3-d]pyrimidone combination 10a showed excellent inhibition of the EGFR enzymatic activity with IC50 = 1.53 µM and 90% inhibition at 10 µM concentration. In silico investigation predicts the possibility of direct binding between the new coumarin-furo[2,3-d]pyrimidone hybrid molecules and the EGFR. The results suggest that coumarin-furo[2,3-d]pyrimidone hybrid molecules are potential antitumor agents targeting human liver cancer cells.

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

Stimuli-responsive nanocarrier delivery systems for Pt-based antitumor complexes: a review.

Platinum-based anticancer drugs play a crucial role in the clinical treatment of various cancers. However, the application of platinum-based drugs is heavily restricted by their severe toxicity and drug resistance/cross resistance. Various drug delivery systems have been developed to overcome these limitations of platinum-based chemotherapy. Stimuli-responsive nanocarrier drug delivery systems as one of the most promising strategies attract more attention. And huge progress in stimuli-responsive nanocarrier delivery systems of platinum-based drugs has been made. In these systems, a variety of triggers including endogenous and extracorporeal stimuli have been employed. Endogenous stimuli mainly include pH-, thermo-, enzyme- and redox-responsive nanocarriers. Extracorporeal stimuli include light-, magnetic field- and ultrasound responsive nanocarriers. In this review, we present the recent advances in stimuli-responsive drug delivery systems with different nanocarriers for improving the efficacy and reducing the side effects of platinum-based anticancer drugs.

Novel Coumarin-furo[2,3-d]pyrimidinone hybrid derivatives as anticancer agents: Synthesis, biological evaluation and molecular docking.

A series of coumarin-furo[2,3-d]pyrimidinone hybrid derivatives were synthesized, characterized by HR-MS, 1H NMR and 13C NMR. All synthesized compounds were evaluated for antiproliferative activities against hepatic carcinoma (HepG2) and cervical carcinoma (Hela) cell lines in vitro, and results shown that most of the compounds exhibited potent antitumor activity. Moreover, compound 3i, 8d and 8i were selected to induce apoptosis in HepG2 cells, and it displayed a significant concentration-dependent. Further, transwell migration assay was used to detect the most potent compound 8i, and the results revealed that 8i can significantly inhibit HepG2 cells migration and invasion. In addition, kinase activity assay showed compound 8i may be a multi-target inhibitor, which 8i has an inhibition rate of 40-20% on RON, ABL, GSK3α and so on ten different kinases at the concentration 1 µmol/L. At the same time, molecular docking studies revealed the possible binding modes of compounds 3i, 8d and 8i with kinase recepteur d'origine nantais (RON). A comparative molecular field analysis (CoMFA) model was established from 3D-QSAR study that guide us to a more bulkly and electro-positive Y group at the C-2 position of furo[2,3-d]pyrimidinone ring was preferable for the bioactivity improvement of our compounds. Our preliminary research indicated that the coumarin skeleton introducing to the furo[2,3-d]pyrimidine system had a significantly influence on the biological activities.

Design of High-Entropy Alloy Coating for Cavitation Erosion Resistance by Different Energy-Induced Dynamic Cyclic Behaviors.

The dispute over the effect of cavitation heat on material surface intensifies the fuzziness of cavitation erosion (CE) mechanism and limits the development of protective materials. Here, an anti-CE Al10Cr28Co28Ni34 high-entropy alloy (HEA) coating with single face-centered cubic (FCC), prepared by high-velocity oxy-fuel (HVOF) spraying technologies, was designed by inducing mechanical and thermal energy-induced behaviors to transform or counteract each other. The results showed that, on the one hand, this coating underwent the refinement of the average grain size from 1.22 to 1.02 µm, the increase in dislocation density from 1.28 × 10-10 to 1.83 × 10-10 m-2, and the martensitic transformation from FCC to body-centered cubic (BCC) under the cavitation load; on the other hand, cavitation heat could indeed induce grain growth and realize structural relaxation, which confirmed that cavitation heat acting on the material surface at temperatures theoretically above 1206.28 K also played a significant role in the CE mechanism. That is, the surface microstructure of this coating was always in a dynamic cycle during the CE process. Therefore, the coating achieved the simultaneous absorption of mechanical impact energy and thermal energy released by the bubble collapse while effectively avoiding the overenrichment of crystal defects and finally exhibited a CE resistance 2 times better than that of the classical AlCrCoFeNi HEA coating. This design concept of inducing different energy restraints or neutralization through the special response behaviors of surface microstructure provides a completely new way for the development of CE-resistant materials.

Light-responsive nanochannels based on the supramolecular host-guest system.

The light-responsive nanochannel of rhodopsin gained wider research interest from its crucial roles in light-induced biological functions, such as visual signal transduction and energy conversion, though its poor stability and susceptibility to inactivation in vitro have limited its exploration. However, the fabrication of artificial nanochannels with the properties of physical stability, controllable structure, and easy functional modification becomes a biomimetic system to study the stimulus-responsive gating properties. Typically, light-responsive molecules of azobenzene (Azo), retinal, and spiropyran were introduced into nanochannels as photo-switches, which can change the inner surface wettability of nanochannels under the influence of light; this ultimately results in the photoresponsive nature of biomimetic nanochannels. Furthermore, the fine-tuning of their stimulus-responsive properties can be achieved through the introduction of host-guest systems generally combined with a non-covalent bond, and the assembling process is reversible. These host-guest systems have been introduced into the nanochannels to form different functions. Based on the host-guest system of light-responsive reversible interaction, it can not only change the internal surface properties of the nanochannel and control the recognition and transmission behaviors but also realize the controlled release of a specific host or guest molecules in the nanochannel. At present, macrocyclic host molecules have been introduced into nanochannels including pillararenes, cyclodextrin (CD), and metal-organic frameworks (MOFs). They are introduced into the nanochannel through chemical modification or host-guest assemble methods. Based on the changes in the light-responsive structure of azobenzene, spiropyran, retinal, and others with macrocycle host molecules, the surface charge and hydrophilic and hydrophobic properties of the nanochannel were changed to regulate the ionic and molecular transport. In this study, the development of photoresponsive host and guest-assembled nanochannel systems from design to application is reviewed, and the research prospects and problems of this photo-responsive nanochannel membrane are presented.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.

Recent Advances of Nanotechnology-Facilitated Bacteria-Based Drug and Gene Delivery Systems for Cancer Treatment.

Cancer is one of the most devastating and ubiquitous human diseases. Conventional therapies like chemotherapy and radiotherapy are the most widely used cancer treatments. Despite the notable therapeutic improvements that these measures achieve, disappointing therapeutic outcome and cancer reoccurrence commonly following these therapies demonstrate the need for better alternatives. Among them, bacterial therapy has proven to be effective in its intrinsic cancer targeting ability and various therapeutic mechanisms that can be further bolstered by nanotechnology. In this review, we will discuss recent advances of nanotechnology-facilitated bacteria-based drug and gene delivery systems in cancer treatment. Therapeutic mechanisms of these hybrid nanoformulations are highlighted to provide an up-to-date understanding of this emerging field.

Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2.

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10-8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10-7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.

Ethyl 3-{[(3-methyl-anilino)(1H-1,2,4-triazol-1-yl)methyl-idene]amino}-1-benzofuran-2-carboxyl-ate.

The crystal structure of the title compound, C(21)H(19)N(5)O(3), is stabilized by inter-molecular N-H⋯N and C-H⋯O hydrogen bonds. The mol-ecule contains a planar [maximum deviations = -0.026 (1) and 0.027 (2) Å] benzofuran ring system, which forms dihedral angles of 78.75 (8) and 39.78 (7)° with the benzene and triazole rings, respectively.

2-Anilino-3-(2-hy-droxy-phen-yl)quinazolin-4(3H)-one methanol monosolvate.

In the title compound, C(20)H(15)N(3)O(2)·CH(3)OH, the quinazolin-one ring system is approximately planar, the dihedral angle between the pyrimidinone ring and the adjacent benzene ring being 1.73 (6)°. The pyrimidinone ring makes dihedral angles of 77.58 (6) and 29.62 (6)°, respectively, with the hy-droxy-phenyl and phenyl rings. In the crystal, the components are connected by O-H⋯O and C-H⋯O hydrogen bonds, forming a zigzag chain along the b axis.