pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties.

The host-guest interactions between baicalein (BALE) and cucurbit[8]uril (Q[8]) and the corresponding properties of the inclusion complex were studied using 1H NMR, IR and UV-vis spectroscopy and DTA. The results showed that BALE forms an inclusion compound (1:1) with Q[8], and the properties of baicalein are changed by cucurbit[8]uril.

Sphingomonas oleivorans sp. nov., isolated from oil-contaminated soil.

Strain FW-11T was isolated from oil-contaminated soil from Panjin in Liaoning, China. It was a Gram-stain-negative, aerobic and rod-shaped bacterium. The strain was confirmed to be a member of the genus Sphingomonas based on phylogenetic inference and phenotypic characteristics. The best growth of strain FW-11T occurred at 30 °C and pH 6.0-7.0. The strain was non-spore-forming, catalase-negative and oxidase-negative. The main polar lipids were sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and unidentified lipids. The cell-wall peptidoglycan of strain FW-11T included alanine, glycine, glutamic acid, aspartic acid and meso-diaminopimelate. The predominant isoprenoid quinones were ubiquinone Q-10 (93.2 %) and Q-9 (6.8 %). The fatty acid profile (>5 %) included C18 : 1ω6c (43.1 %), C16 : 0 (14.6 %), C17 : 1ω6c (14.0 %) and C14 : 0 2-OH (11.1 %). The most similar neighbours of FW-11T were Sphingomonas fennica K101T (97.4 %) and Sphingomonas haloaromaticamans A175T (97.0 %). The average nucleotide identity relatedness values between strain FW-11T and the two type strains (S. fennica K101T and S. haloaromaticamans A175T) were 73.2 and 75.3 %, respectively. The genome size of FW-11T was 3.8 Mbp, comprising 3735 predicted genes with a DNA G+C content of 64.0 mol%. Based on phenotypic, chemotaxonomic and phylogenetic data, strain FW-11T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas oleivorans sp. nov. is proposed. The type strain is FW-11T (=LMG 29274T=HAMBI 3659T).

Gene expression profiling analysis of the effects of low-intensity pulsed ultrasound on induced pluripotent stem cell-derived neural crest stem cells.

Low-intensity pulsed ultrasound (LIPUS) is a noninvasive technique that has been shown to affect cell proliferation, migration, and differentiation and promote the regeneration of damaged peripheral nerve. Our previous studies had proved that LIPUS can significantly promote the neural differentiation of induced pluripotent stem cell-derived neural crest stem cells (iPSCs-NCSCs) and enhance the repair of rat-transected sciatic nerve. To further explore the underlying mechanisms of LIPUS treatment of iPSCs-NCSCs, this study reported the gene expression profiling analysis of iPSCs-NCSCs before and after LIPUS treatment using the RNA-sequencing (RNA-Seq) method. It was found that expression of 76 genes of iPSCs-NCSCs cultured in a serum-free neural induction medium and expression of 21 genes of iPSCs-NCSCs cultured in a neuronal differentiation medium were significantly changed by LIPUS treatment. The differentially expressed genes are related to angiogenesis, nervous system activity and functions, cell activities, and so on. The RNA-seq results were further verified by a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). High correlation was observed between the results obtained from qRT-PCR and RNA-Seq. This study presented new information on the global gene expression patterns of iPSCs-NCSCs after LIPUS treatment and may expand the understanding of the complex molecular mechanism of LIPUS treatment of iPSCs-NCSCs.

Three-dimensional co-culture microfluidic model and its application for research on cancer stem-like cells inducing migration of endothelial cells.

OBJECTIVES: To build a three-dimensional co-culture model in a microfluidic device for cancer research and evaluate its feasibility by investigating cancer stem-like cells (SCs) induced migration of human umbilical vein endothelial cells (ECs). RESULTS: The microfluidic device provided two-dimensional and three-dimensional (2D/3D) culture and co-culture environments without affecting cell viability. The device also provided an effective concentration for the chemiotaxis of cells, and to support real-time monitoring of cell behavior. In this model, SCs significantly increased the migration area of ECs with a hepatocarcinoma cell line (MHCC97H; MCs). The presence of ECs also induced both MCs and SCs invasion into Matrigel. The migration area of MCs and SCs significantly increased when co-cultured with ECs. CONCLUSIONS: This 3D co-culture microfluidic model is a suitable model in cancer research. Compared with MCs, SCs had greater potential in inducing EC migration and interacting with ECs.

Alcohol-Mediated Resistance-Switching Behavior in Metal-Organic Framework-Based Electronic Devices.

Metal-organic frameworks (MOFs) have drawn increasing attentions as promising candidates for functional devices. Herein, we present MOF films in constructing memory devices with alcohol mediated resistance switching property, where the resistance state is controlled by applying alcohol vapors to achieve multilevel information storage. The ordered packing mode and the hydrogen bonding system of the guest molecules adsorbed in MOF crystals are shown to be the reason for the alcohol mediated electrical switching. This chemically mediated memory device can be a candidate in achieving environment-responsive devices and exhibits potential applications in wearable information storage systems.

Mechano-growth factor enhances differentiation of bone marrow-derived mesenchymal stem cells.

OBJECTIVES: To investigate the effect of mechano-growth factor (MGF) on the differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro. RESULTS: Flow cytometry assay identified the isolated cells were human bone marrow mesenchymal stem cells, which had differentiation ability when cultured with specific induction culture media. Alizarin Red S, Oil Red O and Alcian Blue staining showed osteogenic, adipogenic and chondrogenic differentiation were significantly increased after hBMSCs were treated with MGF E peptide. Collagen II expression was considerably increased after hBMSCs were induced with chondrogenic induction culture medium supplemented with TGF-ß3 and MGF E peptide. Overexpression of MGF by an expression plasmid further confirmed the MGF could enhance tri-lineage differentiation of hBMSCs. Moreover, we found that hBMSCs proliferation rate was decreased and G1 phase of the cell cycle was lengthened after MGF treatment when compared to the control group. CONCLUSIONS: MGF can enhance differentiation of hBMSCs during specific induction culture media induction by lengthening G1 phase of cell cycle.

[Advance on chemical compounds of Ainsliaea genus].

Plants in Ainsliaea genus, belongs to Compositae family, are traditional Chinese medicine and widely used in folk. These plants contain various types of chemical components, and main components are sesquiterpene lactone and its glycosides. In addition, there are triterpenoids, flavonoids, steroids, phenolic acid, long chain fatty acid and volatile oils. Recently, much attention has been payed to varlous research of A. fragrans. This paper reviewed and summarized the chemical components to provide the theoretical basis for the use of Ainsliaea.

[Hypoxia-responsive factor PHD2 and angiogenic diseases].

Prolyl-4-hydroxylase domain (PHDs) family is one of the most important regulatory factors in hypoxic stress. PHD2 plays a critical role in cells and tissues adaptation to the low oxygen environment. Its hydroxylation activity regulates the stability and transcriptional activity of the hypoxia-inducible factor 1 (HIF-1), which is the key factor in response to hypoxic stress. Subsequently, PHD2 acts as an important factor in oxygen homeostasis. Studies have shown that PHD2, through its regulation on HIF-1, plays an important role in the post-ischemic neovascularization. Furthermore, under hypoxic condition, PHD2 also regulates other pathways that positively regulate angiogenesis factors HIF-1 independently. Moreover, recently, several evidences have also shown that PHD2 also affects tumor growth and metastasis in a tumor microenvironment. Based on these facts, PHD2 have been considered as a potential therapeutic target both in treating ischemic diseases and tumors. Here, we review the molecular regulation mechanism of PHD2 and its physiological and pathological functions. We focus on the role of PHD2 in both therapeutic angiogenesis for ischemic disease and tumor angiogenesis, and the current progress in utilizing PHD2 as a therapeutic target.

Macular Neural and Microvascular Alterations in Type 2 Diabetes Without Retinopathy: A SS-OCT Study.

PURPOSE: To identify specific markers indicative of macular neural and microvascular alterations in individuals with Type 2 Diabetes Mellitus (T2DM) without clinically observable retinopathy. DESIGN: Prospective cross-sectional study. METHODS: Using the PLEX Elite 9000, all eyes underwent swept-source optical coherence tomography (SS-OCT) angiography. Quantitative analysis of acquired images compared macular neural and microvascular alterations in T2DM patients without retinopathy to age-matched controls. Precise assessments encompassed measuring the thickness of each individual retinal layer and evaluating macular vascular indices within different capillary plexuses. RESULTS: Forty-nine T2DM patients and 51 age-matched controls participated. T2DM patients exhibited a significant reduction in the mean macular thickness of the ganglion cell-inner plexiform layer (GC-IPL) (82.5 ± 5.5 µm vs 86.2 ± 5.0 µm, P = .001) and macular retinal nerve fiber layer (RNFL) (45.8 ± 3.0 µm vs 48.1 ± 3.7 µm, P = .001). Furthermore, macular full retinal thickness was significantly lower in diabetic eyes than controls (324.9 ± 16.3 µm vs 332.8 ± 13.7 µm, P = .009). Vascular measurements revealed subtle changes in macular vascular skeleton density within the total capillary plexuses in T2DM patients (0.132 ± 0.005 vs 0.135 ± 0.005, P = .019). CONCLUSIONS: Metrics derived from SS-OCT, particularly macular RNFL and GC-IPL thicknesses, emerged as superior indicators for the early detection of diabetic retinal disease in individuals with T2DM without clinically observable retinopathy. Further investigations are warranted to comprehensively understand the clinical implications of these findings.

A novel ratiometric fluorescent probe with high selectivity for lysosomal nitric oxide imaging.

Nitric oxide (NO) plays critical roles in both physiology and pathology, serving as a significant signaling molecule. Recent investigations have uncovered the pivotal role of lysosome as a critical organelle where intracellular NO exists and takes function. In this study, we developed a novel ratiometric fluorescent probe called XL-NO and modified it with a morpholine unit, which followed the intramolecular charge transfer (ICT) mechanism. The probe could detect lysosomal nitric oxide with high selectivity and sensitivity. The probe XL-NO contained a secondary amine moiety that could readily react with NO in lysosomes, leading to the formation of the N-nitrosation product. The N-nitroso structure enhanced the capability in push-pull electron, which obviously led to the change of fluorescence from 621 nm to 521 nm. In addition, XL-NO was discovered to have some evident advantages, such as significant ratiometric signal (I521/I621) change, strong anti-interference ability, good biocompatibility, and a low detection limit (LOD = 44.3 nM), which were crucial for the detection of lysosomal NO. To evaluate the practical application of XL-NO, NO imaging experiments were performed in both living cells and zebrafish. The results from these experiments confirmed the feasibility and reliability of XL-NO for exogenous/endogenous NO imaging and lysosome targeting.

Effect of Substrate Surface Charges on Proton Conduction of Ultrathin Nafion Films.

A potential approach to enhance the suppressed proton conductivity of nanoscale ultrathin Nafion films is to adjust the ionomer structure via regulating the catalyst-ionomer interaction. To understand the interaction between substrate surface charges and Nafion molecules, self-assembled ultrathin films (∼20 nm) were prepared on the SiO2 model substrates, which were modified with silane coupling agents to carry either negative (COO-) or positive (NH3+) charges. Specifically, the surface energy, phase separation, and proton conductivity were investigated by contact angle measurements, atomic force microscopy, and microelectrodes to illuminate the relationship between the substrate surface charge, thin-film nanostructure, and proton conduction. Compared to electrically neutral substrates, ultrathin films formed faster on the negatively charged substrate with an 83% increase in proton conductivity but formed more slowly on the positively charged substrate, with proton conductivity decreased by 35% at 50 °C. The surface charges interact with sulfonic acid groups of Nafion molecules to alter molecular orientation, resulting in different surface energies and phase separation, which are responsible for proton conductivity variation.

Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy.

BACKGROUND: Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting. OBJECTIVE: This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also studied. METHODS: Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively. RESULTS: The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6±8.5 nm, 22.3±1.7 mV, and 98.63±1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P<0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P<0.05). In in vivo antitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively. CONCLUSION: FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.

COX2-ATP Synthase Regulates Spine Follicle Size in Hedgehogs.

Skin evolves essential appendages with adaptive patterns that synergistically insulate the body from environmental insults. How similar appendages in different animals generate diversely-sized appendages remain elusive. Here we used hedgehog spine follicles and mouse hair follicles as models to investigate how similar follicles form in different sizes postnatally. Histology and immunostaining show that the spine follicles have a significantly greater size than the hair follicles. By RNA-sequencing analysis, we found that ATP synthases are highly expressed in hedgehog skin compared to mouse skin. Inhibition of ATP synthase resulted in smaller spine follicle formation during regeneration. We also identified that the mitochondrial gene COX2 functions upstream of ATP synthase that influences energy metabolism and cell proliferation to control the size of the spine follicles. Our study identified molecules that function differently in forming diversely-sized skin appendages across different animals, allowing them to adapt to the living environment and benefit from self-protection.

Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation.

Stromal cell-derived factor 1 (SDF-1) is a critical regulator of endothelial progenitor cells (EPCs) mediated physiological and pathologic angiogenesis. It was considered to act via its unique receptor CXCR4 for a long time. CXCR7 is a second, recently identified receptor for SDF-1, and its role in human EPCs is unclear. In present study, CXCR7 was found to be scarcely expressed on the surface of human EPCs derived from cord blood, but considerable intracellular CXCR7 was detected, which differs from that on EPCs derived from rat bone marrow. CXCR7 failed to support SDF-1 induced human EPCs migration, proliferation, or nitric oxide (NO) production, but mediated human EPCs survival exclusively. Besides that, CXCR7 mediated EPCs tube formation along with CXCR4. Blocking CXCR7 with its antagonist CCX733 impaired SDF-1/CXCR4 induced EPCs adhesion to active HUVECs and trans-endothelial migration. Those results suggested that CXCR7 plays an important role in human cord blood derived EPCs in response to SDF-1.

Recent progress in single-atom alloys: Synthesis, properties, and applications in environmental catalysis.

Heterogeneous catalysts have made outstanding advancements in pollutants elimination as well as energy and materials production over the past decades. Single-atom alloys (SAAs) are novel environmental catalysts prepared by dispersing single metal atoms on other metals. Integrating the advantages of single atom and alloys, SAAs can maximize atom utilization, reduce the use of noble metals and enhance catalytic performances. The synergistic, electronic and geometric effects of SAAs are effective to modulate the activation energy and adsorption strength, consequently breaking linear scaling relationship as well as offering an excellent catalytic activity and selectivity. Moreover, SAAs possess clear atomic structure, active sites and reaction mechanisms, providing an opportunity to tailor catalytic properties and develop effective environmental catalysts. In this review, we provide the recent progress on synthetic strategies, catalytic properties and catalyst design of SAAs. Furthermore, the applications of SAAs in environmental catalysis are introduced towards catalytic conversion and elimination of different air pollutants in many important reactions including (electrochemical) oxidation of volatile organic compounds (VOCs), dehydrogenation of VOCs, CO2 conversion, NOx reduction, CO oxidation, SO3 decomposition, etc. Finally, challenges and opportunities of SAAs in a broad environmental field are proposed.

Leader-chasing behavior in negative artificial triggered lightning flashes.

Two special cases of dart leader propagation were observed by the high-speed camera in the leader/return stroke sequences of a classical triggered lightning flash and an altitude-triggered lightning flash, respectively. Different from most of the subsequent return strokes preceded by only one leader, the return stroke in each case was preceded by two leaders occurring successively and competing in the same channel, which herein is named leader-chasing behavior. In one case, the polarity of the latter leader was opposite to that of the former leader and these two combined together to form a new leader, which shared the same polarity with the former leader. In the other case, the latter leader shared the same polarity with the former leader and disappeared after catching up with the former leader. The propagation of the former leader in this case seems not to be significantly influenced by the existence of the latter leader.

Suspension State Promotes Drug Resistance of Breast Tumor Cells by Inducing ABCC3 Overexpression.

Mechanical microenvironment plays a critical role in cancer drug resistance and this study supposed that suspension state might be involved in drug resistance of breast tumor cells. The viability of cell was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell cycle and apoptosis were detected by flow cytometry. Gene and protein were tested by RT-qPCR and Western blot, respectively. Drug resistance of MDA-MB-231 cells cultured for 72 h under suspension state was significantly increased. Suspension state was found to induce the overexpression of adenosine triphosphate-binding cassette subfamily C member 3 (ABCC3) in MDA-MB-231 cells. Silencing of ABCC3 significantly decreased drug resistance of suspension MDA-MB-231 cells. Moreover, suspension state was able to increase lamin A/C accumulation in MDA-MB-231 cells and lamin A/C regulated the expression of ABCC3. Moreover, lamin A/C knockdown also decreased drug resistance of suspension MDA-MB-231 cells, but the effect on drug resistance was less than that of ABCC3 knockdown. Suspension state plays a vital role in promoting drug resistance of MDA-MB-231 cells by inducing ABCC3 overexpression, and lamin A/C accumulation is associated with this process.

Scaffold strategies for modulating immune microenvironment during bone regeneration.

Implanted bone scaffolds often fail to successfully integrate with the host tissue because they do not elicit a favorable immune reaction. Properties of bone scaffold not only provide mechanical and chemical signals to support cell adhesion, migration, proliferation and differentiation, but also play a pivotal role in determining the extent of immune response during bone regeneration. Appropriate design parameters of bone scaffold are of great significance in the process of developing a new generation of bone implants. Herein, this article addresses the recent advances in the field of bone scaffolds for immune response, particularly focusing on the physical and chemical properties of bone scaffold in manipulating the host response. Furthermore, incorporation of bioactive molecules and cells with immunoregulatory function in bone scaffolds are also presented. Finally, continuing challenges and future directions of scaffold-based strategies for modulating immune microenvironment are discussed.

[Application of endothelial progenitor cells in vascular tissue engineering].

Endothelial progenitor cells (EPCs) are immature endothelial cells which have the capacity to proliferate, migrate and differentiate into mature endothelial cells from bone marrow to the peripheral circulation. EPCs have been shown to participate in postnatal endothelial repair and neovascularization of ischemic organs, and have been used as a new source of seeded cells in vascular tissue engineering. In this review, we focus on the origin, identification, property and function of EPCs as well as their application in vascular tissue engineering.