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Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Mobius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4+ and CD8+T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.

A direct cross-coupling between 9H-fluoren-9-ols and organic azides for the synthesis of steric hindered 2-amino-2'-ketonyl biaryls was reported. The reaction featured an acid-mediated azidation/ring-expansion/hydrolysis cascade, which formally realized the C-N bond coupling reaction via cleavage of a C-C single bond. This method was applicable to chiral helical structure to give bulky axially chiral biaryls with full stereospecificity.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.

As a secondary Li-ion battery with high energy density, lithium-sulfur (Li-S) batteries possess high potential development prospects. One of the important ingredients to improve the safety and energy density in Li-S batteries is the solid-state electrolyte. However, the poor ionic conductivity largely limits its application for the commercial market. At present, the gel electrolyte prepared by combining the electrolyte or ionic liquid with the all-solid electrolyte is an effective method to solve the low ion conductivity of the solid electrolyte. We present a cross-linked gel polymer electrolyte with fluoroethylene carbonate (FEC) as a solid electrolyte interface (SEI) film formed for Li-S quasi-solid-state batteries, which can be simply synthesized without initiators. This gel polymer electrolyte with FEC as an additive (GPE@FEC) possesses high ionic conductivity (0.830 × 10-3 S/cm at 25 °C and 1.577 × 10-3 S/cm at 85 °C) and extremely high Li-ion transference number (tLi+ = 0.674). In addition, the strong ability toward anchoring polysulfides resulting in the high electrochemical performance of Li-S batteries was confirmed in GPE@FEC by the diffusion experiment, X-ray photoelectron spectroscopy analysis (XPS), and scanning electron microscopy (SEM) mapping of the S element. Such a high ion conductivity (IC) gel polymer electrolyte enables a competitive specific capacity of 940 mAh/g at 0.2C and supreme cycling performance for 180 cycles at 0.5C, which is far beyond that of conventional poly(ethylene oxide)-based quasi-solid-state Li-S batteries.

Combining chiral molecules and covalent organic frameworks (COFs) with ordered pores can result in chiral COFs, which may be employed in the fields of chiral chemistry. In this study, we constructed a novel carboxyl-functionalized COF TpBD-3COOH first and then integrated a chiral molecule, heptakis (6-amino-6-deoxy)-β-CD (Am7CD), into TpBD-3COOH to obtain TpBD-Am7CD. Comparing TpBD-3COOH with TpBD-Am7CD, it could be observed that chiral selectivities improved significantly after decorating TpBD-3COOH with Am7CD in the adsorption experiment. Meanwhile, TpBD-Am7CD exhibited similar chiral selective abilities as the previously reported β-CD COF when it was employed to adsorb amino acid enantiomers, while the content of Am7CD was much less than that in β-CD COF. This indicated that the framework of TpBD-3COOH enhanced the chiral selective ability of Am7CD, which would be a great chiral carrier material for further application. This work provides a new insight for establishing materials for application in the chiral recognition field. Besides, TpBD-Am7CD resulted in an insoluble powder, which endowed this material with the possibility to be an adsorbent and a stationary phase in chromatography.

Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C-H amination reaction.

MicroRNA-221 (miRNA-221) is upregulated in several malignant tumors and is associated with poor patient prognosis. Therefore, the present study aimed to investigate the role and underlying mechanism of miRNA-221 in doxorubicin (DOX) resistance in osteosarcoma cells. We constructed DOX-resistant Saos-2/DOX cells and treated them with DOX. Cell viability was determined by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells were transfected with either miRNA-221 mimic or miRNA-221 inhibitor; quantitative (q)RT-PCR was performed to detect the expression of miRNA-221. Flow cytometry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) staining were used to detect cell apoptosis. The immunofluorescence method was also used to detect cell signal transduction and activator of transcription 3 (Stat3) protein expression distribution. In addition, Western blotting was used to detect changes in the expression of each protein. We found that miRNA-221 was upregulated in Saos-2/DOX cells. Moreover, the miRNA-221 mimic induced DOX resistance in Saos-2 cells, whereas the miRNA-221 inhibitor enhanced DOX sensitivity in Saos-2/DOX cells. The miRNA-221 mimic upregulated the expression of phosphorylated-Stat3, P-glycoprotein (P-gp), and B-cell lymphoma-2 (Bcl-2) proteins in Saos-2 cells and induced the entry of Stat3 into the nucleus, whereas the miRNA-221 inhibitor exerted the opposite effect. Pretreatment with the Stat3 chemical inhibitor, STAT3-IN-3, significantly inhibited the upregulation of P-gp and Bcl-2 protein expression induced by the miRNA-221 mimic in Saos-2 cells; it also caused the Saos-2 cells to overcome DOX resistance induced by the miRNA-221 mimic. Thus, miRNA-221 increased the expression of P-gp and Bcl-2 by activating the Stat3 pathway to promote DOX resistance in osteosarcoma cells, indicating a potential use of miRNA-221 in osteosarcoma treatment.

A novel approach to synthesize 3-methylisoquinolines via a one-pot, two-step, palladium(II)-catalyzed tandem C-H allylation/intermolecular amination and aromatization is reported. A wide series of 3-methylisoquinoline derivatives were obtained directly using this method in moderate to good yields, and we highlight the synthetic importance of this new transformation.

Urea/1-ethyl-3-methylimidazolium chloride (urea-EMIC) was developed to electrodeposit Cu from Cu2O at room temperature. Density, viscosity and conductivity of this urea-EMIC system were obtained. The cyclic voltammograms illustrated that the electroreduction of copper ion (Cu(I) ion) involves a quasi-reversible and one-step single electron transfer process. Chronoamperometric studies showed that the copper electrodeposition proceeds a three-dimensional (3D) progressive model. With an increase in temperature, on voltammograms the onset potentials for copper ion reduction shifted anodically and the diffusion coefficient determined using chronoamperometry increased from 5.40 × 10−11 m2 s−1 at 333 K to 1.02 × 10−10 m2 s−1 at 363 K. Also, potentiostatic electrolysis was conducted on tungsten substrates at − 0.65 V (vs. Ag) and 363 K. Then spherical metallic copper electrodeposits were obtained.

The continuous growth of the solid-electrolyte interface (SEI) and material crushing are the fundamental issues that hinder the application of Ge anodes in lithium-ion batteries. Solving Ge deformation crushing during discharge/charge cycles is challenging using conventional carbon coating modification methods. Due to the chemical stability and high melting point of carbon (3500 °C), Ge/carbon hybridization at the atomic level is challenging. By selecting a suitable carbon source and introducing an active medium, we have achieved the Ge/carbon doping at the atom-level, and this Ge/carbon anode shows excellent electrochemical performance. The reversible capacity is maintained at 1127 mAh g-1 after 1000 cycles (2 A g-1 (2-71 cycles), 4 A g-1 (72-1000 cycles)) with a retention of 84 % compared to the second cycle. The thickness of the SEI is only 17.4 nm after 1000 cycles. The excellent electrochemical performance and stable SEI fully reflect the application potential of this material.

The thermal-condensation method is widely used for the synthesis of K-doped g-C3N4 photocatalysts, but the presence of organic byproducts in the resultant products is often overlooked in previous reports. Here, we demonstrated the universal presence of organic byproducts in K-doped g-C3N4 synthesized by typical thermal condensation of KOH/melamine, KOH/dicyandiamide, or KOH/urea. Taking the K-doped g-C3N4 photocatalysis for the degradation of dimethyl phthalate as an example, the negative influence of the organic byproducts on K-doped g-C3N4 photocatalysis was confirmed. Specifically, the organic byproducts can be gradually dissolved into the photocatalytic system of K-doped g-C3N4 as new and stable pollutants. Based on the solubility investigations on the byproducts in several solvents, hot-water washing was demonstrated to be a relatively effective approach to remove the organic byproducts from K-doped g-C3N4. The formation of organic byproducts during the synthesis of K-doped g-C3N4 could be ascribed to the fact that the presence of K salts in melamine, dicyandiamide, or urea molecules results in their insufficient thermal condensation into expected g-C3N4. The present work provides objective information about the K-doped g-C3N4 photocatalysts and reminds researchers about the influence of the organic byproducts on the applications of the other impurity-doped g-C3N4 photocatalysts.

To electrochemically extract Pb from PbO at room temperature, a new electrolyte, urea−1-ethyl-3- methylimidazolium fluoride (urea−[EMIM]F), was synthesized to dissolve PbO. Afterwards, the electrochemical behavior of Pb in this electrolyte was studied. The density, viscosity and conductivity of this electrolyte were investigated before electroextraction. The electrochemical behavior of Pb in the urea−[EMIM]F system was recorded via cyclic voltammograms, chronoamperometry and potentiostatic electrolysis. The results illustrate that Pb can be electrochemically extracted from PbO in this system at room temperature and that Pb reduction involves a quasireversible process and follows a one-step and two-electron transfer process. The reduction of Pb proceeds with a three-dimensional (3D) progressive model. With an increase in temperature, the onset potentials for Pb reduction shift anodically. The diffusion coefficient of Pb(II) is determined to be 6.88×10−10 cm2/s at 353 K. Additionally, spherical Pb particles are obtained after electrodeposition in the urea−[EMIM]F system via potentiostatic electrolysis.

Polycyclic aromatic hydrocarbons (PAHs) are regarded as promising electrochemiluminescent (ECL) emitters owing to their high quantum efficiency and inexpensive production. Despite the fact that the ECL properties of the pure PAH microcrystal (such as rubrene microcrystals, Rub MCs) have gained extensive attention, it is a challenge in controlling the morphology and size to reduce the inner filter effect. Herein, an advanced ECL emitter of palladium nanoparticle-functionalized hollow PAH-metal nanocubes was prepared by an in situ redox deposition method (the resultant nanocomposites were abbreviated as Pd-Rub-Ag@Au nanocubes). Specifically, the rubrene-decorated Ag@Au nanocubes (Rub-Ag@Au nanocubes) were prepared using the Ag@Au nanocubes as a template and a rubrene cation radical (Rub•+) as a reductant, and then Pd nanoparticles (Pd NPs) were in situ reduced on the surface of Rub-Ag@Au nanocubes. Impressively, compared with the Rub MCs, Pd-Rub-Ag@Au nanocubes showed uniform size and significantly enhanced ECL efficiency and intensity in the aqueous media. As a proof-of-concept, the Pd-Rub-Ag@Au nanocube-based ECL biosensing platform combined with a multisite-anchored DNA nanomachine was constructed for ochratoxin A (OTA, a type of mycotoxin) detection. The DNA nanomachine covered with high-density recognizing sequences could operate toehold-mediated strand displacement amplification on the sensing platform and promote the movement efficiency and velocity greatly. Due to the advanced performance of Pd-Rub-Ag@Au nanocubes and high recognition efficiency of the DNA nanomachine, the proposed biosensor for OTA detection can achieve a detection limit of 4.7 fg/mL ranging from 0.01 to 100 pg/mL, which offers an ingenious method for the further application of PAHs.

Ultradeep carbonate gas reservoirs are a major resource of interest in clean energy development, and complex pore structures and reservoir conditions with high-temperatures and pressures are great ...

A ternary biochar/vanadium pentoxide/graphite like carbon nitride (BC/V2O5/g-C3N4 denoted BC/VO/CN) composite was prepared by a simple hydrothermal method and its photocatalytic performance was investigated under simulated solar irradiation. The BC/VO/CN was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, and photoluminescence spectroscopy. Within the BC/VO/CN composites VO nanoparticles were highly crystalline and intertwined with the lamellas of CN, resulting in the formation of well-defined Z-type heterostructures. The photocatalytic activity was evaluated using Rhodamine B as a model pollutant. Under simulated solar (230–780 nm) irradiation the as-prepared BC/VO/CN hybrid materials demonstrated highly improved photocatalytic activity compared to CN, VO and VO/CN. The cause of the solar enhancement could be ascribed to the formation of Z-type heterojunctions between VO and CN, which promoted faster electron–hole separation and more efficient charge transfer. BC, as an electron transfer medium, accelerated the transfer of photogenerated charge carriers and inhibited their recombination.

Lithium metal anode provides a direction for the development of high-energy-density lithium ion batteries. In order to solve lithium dendritic growth and low Coulombic efficiency in lithium plating/stripping process, designing a three-dimensional (3D) host structure is a feasible solution. Herein, carbon-rich conjugated framework poly(1,3,5-triethynylbenzene) in-situ coated copper nanowires on copper foam is constructed as 3D lithium host, which effectively endows low nucleation overpotential, smooth lithium deposition, and improved cycle stability. The well-designed 3D host structure could achieve high Coulombic efficiency over 99% for 150 cycles and reversible lithium plating/stripping stability over 800 h at 2 mA cm-2. This work highlights the interface modification strategy, and proposes a feasible route for 3D host structure design in the development of lithium metal anode.

Herein we disclose a novel radical-mediated [3 + 2]-cycloaddition reaction of alkenes under photochemical conditions. A set of rationally designed bromodifluoromethyl alkynyl ketones were prepared and applied in the cascade reaction. The protocol features broad functional group tolerance and excellent regio- and stereo-selectivity. Both activated and unactivated alkenes were suitable substrates. The transformation gives rise to a variety of valuable α,α-difluorocyclopentanones bearing a tetra-substituted E-alkene.

One polysaccharide, designated as WPEP-A, was isolated from Passiflora edulis Sims peel and its hypoglycemic effects on diabetic db/db mice were evaluated. Physicochemical characterization showed that WPEP-A was composed of galactose, glucose, xylose, rhamnose, galacturonic acid and glucuronic acid with a molecular weight of 9.51 × 104 Da. We observed an inhibition in weight gain and blood glucose levels. Glucose tolerance and insulin tolerance improved after the administration of WPEP-A. In addition, our data showed increased antioxidant enzyme activities. Furthermore, the levels of serum insulin and triglyceride decreased with the recovery of liver damage. Meanwhile, positive changes in short chain fatty acid content were observed, and the mRNA levels of glucagon-like peptide 1 receptor, glucagon and prohormone convertase 3 were up-regulated in the intestinal tract. In summary, our results showed that WPEP-A had hypoglycemic activity and improved intestinal function in diabetic mice, which may contribute to the attenuation of the hypoglycemia effects.

An organic superbase-catalyzed aminocarbonylation reaction of α,β-unsaturated ketones was reported. Under the catalysis of 10 mol% Schwesinger's superbase t-Bu-P4, a variety of enones and ynones reacted with N,N-dimethyl carbamoylsilane to afford α-siloxyamides or α-hydroxyamides in 56–82% yields.

Tryptophan (Trp) is one of the essential amino acids, which plays important roles in biological systems and the normal growth of human beings, and it is of great significance to be able to detect Trp in a rapid, efficient, and sensitive way. Herein, a 3D network metal–organic framework ([Sm2(BTEC)1.5(H2O)8]·6H2O) with excellent thermal and water stability was synthesized by a hydrothermal method. Interestingly, it could discriminate Trp from other natural amino acids in aqueous solution through a significant fluorescence enhancement effect, and showed high detection sensitivity (LOD = 330 nM) and outstanding anti-interference ability. The sensor system was successfully applied to the detection of Trp in practical samples, so it was expected to be a sensitive and efficient Trp sensor. In addition, the sensing mechanism was explained in detail by a series of characterization methods combined with density functional theory (DFT). There were many coordination water molecules in the crystal structure of the complex. Based on the small steric hindrance and molecular structure of water molecules, it provided the possibility for coordination interaction between Trp and Sm3+. On the other hand, the triplet energy level (T1) of Trp matched with the 4G5/2 vibrational energy level of Sm3+, so Trp could be used as the second “antenna molecule” besides 1,2,4,5-benzenetetracarboxylic acid (H4BTEC). Therefore, it effectively broadened the way for Sm-MOF to absorb excitation light.

By a bifunctional organic ligand 2-(benzimidazol-1-yl)terephthalic acid (H2bitp) featuring both imidazol-carboxylate groups, two new Cu(II)-containing coordination polymers (CPs) with the chemical ...

Current yeast metabolic engineering in isoprenoids production mainly focuses on rewiring of cytosolic metabolic pathway. However, the precursors, cofactors and the enzymes are distributed in various sub-cellular compartments, which may hamper isoprenoid biosynthesis. On the other side, pathway compartmentalization provides several advantages for improving metabolic flux toward target products. We here summarize the recent advances on harnessing sub-organelle for isoprenoids biosynthesis in yeast, and analyze the knowledge about the localization of enzymes, cofactors and metabolites for guiding the rewiring of the sub-organelle metabolism. This review may provide some insights for constructing efficient yeast cell factories for production of isoprenoids and even other natural products.

Decidualization is essential for successful pregnancy in rodents and primates. Although L-Tryptophan and its metabolites are essential for mammalian pregnancy, the underlying mechanism is poorly defined. We explored effects of tryptophan and kynurenine on human in vitro decidualization in human endometrial stromal cell line and primary endometrial stromal cells. Tryptophan significantly stimulates the expression of prolactin and insulin growth factor binding protein 1, reliable markers for human decidualization. When stromal cells are treated with tryptophan, tryptophan hydroxylase-1 remains unchanged, but indoleamine 2,3-dioxygenase 1 is significantly increased, suggesting tryptophan is mainly metabolized through kynurenine pathway. Kynurenine significantly stimulates insulin growth factor binding protein 1 expression. Aryl hydrocarbon receptor and its target genes (P450 1A1 and P450 1B1) are significantly increased by tryptophan and kynurenine. The induction of tryptophan and kynurenine on insulin growth factor binding protein 1 is abrogated by CH223191, an aryl hydrocarbon receptor inhibitor. Cytochrome P450 1A1 and P450 1B1 catalyze the oxidative metabolism of estradiol to catechol estrogens (2-hydroxy estradiol and 4-hydroxy estradiol), respectively. Insulin growth factor binding protein 1 is up-regulated by 2-hydroxy estradiol and 4-hydroxy estradiol. Interferon-γ significantly induces the expression of indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor and insulin growth factor binding protein 1. All the data are also verified in primary human stromal cells. Our data indicate that Interferon-γ-induced kynurenine pathway promotes human decidualization via aryl hydrocarbon receptor signaling.

Bilayer barium titanate (BaTiO3, BTO)/bismuth ferrite (BiFeO3, BFO) capacitive devices were fabricated and systematically analyzed from the aspects of thin-film material crystallography and electrical characterization. The tetragonal phase (T) of BTO with the reducing thickness (150 nm) was demonstrated through carefully adjusting the conditions of sputtering process and post-thermal treatments. The thickness dependence of polarization, energy density, permittivity, and leakage current was investigated in the BTO/BFO bilayer system. It showed that 150-nm BFO film is an optimal thickness, which led to the substantial increase in energy density up to 920 mJ/cm3 with the charge/discharge efficiency of 79.7% at 10 V. The permittivity of 150-nm BFO bilayer device was found to be 258, which is much higher than the single -layer BFO and other BTO/BFO devices with different BFO thicknesses. Leakage current could be reduced by three orders with the increasing thickness of BFO layer from 30 to 225 nm. In addition, the leakage current of BTO/BFO bilayer capacitors was 102 times lower than BFO single layer with the same total thickness. The result showed that the leakage current of BFO material could be significantly reduced in the bilayer system. The performance of BTO/BFO bilayer capacitors indicates that it is a promising technique for the implementation of nanoscale, lead-free, and nonelectrochemical thin-film energy storage-related applications.

The first synthesis of benzyne-derived stable zwitterions is reported. Benzynes generated in situ from 2-(trimethylsilyl)aryl triflates undergo a multicomponent reaction with phosphines and CO2 to produce the stable 1,5-zwitterionic species in moderate to excellent isolated yields, which provides a novel method for the preparation of phosphonium inner salts under mild and transition-metal-free conditions.

Objective: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for vascular remodeling. Natural compounds with diterpene chinone or phenolic acid structure from Salvia miltiorrhiza, an eminent medicinal herb widely used to treat cardiovascular diseases in China, can effectively attenuate vascular remodeling induced by vascular injury. However, it remains unknown whether Salvia miltiorrhiza-derived miRNAs can protect VSMCs from injury by environmental stimuli. Here, we explored the role and underlying mechanisms of Salvia miltiorrhiza-derived Sal-miR-1 and 3 in the regulation of VSMC migration and monocyte adhesion to VSMCs induced by thrombin. Methods: A mouse model for intimal hyperplasia was established by the ligation of carotid artery and the injured carotid arteries were in situ-transfected with Sal-miR-1 and 3 using F-127 pluronic gel. The vascular protective effects of Sal-miR-1 and 3 were assessed via analysis of intimal hyperplasia with pathological morphology. VSMC migration and adhesion were analyzed by the wound healing, transwell membrane assays, and time-lapse imaging experiment. Using loss- and gain-of-function approaches, Sal-miR-1 and 3 regulation of OTUD7B/KLF4/NMHC IIA axis was investigated by using luciferase assay, co-immunoprecipitation, chromatin immunoprecipitation, western blotting, etc. Results: Salvia miltiorrhiza-derived Sal-miR-1 and 3 can enter the mouse body after intragastric administration, and significantly suppress intimal hyperplasia induced by carotid artery ligation. In cultured VSMCs, these two miRNAs inhibit thrombin-induced the migration of VSMCs and monocyte adhesion to VSMCs. Mechanistically, Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3'UTR. Most importantly, OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels via decreasing its deubiquitylation, whereas decreased KLF4 relieves its repression of transcription of NMHC IIA gene and thus increases NMHC IIA expression levels. Further, increased NMHC IIA represses VSMC migration and monocyte adhesion to VSMCs via maintaining the contractile phenotype of VSMCs. Conclusions: Our studies not only found the novel bioactive components from Salvia miltiorrhiza but also clarified the molecular mechanism underlying Sal-miR-1 and 3 inhibition of VSMC migration and monocyte adhesion to VSMCs. These results add important knowledge to the pharmacological actions and bioactive components of Salvia miltiorrhiza. Sal-miR-1 and 3-regulated OTUD7B/KLF4/NMHC IIA axis may represent a therapeutic target for vascular remodeling.

Clinical studies have indicated that the long-term use of topical antiglaucoma drugs, such as carbonic anhydrase inhibitors (CAIs), may lead to meibomian gland dysfunction (MGD). We hypothesize that these adverse effects involve a direct influence on human MG epithelial cells (HMGECs). The purpose our present investigation was to test our hypothesis and determine whether exposure to dorzolamide, a CAI, impacts the proliferation, intracellular signaling and differentiation of HMGECs.We cultured immortalized (i) HMGECs with vehicle or various concentrations of dorzolamide for 6 days. Cells were enumerated with a hemocytometer, and examined for their morphology, Akt signaling activity, accumulation of neutral lipids, phospholipids and lysosomes, and the expression of protein biomarkers for lipogenesis regulation, lysosomes and autophagosomes.Our results show that a high, 500 µg/ml concentration of dorzolamide causes a significant decrease in Akt signaling and the proliferation of iHMGECs. However, the high dose of dorzolamide also promotes the differentiation of iHMGECs. This response features increases in the number of lysosomes, the accumulation of phospholipids, and the expression of the light chain 3A biomarker for autophagosomes. In contrast, the therapeutic amount (50 µg/ml) of dorzolamide has no impact on the proliferative or differentiative abilities of iHMGECs.Our results support our hypothesis and demonstrate that the CAI dorzolamide does exert a direct influence on the proliferation and differentiation of iHMGECs. However, this effect is elicited only by a high, and not a therapeutic, amount of dorzolamide.

Silica-based controlled-release materials show great potential for medical therapy applications, but have also been introduced into the area of metal anti-corrosion. However, few silica—based contr...

Two naphthoquinone-derived heterodimers with unprecedented carbon skeletons, eleucanainones A (1) and B (2), were isolated from the bulbs of Eleutherine americana. Their structures were elucidated ...

Dielectric properties of oxyfluorosilicate (OFS) glasses have been characterized using Terahertz (THz)-time domain spectroscopy in the sub-THz region as well as optical reflection measurement. OFS glass containing 20 mol% of Nb2O5, which is termed ZNbKLSNd glass, has the highest refractive index of 3.70 in the sub-THz region. The THz and optical refractive indices of various silicate oxide glasses, including OFS glasses, have been confirmed to be correlated by a unified relationship utilizing a parameter defined by the ratio of ionic to electronic polarizability. Additionally, the frequency dependence of the THz dielectric constant has been interpreted by a single oscillator model for all silicate oxide glasses including OFS glasses. On the basis of the present unified dielectric model, the very high refractive index of ZNbKLSNd glass has been attributed to the lowering of oscillator resonance wavelength originated from the incorporation of Nb2O5 intermediate network former.