Baicalin Inhibits Hypoxia-Induced Pulmonary Artery Smooth Muscle Cell Proliferation via the AKT/HIF-1α/p27-Associated Pathway

Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has been shown to possess various pharmacological actions. Previous studies have revealed that baicalin inhibits the growth of cancer cells through the induction of apoptosis. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by enhanced pulmonary artery smooth muscle cell (PASMCs) proliferation and suppressed apoptosis. However, the potential mechanism of baicalin in the regulation of PASMC proliferation and the prevention of cardiovascular diseases remains unexplored. To test the effects of baicalin on hypoxia, we used rats treated with or without baicalin (100 mg·kg⁻¹ each rat) at the beginning of the third week after hypoxia. Hemodynamic and pulmonary pathomorphology data showed that right ventricular systolic pressures (RVSP), the weight of the right ventricle/left ventricle plus septum (RV/LV + S) ratio and the medial width of pulmonary arterioles were much higher in chronic hypoxia. However, baicalin treatment repressed the elevation of RVSP, RV/LV + S and attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia. Additionally, baicalin (10 and 20 μmol·L⁻¹) treatment suppressed the proliferation of PASMCs and attenuated the expression of hypoxia-inducible factor-α (HIF-α) under hypoxia exposure. Meanwhile, baicalin reversed the hypoxia-induced reduction of p27 and increased AKT/protein kinase B phosphorylation p-AKT both in vivo and in vitro. These results suggested that baicalin could effectively attenuate PVSR and hypoxic pulmonary hypertension.     

Discovery of 6-Arylurea-2-arylbenzoxazole and 6-Arylurea-2-arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design,Synthesis and in vitro Biological Evaluation

We embarked on a structural optimization campaign aimed at the discovery of novel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as a lead compound. A library of 29 compounds was synthesized. Several title compounds exhibited selective inhibitory activities against vascular endothelial growth factor receptor 2 (VEGFR-2) over epidermal growth factor receptor (EGFR) kinase; these compounds also displayed selective and potent antiproliferative activity against three cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis activity by chick chorioallantoic membrane (CAM) assay. Among them, 1-(2-(2-chlorophenyl)benzo[d]oxazol-5-yl)-3-(4-(trifluoromethoxy)phenyl)urea (compound 5 n ) showed the most potent anti-angiogenesis capacity, efficient cytotoxic activities (in vitro against human umbilical vein endothelial cells (HUVEC), H1975, A549, and HeLa cell lines, with respective IC₅₀ values of 8.46, 1.40, 7.61, and 0.28 μm ), and an acceptable level of VEGFR-2 kinase inhibition (IC₅₀=0.25 μm ). Molecular docking analysis revealed 5 n to be a type II inhibitor of VEGFR-2 kinase. In general, these results indicate that these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for potential development into anti-angiogenesis drugs.     

Composition of Pd-La/α-Al2O3 catalysts

The objective of this study is to investigate the structure of the Pd-La/-Al₂O₃ catalyst. X-ray diffraction (XRD) and temperature-programmed reduction (TPRd) were used as characterization techniques. Contrary to the assertions in the literature, XRD studies conducted on La/-Al₂O₃ composite oxides and Pd-La/-Al₂O₃ catalysts show that Pd catalyzes the solid state reaction between A1₂O₃ and Al₂O₃ to form LaAlO₃. TPRd studies conducted on Pd/-Al₂O₃, Pd/La₂O₃, Pd/LaAlO₃, and Pd-La/-Al₂O₃ catalysts suggest that Pd in the Pd-La/-Al₂O₃ catalyst interacts more strongly with LaAlO₃ than with -Al₂O₃. Reaction studies were conducted to investigate the activity of Pd/-Al₂O₃, Pd/La₂O₃, Pd/LaA10₃, and Pd-La/-Al₂O₃ catalysts for nitric oxide (NO) reduction. These studies show that Pd/LaAlO₃ catalysts are most active for NO removal at stoichiometric and under net reducing conditions.     

Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility

Heterotrimeric G proteins are classified into four subfamilies and play a key role in signal transduction. They transmit extracellular signals to intracellular effectors subsequent to the activation of G protein-coupled receptors (GPCRs), which are targeted by over 30 % of FDA-approved drugs. However, addressing G proteins as drug targets represents a compelling alternative, for example, when G proteins act independently of the corresponding GPCRs, or in cases of complex multifunctional diseases, when a large number of different GPCRs are involved. In contrast to Gαq, efforts to target Gαi/s by suitable chemical compounds has not been successful so far. Here, a comprehensive analysis was conducted examining the most important interface regions of Gαi/s with its upstream and downstream interaction partners. By assigning the existing compounds and the performed approaches to the respective interfaces, the druggability of the individual interfaces was ranked to provide perspectives for selective targeting of Gαi/s in the future.     

Enantioselective Extraction of Racemic Mandelic Acid by Di(2‐ethylhexyl) Phosphoric Acid and Tartaric Acid Derivatives as Mixed Complex Chiral Selectors

The distribution behavior of mandelic acid (MA) enantiomers was examined in a two‐phase system containing di(2‐ethylhexyl) phosphoric acid (D2EHPA) with two tartaric acid derivatives as complex chiral selectors in n‐octanol. Factors affecting the extraction were investigated, including the structure and concentration of tartaric acid as well as the concentration of D2EHPA and D,L‐MA. The results showed that both the distribution ratio and enantioselectivity were greatly improved by using a complex chiral selector rather than using the tartaric acid derivative by itself. Finally, it was found that the formation of mixed complex chiral selectors by mixing two tartaric acid derivatives with D2EHPA can improve the capacity of enantioselective extraction.     

Broadband dielectric spectroscopy of PbMg1/3Nb2/3O3–PbSc1/2Nb1/2O3 ceramics

Broadband dielectric spectroscopy results of various ordered and disordered (1 ? x)Pb(Mg_1/3Nb_2/3)O₃–(x)Pb(Sc_1/2Nb_1/2)O₃ (PMN–PSN) ceramics are investigated in the temperature range from 80 K to 300 K and frequency range from 20 Hz to 2 THz. Dielectric dispersion is very broad and in the ferroelectrics case (x = 1, 0.95) consists of two parts: low-frequency part caused by ferroelectric domains and higher frequency part caused by soft mode. The relaxational soft mode exhibits pronounced softening close to phase transition temperature, as it is typical for order–disorder phase transitions. By substituting Sc³⁺ by Mg²⁺ in PMN–PSN ceramics relaxation slows down, and for relaxors (x = 0.2) the most probable relaxation frequency decreases on cooling according to Vogel–Fulcher law.     

Effects of CNTs content on microstructure and mechanical properties of Cnt/α-Al2O3 and Cnt-Csf/α-Al2O3 composites

In this work, CNTs and short carbon fiber reinforced α-Al₂O₃ matrix composites (i.e., C_nt/α-Al₂O₃ and C_nt-C_sf/α-Al₂O₃) were prepared by sol-gel dispersing method followed by hot pressing process. Effects of CNTs content on the mechanical properties of C_nt/α-Al₂O₃ and C_nt-C_sf/α-Al₂O₃ composites were investigated and the inter- and transgranular fracture mechanisms in C_nt-C_sf/α-Al₂O₃ composites were analyzed. The hardness and relative density of C_nt/α-Al₂O₃ and C_nt-C_sf/α-Al₂O₃ composites slightly decrease as CNTs content increases. The flexural strength and fracture toughness monotonically increase with the increase in C_nt content for both C_nt/α-Al₂O₃ and C_nt-C_sf/α-Al₂O₃ composites. Addition of C_sf and CNTs into α-Al₂O₃ matrix results in a bimodal grain size microstructure of C_nt-C_sf/α-Al₂O₃ composites, which accounts for the unique fractograph and the enhanced toughness of C_nt-C_f/α-Al₂O₃ composites. The flexural strength and fracture toughness of C_sf5-nt06 composite are 465 MPa and 7.08 MPa/m², 37% and 13% higher than that of C_nt06, and 42% and 34% higher than that of C_sf5, respectively.     

The effect of Fe-acceptor doping on the electrical properties of Na1/2Bi1/2TiO3 and 0.94 (Na1/2Bi1/2)TiO3–0.06 BaTiO3

Na_1/2Bi_1/2TiO₃ (NBT) based ceramics are amongst the most promising lead-free ferroelectric materials. It was expected that the defect chemistry and the effect of doping of NBT would be similar to that observed for lead based materials, however, acceptor doping does not lead to ferroelectric hardening. Instead, high oxygen ionic conductivity is induced. Nevertheless, for solid solutions with BaTiO₃ (BT), which are more relevant with respect to ferroelectric applications, such a drastic change of electrical properties has not been observed so far. To rationalize the difference in defect chemistry between NBT and its solid solution 94(Na_1/2Bi_1/2TiO₃)–0.06 BaTiO₃ (NBT–6BT) compositions with different concentrations of Fe-dopant were investigated. The study illustrates that the materials exhibit very similar behavior to NBT, and extraordinarily high oxygen ionic conductivity could also be induced in NBT–6BT. The key difference between NBT–6BT and NBT is the range of the dependence of ionic conductivity with dopant concentration. Previous studies of NBT–6BT have not reached sufficiently high dopant concentrations to observe high conductivity. In consequence, the same defect chemical model can be applied to both NBT and its solid solutions. This will help to rationalize the effect of doping on ferroelectric properties of NBT-ceramics and defect chemistry related degradation and fatigue.     

Anthocyanin Attenuates Doxorubicin-Induced Cardiomyotoxicity via Estrogen Receptor-α/β and Stabilizes HSF1 to Inhibit the IGF-IIR Apoptotic Pathway

Doxorubicin (Dox) is extensively used for chemotherapy in different types of cancer, but its use is limited to because of its cardiotoxicity. Our previous studies found that doxorubicin-induced insulin-like growth factor II receptor (IGF-IIR) accumulation causes cardiomyocytes apoptosis via down-regulation of HSF1 pathway. In these studies, we demonstrated a new mechanism through which anthocyanin protects cardiomyoblast cells against doxorubicin-induced injury. We found that anthocyanin decreased IGF-IIR expression via estrogen receptors and stabilized heat shock factor 1 (HSF1) to inhibit caspase 3 activation and apoptosis of cardiomyocytes. Therefore, the phytoestrogen from plants has been considered as another potential treatment for heart failure. It has been reported that the natural compound anthocyanin (ACN) has the ability to reduce the risk of cardiovascular disease (CVD). Here, we demonstrated that anthocyanin acts as a cardioprotective drug against doxorubicin-induced heart failure by attenuating cardiac apoptosis via estrogen receptors to stabilize HSF1 expression and down-regulated IGF-IIR-induced cardiomyocyte apoptosis.     

Magnetic and dielectric properties of BaFe1/2Sn1/2O3-δ ceramics

Ceramic samples of barium ferrostannate BaFe_1/2Sn_1/2O_3-δ have been prepared by the sol-gel and hydrothermal synthesis methods. To reduce the number of oxygen vacancies, annealing in oxygen has been performed. The heat capacity, magnetization, Mössbauer and dielectric spectroscopy data point to the appearance of antiferromagnetic ordering below ～55 K followed by further spin glass magnetic ordering below 15 K. The giant dielectric response seems to be due to the relaxation of electrons trapped by oxygen vacancies. Comparison of the Fe K-edge X-ray absorption spectra of BaFe_1/2Sn_1/2O_3-δ confirmed substantial difference from those of the similar stoichiometric BaFe_1/2Nb_1/2O₃ perovskite.     

The Effects of CoCl2 on HIF-1α Protein under Experimental Conditions of Autoprogressive Hypoxia Using Mouse Models

It is well known that cobalt chloride (CoCl₂) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl₂ on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl₂ and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl₂ group. Over-induction of HIF-1α by pretreatment with CoCl₂ before hypoxia did not increase the hypoxia tolerance.     

Gas sensing properties of asymmetrically reduced Na1/2Bi1/2TiO3–based ceramics

We report the gas sensing properties of a type of new materials, Na_1/2Bi_1/2TiO₃ (NBT)-based ceramics. After the NBT-based ceramics were asymmetrically reduced and coated with Au electrodes, the materials exhibit relatively large electrical responses when exposed to oxygen and some oxidizable gases at a relatively low temperature (≤300 °C). An electric voltage ～60 mV is measured in the mixture of O₂ and N₂ (1% O₂). In oxidizable gases, a negative response can be obtained. The measured voltages are ?45 mV and ?98 mV in the mixtures of H₂/air (1000 ppm H₂) and C₂H₅OH/air (1000 ppm C₂H₅OH), respectively. The electrical responses are proportional to the logarithm of the concentrations of the analyzed gases. Also, the electrical responses to oxygen and oxidizable gases have opposite signs, and the model of mixed-potential is proposed to explain the gas sensing phenomenon. This study provides a new material and a simple design for gas sensors. The proposed gas sensor comprises a reduced NBT-based ceramic wafer with the same electrodes on the opposite surfaces. Additional components in traditional gas sensors, such as sensing or reference electrode, are unnecessary.     

Depolarization temperature and piezoelectric properties of (Bi1/2Na1/2)TiO3–(Bi1/2Li1/2)TiO3–(Bi1/2K1/2)TiO3 lead-free piezoelectric ceramics

The phase transition temperature and piezoelectric properties of x(Bi_1/2Na_1/2)TiO₃–y(Bi_1/2Li_1/2)TiO₃–z(Bi_1/2K_1/2)TiO₃ [x + y + z = 1] (abbreviated as BNLKT100y–100z) ceramics were investigated. BNLKT100y–100z ceramics were prepared by conventional ceramic fabrication. The depolarization temperature T_d was determined by the temperature dependence of the dielectric and piezoelectric properties. This study focuses on the effect of Li¹⁺ and K¹⁺ ions on T_d and the piezoelectric properties of BNT ceramics. BNLKT100y–100z (y = 0–0.08) has a morphotropic phase boundary (MPB) between rhombohedral and tetragonal phases at z = 0.18–0.20, and high piezoelectric properties were obtained at the MPB composition. The piezoelectric constant d₃₃ increased with increasing y; however, T_d decreased above y = 0.06. The d₃₃ and T_d values of BNLKT4-20 and BNLKT8-20 were 176 pC/N and 171 °C, and 190 pC/N and 115 °C, respectively.     

Expanding Synthetic Applications of Δ1-Piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate Reductase from Pseudomonas syringae (DpkAPsyrin). Biocatalytic Asymmetric Synthesis of (S,E)-2-hydroxy-4-arylbut-3-enoic Acid Derivatives

Chiral 2-hydroxy-4-arylbut-3-enoic acid derivatives are important precursors for the synthesis of angiotensin converting enzyme (ACE) inhibitors, such as enalapril, lisinopril, cilapril or benazepril. In this work, we take advantage of the unexplored promiscuous ketoreductase activity of Δ¹-piperidine-2-carboxylate/Δ¹-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkA_Psyrin) for the synthesis of (S,E)-2-hydroxy-4-arylbut-3-enoic acids. The strategy was designed as an enzymatic cascade comprising an aldol condensation between pyruvate with aryl aldehydes, catalyzed by the trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPA_Pputida), for the construction of carbon scaffold, and an ensuing asymmetric reduction of the carbonyl group catalyzed by DpkA_Psyrin. The enzymatic cascade provided quantitative conversions, with global isolated yields between 57–85%. A total of nine structurally diverse (S,E)-2-hydroxy-4-arylbut-3-enoic acids were prepared in ee between 87–99%.     

Microwave dielectric characteristics of 0.75(Al1/2Ta1/2)O2–0.25(Ti1−xSnx)O2 ceramics

The microwave dielectric characteristics of 0.75(Al_1/2Ta_1/2)O₂–0.25(Ti_1−xSn_x)O₂ ceramics were investigated. The microwave dielectric properties of 0.75(Al_1/2Ta_1/2)O₂–0.25TiO₂ sintered at 1450 °C exhibited a dielectric constant (ϵ_r) of 31.2, a Q·f₀ of 54,590 GHz, and the temperature coefficient of resonant frequency (τ_f) of +12.8 ppm/°C. To control of the τ_f and enhance the Q·f₀ for 0.75(Al_1/2Ta_1/2)O₂–0.25TiO₂, Sn⁴⁺ was substituted for Ti⁴⁺. With an increase of Sn content from 5 to 50 mol%, the ε_r slightly decreased, the Q·f₀ increased and the τ_f shifted from positive to negative value. The τ_f within ±10 ppm/°C of zero was realized for the Sn content below 30 mol% and the microwave dielectric properties had the ε_r value of 31.2–26.3, the Q·f₀ of 54,600–70,700 GHz, and τ_f of +12.8–−9.3 ppm/°C for this compositions. The relationship between microstructure and microwave dielectric characteristics was investigated.     

Chiral separation of racemic amino acids with novel polyamides having N-α-acetyl-l-glutamyl residue as a diacid component

Novel polyamides with asymmetric carbons in their main chains were obtained from aromatic diamines, 4,4′-diaminodiphenylmethane (DADPM) or 1,3-phenylenediamine (1,3-PDA), and N-α-protected l-glutamic acid, N-α-acetyl-l-glutamic acid (Ac-l-Glu-OH). Newly prepared polyamides showed optical rotation, implying that optically active polyamides were successfully obtained in the present study. These two types of chiral polyamides showed chiral recognition ability, which was studied by surface plasmon resonance (SPR) spectroscopy; they recognized d-glutamic acid in preference to the corresponding l-isomer. The adsorption selectivity was determined to be 1.66 for 1,3-PDA-Ac-l-Glu and 1.49 for DADPM-Ac-l-Glu. Enantioselective electrodialysis was studied adopting racemic N-α-acetyl-tryptophan (Ac-Trp) mixtures as model pairs of enantiomers. The membranes selectively transported Ac-d-Trp. Permselectivity toward the d-isomer reached 2.03.     

Cavity-like hierarchical architecture of WS2/α-NiMoO4 electrodes for supercapacitor application

In this study, we fabricated a nano/micro cavity-like hierarchical architecture of WS₂/α-NiMoO₄ composite using microwave hydrothermal and calcination processes. The composite was characterized by X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, and X-ray photoelectron spectroscopy. The electrochemical measurements of the WS₂/α-NiMoO₄ composite electrode for application in supercapacitors (SCs) were performed through cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy. The WS₂/α-NiMoO₄ nanocomposite exhibited a specific capacity of 460 F g^-1 at 1 A g^-1 current density and a capacitor retention of 92% after 2000 cycles. However, α-NiMoO₄ spherical nanoparticles had a specific capacity of 231 F g^-1 at 1 A g^-1 current density and capacitor retention of 73% after 2000 cycles. The excellent specific area, formation of cavity-like structures, increase in pore size, superior electrical conductivity, and robust stability of WS₂/α-NiMoO₄ enhanced the effectiveness of the electrode composite material for supercapacitor application.