Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.Subject terms: Heart failure, Embryonic stem cells, Stem-cell differentiation     

Bioavailability Enhancement of Cepharanthine via Pulmonary Administration in Rats and Its Therapeutic Potential for Pulmonary Fibrosis Associated with COVID-19 Infection

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.     

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide

Therapeutic iodoform (CHI₃) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.     

Impact of the Acetaldehyde-Mediated Condensation on the Phenolic Composition and Antioxidant Activity of Vitis vinifera L. Cv. Merlot Wine

Acetaldehyde is a critical reactant on modifying the phenolic profile during red wine aging, suggesting that the acetaldehyde-mediated condensation can be responsible for the variation of antioxidant activity during the aging of this beverage. The present study employs exogenous acetaldehyde at six levels of treatment (7.86 ± 0.10–259.02 ± 4.95 mg/L) before the bottle aging of Merlot wines to encourage phenolic modification. Acetaldehyde and antioxidant activity of wine were evaluated at 0, 15, 30, 45, 60 and 75 days of storage, while monomeric and polymeric phenolics were analyzed at 0, 30 and 75 days of storage. The loss of acetaldehyde was fitted to a first-order reaction model, the rate constant (k) demonstrated that different chemical reaction happened in wines containing a different initial acetaldehyde. The disappearance of monomeric phenolics and the formation of polymeric phenolics induced by acetaldehyde could be divided into two phases, the antioxidant activity of wine did not alter significantly in the first phase, although most monomeric phenolics vanished, but the second phase would dramatically reduce the antioxidant activity of wine. Furthermore, a higher level of acetaldehyde could shorten the reaction time of the first phase. These results indicate that careful vinification handling aiming at controlling the acetaldehyde allows one to maintain prolonged biological activity during wine aging.     

（Ti,Al）N薄膜光学性能的研究

研究了（Ｔｉ，Ａｌ）薄膜的光学特性，对其反射和透射光谱作了仔细分析。运用Ｈａｄｌｅｙ方程，算出一定成分（Ｔｉ，Ａｌ）Ｎ膜的折射率ｎ，消光系数ｋ随波长的变化关系。又根据透射曲线，计算出了（Ｔｉ，Ａｌ）Ｎ膜的光隙能。     

CeO_2和Y_2Ba_1Cu_1O_(5-δ)共同掺杂对Y_1Ba_2Cu_3O_(7-δ)的超导电性及其晶格结构的影响

采用固相反应法成功制备出一批Y123与Y211的摩尔比为1∶0.47的混合物,并在此混合物的基础上掺入CeO2,掺入的比例x分别为0.5wt%、1.0wt%、2.0wt%、3.0wt%、4.0wt%。采用了X-射线衍射仪对样品的晶格结构进行了分析,测量结果表明:x=1.0wt%时掺杂效果最好,同时也充分说明Y123的晶格结构与其超导电性之间存在着一种内在的必然关联。并通过对其测试临界转变温度以及转变宽度,测量结果也充分验证了上述结论。     

Dynamical measurements on viscoelastic behaviors of spiders in electro-dynamic loudspeakers

Spiders in electro-dynamic loudspeakers are most commonly concentrically corrugated fabric disks, and their viscoelastic behaviors affect the loudspeaker reproductions. A noncontact dynamic measuring technology is presented by a subwoofer closed box to excite the tested spiders pneumatically with a Laser Doppler Vibrometer (LDV) to measure the velocity of the moving spiders. Correlation techniques were employed to get an accurate and reliable acoustical transfer function between the measured velocity and sound pressure. The Young’s moduli of the tested spider composite materials were derived from the measured vibration modes. The creep effect and the level dependent behaviors of tested spiders were investigated. The results indicate that, the Young’s moduli of the tested spiders are frequency dependent. The mechanical stiffness increases with a small slope in low frequency range while a large slope in high frequency range. The loss factor exhibits the maximum around the resonance frequency, and after that it decreases with increasing frequency. The effective stiffness has a monotonic decrease with input voltage levels and the harder the spider, the less stiffness changes with input levels.     

Preparation of nano-hydroxyapatite/poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) biocomposite microspheres

Nano-hydroxyapatite (HA)/poly(l-lactide) (PLLA) composite microspheres with relatively uniform size distribution were prepared by a solid-in-oil-in-water (s/o/w) emusion solvent evaporation method. The encapsulation of the HA nanopaticles in microshperes was significantly improved by grafting PLLA on the surface of the HA nanoparticles (p-HA) during emulsion process. This procedure gave a possibility to obtain p-HA/PLLA composite microspheres with uniform morphology and the encapsulated p-HA nanoparticle loading reached up to 40 wt% (33 wt% of pure HA) in the p-HA/PLLA composite microspheres. The microstructure of composite microspheres from core-shell to single phase changed with the variation of p-HA to PLLA ratios. p-HA/PLLA composite microspheres with the diameter range of 2–3 μm were obtained. The entrapment efficiency of p-HA in microspheres could high up to 90 wt% and that of HA was only 13 wt%. Surface and bulk characterizations of the composite microspheres were performed by measurements such as wide angle X-ray diffraction (WAXD), thermal gravimetric analysis (TGA), environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM).     

An extensive review of studies on mycobacterium cell wall polysaccharide-related oligosaccharides – part II: Synthetic studies on complex arabinofuranosyl oligosaccharides carrying other functional motifs and related derivatives and analogs

Abstract

Lipoarabinomannan (LAM), mannosyl LAM (ManLAM), and mycolyl-arabinogalactan (mAG) are unique and ubiquitous cell wall constituents of Mycobacterium tuberculosis (M. tb), the bacterium causing tuberculosis (TB). It has been well documented that LAM, ManLAM, and mAG play an important role in mycobacterial infections and in the elicitation of specific immune responses against M. tb in the host. Therefore, LAM, ManLAM, mAG, and related molecules are attractive targets for the development of novel TB diagnostic and therapeutic strategies. Accordingly, numerous research groups have spent great effort on the chemical synthesis and biological studies of mycobacterium-related arabinofuranosyl oligosaccharides and their mimetics and conjugates. This article provides an extensive review about the progresses in this area. Due to the page limit of this journal, the review is published in three parts separately. This part (Part II) is focused on the synthesis of various ManLAM and mAG analogs containing mannose, galactose or galactosamine units and other natural structural motifs, as well as arabinofuranosyl oligosaccharide C-analogs and other derivatives.