Unveiling the Therapeutic Potential of Herba Epimedii: Enhancing Bone Healing Through Cytoskeletal Regulation of RhoA/Rock1 Pathway.

Herba Epimedii is widely used to promote bone healing, and their active ingredients are total flavonoids of Epimedium (TFE). Ras homolog gene family member A / Rho-associated protein kinase (RhoA/Rock), an important pathway regulating the cytoskeleton, has been proven to affect bone formation. However, whether TFE promotes bone healing via this pathway remains unclear. In this study, the therapeutic effects of TFE were estimated using micro-computed tomography and hematoxylin and eosin staining of pathological sections. F-actin in osteoblasts was stained to investigate the protective effects of TFE on the cytoskeleton. Its regulatory effects on the RhoA/Rock1 pathway were explored using RT-qPCR and Western blot analysis. Besides, flow cytometry, alkaline phosphatase and nodule calcification staining were performed to evaluate the effects on osteogenesis. The bone healing in rats was improved, the cytoskeletal damage in osteoblasts was reduced, the RhoA/Rock1 pathway was downregulated, and osteogenesis was enhanced after TFE treatment. Thus, TFE can promote bone formation at least partially by regulating the expression of key genes and proteins in the cytoskeleton. The findings of this study provided evidence for clinical applications and would contribute to a better understanding of Epimedium's mechanisms in treating bone defects.

Na2BaB12O18F4: A Mixed Alkali/Alkaline-Earth Metal Fluorooxoborate with Two Unprecedented Interpenetrating Three-Dimensional B-O/F Anionic Networks and a Short Ultraviolet Cutoff Edge.

Fluorooxoborates are promising yet largely untapped crystal materials for linear and nonlinear optical applications. The introduction of a strong electronegative F atom into an oxyboron anionic group offers a virtually unlimited chance for structural engineering and ultimately purposeful tuning of the macroscopic optical properties of the crystal. Herein, a new mixed alkali/alkaline-earth fluorooxoborate, Na2BaB12O18F4, was synthesized in a closed system. Na2BaB12O18F4 features a [B6O11F2] fundamental building unit (FBB), which polymerizes into two new (first example) independent interpenetrating three-dimensional (3D) B-O/F anionic networks constructed entirely from BO3 and BO3F units. Based on optical characterizations and the first-principles calculations, Na2BaB12O18F4 exhibits a moderate birefringence (0.054 @ 1064 nm) and a short ultraviolet (UV) cutoff edge (below 190 nm). The successful synthesis and characterization of Na2BaB12O18F4 may speed up the subsequent discovery of other mixed alkali/alkaline-earth metal fluorooxoborates.

Enormous electro-optic effect in paraelectric nanodisordered KTa1-xNbxO3 crystal.

Recent experiments have revealed that the order of the electro-optic (EO) effect depends on the frequency of electric field in paraelectric nanodisordered KTa1-xNbxO3 (KTN) crystal. Through the dielectric frequency spectrum under the bias electric field, enormous linear and quadratic EO effects were discovered at the resonance frequencies, which changed the perception that only the quadratic EO effect exists. Applying just a small AC electric field of 6 V/mm, the effective linear EO coefficient reached 478 pm/V at 609 kHz, and the effective quadratic EO coefficient reached 4.39*10-13m2V-2at 302 kHz. The reason why an extremely low electric field results in an enormous EO coefficient is attributed to the resonance between the polar nanoregions (PNRs) and the electric field, induced by the field-driven reorientation of free dipoles on the boundary of the PNRs. In addition, the order of EO effect depending on the frequency of electric field was attributed to the motion modes of the PNR. This finding improves the understanding of how the EO effect is caused by field-driven PNR dynamics, but also provides a basis for the development of EO devices.

The miRNA-144-5p/IRS1/AKT axis regulates the migration, proliferation, and mineralization of osteoblasts: A mechanism of bone repair in diabetic osteoporosis.

Diabetic osteoporosis (DOP) is a disorder of bone metabolism induced by multiple mechanisms. Previous studies have revealed that microRNAs (miRNAs) play crucial roles in bone metabolism. MiRNA-144-5p has been proven to participate in the regulation of osteoblast activities; however, its specific mechanism in DOP has not been elucidated. This study investigated whether high glucose (HG) inhibited osteoblasts by regulating miRNA-144-5p. Our results showed that HG inhibited bone formation not only in vivo but also in vitro. We observed that HG severely hindered the migration, proliferation and mineralization of osteoblasts, while miRNA-144-5p was upregulated by way of the cell counting kit-8 assay, wound healing assay, alkaline phosphatase (ALP) activity assay and alizarin red staining. Double luciferase reporter experiments showed that miRNA-144-5p directly targeted insulin receptor substrate 1 (IRS1). The IRS1/AKT signaling pathway is closely related to osteoblasts' migration, proliferation, and mineralization. Silencing miRNA-144-5p promoted the mRNA, and protein expression of IRS1, thereby letting the expression of total AKT down, and then preventing phosphorylation of AKT into the nucleus to regulate migration, proliferation, and mineralization genes of osteoblasts. In conclusion, this study indicated that HG regulated the migration, proliferation, and mineralization of osteoblasts via the miRNA-144-5p/IRS1/AKT axis, which suggested a possible mechanism for DOP pathology.

Unique beam deflection based on dynamic polarized nano-domains in Cu-doped KTN.

In this report, we successfully implement a unique cross-field beam deflector by exploiting the modulation of a one-dimensional refractive index in a copper-doped potassium tantalite niobite crystal. A theoretical model is established based on an electrostrictive effect regulated by the dynamic polarized nano-domains to explicate the mechanism of the abnormal beam deflection which is perpendicular to the applied electric field. Experimental results agree well with our theoretical deduction while validating the interactions between the dynamic polarized nano-domains and the applied electric field. Our findings will break the limitation of conventional electro-optic deflectors, paving the way to develop promising optical functional devices with a large field-of-view scanning angle and ultra-low driving voltage.

Super electro-optic modulation in bulk KTN:Cu based on electric-field-enhanced permittivity.

The electric-field-enhanced effect of permittivity can improve the performance of electro-optic modulators and deflectors. A theoretical model of super electro-optic modulation based on the field-enhanced effect of the permittivity was proposed. Results showed that a strong field-enhanced effect can greatly reduce the half-wave voltage and increase the modulation depth as a result of increased relative dielectric permittivity and permittivity gradient to the electric field. For bulk paraelectric KTN:Cu near the Curie temperature, we found a novel phenomenon that the response of relative dielectric permittivity to the bias electric field was closely related to the frequency, including attenuation, invariance, and enhancement. We effectively selected the frequencies corresponding to the strong field-enhanced effect by measuring the dielectric-frequency spectrum under the bias voltage. At these frequencies, a phase retardation of π was achieved through 2Vpp AC modulation voltage, indicating that the half-wave voltage was reduced by one order of magnitude.

Effects of mulberry pomace on physicochemical and textural properties of stirred-type flavored yogurt.

Adding functional ingredients is an important method to develop functional dairy products. Mulberry pomace (MPo), a byproduct of mulberry fruit processing, is rich in phenolic compounds and anthocyanins and can be served as the functional ingredient in functional dairy products. The aim of this work was to prepare a functional flavored yogurt by incorporating MPo into stirred yogurt and to investigate the effects of MPo on the physicochemical and textural properties of the product during cold storage. We supplemented MPo powder up to 3% (wt/wt) in fermented milk, and the changes in color, pH, titratable acidity (TA), total phenol content (TPC), total anthocyanin content (TAC), water-holding capacity, rheological behavior, texture, and microstructure of the functional flavored yogurt were monitored during storage under 4°C for 28 d. The MPo powder brought a pink to dark red color to the yogurt, decreased the lightness (L*) and yellow-blue color (b*) values, increased the red-green color (a*) values, decreased the pH value, and increased the contents of TA, TPC, and TAC in a dose-dependent manner. The addition of MPo at 1%, 2%, and 3% (wt/wt) significantly increased water-holding capacity, consistency, viscosity, and viscosity index, and reduced firmness of yogurt samples. Supplementation of MPo significantly reduced the pore spaces and channels inside the samples and improved microstructure of the functional yogurt. During the 28 d of cold storage, MPo-fortified yogurt samples kept relatively constant color, although their L*, a*, and b* showed a decreasing tendency. The pH of all yogurt samples gradually decreased with increasing of TA. Interestingly, TPC and TAC contents and the texture parameters of MPo-fortified yogurt increased gradually and continuously during the 28 d of cold storage. Mulberry pomace is beneficial to improve the physicochemical and textural properties of yogurt and has the potential as a natural stabilizer to be used in functional yogurt rich in phytochemicals.

Effects of slight structural distortion on the luminescence performance in (Ca1-x Eux )WO4 luminescent materials.

(Ca1-x Eux )WO4 (x = 0-21 mol%) phosphors were prepared using the classical solid-state reaction method. The influence of Eu3+ ion doping on lattice structure was observed using powder X-ray diffraction and Fourier transform infrared spectroscopy. Furthermore, under this influence, the luminescence properties of all samples were analyzed. The results clearly illustrated that the element europium was successfully incorporated into the CaWO4 lattice with a scheelite structure in the form of a Eu3+ ion, which introduced a slight lattice distortion into the CaWO4 matrix. These lattice distortions had no effect on phase purity, but had regular effects on the intrinsic luminescence of the matrix and the f-f excitation transitions of Eu3+ activators. When the Eu3+ concentration was increased to 21 mol%, a local luminescence centre of [WO4 ]2- groups was detected in the matrix and manifested as the decay curves of [WO4 ]2- groups and luminescence changed from single exponential to double exponential fitting. Furthermore, the excitation transitions of Eu3+ between different energy levels (such as 7 F0 →5 L6 , 7 F0 →5 D2 ) also produced interesting changes. Based on analysis of photoluminescence spectra and the chromaticity coordinates in this study, it could be verified that the nonreversing energy transfer of [WO4 ]2- →Eu3+ was efficient and incomplete.

Potassium tantalate niobate (KTN) crystal-based polarization-modulated 3D ladar with a large field of view.

An innovative 3D ladar that utilizes potassium tantalate niobate (KTN) crystal as a polarization modulator is proposed in this Letter. The optical isotropy of KTN in cubic phase can effectively suppress the range errors induced by the incident angles of collected beams in 3D imaging. The giant quadratic electro-optic coefficient can dramatically lower the voltage that is required to modulate the polarization so that a high voltage amplifier with less noise can be used to improve the ranging performances. By virtue of these two advantages, a range error of 4.8 cm and a range precision of 4.4 cm at 15 m have been achieved under a large field of view of 20° (about 0.35 rad) and a maximum detection range without ambiguity of 60 m.

Preparation and application of polyvinyl alcohol-decorated cell membrane chromatography for screening anti-osteoporosis components from Liuwei Dihuang decoction-containing serum.

Cell membrane chromatography is a powerful tool for screening active components from complex matrices. New cell membrane carriers need to be developed to increase the coverage of cell membranes on the surface of stationary phases, thereby improving cell membrane chromatographic retention. In this work, we prepared polyvinyl alcohol-poly dimethyl diallyl ammonium chloride modified silica gel as a cell membrane carrier. Osteoblast cell was used as cell membrane source, which was widely used to evaluate the osteogenic activity of drugs. The new cell membrane chromatographic stationary phase was used to screen anti-osteoporosis components in Liuwei Dihuang decoction-containing serum. The chemical structures of the new modified materials were characterized by scanning electronic microscopy, Fourier transform infrared spectroscopy, and elemental analysis characterization. Compared with the common cell membrane column, the cell membrane coverage of this modified material was increased by 30%, and thus provided a stronger retention effect in positive drugs. Nineteen metabolites in rat serum samples were retained on the cell membrane chromatography and identified by ultra-high-performance liquid chromatography/time-of-flight mass spectrometry. Among those, four components (morroniside, catalpol, loganin, and acteoside) were selected for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation. The new modified material was successfully applied to screen anti-osteoporosis components from Liuwei Dihuang Decoction-containing serum.

Molten salt synthesis and luminescence of Dy3+ -doped Y3 Al5 O12 phosphors.

Dy3+ -doped Y3 Al5 O12 phosphors were prepared at a relatively low temperature using molten salt synthesis. The phase of the prepared Dy3+ -doped Y3 Al5 O12 phosphors was confirmed using X-ray powder diffraction. Results indicated that Dy3+ doping did not change the Y3 Al5 O12 phase. Following excitation at 352 nm, emission spectra of the Dy3+ -doped Y3 Al5 O12 phosphors consisted of blue, yellow, and red emission bands. The influence of Dy3+ concentration and excitation wavelength on emission was investigated. The ratio of yellow light to blue light varied with change in Dy3+ doping concentration, due to changes in the structure around Dy3+ . Emission intensities also changed when the excitation wavelength was changed. This variation is luminescence generated a system for tunable white light for Dy3+ -doped Y3 Al5 O12 phosphors.

Theoretical Investigation on the Microscopic Mechanism of Lattice Thermal Conductivity of ZnXP2 (X = Si, Ge, and Sn).

Thermal conductivity is an important physical parameter for the application of nonlinear optical single crystal materials. The underlying science of thermal transport behavior is not well established both experimentally and theoretically. In the present work, we have studied the microscopic picture of lattice thermal conductivity of ZnXP2 (X = Si, Ge, Sn), chalcopyrite ABC2 type infrared optical crystals, by using a harmonic and anharmonic lattice dynamic method and phonon Boltzmann transport equation based on first-principle calculations. With the mass of atom X increased, the phonon frequencies and phonon group velocities of ZnXP2 (X = Si, Ge, Sn) are shown not surprisingly to be decreased. Nevertheless, the phonon lifetime of ZnXP2 is unexpectedly increased, which is the governing mechanism for the increased thermal conductivity as 12.5 W/(m·k), 31.6 W/(m·k), and 35.4 W/(m·k), for ZnSiP2, ZnGeP2, and ZnSnP2, respectively, at 300 K. The contributions of optical phonons (with the frequency below 150 cm-1) to the total thermal conductivity are remarkable, reaching 18%, 31%, and 34% for three compounds, due to the significantly increased phonon lifetime in the frequency range 50-150 cm-1. To explore the physical insights of phonon lifetime and phonon anharmonicity, three-phonon scattering phase space and electronic localization function analysis of the X-P bond are provided. The results show that the covalent nature of X-P bonds is enhanced with the increased mass of atom X = Si, Ge, Sn, which induces the reduction of three-phonon scattering phase space in the frequency range 50-150 cm-1, leading to the enhancement of the phonon lifetime and thermal conductivity of ZnXP2.

Static volumetric three-dimensional display based on an electric-field-controlled two-dimensional optical beam scanner.

Using the quadratic electro-optic effect and the gradient of the composition ratio m [Nb/(Ta+Nb) in mol. %] in a potassium tantalate niobate crystal, we have designed an electric-field-controlled two-dimensional optical beam scanner with a wide wavelength range and fast response. This scanner is used to realize a volumetric display based on a two-frequency, two-step upconversion technique that is used to address the imaging volume. Use of appropriately designed imaging optics and custom-designed software to convert 2D renderings of volumetric images into control signals for the scanner along with appropriate infrared laser source selection allows efficient single-color image generation with a large viewing zone, without flicker and with natural depth cues. The resulting system has the potential to increase image resolution to nearly 61.5×109 with high scanning frequency and to expand to display three-color imagery.

ALDH2 mediates the dose-response protection of chronic ethanol against endothelial senescence through SIRT1/p53 pathway.

Aldehyde dehydrogenase 2 (ALDH2) plays essential roles in drinking-associated diseases or effects. As we have previously reported, ALDH2 mediates acute ethanol-induced eNOS activation in vitro. However, whether chronic ethanol treatment has a dose-response endothelial protection, as well as the possible mediating role of ALDH2 involved, is unclear. Here, we show that appropriate dose of ethanol preserved the expression and activity of ALDH2 and eNOS, and alleviated senescence-associated phenotypes in human aortic endothelial cells. Furthermore, ALDH2 deficiency impairs the dose-response protection of ethanol against endothelial senescence by promoting the accumulation of 4-HNE, the formation of 4-HNE-SIRT1 protein adducts and the subsequent decrease in SIRT1-dependent p53 deacetylation. Collectively, our data indicate that ALDH2 mediates the protection of appropriate ethanol by modulating SIRT1/p53-dependent endothelial senescence.

Intrinsic sources of high thermal conductivity of CdSiP2 determined by first-principle anharmonic calculations.

CdSiP2 is an outstanding mid-infrared nonlinear optical crystal material with high thermal conductivity. However, the microscopic physics behind its thermal transport behavior is still unclear. In this study, we have investigated the source of the thermal conductivity of CdSiP2 based on anharmonicity lattice dynamics (ALD) and the first-principle calculation. The results are well accordance with the experimental measurement in a wide temperature range. Based on our results, the acoustic phonon lifetime of CdSiP2 is higher than that of the thermoelectric and semiconducting materials reported in previous studies, which is induced by the low lattice anharmonicity demonstrated by CdSiP2. The mode-dependent thermal conductivity is obtained with the contribution of optical phonons being significant (27%) above 300 K; this is mainly due to the high phonon group velocity and relatively long phonon lifetime of low-energy optical phonons (80-200 cm-1). A high lifetime of acoustic phonons and remarkable contribution of low-energy optical phonons can be responsible for the high thermal conductivity of CdSiP2.

Effects of alkaloids from Sophora flavescens on osteoblasts infected with Staphylococcus aureus and osteoclasts.

Chronic osteomyelitis is primarily caused by infection with Staphylococcus aureus (S. aureus). Antibiotics are commonly administered; however, it is a challenge to promote bone healing. The aim of this study was to investigate the in vitro effects of alkaloids from the herbal remedy Sophora flavescens (ASF) on rat calvarial osteoblasts (ROBs) infected with S. aureus and healthy osteoclasts. Cell proliferation and alkaline phosphatase, interleukin-6, and tumour necrosis factor-α activity was measured in infected ROBs; tartrate-resistant acid phosphatase was evaluated in osteoclasts via enzyme-linked immunosorbent assay. The mRNA and protein expression levels of bone morphogenetic protein 2, runt-related transcription factor 2, osteoprotegerin, and receptor activator of nuclear factor kappa-B ligand were assessed in infected ROBs through reverse transcription-polymerase chain reaction and western blotting analysis, respectively. Results indicated that ASF increased the viability of uninfected ROBs and infected ROBs treated with vancomycin via regulation of bone morphogenetic protein 2, runt-related transcription factor, osteoprotegerin, and receptor activator of nuclear factor kappa-B ligand mRNA and protein expression levels. In addition, the secretion of the inflammatory factor tumour necrosis factor-α was decreased and alkaline phosphatase activity was increased, inhibiting the viability of osteoclasts and tartrate-resistant acid phosphatase activity. Therefore, the herbal remedy ASF has potential as a new treatment for chronic osteomyelitis.

Enhancing H2O2 resistance of an esterase from Pyrobaculum calidifontis by structure-guided engineering of the substrate binding site.

Green technologies are attracting increasing attention in industrial chemistry where enzymatic reactions can replace dangerous and environmentally unfriendly chemical processes. In situ enzymatic synthesis of peroxycarboxylic acid is an attractive alternative for several industrial applications although concentrated H2O2 can denature the biocatalyst, limiting its usefulness. Herein, we report the structure-guided engineering of the Pyrobaculum calidifontis esterase (PestE) substrate binding site to increase its stability and perhydrolysis activity. The L89R/L40A PestE mutant showed better tolerance toward concentrated H2O2 compared with wild-type PestE, and retained over 72% of its initial activity after 24-h incubation with 2 M H2O2. Surprisingly, the half-life (t 1/2, 80 °C) of PestE increased from 28 to 54 h. The k cat/K m values of the mutant increased 21- and 3.4-fold toward pentanoic acid and H2O2, respectively. This work shows how protein engineering can be used to enhance the H2O2 resistance and catalytic efficiency of an enzyme.

A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

The histone demethylase PHF8 represses cardiac hypertrophy upon pressure overload.

BACKGROUND: Mammalian hearts undergo hypertrophy upon pressure overload to support increased workload. Sustained hypertrophy results in cardiac decompensation and subsequently heart failure. The mechanism that prevents the development of cardiac hypertrophy is still not fully understood. Here we elucidate the anti-hypertrophic role of the histone demethylase PHF8. METHODS AND RESULTS: PHF8 protein and mRNA levels were down-regulated in human failing hearts, mouse hypertrophic hearts and neonatal rat ventricle myocytes that underwent hypertrophy. Then we generated a cardiac-specific PHF8 transgenic mice, and found that PHF8 overexpression reversed cardiac dysfunction, hypertrophy and fibrosis upon pressure overload. In vivo evidence showed that PHF8 blocked protein synthesis and hypertrophic fetal genes expression. Furthermore, we found that PHF8 inhibited Akt-mTOR pathway in hypertrophic hearts and neonatal rat ventricle myocytes, and rapamycin treatment rescues the effects of PHF8 loss. CONCLUSION: These results indicate that PHF8 serves as an endogenous factor that the host uses to attenuate cardiac hypertrophy upon cardiac overload. Strategies based on its enhancement might be of benefit in the treatment of hypertrophic cardiomyopathy.

Monosaccharide composition analysis of immunomodulatory polysaccharides by on-line hollow fiber microextraction with high-performance liquid chromatography.

The monosaccharide compositions of functional polysaccharides are essential for structure elucidation and biological activity determination. A sensitive method based on on-line hollow-fiber liquid-phase microextraction with high-performance liquid chromatography has been established for the analysis of ten monosaccharide compositions (two uronic acids, two amino sugars and six neutral sugars) of the immunomodulatory polysaccharides. After derivatization, the sample was injected into the lumen of a hollow fiber immersed in butyl ether and separated by liquid chromatography. Under optimized conditions, the calibration curves were linear (r ≥ 0.9996) in the range of 10-2000 µmol L(-1) . The limits of detection were in the range of 0.04-1.58 µmol L(-1) , and the recoveries were in the range of 92.1-99.6%, which shows that the method is applicable to the analysis of the monosaccharide composition of various polysaccharides.