Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway.

BACKGROUND: Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in the treatment of osteosarcoma (OS) and to investigate the underlying mechanisms, particularly focusing on mitophagy. METHODS: The effects of SI on the proliferation, apoptosis, migration, and invasion of U2OS cells were analyzed. Mitophagy was assessed through multiple parameters: mitochondrial autophagosomes, mitochondrial membrane potential, autophagy-related proteins, reactive oxygen species (ROS), and oxygen consumption rate (OCR). Protein levels related to apoptosis, autophagy, and the AKT/mTOR pathway were analyzed using western blot. The therapeutic efficacy of SI was further identified using a mouse tumor xenograft model. Cell apoptosis and proliferation in tumor xenografts were detected by TUNEL staining and immunohistochemistry (IHC), respectively. RESULTS: SI dose-dependently suppressed the viability, colony formation, migration, and invasion of U2OS cells, and enhanced the apoptosis. SI also dose-dependently induced mitophagy in OS cells, evidenced by an increase in autophagosomes and ROS levels, a decrease in mitochondrial membrane potential and OCR, and concomitant changes in autophagy-related proteins. Mdivi-1, an inhibitor of mitophagy, reversed the anti-tumor effects of SI on U2OS cells. In addition, SI blocked the AKT/mTOR pathway in U2OS cells. SC-79, an AKT agonist, reversed the effect of SI on inducing mitophagy. Moreover, SI also promoted cell apoptosis and mitophagy in tumor xenografts in vivo. CONCLUSIONS: SI induces mitophagy in OS cells by blocking the AKT/mTOR pathway, contributing to the inhibition of OS.

Robust Nuclear Spin Polarization via Ground-State Level Anticrossing of Boron Vacancy Defects in Hexagonal Boron Nitride.

Nuclear spin polarization plays a crucial role in quantum information processing and quantum sensing. In this work, we demonstrate a robust and efficient method for nuclear spin polarization with boron vacancy (V_{B}^{-}) defects in hexagonal boron nitride (h-BN) using ground-state level anticrossing (GSLAC). We show that GSLAC-assisted nuclear polarization can be achieved with significantly lower laser power than excited-state level anticrossing, making the process experimentally more viable. Furthermore, we have demonstrated direct optical readout of nuclear spins for V_{B}^{-} in h-BN. Our findings suggest that GSLAC is a promising technique for the precise control and manipulation of nuclear spins in V_{B}^{-} defects in h-BN.

DC Magnetic Field Sensitivity Optimization of Spin Defects in Hexagonal Boron Nitride.

Spin defects existing in van der Waals materials attract wide attention thanks to their natural advantages for in situ quantum sensing, especially the negatively charged boron vacancy (VB-) centers in hexagonal boron nitride (h-BN). Here we systematically investigate the laser and microwave power broadening in continuous-wave optically detected magnetic resonance (ODMR) of the VB- ensemble in h-BN, by revealing the behaviors of ODMR contrast and line width as a function of the laser and microwave powers. The experimental results are well explained by employing a two-level simplified model of ODMR dynamics. Furthermore, with optimized power, the DC magnetic field sensitivity of VB- ensemble is significantly improved up to 2.87 ± 0.07 µT/Hz. Our results provide important suggestions for further applications of VB- centers in quantum information processing and ODMR-based quantum sensing.

Engineering Refractive Index Contrast in Thin Film Barium Titanate-on-Insulator.

Barium titanate-on-insulator has demonstrated excellent vertical optical confinement, low loss, and strong electro-optic properties. To fabricate a waveguide-based device, a region of higher refractive index must be created to confine a propagating mode, one way of which is through dry etching to form a ridge. However, despite recent progress achieved in etching barium titanate and similar materials, the sidewall and surface roughness resulting from the physical etching typically used limit the achievable ridge depth. This motivates the exploration of etch-free methods to achieve the required index contrast. Here, we introduce three etch-free methods to create a refractive index contrast in barium titanate-on-insulator, including a metal diffusion method, proton beam irradiation method, and crystallinity control method. Notably, molybdenum-diffused barium titanate leads to a large index change of up to 0.17. The methods provided in this work can be further developed to fabricate various on-chip barium titanate optical waveguide-based devices.

Gate-Tunable Bound Exciton Manifolds in Monolayer MoSe2.

Two-dimensional (2D) semiconductors with point defects are predicted to host a variety of bound exciton complexes analogous to trions and biexcitons due to strong many-body effects. However, despite the common observation of defect-mediated subgap emission, the existence of such complexes remains elusive. Here, we report the observation of bound exciton (BX) complex manifolds in monolayer MoSe2 with intentionally created monoselenium vacancies (VSe) using proton beam irradiation. The emission intensity of different BX peaks is found to exhibit contrasting dependence on electrostatic doping near the onset of free electron injection. The observed trend is consistent with the model in which free excitons exist in equilibrium with excitons bound to neutral and charged VSe defects, which act as deep acceptors. These complexes are more strongly bound than trions and biexcitons, surviving up to around 180 K, and exhibit moderate valley polarization memory, indicating partial free exciton character.

All-fiber optic displacement sensing system for an Ilizarov transverse tibial bone transport device.

A single-mode-multimode-single-mode (SMS) optical fiber-based displacement sensing system mounted on an Ilizarov transverse tibial bone transport device for microcirculation reconstruction is reported. Wide-range displacement is approximated as a uniform extension of a spring that is connected to an SMS optical fiber structure acting as the displacement sensor and allowing full displacement characterization. Transmission spectrum changes are measured, providing a displacement range of 24 mm with a sensitivity of $ - {55.42}\;{\rm pm/mm}$-55.42pm/mm and a resolution of 45.2 µm. The experimental results are characterized using a polynomial response curve for measuring the displacement due to transverse distraction of the Ilizarov device. The SMS fiber interrogation system is based on a macrobending fiber edge filter-based ratiometric measurement system. The use of SMS fibers together with the macrobending fiber-based interrogation system eliminates the influence of temperature on the displacement measurement. The implementation of the all-fiber sensing system of this investigation has uniquely facilitated a smart clinical device with a wide displacement range as well as operating in real-time monitoring when attached to the Ilizarov transverse tibial bone transport device. It also means that this fiber-optic sensing device can be made more cost-effective, simpler in construction, and more versatile while providing a high degree of measurement accuracy and resolution.

Multimode-interference-effect-based all-fiber displacement sensing system for an orthopedic Ilizarov apparatus device.

The paper describes a multimode-interference-effect-based single-mode-multimode-single-mode (SMS) fiber optic sensing system for wide-range displacement monitoring on an Ilizarov orthopedic external fixation device. Displacement measurement is implemented as the uniform extension of a spring, which is connected to an SMS optical fiber displacement sensor, allowing full displacement characterization. SMS fiber structures are used together with a macrobending-fiber-based interrogation system to measure temperature perturbation and hence eliminate its effect on the displacement measurement. Transmission spectra are measured, achieving a displacement measurement range of 110 mm with maximum sensitivity of -53 pm/mm and a resolution of 500 µm. The all-fiber sensing system has facilitated a clinical device with a wide displacement range operating in real-time when attached to the Ilizarov apparatus.

Ultra-low loss ridge waveguides on lithium niobate via argon ion milling and gas clustered ion beam smoothening.

Lithium niobate's use in integrated optics is somewhat hampered by the lack of a capability to create low loss waveguides with strong lateral index confinement. Thin film single crystal lithium niobate is a promising platform for future applications in integrated optics due to the availability of a strong electro-optic effect in this material coupled with the possibility of strong vertical index confinement. However, sidewalls of etched waveguides are typically rough in most etching procedures, exacerbating propagation losses. In this paper, we propose a fabrication method that creates significantly smoother ridge waveguides. This involves argon ion milling and subsequent gas clustered ion beam smoothening. We have fabricated and characterized ultra-low loss waveguides with this technique, with propagation losses as low as 0.3 dB/cm at 1.55 µm.

Strain sensor based on gourd-shaped single-mode-multimode-single-mode hybrid optical fibre structure.

A fibre-optic strain sensor based on a gourd-shaped joint multimode fibre (MMF) sandwiched between two single-mode fibres (SMFs) is described both theoretically and experimentally. The cladding layers of the two MMFs are reshaped to form a hemisphere using an electrical arc method and spliced together, yielding the required gourd shape. The gourd-shaped section forms a Fabry-Perot cavity between the ends of two adjacent but non-contacting multimode fibres' core. The effectiveness of the multimode interference based on the Fabry-Perot interferometer (FPI) formed within the multimode inter-fibre section is greatly improved resulting in an experimentally determined strain sensitivity of -2.60 pm/µÎµ over the range 0-1000 µÎµ. The sensing characteristics for temperature and humidity of this optical fibre strain sensor are also investigated.

EZH2-H3K27me3-Mediated Epigenetic Silencing of DKK1 Induces Nucleus Pulposus Cell Pyroptosis in Intervertebral Disc Degeneration by Activating NLRP3 and NAIP/NLRC4.

Nucleus pulposus (NP) cell pyroptosis is crucial for intervertebral disc degeneration (IDD). However, the precise mechanisms underlying pyroptosis in IDD remain elusive. Therefore, this study aimed to investigate how dickkopf-1 (DKK1) influences NP cell pyroptosis and delineate the regulatory mechanisms of IDD. Behavioral tests and histological examinations were conducted in rat IDD models to assess the effect of DKK1 on the structure and function of intervertebral discs. Detected pyroptosis levels using Hoechst 33,342/propidium iodide (PI) double staining, and determined pyroptosis-related protein expression via western blotting. The cellular mechanisms of DKK1 in pyroptosis were explored in interleukin (IL)-1ß-induced NP cells transfected with or without DKK1 overexpression plasmids (oe-DKK1). In addition, IL-1ß-treated NP cells transfected with sh-EZH2 and/or sh-DKK1 were utilized to clarify the interplay between the enhancer of zeste homologue 2 (EZH2) and DKK1 in pyroptosis. Additionally, the epigenetic regulation of DKK1 by EZH2 was explored in NP cells treated with the EZH2 inhibitors GSK126/DZNep. DKK1 expression decreased in IDD rats. Transfection with oe-DKK1 reduced pro-inflammatory factors and extracellular matrix markers in IDD rats. In IL-1ß-induced NP cells, DKK1 overexpression suppressed pyroptosis and inhibited the NLRP3 and NAIP/NLRC4 inflammasome activation. EZH2 knockdown increased DKK1 expression and reduced pyroptosis-related proteins. Conversely, DKK1 downregulation reversed the inhibitory effects of EZH2 knockdown on pyroptosis. Furthermore, EZH2 suppressed DKK1 expression via H3K27 methylation at the DKK1 promoter. EZH2 negatively regulates DKK1 expression via H3K27me3 methylation, promoting NP cell pyroptosis in IDD patients. This regulatory effect involves the activation of NLRP3 and NAIP/NLRC4 inflammasomes.

MFAP2 induces epithelial-mesenchymal transformation of osteosarcoma cells by activating the Notch1 pathway.

Background: Osteosarcoma (OS) is a malignancy originating from mesenchymal tissue. Microfibril-associated protein 2 (MFAP2) plays a crucial role in cancer, notably promoting epithelial-mesenchymal transition (EMT). However, its involvement in OS remains unexplored. Methods: MFAP2 was silenced in U2OS cells using shRNA targeting MFAP2 (sh-MFAP2) and validated by quantitative real-time polymerase chain reaction (qRT-PCR). We extracted gene chip data of MFAP2 from multiple databases (GSE28424, GSE42572, and GSE126209). Correlation analyses between MFAP2 and the Notch1 pathway identified through the gene set variation analysis (GSVA) enrichment analysis were conducted using the Pearson correlation method. Cellular behaviors (viability, migration, and invasion) were assessed via the Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays. EMT markers (N-cadherin, vimentin, and ß-catenin) and Notch1 levels were examined by western blotting and qRT-PCR. Cell morphology was observed microscopically to evaluate EMT. Finally, the role of MFAP2 in OS was validated through a xenograft tumor model. Results: OS cell lines exhibited higher MFAP2 mRNA expression than normal osteoblasts. MFAP2 knockdown in U2OS cells significantly reduced viability, migration, and invasion, along with downregulation of N-cadherin and vimentin, as well as upregulation of ß-catenin. MFAP2 significantly correlated with the Notch1 pathway in OS and its knockdown inhibited Notch1 protein expression. Furthermore, Notch1 activation reversed the inhibitory effects of MFAP2 knockdown on the malignant characteristic of U2OS cells. Additionally, MFAP2 knockdown inhibited tumor growth, expression levels of EMT markers, and Notch1 expression in OS tumor tissues. Conclusions: Our study revealed that MFAP2 was an upstream regulator of the Notch1 signaling pathway to promote EMT in OS. These findings suggested MFAP2 as a potential OS therapy target.

Defect Engineering and Emission Tuning of Wide-Bandgap MAPbCl3 Perovskite.

Lead-chloride perovskites are promising candidates for optoelectronic applications, such as visible-blind UV photodetection. It remains unclear how the deep defects in this wide-bandgap material impact the carrier recombination dynamics. In this work, we study the defect properties of MAPbCl3 (MA = CH3NH3) based on photoluminescence (PL) measurements. Our investigations show that apart from the intrinsic emission, four sub-bandgap emissions emerge, which are very likely to originate from the radiative recombination of excitons bound to several intrinsic vacancy and interstitial defects. The intensity of various emission features can be tuned by adjusting the type and ratio of precursors used during synthesis. Our study not only provides important insights into the defect property and carrier recombination mechanism in this class of material but also demonstrates efficient strategies for defect passivation and engineering, paving the way for further development of lead-chloride perovskite-based optoelectronic devices.

An antiferromagnetic spin phase change memory.

The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Effect of ischemia post-conditioning on skeletal muscle oxidative injury, mTOR, Bax, Bcl-2 proteins expression, and HIF-1α/ß-actin mRNA, IL-6/ß-actin mRNA and caveolin-3/ß-actin mRNA expression in ischemia-reperfusion rabbits.

This study is designed to investigate the effect of ischemia post-conditioning on IR-induced skeletal muscle injury in limbs of experimental rabbits. Rabbits are randomized to one of the following three groups: sham control, ischemic reperfusion, ischemic postconditioning. The lipid peroxidation level, antioxidant enzymes activities, skeletal muscle mammalian target of rapamycin (mTOR), Bax, Bcl-2 proteins expression and Bcl-2/Bax, and HIF-1α/ß-actin mRNA, interleukin-6 (IL-6)/ß-actin mRNA and caveolin-3/ß-actin mRNA expression were tested in the current study. The results suggested that ischemic postconditioning might decrease lipid peroxidation level, lactic dehydrogenase (LDH), creatine kinase (CK) activities, Bcl-2 proteins expression and Bcl-2/Bax, HIF-1α/ß-actin mRNA expression and increase skeletal muscle antioxidant enzymes activities, Bax protein expression and IL-6/ß-actin mRNA and caveolin-3/ß-actin mRNA expression. These indicated that protective effect of ischemic postconditioning against IR-induced skeletal muscle injury involve into a complex molecular mechanism. Our research results may offer a theoretical guidance for therapy of related clinical diseases.

Cistanches Herba aqueous extract affecting serum BGP and TRAP and bone marrow Smad1 mRNA, Smad5 mRNA, TGF-ß1 mRNA and TIEG1 mRNA expression levels in osteoporosis disease.

We studied molecular mechanism of Cistanches Herba aqueous extract (CHAE) in ovariectomized (OVX) rats, as an experimental model of postmenopausal osteoporosis. Female rats were either sham-operated or bilaterally OVX; and at 60 days postoperatively. The OVX group (n = 8) received an ovariectomy and treatment with normal saline for 90 days commencing from 20th post ovariectomy day. The ovariectomized +CHAE (OVX + CHAE) group (n = 8) received an ovariectomy and were treated with Cistanches Herba aqueous extract of 100 mg/kg body weight daily for 90 days commencing from 22nd post ovariectomy day. The ovariectomy +CHAE (OVX + CHAE) group (n = 8) received an ovariectomy, and were treated with the of 200 mg/kg body weight daily for 90 days commencing from 20th post ovariectomy day. Serum BGP and TRAP, E2, FSH and LH level, bone marrow Smad1, Smad5, TGF-ß1 and TIEG1 mRNA expression levels were examined. Results showed that serum BGP and TRAP, FSH and LH levels were significantly increased, whereas E2, Smad1, Smad5, TGF-ß1 and TIEG1 mRNA and proteins expression levels were significantly decreased in OVX rats compared to sham rats. 90 days of CHAE treatment could significantly decrease serum BGP and TRAP, FSH and LH levels, and increase E2, Smad1, Smad5, TGF-ß1 and TIEG1 mRNA and proteins expression levels in OVX rats. It can be concluded that CHAE play its protective effect against OVX-induced bone degeneration partly by regulating some bone metabolism related genes, e.g. Smad1, Smad5, TGF-ß1 and TIEG1.

Lycopene effects on serum mineral elements and bone strength in rats.

This study investigated the beneficial effect of lycopene on bone biomarkers in ovariectomized (OVX) rats. Female Wistar rats were either sham operated or surgically ovariectomized and then fed with lycopene for 8 weeks. Serum Ca, P, alkaline phosphatase (ALP), interleukin 6 (IL-6) and bone gla protein (BGP) concentration was significantly higher in the untreated OVX group compared with that of the sham group, whereas serum estrogen levels were lower. Bone mineral density (BMD), BMD/wt, bone mineral content (BMC), BMC/wt values, maximum load, stiffness, energy and maximum stress were significantly lower in the untreated OVX group compared with that of the sham group. Administration of lycopene (20, 30 and 40 mg/kg b.w.) for 8 weeks significantly decreased serum Ca, P, ALP, and IL-6 concentration, and enhanced serum estrogen level, BMD, BMD/wt, BMC, BMC/wt values, maximum load, stiffness, energy and maximum stress in lycopene-treated OVX groups. In conclusion, the consumption of lycopene may have the most protective effect on bone in OVX rats.

Influence of ShuJinHuoXue tablets on ischemia reperfusion injury of animals' skeletal muscle.

Ischemia-reperfusion (IR) can lead to serious tissue oxidative injury in animals. ShuJinHuoXue tablet (SJHXT) is a Chinese Traditional Medicine which can relax the muscles and stimulate the blood circulation and has been used as a clinical medicine. In the present study, we investigated the effects of SJHXT pretreatment on oxidative injury using an animal model of acute limb IR. Results showed that SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced serum endothelin-1 (ET-1), thromboxane B2 (TXB2) levels and thromboxane B2/6-keto- prostaglandin F1α (TXB2/6-Keto-PGF(1α)), wet weight/dried weight (W/D) ratio, myeloperoxidase (MPO), creatine kinase (CK), lactate dehydrogenase (LDH) activities, and increased serum nitric oxide (NO), 6-Keto-PGF(1α) levels and NO/ET-1 ratio in the IR+SJHXT groups. In addition, the SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced skeletal muscle Ca²âº, malondialdehyde (MDA) levels, increased Na⁺-K⁺-ATPase, Ca²âº-Mg²âº-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. Our results suggest that SJHXT pre-treatment may improve skeletal muscle blood vessel microcirculation, decrease skeletal muscle oxidative injury and enhance antioxidant enzymes activities in IR animals.

BMSC-EV-derived lncRNA NORAD Facilitates Migration, Invasion, and Angiogenesis in Osteosarcoma Cells by Regulating CREBBP via Delivery of miR-877-3p.

Bone marrow mesenchymal stem cells (BMSCs) can boost osteosarcoma (OS) cell proliferation and invasion, yet the function of extracellular vesicles (EVs) derived from BMSCs on OS is scarcely known. This study is aimed at examining the role of BMSC-EVs in OS cells. BMSCs and BMSC-EVs were isolated and identified. The effect of EVs and EVs-si-NORAD on OS cell proliferation, invasion, migration, and angiogenesis was determined. Expressions of NORAD, miR-877-3p, and CREBBP were detected. The binding relationship among NORAD, miR-877-3p, and CREBBP was verified. The miR-877-3p inhibitor or pc-CREBBP was delivered into OS cells treated with EVs-si-NORAD for in vitro analysis. The nude mouse model of the subcutaneous tumor xenograft was established for in vivo analysis. BMSC-EVs promoted OS cell proliferation, invasion, migration, and angiogenesis. BMSC-EVs carried NORAD into OS cells and upregulated CREBBP by sponging miR-877-3p. miR-877-3p downregulation or CREBBP overexpression partly inverted the inhibitory effect of EVs by silencing NORAD on OS cell proliferation, invasion, migration, and angiogenesis. In vivo experiments validated that BMSC-EV-derived NORAD facilitated tumor growth by upregulating CREBBP via miR-877-3p. To conclude, BMSC-EV-derived NORAD facilitated OS cell proliferation, invasion, migration, and angiogenesis by modulating CREBBP via miR-877-3p, which may offer new insights into OS treatment.

Effect of Cistanches Herba aqueous extract on bone loss in ovariectomized rat.

To assess the ability of traditional Chinese medicine Cistanches Herba extract (CHE) to prevent bone loss in the ovariectomized (OVX) rat, Cistanches Herba extract (CHE) was administered intragastrically to the rats. Female rats were anesthetized with pentobarbital sodium (40 mg kg(-1), i.p.), and their ovaries were removed bilaterally. The rats in the sham-operated group were anesthetized, laparotomized, and sutured without removing their ovaries. After 1 week of recovery from surgery, the OVX rats were randomly divided into three groups and orally treated with H(2)O (OVX group) or CHE (100 or 200 mg kg(-1) daily) for 3 months. The sham-operated group (n = 8) was orally treated with H(2)O. After 3 months, the total body bone mineral density (BMD), bone mineral content (BMC), Bone biomechanical index, blood mineral levels and blood antioxidant enzymes activities were examined in sham-operated, ovariectomized and Cistanches Herba extract treated rats. Results showed that Cistanches Herba extract treatment significantly dose-dependently enhanced bone mineral density (BMD), bone mineral content (BMC), maximum load, displacement at maximum load, stress at maximum load, load at auto break, displacement at auto break, and stress at auto break, and blood antioxidant enzymes activities, decreased blood Ca, Zn and Cu levels compared to the OVX group. This experiment demonstrates that the administration of Cistanches Herba extract to ovariectomized rats reverses bone loss and prevents osteoporosis.

Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.

The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.