Multifunctional nanomaterials via cell cuproptosis and oxidative stress for treating osteosarcoma and OS-induced bone destruction.

Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.

Nitisinone attenuates cartilage degeneration and subchondral osteoclastogenesis in osteoarthritis and concomitantly inhibits the cGAS/STING/NF-κB pathway.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and subchondral bone remodelling. Currently, conservative treatment strategies cannot effectively alleviate the progression of OA. In this study, we used computer network analysis to show that Nitisinone (NTBC) is closely related to extracellular matrix degradation in OA and mainly interferes with the TNF-α signaling pathway. NTBC is an orphan drug used to treat hereditary type I tyrosinemia by altering phenylalanine/tyrosine metabolic flow. In this study, we found that NTBC effectively reduced chondrocyte inflammation and extracellular matrix degradation induced by TNF-α. Mechanistically, NTBC inhibited the cGAS/STING signaling pathway and reduced activation of the STING-dependent NF-κB pathway to alleviate inflammation. In addition, NTBC inhibited osteoclastogenesis and delayed the occurrence of subchondral bone remodelling. In mice with ACLT-induced osteoarthritis, intra-articular injection of NTBC significantly reduced cartilage degradation and subchondral bone remodelling. NTBC showed impressive therapeutic efficacy as a potential pharmaceutical intervention for the treatment of OA.

Macrophage migration inhibitory factor (MIF) promotes intervertebral disc degeneration through the NF-κB pathway, and the MIF inhibitor CPSI-1306 alleviates intervertebral disc degeneration in a mouse model.

Lumbar intervertebral disc degeneration(IDD) is a prevalent inflammatory disease caused by many proinflammatory factors, such as TNF and IL-1ß. Migration inhibitory factor (MIF) is an upstream inflammatory factor widely expressed in vivo that is associated with a variety of inflammatory diseases or malignant tumors and has potential therapeutic value in many diseases. We explored the role of MIF in intervertebral disc degeneration by regulating the content of exogenous MIF or the expression of MIF in cells. Upon inducing degeneration of nucleus pulposus (NP) cells with IL-1ß, we found that the increase in intracellular and exogenous MIF promoted the catabolism induced by proinflammatory factors in NP cells, while silencing of the MIF gene alleviated the degeneration to some extent. In a mouse model, the intervertebral disc degeneration of MIF-KO mice was significantly less than that of wild-type mice. To explore the treatment of intervertebral disc degeneration, we selected the small-molecular MIF inhibitor CPSI-1306. CPSI-1306 had a therapeutic effect on intervertebral disc degeneration in the mouse model. In summary, we believe that MIF plays an important role in intervertebral disc degeneration and is a potential therapeutic target for the treatment of intervertebral disc degeneration.

Wide field of view optical phased array with a high-directionality antenna.

Light detection and ranging (LiDAR) is a widely utilized technology for extracting information from the outside world in fields such as automotive, robotics, and aerospace. Optical phased array (OPA) is a promising solution for LiDAR technology, although its application is limited by loss and alias-free steering range. In this paper, we propose a dual-layer antenna that achieves a peak directionality of over 92%, thereby mitigating antenna loss and enhancing power efficiency. Based on this antenna, we design and fabricate a 256-channel non-uniform OPA that achieves 150° alias-free steering.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

Overexpression of miR-148a-3p inhibits extracellular matrix degradation and alleviates IL-1ß-induced intervertebral disc degeneration.

Objectives: Recently, studies on microRNAs (miRNAs) and their targets and related genes have provided new therapeutic opportunities for controlling intervertebral disc degeneration (IDD). We aimed to investigate the effects of miR-148a-3p overexpression on IDD progression. Materials and Methods: This study used microRNA microarrays to analyze key regulators of IDD. Q-PCR was used to verify the IL-1ß-induced down-regulation of miR-148a-3p expression both in nucleus pulposus (NP) tissues of IDD patients and in degenerated NP cells (NPCs) of rats. Rat NPC micromass cultures and ex vivo intervertebral disc (IVD) culture models were established, and histological staining was performed to verify the effect of miR-148a-3p on the general morphology and proteoglycan and collagen contents of IVDs. In addition, q-PCR and western blotting analyses were performed to examine the expression of ECM molecules and matrix-degrading enzymes. A luciferase reporter assay was used to confirm the target genes of miR-148a-3p. Results: Our data revealed that miR-148a-3p was down-regulated in IDD. Overexpression of miR-148a-3p had no effect on ACAN or COL2A1 gene expression but decreased MMP3, MMP13, and ADAMTS5 gene expression. The matrix deposited by miR-148a-3p-overexpressing rat NPCs contained high levels of proteoglycans and collagen. The ex vivo experiments verified that agomiR-148a-3p alleviated the NPC matrix degradation induced by IL-1ß. A luciferase reporter assay confirmed that miR-148a-3p directly targeted ADAMTS5 and MMP13. Conclusion: We proved that miR-148a-3p can attenuate ECM loss and protect NP function by inhibiting matrix-degrading enzymes.

Two-dimensional scanning of silicon-based focal plane array with field-of-view splicing technology.

All-solid-state beam scanning chip is ideal for next-generation LiDAR due to its reliability and small size. Here we propose a focal plane array chip for two-dimensional scanning using field-of-view splicing technology on silicon photonics platform. The chip has two rotationally symmetric structures, each including a 1 × 64 antenna array accompanied by a 1 × 64 micro-ring optical switch array. We demonstrate a two-dimensional scanning equivalent to an 8-line LiDAR with a field-of-view of 82° × 32°, a beam divergence angle of 0.07° × 0.07°, and a background suppression ratio of over 20 dB. Our chip works in such a simple way that only one optical switch needs to be turned on each time the beam is emitted. And the chip is scalable that a larger range of two-dimensional scanning can be achieved when using more antennas for field-of-view splicing and cascading more optical switches.

MiR-148a deletion protects from bone loss in physiological and estrogen-deficient mice by targeting NRP1.

Bone metabolic homeostasis is largely dependent on the dynamic balance between osteoblasts and osteoclasts. MicroRNAs (miRNAs) play critical roles in regulating bone metabolism. In this study, we explored the role of a new miRNA (miR-148a) in osteoporosis. We compared the bone phenotype between miR-148a knockout (KO) mice and the wild-type (WT) littermates. We found miR-148a KO mice exhibited an increased bone mass phenotype and decreased osteoclastogenesis compared to the WT group. In vitro, miR-148a overexpression promoted osteoclastogenesis and bone resorption function. Mechanistically, NRP1 was identified as a novel direct target of miR-148a, and NRP1 silencing reversed the effect of miR-148a knockout. In OVX and calvarial osteolysis models, miR-148a KO protects mice against excessive bone resorption, while miR-148a agomiR/AAV-shNRP1 accelerates pathologic bone loss. Finally, the miR-148a level was found to be positively correlated with ß-CTX in postmenopausal osteoporosis (PMOP) serum specimens. In summary, our findings revealed that miR-148a genetic deletion ameliorates bone loss under physiological and pathological conditions by targeting NRP1. In osteoclast-related bone metabolic diseases such as PMOP, miR-148a may be an attractive therapeutic target in the future.

Adoption of large aperture chirped grating antennas in optical phase array for long distance ranging.

Optical phased array can be widely used in many fields benefiting from its superior performance. We designed and fabricated chirped grating antennas and uniform grating antennas for the optical phased array. The effective aperture of the chirped grating antennas is about twice that of the uniform grating antennas. The chirped grating optical phased array can receive the reflected signal of the object at a distance of 100 m, while the uniform grating optical phased array can only receive 50 m under the same conditions. Additionally, a ranging distance of 25 m is achieved when two chirped grating optical phased arrays are set as the transmitter and receiver.

Hybrid modeling of perovskite light-emitting diodes with nanostructured emissive layers.

Perovskite light-emitting diodes (PeLEDs) have attracted much attention due to their superior performance. When a bottleneck of energy conversion efficiency is achieved with materials engineering, nanostructure incorporation proves to be a feasible approach to further improve device efficiencies via light extraction enhancement. The finite-difference time-domain simulation is widely used for optical analysis of nanostructured optoelectronic devices, but reliable modeling of PeLEDs with nanostructured emissive layers remains unmet due to the difficulty of locating dipole light sources. Herein we established a hybrid process for modeling light emission behaviors of such nanostructured PeLEDs by calibrating light source distribution through electrical simulations. This hybrid modeling method serves as a universal tool for structure optimization of light-emitting diodes with nanostructured emissive layers.

Non-uniform optical phased array with a large steering angle and high side mode suppression ratio.

An optical phased array (OPA) is one of the most promising methods of light detection and ranging. A non-uniform array with different emitter distances is a method to realize OPA steering without grating lobes or a distance between two adjacent emitters larger than λ/2. However, the side mode suppression ratio (SMSR) will decrease as OPA turns into a large angle. In this paper, 64-, 128-, and 256-channel non-uniform OPAs are optimized by non-dominated sorting genetic algorithm-II (NSGA-II), which is a multi-objective optimization algorithm. Compared with arrays optimized by a genetic algorithm, the SMSR at 80° improves by 2.18, 2.61, and 2.56 dB, respectively.

SIS3 suppresses osteoclastogenesis and ameliorates bone loss in ovariectomized mice by modulating Nox4-dependent reactive oxygen species.

Osteoporosis is a metabolic disorder of reduced bone mass, accompanied by the deterioration of the bone microstructure, resulting in increased brittleness and easy fracture. Its pathogenesis can be explained by mainly excessive osteoclast formation or bone resorption hyperfunction. Oxidative stress is intricately linked with bone metabolism, and the maturation and bone resorption of osteoclasts respond to intracellular ROS levels. SIS3 is a small-molecule compound that selectively suppresses Smad3 phosphorylation in the TGF-ß/Smad signaling pathway and attenuates the ability to bind to target DNA. Several studies have reported that Smad3 plays a significant role in bone metabolism. However, whether SIS3 can modulate bone metabolism by affecting osteoclastogenesis and the specific molecular mechanisms involved remain unknown. Here, we demonstrated that SIS3 could suppress osteoclastogenesis and ameliorate bone loss in ovariectomized mice. Mechanistically, SIS3 inhibited Smad3 phosphorylation in BMMs, and the deficiency of phosphorylated Smad3 downregulated ROS production and Nox4-dependent expression during osteoclast formation, thereby blocking MAPK phosphorylation and the synthesis of downstream osteoclast marker proteins. Similarly, Nox4 plasmid transfection significantly alleviated osteoclast formation inhibited by SIS3. In addition, we identified the interaction region between Smad3 and Nox4 by ChIP and dual luciferase reporter assays. Collectively, we found that SIS3 could inhibit Smad3 phosphorylation, reduce Nox4-dependent ROS generation induced by RANKL, and prevent osteoclast differentiation and maturation, making it a promising alternative therapy for osteoporosis.

Azilsartan Suppresses Osteoclastogenesis and Ameliorates Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species Production and Activating Nrf2 Signaling.

Osteoporosis is characterized by a decrease in bone mass and destruction of the bone microarchitecture, and it commonly occurs in postmenopausal women and the elderly. Overactivation of osteoclasts caused by the inflammatory response or oxidative stress leads to osteoporosis. An increasing number of studies have suggested that intracellular reactive oxygen species (ROS) are strongly associated with osteoclastogenesis. As a novel angiotensin (Ang) II receptor blocker (ARB), azilsartan was reported to be associated with the inhibition of intracellular oxidative stress processes. However, the relationship between azilsartan and osteoclastogenesis is still unknown. In this study, we explored the effect of azilsartan on ovariectomy-induced osteoporosis in mice. Azilsartan significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, and Ctsk) in vitro. Furthermore, azilsartan reduced RANKL-induced ROS production by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, azilsartan inhibited the activation of MAPK/NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of azilsartan on MAPK/NF-κB signaling pathways. Consistent with the in vitro data, azilsartan administration ameliorated ovariectomy (OVX)-induced osteoporosis, and decreased ROS levels in vivo. In conclusion, azilsartan inhibited oxidative stress and may be a novel treatment strategy for osteoporosis caused by osteoclast overactivation.

Inclined emitting slotted single-mode laser with 1.7° vertical divergence angle for PIC applications.

In this Letter, a new type of single-mode slotted laser used for an on-chip light source in photonic integrated circuits is proposed. An inclined light beam with a low vertical divergence angle can be directly coupled into the surface grating of the silicon to form an integrated light source. Experimentally, a III-V laser with a 54.6° inclined angle and a vertical divergence angle of 1.7° is achieved by introducing a kind of specially distributed microstructure. The side mode suppression ratio is better than 45 dB, and the continuous wave output power reaches 6.5 mW at room temperature. We report the inclined emitting microstructured single-mode laser with a low divergence angle for the first time, to the best of our knowledge.

High-brightness single-mode double-tapered laser diodes with laterally coupled high-order surface grating.

Double-tapered laser diodes with 23rd order laterally coupled surface gratings are fabricated at 913 nm. A narrow ridge waveguide restricts the lateral mode number, and tapered waveguides are utilized to enhance the output power. The gratings defined on the sides of ridge waveguide filter not only the longitudinal modes but also the high-order lateral modes. Experimentally, continuous wave power of over 560 mW/facet is achieved. The lateral far-field pattern exhibits a single-lobe profile and narrow divergence, and the lowest divergence angle is only twice the diffraction-limited one. The measured side-mode suppression ratio is about 27 dB. This device has great potential for high-power single-mode near-diffraction-limited laser emission with easy fabrication.

High-brightness diode laser arrays integrated with a phase shifter designed for single-lobe far-field pattern.

High-brightness, edge-emitting diode laser arrays integrated with a phase shifter have been designed and fabricated at a wavelength of about 910 nm. Stable out-of-phase mode is generated through coupling evanescently and converted to be nearly in-phase by the phase modulation from the phase shifter. With a very simple manufacture process, stable single-lobe far-field pattern is achieved in the slow axis when the continuous wave output power exceeds 460 mW/facet, and the divergence angle is only 2.7 times the diffraction-limited value. Such device shows a promising future for high-brightness application with low cost and easy fabrication.

Hybrid III-V/silicon single-mode laser with periodic microstructures.

In this Letter, a III-V/silicon hybrid single-mode laser operating at C band for photonic integration circuit is presented. The InGaAlAs gain structure is bonded onto a patterned silicon-on insulator through wafer to wafer directly. The mode selected mechanism based on a hybrid III-V/silicon straight cavity with periodic microstructures is applied, which only need low cost i-line projection photolithography in the whole technological process. At room temperature, we obtain 0.62 mW output power in continuous-wave. The side mode suppression ratio of larger than 20 dB is obtained from experiments. [corrected].

A hybrid silicon single mode laser with a slotted feedback structure.

In this paper, a III-V/Silicon hybrid single mode laser operating at a long wavelength for photonic integration circuit is presented. The InGaAlAs gain structure is bonded onto a patterned silicon-on insulator wafer directly. The novel mode selected mechanism based on a slotted silicon waveguide is applied, which only need standard photolithography in the whole technological process. The side mode suppression ratio of larger than 20dB is obtained from experiments.

Ultracompact 1×4 TM-polarized beam splitter based on photonic crystal surface mode.

We provide an improved surface-mode photonic crystal (PhC) T-junction waveguide, combine it with an improved PhC bandgap T-junction waveguide, and then provide an ultracompact 1×4 TM-polarized beam splitter. The energy is split equally into the four output waveguides. The maximal transmission ratio of each output waveguide branch equals 24.7%, and the corresponding total transmission ratio of the ultracompact 1×4 beam splitter equals 98.8%. The normalized frequency of maximal transmission ratio is 0.397(2πc/a), and the bandwidth of the ultracompact 1×4 TM-polarized beam splitter is 0.0106(2πc/a). To the best of our knowledge, this is the first time such a high-efficiency 1×4 beam splitter exploiting the nonradiative surface mode as a guided mode has been proposed. Although we only employed a 1×4 beam splitter, our design can easily be extended to other 1×n beam splitters.

Chromatic dispersion and PMD monitoring and compensation techniques studies in optical communication systems with single channel speed 40Gbit/s and CSRZ format.

We study a whole compensation system for chromatic dispersion and polarization mode dispersion, including monitoring subsystems and compensation subsystems in optical communication systems with single channel speed 40Gbit/s and CSRZ format. We employed the spectral shift effect of a semiconductor optical amplifier for chromatic dispersion monitoring, and a non-linearly chirped fiber Bragg grating for chromatic dispersion compensation. The degree of polarization characterizes is used as feedback control signal of polarization mode dispersion monitoring, and a polarization controller and a polarization maintaining fiber are formed a polarization mode dispersion compensator. The transmission experiment demonstrates that the whole compensation system is effective. It is suit for chromatic dispersion management and polarization mode dispersion eliminating in optical communication systems with high single channel speed and CSRZ format.