CHMP5 attenuates osteoarthritis via inhibiting chondrocyte apoptosis and extracellular matrix degradation: involvement of NF-κB pathway.

BACKGROUND: Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear. METHODS: In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1ß) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1ß-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays. RESULTS: Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway. CONCLUSIONS: This study demonstrated that CHMP5 repressed IL-1ß-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.

A Critical Review on Recent Progress of Solution-Processed Monolayer Assembly of Nanomaterials and Applications.

The rapid development in nanotechnology has necessitated accurate and efficient assembly strategies for nanomaterials. Monolayer assembly of nanomaterials (MAN) represents a challenging and important architecture to manufacture and is critical in understanding interactions among nanomaterials, solvents, and substrates. MAN enables highly tunable performance in electronic and photonic devices. This review summarizes the recent progress on the methods to achieve MAN and discusses important control factors. Moreover, the importance of MAN is elaborated by a broad range of applications in electronics and photonics. In the end, the opportunities as well as challenges in manufacturing and new applications are outlooked.

MSRB2 Ameliorates H2O2-induced Chondrocyte Oxidative Stress and Suppresses Apoptosis in Osteoarthritis.

BACKGROUND: Chondrocyte oxidative stress and apoptosis are critical factors contributing to the pathogenesis of osteoarthritis (OA). Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cells from oxidative stress and is involved in apoptosis. This study aimed to investigated the expression of MSRB2 in articular cartilage tissues and elucidated its effect on H2O2-stimulated chondrocytes. METHODS: Human chondrocytes were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12. MSRB2 overexpression in chondrocytes was achieved by transfecting with an MSRB2 overexpression plasmid. Western blot, quantitative RT-PCR, Immunofluorescence staining, and TUNEL assay were employed in this study. RESULTS: MSRB2 expression was found to be reduced in OA patients. Furthermore, overexpression of MSRB2 in H2O2-induced chondrocytes mitigated apoptosis and enhanced cell viability. Elevated MSRB2 expression diminished chondrocyte ROS contents, decreased cytochrome C (Cyc) in the cytoplasm, and regulated mitochondrial membrane potential to maintain mitochondrial homeostasis. Interestingly, knockdown of charged multivesicular body protein 5 (CHMP5) led to a decreased inMSRB2 expression in chondrocytes. Additionally, protein levels of CHMP5 and MSRB2 were reduced in H2O2-stimulated chondrocytes, and silencing CHMP5 reduced MSRB2 expression. Knockdown of CHMP5 increased cleaved caspase-3 expression in H2O2-induced chondrocytes and elevated TUNEL-positive chondrocytes. CONCLUSION: MSRB2 decreased in OA, and overexpression of MSRB2 alleviated oxidative stress and apoptosis of chondrocyte.

BASP1 knockdown suppresses chondrocyte apoptosis and extracellular matrix degradation in vivo and in vitro: A possible therapeutic approach for osteoarthritis.

Osteoarthritis(OA) is an age-related degenerative disease involving chondrocyte apoptosis and extracellular matrix(ECM) degradation.Brain acid soluble protein 1(BASP1) has been reported to induce apoptosis.Thus, we speculated that BASP1 might regulate OA progression by inducing apoptosis, which is also the purpose of this study.The cartilage of the knee joint was collected from OA patients who received the joint replacement.In OA cartilage tissue,we found BASP1 expression was highly expressed, which inferred that BASP1 might be involved in OA.To validate our hypothesis, destabilization of the medial meniscus (DMM) surgery-induced male C57BL/6mice and interleukin-1ß (IL-1ß)-treated human chondrocytes were used to mimic the OA environment.BASP1 knockdown in mice and chondrocytes was achieved by adenovirus carried with BASP1-specific shRNA.High expression of BASP1 was observed in OA mice, which was also verified in IL-1ß-treated chondrocytes.The potential mechanism of BASP1 in OA was further explored in vitro.BASP1 knockdown alleviated IL-1ß-induced apoptosis and ECM degradation, as reflected by the decreased number of apoptotic cells and matrix metalloproteases 13 expression,and the increased collagen II expression.Our findings indicated that BASP1 knockdown alleviated OA progression by inhibiting apoptosis and ECM degradation, suggesting that inhibiting BASP1 may be a potentially applicable method for preventing OA.

Transition from Diffusive to Superdiffusive Transport in Carbon Nanotube Networks via Nematic Order Control.

The one-dimensional confinement of quasiparticles in individual carbon nanotubes (CNTs) leads to extremely anisotropic electronic and optical properties. In a macroscopic ensemble of randomly oriented CNTs, this anisotropy disappears together with other properties that make them attractive for certain device applications. The question however remains if not only anisotropy but also other types of behaviors are suppressed by disorder. Here, we compare the dynamics of quasiparticles under strong electric fields in aligned and random CNT networks using a combination of terahertz emission and photocurrent experiments and out-of-equilibrium numerical simulations. We find that the degree of alignment strongly influences the excited quasiparticles' dynamics, rerouting the thermalization pathways. This is, in particular, evidenced in the high-energy, high-momentum electronic population (probed through the formation of low energy excitons via exciton impact ionization) and the transport regime evolving from diffusive to superdiffusive.

Effects of interlayer reflection and interpixel interaction in diffractive optical neural networks.

Multilayer diffractive optical neural networks (DONNs) can perform machine learning (ML) tasks at the speed of light with low energy consumption. Decreasing the number of diffractive layers can reduce inevitable material and diffraction losses to improve system performance, and incorporating compact devices can reduce the system footprint. However, current analytical DONN models cannot accurately describe such physical systems. Here we show the ever-ignored effects of interlayer reflection and interpixel interaction on the deployment performance of DONNs through full-wave electromagnetic simulations and terahertz (THz) experiments. We demonstrate that the drop of handwritten digit classification accuracy due to reflection is negligible with conventional low-index THz polymer materials, while it can be substantial with high-index materials. We further show that one- and few-layer DONN systems can achieve high classification accuracy, but there is a trade-off between accuracy and model-system matching rate because of the fast-varying spatial distribution of optical responses in diffractive masks. Deep DONNs can break down such a trade-off because of reduced mask spatial complexity. Our results suggest that new accurate and trainable DONN models are needed to advance the development and deployment of compact DONN systems for sophisticated ML tasks.

Phonon-Assisted Intertube Electronic Transport in an Armchair Carbon Nanotube Film.

The electrical conductivity of a macroscopic assembly of nanomaterials is determined through a complex interplay of electronic transport within and between constituent nano-objects. Phonons play dual roles in this situation: their increased populations tend to reduce the conductivity via electron scattering, while they can boost the conductivity by assisting electrons to propagate through the potential-energy landscape. We identified a phonon-assisted coherent electron transport process between neighboring nanotubes in temperature-dependent conductivity measurements on a macroscopic film of armchair single-wall carbon nanotubes. Through atomistic modeling of electronic states and calculations of both electronic and phonon-assisted junction conductances, we conclude that phonon-assisted conductance is the dominant mechanism for observed high-temperature transport in armchair carbon nanotubes. The unambiguous manifestation of coherent intertube dynamics proves a single-chirality armchair nanotube film to be a unique macroscopic solid-state ensemble of nano-objects promising for the development of room-temperature coherent electronic devices.

SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-κB signaling pathway in osteoarthritis.

Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-ß signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1ß)-induced chondrocytes. The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1ß-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1ß-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.

Graphene plasmonic spatial light modulator for reconfigurable diffractive optical neural networks.

Terahertz (THz) diffractive optical neural networks (DONNs) highlight a new route toward intelligent THz imaging, where the image capture and classification happen simultaneously. However, the state-of-the-art implementation mostly relies on passive components and thus the functionalities are limited. The reconfigurability can be achieved through spatial light modulators (SLMs), while it is not clear what device specifications are required and how challenging the associated device implementation is. Here, we show that a complex-valued modulation with a π/2 phase modulation in an active reflective graphene-plasmonics-based SLM can be employed for realizing the reconfigurability in THz DONNs. By coupling the plasmonic resonance in graphene nanoribbons with the reflected Fabry-Pérot (F-P) mode from a back reflector, we achieve a minor amplitude modulation of large reflection and a substantial π/2 phase modulation. Furthermore, the constructed reconfigurable reflective THz DONNs consisting of designed SLMs demonstrate >94.0% validation accuracy of the MNIST dataset. The results suggest that the relaxation of requirements on the specifications of SLMs should significantly simplify and enable varieties of SLM designs for versatile DONN functionalities.

Bioinformatics-based study to identify immune infiltration and inflammatory-related hub genes as biomarkers for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose principal pathological change is aggressive chronic synovial inflammation; however, the specific etiology and pathogenesis have not been fully elucidated. We downloaded the synovial tissue gene expression profiles of four human knees from the Gene Expression Omnibus database, analyzed the differentially expressed genes in the normal and RA groups, and assessed their enrichment in functions and pathways using bioinformatics methods and the STRING online database to establish protein-protein interaction networks. Cytoscape software was used to obtain 10 hub genes; receiver operating characteristic (ROC) curves were calculated for each hub gene and differential expression analysis of the two groups of hub genes. The CIBERSORT algorithm was used to impute immune infiltration. We identified the signaling pathways that play important roles in RA and 10 hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. The diagnostic value of these 10 hub genes for RA was confirmed using ROC curves and expression analysis. Adcy2, Cxcl13, and Ccr5 are strongly associated with RA development. The study also revealed that the differential infiltration profile of different inflammatory immune cells in the synovial tissue of RA is an extremely critical factor in RA progression. This study may contribute to the understanding of signaling pathways and biological processes associated with RA and the role of inflammatory immune infiltration in the pathogenesis of RA. In addition, this study shows that Adcy2, Cxcl13, and Ccr5 have the potential to be biomarkers for RA treatment.

Groove-Assisted Global Spontaneous Alignment of Carbon Nanotubes in Vacuum Filtration.

Ever since the discovery of carbon nanotubes (CNTs), it has long been a challenging goal to create macroscopically ordered assemblies, or crystals, of CNTs that preserve the one-dimensional quantum properties of individual CNTs on a macroscopic scale. Recently, a simple and well-controlled method was reported for producing wafer-scale crystalline films of highly aligned and densely packed CNTs through spontaneous global alignment that occurs during vacuum filtration (Nat. Nanotechnol. 2016, 11, 633). However, a full understanding of the mechanism of such global alignment has not been achieved. Here, we report results of a series of systematic experiments that demonstrate that the CNT alignment direction can be controlled by the surface morphology of the filter membrane used in the vacuum filtration process. More specifically, we found that the direction of parallel grooves pre-existing on the surface of the filter membrane dictates the direction of the resulting CNT alignment. Furthermore, we intentionally imprinted periodically spaced parallel grooves on a filter membrane using a diffraction grating, which successfully defined the direction of the global alignment of CNTs in a precise and reproducible manner. These results are promising not only for developing novel devices based on macroscopically aligned CNTs but also for understanding the microscopic physical mechanism of the alignment process.

Terahertz Excitonics in Carbon Nanotubes: Exciton Autoionization and Multiplication.

Excitons play major roles in optical processes in modern semiconductors, such as single-wall carbon nanotubes (CNTs), transition metal dichalcogenides, and 2D perovskite quantum wells. They possess extremely large binding energies (>100 meV), dominating absorption and emission spectra even at high temperatures. The large binding energies imply that they are stable, that is, hard to ionize, rendering them seemingly unsuited for optoelectronic devices that require mobile charge carriers, especially terahertz emitters and solar cells. Here, we have conducted terahertz emission and photocurrent studies on films of aligned single-chirality semiconducting CNTs and find that excitons autoionize, i.e., spontaneously dissociate into electrons and holes. This process naturally occurs ultrafast (<1 ps) while conserving energy and momentum. The created carriers can then be accelerated to emit a burst of terahertz radiation when a dc bias is applied, with promising efficiency in comparison to standard GaAs-based emitters. Furthermore, at high bias, the accelerated carriers acquire high enough kinetic energy to create secondary excitons through impact exciton generation, again in a fully energy and momentum conserving fashion. This exciton multiplication process leads to a nonlinear photocurrent increase as a function of bias. Our theoretical simulations based on nonequilibrium Boltzmann transport equations, taking into account all possible scattering pathways and a realistic band structure, reproduce all of our experimental data semiquantitatively. These results not only elucidate the momentum-dependent ultrafast dynamics of excitons and carriers in CNTs but also suggest promising routes toward terahertz excitonics despite the orders-of-magnitude mismatch between the exciton binding energies and the terahertz photon energies.

Observation of Photoinduced Terahertz Gain in GaAs Quantum Wells: Evidence for Radiative Two-Exciton-to-Biexciton Scattering.

We have observed photoinduced negative optical conductivity, or gain, in the terahertz frequency range in a GaAs multiple-quantum-well structure in a strong perpendicular magnetic field at low temperatures. The gain is narrow band: it appears as a sharp peak (linewidth <0.45 meV) whose frequency shifts with applied magnetic field. The gain has a circular-polarization selection rule: a strong line is observed for hole-cyclotron-resonance-active polarization. Furthermore, the gain appears only when the exciton 1s state is populated, which rules out intraexcitonic transitions to be its origin. Based on these observations, we propose a possible process in which the stimulated emission of a terahertz photon occurs while two free excitons scatter into one biexciton in an energy and angular-momentum conserving manner.

Solving the Thermoelectric Trade-Off Problem with Metallic Carbon Nanotubes.

Semiconductors are generally considered far superior to metals as thermoelectric materials because of their much larger Seebeck coefficients (S). However, a maximum value of S in a semiconductor is normally accompanied by a minuscule electrical conductivity (σ), and hence, the thermoelectric power factor (P = S2σ) remains small. An attempt to increase σ by increasing the Fermi energy (EF), on the other hand, decreases S. This trade-off between S and σ is a well-known dilemma in developing high-performance thermoelectric devices based on semiconductors. Here, we show that the use of metallic carbon nanotubes (CNTs) with tunable EF solves this long-standing problem, demonstrating a higher thermoelectric performance than semiconducting CNTs. We studied the EF dependence of S, σ, and P in a series of CNT films with systematically varied metallic CNT contents. In purely metallic CNT films, both S and σ monotonically increased with EF, continuously boosting P while increasing EF. Particularly, in an aligned metallic CNT film, the maximum of P was ∼5 times larger than that in the highest-purity (>99%) single-chirality semiconducting CNT film. We attribute these superior thermoelectric properties of metallic CNTs to the simultaneously enhanced S and σ of one-dimensional conduction electrons near the first van Hove singularity.

A case-control study and meta-analysis reveal the association between COX-2 G-765C polymorphism and primary end-stage hip and knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a popular arthrosis featured as pain, limited joint activity, and deformity. Cyclooxygenase-2 (COX-2) has been reported to be up-regulated in arthritic tissues and is integral to the progression of osteoarthritis (OA). Previous studies showed the COX-2 promoter G-765C polymorphism could influence COX-2 expression. However, the relationship between the variant and OA risk is contrasting. METHODS: We conducted a case-control study with 196 primary end-stage hip and knee OA cases and 196 controls in a Chinese Han population. Subsequently, we integrated this case-control study in a meta-analysis to acquire greater statistical power. The results from our case-control study using MassARRAY genotyping technology and binary logistic regression statistical methods. RESULTS: The variant carriers in the Chinese Han population had a lower primary end-stage hip and knee OA susceptibility (C vs G: OR = 0.350, 95%CI: 0.154-0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI: 0.118-0.676, P = .005). Stratification studies indicated that a higher GC frequency in women decreased not only knee OA susceptibility but also unilateral knee OA risk. The meta-analysis showed that the variant exhibited a significantly decreased OA risk through comparisons involving allelic, homozygous, heterozygous, and dominant models. CONCLUSION: Our findings suggest that the COX-2 G-765C polymorphism exerts a protective effect against primary end-stage knee osteoarthritis in a female Chinese Han population.

Ultra-compact tunable silicon nanobeam cavity with an energy-efficient graphene micro-heater.

We propose and experimentally demonstrate an ultra-compact silicon photonic crystal nanobeam (PCN) cavity with an energy-efficient graphene micro-heater. Owing to the PCN cavity with an ultra-small optical mode volume of 0.145 µm3, the light-matter interaction is greatly enhanced and the thermo-optic (TO) tuning efficiency is increased. The TO tuning efficiency is measured to be as high as 1.5 nm/mW, which can be further increased to 3.75 nm/mW based on numerical simulations with an optimized structure. The time constants with a rise time constant of τrise = 1.11 µs and a fall time constant of τfall = 1.47 µs are obtained in the experiment.

Stability of High-Density Two-Dimensional Excitons against a Mott Transition in High Magnetic Fields Probed by Coherent Terahertz Spectroscopy.

We have performed time-resolved terahertz absorption measurements on photoexcited electron-hole pairs in undoped GaAs quantum wells in magnetic fields. We probed both unbound- and bound-carrier responses via cyclotron resonance and intraexciton resonance, respectively. The stability of excitons, monitored as the pair density was systematically increased, was found to dramatically increase with increasing magnetic field. Specifically, the 1s-2p_{-} intraexciton transition at 9 T persisted up to the highest density, whereas the 1s-2p feature at 0 T was quickly replaced by a free-carrier Drude response. Interestingly, at 9 T, the 1s-2p_{-} peak was replaced by free-hole cyclotron resonance at high temperatures, indicating that 2D magnetoexcitons do dissociate under thermal excitation, even though they are stable against a density-driven Mott transition.

3D Band Diagram and Photoexcitation of 2D-3D Semiconductor Heterojunctions.

The emergence of a rich variety of two-dimensional (2D) layered semiconductor materials has enabled the creation of atomically thin heterojunction devices. Junctions between atomically thin 2D layers and 3D bulk semiconductors can lead to junctions that are fundamentally electronically different from the covalently bonded conventional semiconductor junctions. Here we propose a new 3D band diagram for the heterojunction formed between n-type monolayer MoS2 and p-type Si, in which the conduction and valence band-edges of the MoS2 monolayer are drawn for both stacked and in-plane directions. This new band diagram helps visualize the flow of charge carriers inside the device in a 3D manner. Our detailed wavelength-dependent photocurrent measurements fully support the diagrams and unambiguously show that the band alignment is type I for this 2D-3D heterojunction. Photogenerated electron-hole pairs in the atomically thin monolayer are separated and driven by an external bias and control the "on/off" states of the junction photodetector device. Two photoresponse regimes with fast and slow relaxation are also revealed in time-resolved photocurrent measurements, suggesting the important role played by charge trap states.

An Atomically Layered InSe Avalanche Photodetector.

Atomically thin photodetectors based on 2D materials have attracted great interest due to their potential as highly energy-efficient integrated devices. However, photoinduced carrier generation in these media is relatively poor due to low optical absorption, limiting device performance. Current methods for overcoming this problem, such as reducing contact resistances or back gating, tend to increase dark current and suffer slow response times. Here, we realize the avalanche effect in a 2D material-based photodetector and show that avalanche multiplication can greatly enhance the device response of an ultrathin InSe-based photodetector. This is achieved by exploiting the large Schottky barrier formed between InSe and Al electrodes, enabling the application of a large bias voltage. Plasmonic enhancement of the photosensitivity, achieved by patterning arrays of Al nanodisks onto the InSe layer, further improves device efficiency. With an external quantum efficiency approaching 866%, a dark current in the picoamp range, and a fast response time of 87 µs, this atomic layer device exhibits multiple significant advances in overall performance for this class of devices.

Broadband photodetection in a microfiber-graphene device.

We propose and experimentally demonstrate a microfiber-graphene device. Owing to the interaction between the graphene film and the evanescent field leaked from the microfiber, the hybrid photoconductive device exhibits a high photoresponse. A maximum photocurrent responsivity of ~2.81 mA/W is achieved in the telecommunication band. A nearly flat photoresponse spectrum within broad operational band ranging from 1500 nm to 1600 nm is also obtained as a consequence of the dispersionless and flat absorption of graphene. These results show that the proposed photocurrent generation device could provide an effective solution for broadband photodetection.