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Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.

The clinical management of malignant tumours is challenging, often leading to severe adverse effects and death. Drug resistance (DR) antagonises the effectiveness of treatments, and increasing drug dosage can worsen the therapeutic index (TI). Current efforts to overcome DR predominantly involve the use of drug combinations, including applying multiple anti-cancerous drugs, employing drug sensitisers, which are chemical agents that enhance pharmacokinetics (PK), including the targeting of cellular pathways and regulating pertinent membrane transporters. While combining multiple compounds may lead to drug–drug interactions (DDI) or polypharmacy effect, the use of drug sensitisers permits rapid attainment of effective treatment dosages at the disease site to prevent early DR and minimise side effects and will reduce the chance of DDI as lower drug doses are required. This review highlights the essential use of TI in evaluating drug dosage for cancer treatment and discusses the lack of a unified standard for TI within the field. Commonly used benefit–risk assessment criteria are summarised, and the critical exploration of the current use of TI in the pharmaceutical industrial sector is included. Specifically, this review leads to the discussion of drug sensitisers to facilitate improved ratios of effective dose to toxic dose directly in humans. The combination of drug and sensitiser molecules might see additional benefits to rekindle those drugs that failed late-stage clinical trials by the removal of detrimental off-target activities through the use of lower drug doses. Drug combinations and employing drug sensitisers are potential means to combat DR. The evolution of drug combinations and polypharmacy on TI are reviewed. Notably, the novel binary weapon approach is introduced as a new opportunity to improve TI. This review emphasises the urgent need for a criterion to systematically evaluate drug safety and efficiency for practical implementation in the field.

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is the leading risk factor of disability in the elderly. Harmonizing the metabolic actions of bone-making cells and bone resorbing cells to the mineralized matrix network is required to maintain bone mass homeostasis. The tricarboxylic acid (TCA) cycle in mitochondria is a crucial process for cellular energy production and redox homeostasis. The canonical actions of TCA cycle enzymes and intermediates are indispensable in oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis for osteogenic differentiation and osteoclast formation. Knockout mouse models identify these enzymes’ roles in bone mass and microarchitecture. In the noncanonical processes, the metabolites as a co-factor or a substrate involve epigenetic modification, including histone acetyltransferases, DNA demethylases, RNA m6A demethylases, and histone demethylases, which affect genomic stability or chromatin accessibility for cell metabolism and bone formation and resorption. The genetic manipulation of these epigenetic regulators or TCA cycle intermediate supplementation compromises age, estrogen deficiency, or inflammation-induced bone mass loss and microstructure deterioration. This review sheds light on the metabolic functions of the TCA cycle in terms of bone integrity and highlights the crosstalk of the TCA cycle and redox and epigenetic pathways in skeletal tissue metabolism and the intermediates as treatment options for delaying osteoporosis.

A three-layer terahertz dual-function absorber with broadband absorption and narrowband absorption switching is proposed based on the special electrically tunable non-equilibrium optical response of graphene. Instead of using phase change materials, the structure uses patterned graphene in the top layer to achieve the switching effect. Patterned graphene consists of a cross and an external square frame. The relaxation time is adjusted by applying an electric field to the graphene to achieve broadband and narrowband switching. The structure can achieve broadband absorption when the relaxation time of graphene is 0.2 ps. From 1.27 to 2.16 THz, the absorbance of the structure can exceed 90%, and the average absorption rate can reach 96.88%. At 1.68–1.96 THz, the absorbance of the structure can even exceed 99%. When the relaxation time of graphene is 3 ps, the structure achieves narrowband absorption at 1.72 THz with a maximum absorption rate of 99%, achieving “perfect” absorption. Simultaneously, the proposed structure is highly symmetric, both modes are stable in the incidence angle range of 0–60°, and polarization insensitive. Once the absorber achieves broadband absorption, we control the chemical potential of graphene by adjusting the applied voltage to switch the absorption rate from 0% to 99%. Once the absorber achieves narrow-band absorption, we verify that the structure can be used as a sensor by changing the refractive index of the surrounding environment. Accordingly, we demonstrate that the absorber proposed in this study has potential applications in the fields of photoelectric switches, terahertz energy harvesting, and refractive index sensing.

Abstract Epigenome alteration in chondrocytes correlates with osteoarthritis (OA) development. H3K27me3 demethylase UTX regulates tissue homeostasis and deterioration, while its role was not yet studied in articulating joint tissue in situ. We now uncovered that increased UTX and H3K27me3 expression in articular chondrocytes positively correlated with human knee OA. Forced UTX expression upregulated the H3K27me3 enrichment at transcription factor Sox9 promoter, inhibiting key extracellular matrix molecules collagen II, aggrecan, and glycosaminoglycan in articular chondrocytes. Utx overexpression in knee joints aggravated the signs of OA, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss in mice. Chondrocyte-specific Utx knockout mice developed thicker articular cartilage than wild-type mice and showed few gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced joint injury. In vitro, Utx loss changed H3K27me3-binding epigenomic landscapes, which contributed to mitochondrial activity, cellular senescence, and cartilage development. Insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12 were, among others, functional target genes of Utx. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription but inhibited Eed and Suz12 expression. Igf2 blockade or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at Sox9 promoter, compromising Utx loss-induced extracellular matrix overproduction. Taken together, UTX repressed articular chondrocytic activity, accelerating cartilage loss during OA. Utx loss promoted cartilage integrity through epigenetic stimulation of mitochondrial biogenesis and Igf2 transcription. This study highlighted a novel noncanonical role of Utx, in concert with PRC2 core components, in controlling H3K27 trimethylation and articular chondrocyte anabolism and OA development.

This study developed a multiband metamaterial-absorbing device based on an array of gold nano-crosses for visible to near-infrared wavelengths. The proposed absorbing device is deposited on a silicon substrate and uses a metal–insulator–metal (MIM) classical structure. Numerical analyses were performed using the finite difference time domain (FDTD) method. The underlying physical mechanisms were analyzed on the basis of the structural parameters affecting the surface plasmon resonance field in the nanoarray structure. The calculations show that the proposed absorber achieves a five-band absorption in the visible to near-infrared region (700–3000 nm). After parameter adjustment and optimization, there were three absorption peaks with absorption of 99% or more and an average absorption value of 96.4% for the five peaks. Moreover, the array can be used as a biosensor to identify certain viruses, demonstrating its utility in label-free clinical sensing. In addition, the absorber is polarization- and incident-angle-insensitive. Therefore, this device exhibits considerable potential for designing ideal absorbers and nanosensors.

Passive daytime radiant cooling is the process of transferring excess heat to cold spaces. Conventional radiant-cooling devices are usually colored white or silver to achieve high reflectivity in the solar spectrum range; these devices are limited by the high cost of materials and the difficulty of their preparation. Herein, we present a color-tunable radiative cooler consisting of an Ag/SiO2/Ag layer reverse-vaporized on a high-emissivity polymer, namely, polyethylene terephthalate. Because of the materials’ optical properties and synergism, the radiative cooler exhibits a high selective emissivity of 85 % within an atmospheric transparency window. Outdoor experiments in Xiamen, Fujian Province, China showed that the prepared optical films can counter solar heating while achieving color and can realize cooling of up to 6.92 °C below the ambient temperature. This ability was demonstrated by calculating the net cooling power. In addition, the cooling performance of the developed device is better than that of commercial coatings in the same color family, making the use of these colored radiant coolers in the fields of architecture and electronics feasible.

ABSTRACT Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital‐based case–control study conducted in Taiwan with 693 HNC cases and 1,035 controls. A positive association was observed between seropositivity to HPV16 E7 and OPC risk, whereas no significant association was found in the non‐OPC cases. The increased OPC risk associated with seropositivity to HPV16 E7 was more significant among nonbetel quid or noncigarette users. Seropositivity to HPV16 E7 showed moderate agreement with P16 expression in OPC. OPC patients that were seropositive to HPV16 E7 or p16 positive were more highly educated and less likely to use alcohol, betel quids, and cigarettes compared to HPV16 E7 seronegative or p16 negative OPC patients. Furthermore, patients with p16 positive OPC were more likely to be women compared to patients with p16 negative OPC, likely owing to the low prevalence of alcohol, betel quid, and cigarette users among women. Overall, this study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan. With the declining consumption of betel quids and cigarettes in Taiwan, a higher percentage of OPC cases in Taiwan will be attributed to HPV in the future. Public health measures, including HPV vaccination, need to be implemented to prevent the occurrence of HPV‐positive OPC.

THz-time domain spectroscopy is an effective method of label-free molecular detection, but it is limited by the size of the measured samples. Traditional detection approaches will have to overcome challenges when the analyte are in trace amounts. Here, we propose an enhanced mechanism for terahertz molecular fingerprint sensing, involving an all-dielectric metasurface. Based on incident wave angle scanning under light polarization, the broadband light–matter interaction is effectively enhanced, significantly improving the fingerprint signal of the molecule to be detected. The results demonstrate a new method for trace molecular detection in the terahertz region and large-scale molecular screening.

The absorption and reflection of electromagnetic waves by various particles in the earth’s atmosphere allow the passage of only certain electromagnetic wavelengths to reach the ground, called Earth’s atmosphere transparent window. In this study, perfect absorption was theoretically obtained in the range of near- and mid-infrared earth’s atmospheric transparency window using a simple absorber with metal-dielectric-metal structure. The numerical simulations showed the average absorption to reach 96.2% at wavelengths from 2000 to 6000 nm. Also, the broadband absorption was noticed and attributed to combined physical mechanisms, such as anti-reflection effect, localized surface plasmon polariton, propagating surface plasmon polarization, Fabry–Pérot cavity and slow light mode. Meanwhile, the proposed absorber displayed simple-structure, low-cost, wide-angle, and polarization-independent. In sum, the proposed absorber might be useful for future applications related to atmospheric transparency window, such as remote sensing, energy harvesting, infrared detection, and stray light elimination.

In response to changing circumstances, how organizations actively promote organizational performance and member behavior, and enhance competitiveness have become important issues for enterprises. This research utilized the psychological ownership theory to study how organizational members’ organizational identity, organizational performance, and member behavior to fill the research gaps that organizational psychological ownership only explores at the individual level and extend previous research on its antecedents. Hierarchical linear modeling (HLM) analysis was conducted to test the cross-level hypotheses when organizational identity affects organizational psychological ownership. Participants were volunteers of the Republic of China army with a total of 160 group samples and 630 individual samples. The research resulted that organizational identity could affect organizational performance in team level and organizational psychological ownership in individual level. In the psychology process, organizational psychological ownership could mediate the relationship between work value and member behavior.

Electrodeposited hard magnetic thick films have vast applications in the microelectromechanical systems (MEMS). Yet the very large residual stresses (σr) built-up in monolayered thick magnetic films leads to cracks, dimensional changes and deteriorated magnetic properties. Here, we explored quantitatively magnetic properties of CoMnP/Cu multilayers tuned by σr, which in turn are varied by the inserted soft Cu interlayer and thickness of single CoMnP magnetic layers. The configuration of the multilayers is an alternating CoMnP/Cu on Cu-substrate. The thickness of Cu interlayer was 1.4 μm. We kept a sum of all magnetic layers in the multilayers at ∼20 μm to benchmark with a 19.4 μm monolayered CoMnP. The magnetic layers are 94 wt.% Co and possess highly textured (002) hexagonal close packed microstructures. We characterized the apparent crystallite stresses through sin2ψ method by X-ray diffractometer (XRD) and residual film stress by curvature method. The insertion of Cu interlayers effectively reduces σr by 23% through stacking with six single-layered CoMnP. The out-of-plane (OP) anisotropy is slightly reduced. While the maximum energy product in the in-plane (IP) direction can be significantly enhanced by 430% ∼ 690% with increasing the number of the CoMnP single layer in the multilayers. The magneto-elastic behaviors well explain the evolution of the total anisotropy energy of the mono- and multi-layers. By CoMnP/Cu configurations we successfully worked out a strategy to preserve prestigious OP performance while to enhance IP properties by 4 to 6 times to meet ever increasing challenges in MEMS applications.

We theoretically proposed an ultra-broadband infrared light absorber and demonstrated that a high absorption could be obtained in the range of ultra-broadband infrared light using the iron thin layers. The simulation results showed that the proposed absorber could achieve a close-to-unity absorption rate across a wide infrared spectral range, and that the average absorption rate would reach 90.6% over the range of 1.4-11.4μm. The high absorption rate resulted from the excitation of strong localized surface plasmon resonance in the iron layers and the superposition of different resonance frequencies. Numerical analysis results demonstrated that our proposed absorber had a broader efficient absorption range than most previously reported broadband infrared light absorbers.

An atmospheric window is greatly significant in the radiative cooling field. In this study, we preliminarily design a thermally tunable metamaterial emitter that can be used as an internal and external emission switch for a mid-infrared atmospheric window (3.5–5 and 8–14 μm). The proposed emitter has a multilayer metal–dielectric–metal micropyramid structure with thermochromic VO2 spacers. Its broadband emission and thermal tunability are due to the resonance of the hybridization of separate magnetic polaritons, surface plasmon polaritons, and the thermal phase-transition characteristics of VO2. The structure has a warming effect at the temperature below the phase-change temperature. On the contrary, it has a cooling effect at the temperature above the phase-change temperature. These phenomena show the emitter’s potential application in smart temperature control systems.

Abstract Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03‐1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41‐3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65‐1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.

We propose a biaxial hyperbolic metamaterials (HMMs) sawtooth absorber using anisotropic black phosphorus (BP) and demonstrate that it can achieve a topological transition from an elliptical dispersion to a hyperbolic dispersion. We also show the material to be an epsilon-near-zero HMM and validate an effective medium theory. Due to BP’s anisotropic permittivity and light confinement, our absorber achieves an average absorption of up to 93.4%, omnidirectionality (up to 70°), and polarization sensitivity from 30 to 90 μm. We gain physical insights about the high absorption using electric field distributions and absorbed power distribution. Unlike the physical mechanism of common multilayer metal/dielectric sawtooth absorbers, which is related to slow-light effect, the absorption of our proposed absorber is attributed to the localized surface plasmon resonance, plasmon polaritons. Our proposed HMM can be applied in the infrared to terahertz region and we conclude by providing practical guidelines for future research on biaxial hyperbolic metamaterials and anisotropic two-dimensional materials.

Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.

Ulcerative colitis (UC) is an inflammatory disease with chronic relapsing symptoms. This study investigated the effects of Lycium barbarum polysaccharides (LBP) and capsaicin (CAP) in dextran sulfate sodium (DSS)-induced UC rats. Rats were divided into normal, DSS-induced UC, and UC treated with 100 mg LBP/kg bw, 12 mg CAP/kg bw, or 50 mg LBP/kg bw and 6 mg CAP/kg bw. Rats were fed LBP or CAP orally by gavage for 4 weeks, and UC model was established by feeding 5% DSS in drinking water for 6 days during week 3. Oral CAP and mixture significantly reduced disease activity index. Oral LBP significantly decreased serum malondialdehyde, interleukin (IL)-6, colonic tumor necrosis factor (TNF)-α levels, and protein expression of transient receptor potential cation channel V1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), but increased serum catalase activity. Oral CAP significantly suppressed serum IL-6, colonic TRPV1 and TRPA1 protein expression, but elevated IL-10 levels, serum superoxide dismutase and catalase activities. The mixture of LBP and CAP significantly reduced serum IL-6, colonic TNF-α and TRPA1 protein. In conclusion, administration of LBP and/or CAP attenuate DSS-induced UC symptoms through inhibiting oxidative stress, proinflammatory cytokines, and protein expression of TRPV1 and TRPA1.

Abstract Background Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. Methods We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. Results After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Conclusions Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.

Senescent osteoblast overburden accelerates bone mass loss. Little is understood about microRNA control of oxidative stress and osteoblast senescence in osteoporosis. We revealed an association between microRNA-29a (miR-29a) loss, oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG), DNA hypermethylation marker 5-methylcystosine (5mC), and osteoblast senescence in human osteoporosis. miR-29a knockout mice showed low bone mass, sparse trabecular microstructure, and osteoblast senescence. miR-29a deletion exacerbated bone loss in old mice. Old miR-29a transgenic mice showed fewer osteoporosis signs, less 5mC, and less 8-OHdG formation than age-matched wild-type mice. miR-29a overexpression reversed age-induced senescence and osteogenesis loss in bone-marrow stromal cells. miR-29a promoted transcriptomic landscapes of redox reaction and forkhead box O (FoxO) pathways, preserving oxidation resistance protein-1 (Oxr1) and FoxO3 in old mice. In vitro, miR-29a interrupted DNA methyltransferase 3b (Dnmt3b)-mediated FoxO3 promoter methylation and senescence-associated β-galactosidase activity in aged osteoblasts. Dnmt3b inhibitor 5′-azacytosine, antioxidant N-acetylcysteine, or Oxr1 recombinant protein attenuated loss in miR-29a and FoxO3 to mitigate oxidative stress, senescence, and mineralization matrix underproduction. Taken together, miR-29a promotes Oxr1, compromising oxidative stress and FoxO3 loss to delay osteoblast aging and bone loss. This study sheds light on a new antioxidation mechanism by which miR-29a protects against osteoblast aging and highlights the remedial effects of miR-29a on osteoporosis.

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.

Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

Abstract Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.

Abstract Background Although substantial evidence supports a 20–30% risk reduction of colon cancer, breast cancer, and endometrial cancer by physical activity (PA), the evidence for head and neck cancer (HNC) is limited. Three published studies on the association between PA and HNC have generated inconsistent results. The current study examined the association between recreational PA (RPA) and HNC risk with a more detailed assessment on the intensity, frequency, duration, and total years of RPA. Methods Data on RPA were collected from 623 HNC cases and 731 controls by in-person interview using a standardized questionnaire. The association between RPA and HNC risk was assessed using unconditional logistic regression, adjusted for sex, age, educational level, use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits. Results A significant inverse association between RPA and HNC risk was observed in a logistic regression model that adjusted for sex, age, and education (odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.51-0.82). However, after further adjustment for the use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits, RPA was no longer associated with HNC risk (OR =0.97, 95% CI: 0.73-1.28). No significant inverse association between RPA and HNC risk was observed in the analysis stratified by HNC sites or by the use of alcohol, betel quid, or cigarette. Conclusion Results from our study did not support an inverse association between RPA and HNC risk. The major focus of HNC prevention should be on cessation of cigarette smoking and betel chewing, reduction of alcohol drinking, and promotion of healthy diet that contains plenty of fruits and vegetables.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability, as well as the leading monogenic cause of autism spectrum disorders (ASD), in which neurons show aberrant dendritic spine structure. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Targets of FMRP, CLSTN1, and ICAM5, play critical roles in the maturation of dendritic spines, synapse formation and synaptic plasticity. However, the implication of CLSTN1 and ICAM5 in dendritic spine abnormalities and the underlying neuropathologic processes in FXS remain uninvestigated. In this study, we demonstrated that CLSTN1 co-localizes and co-transports with ICAM5 in cultured cortical neurons. Also we showed that shRNA-mediated downregulation of CLSTN1 in cultured WT neurons increases ICAM5 on the surface of synaptic membrane, subsequently affecting the maturation of dendritic spines. Whereas, normalization of CLSTN1 level in Fmr1 KO neurons reduces ICAM5 abundance and rescues impaired dendritic spine phenotypes. Most importantly, CLSTN1 protein is reduced in the postnatal medial prefrontal cortex of Fmr1 KO mice, which is correlated with increased ICAM5 levels on the surface of synapses and excessive filopodia-like spines. In conclusion, this study demonstrates that CLSTN1 plays a critical role in dendritic spine formation and maturation in FXS by regulating ICAM5 redistribution.

Compromised autophagy and mitochondrial dysfunction downregulate chondrocytic activity, accelerating the development of osteoarthritis (OA). Irisin, a cleaved form of fibronectin type III domain containing 5 (FNDC5), regulates bone turnover and muscle homeostasis. Little is known about the effect of Irisin on chondrocytes and the development of osteoarthritis. This study revealed that human osteoarthritic articular chondrocytes express decreased level of FNDC5 and autophagosome marker LC3-II but upregulated levels of oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) and apoptosis. Intra-articular administration of Irisin further alleviated symptoms of medial meniscus destabilization, like cartilage erosion and synovitis, while improved the gait profiles of the injured legs. Irisin treatment upregulated autophagy, 8-OHdG and apoptosis in chondrocytes of the injured cartilage. In vitro, Irisin improved IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production by chondrocytes. Irisin also reversed Sirt3 and UCP-1 pathways, thereby improving mitochondrial membrane potential, ATP production, and catalase to attenuated IL-1β-mediated reactive oxygen radical production, mitochondrial fusion, mitophagy, and autophagosome formation. Taken together, FNDC5 loss in chondrocytes is correlated with human knee OA. Irisin repressed inflammation-mediated oxidative stress and extracellular matrix underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. Our analyses shed new light on the chondroprotective actions of this myokine, and highlight the remedial effects of Irisin on OA development.

Bone turnover is sophisticatedly balanced by a dynamic coupling of bone formation and resorption at various rates. The orchestration of this continuous remodeling of the skeleton further affects other skeletal tissues through organ crosstalk. Chronic excessive bone resorption compromises bone mass and its porous microstructure as well as proper biomechanics. This accelerates the development of osteoporotic disorders, a leading cause of skeletal degeneration-associated disability and premature death. Bone-forming cells play important roles in maintaining bone deposit and osteoclastic resorption. A poor organelle machinery, such as mitochondrial dysfunction, endoplasmic reticulum stress, and defective autophagy, etc., dysregulates growth factor secretion, mineralization matrix production, or osteoclast-regulatory capacity in osteoblastic cells. A plethora of epigenetic pathways regulate bone formation, skeletal integrity, and the development of osteoporosis. MicroRNAs inhibit protein translation by binding the 3′-untranslated region of mRNAs or promote translation through post-transcriptional pathways. DNA methylation and post-translational modification of histones alter the chromatin structure, hindering histone enrichment in promoter regions. MicroRNA-processing enzymes and DNA as well as histone modification enzymes catalyze these modifying reactions. Gain and loss of these epigenetic modifiers in bone-forming cells affect their epigenetic landscapes, influencing bone homeostasis, microarchitectural integrity, and osteoporotic changes. This article conveys productive insights into biological roles of DNA methylation, microRNA, and histone modification and highlights their interactions during skeletal development and bone loss under physiological and pathological conditions.

Glucocorticoid provokes bone mass loss and fatty marrow, accelerating osteoporosis development. Bromodomain protein BRD4, an acetyl–histone-binding chromatin reader, regulates stem cell and tissue homeostasis. We uncovered that glucocorticoid inhibited acetyl Lys-9 at the histone 3 (H3K9ac)-binding Runx2 promoter and decreased osteogenic differentiation, whereas bromodomain protein 4 (BRD4) and adipocyte formation were upregulated in bone-marrow mesenchymal progenitor cells. BRD4 knockdown improved H3K9ac occupation at the Runx2 promoter and osteogenesis, but attenuated glucocorticoid-mediated adipocyte formation together with the unaffected H3K9ac-binding PPARγ2 promoter. BRD4 regulated epigenome related to fatty acid metabolism and the forkhead box P1 (Foxp1) pathway, which occupied the PPARγ2 promoter to modulate glucocorticoid-induced adipocytic activity. In vivo, BRD4 inhibitor JQ-1 treatment mitigated methylprednisolone-induced suppression of bone mass, trabecular microstructure, mineral acquisition, and osteogenic differentiation. Foxp1 signaling, marrow fat, and adipocyte formation in glucocorticoid-treated skeleton were reversed upon JQ-1 treatment. Taken together, glucocorticoid-induced H3K9 hypoacetylation augmented BRD4 action to Foxp1, which steered mesenchymal progenitor cells toward adipocytes at the cost of osteogenic differentiation in osteoporotic skeletons. BRD4 inhibition slowed bone mass loss and marrow adiposity. Collective investigations convey a new epigenetic insight into acetyl histone reader BRD4 control of osteogenesis and adipogenesis in skeleton, and highlight the remedial effects of the BRD4 inhibitor on glucocorticoid-induced osteoporosis.

We reported that the photonic crystal fiber (PCF) filled with TI:Bi2Te3 nanosheets solution could act as an effective saturable absorber (SA). Employing this TI-PCF SA device; we constructed an ytterbium-doped all-fiber laser oscillator and achieved the evanescent wave mode-locking operation. Due to the large cavity dispersion; the fundamental mode-locking pulse had the large full width at half maximum (FWHM) of 2.33 ns with the repetition rate of ~1.11 MHz; and the radio frequency (RF) spectrum with signal-to-noise ratio (SNR) of 61 dB. In addition; the transition dynamics from a bunched state of pulses to harmonic mode-locking (HML) was also observed; which was up to 26th order.

Ischemic damage aggravation of femoral head collapse is a prominent pathologic feature of osteonecrosis of the femoral head (ONFH). In this regard, S100 calcium binding protein A9 (S100A9) is known to deteriorate joint integrity, however, little is understood about which role S100A9 may play in ONFH. In this study, a proteomics analysis has revealed a decrease in the serum S100A9 level in patients with ONFH upon hyperbaric oxygen therapy. Serum S100A9 levels, along with serum vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), and tartrate-resistant acid phosphatase 5b levels were increased in patients with ONFH, whereas serum osteocalcin levels were decreased as compared to healthy controls. Serum S100A9 levels were increased with the Ficat and Arlet stages of ONFH and correlated with the patients with a history of being on glucocorticoid medication and alcohol consumption. Osteonecrotic tissue showed hypovasculature histopathology together with weak immunostaining for vessel marker CD31 and von Willrbrand factor (vWF) as compared to femoral head fracture specimens. Thrombosed vessels, fibrotic tissue, osteocytes, and inflammatory cells displayed strong S100A9 immunoreactivity in osteonecrotic lesion. In vitro, ONFH serum and S100A9 inhibited the tube formation of vessel endothelial cells and vessel outgrowth of rat aortic rings, whereas the antibody blockade of S100A9 improved angiogenic activities. Taken together, increased S100A9 levels are relevant to the development of ONFH. S100A9 appears to provoke avascular damage, ultimately accelerating femoral head deterioration through reducing angiogenesis. This study provides insight into the molecular mechanism underlying the development of ONFH. Here, analysis also highlights that serum S100A9 is a sensitive biochemical indicator of ONFH.

Rotator cuff lesion with shoulder stiffness is a major cause of shoulder pain and motionlessness. Subacromial bursa fibrosis is a prominent pathological feature of the shoulder disorder. MicroRNA-29a (miR-29a) regulates fibrosis in various tissues; however, the miR-29a action to subacromial bursa fibrosis remains elusive. Here, we reveal that subacromial synovium in patients with rotator cuff tear with shoulder stiffness showed severe fibrosis, hypertrophy, and hyperangiogenesis histopathology along with significant increases in fibrotic matrices collagen (COL) 1A1, 3A1, and 4A1 and inflammatory cytokines, whereas miR-29a expression was downregulated. Supraspinatus and infraspinatus tenotomy-injured shoulders in transgenic mice overexpressing miR-29a showed mild swelling, vascularization, fibrosis, and regular gait profiles as compared to severe rotator cuff damage in wild-type mice. Treatment with miR-29a precursor compromised COL3A1 production and hypervascularization in injured shoulders. In vitro, gain of miR-29a function attenuated COL3A1 expression through binding to the 3’-untranslated region (3′-UTR) of COL3A1 in inflamed tenocytes, whereas silencing miR-29a increased the matrix expression. Taken together, miR-29a loss is correlated with subacromial bursa inflammation and fibrosis in rotator cuff tear with shoulder stiffness. miR-29a repressed subacromial bursa fibrosis through directly targeting COL3A1 mRNA, improving rotator cuff integrity and shoulder function. Collective analysis offers a new insight into the molecular mechanism underlying rotator cuff tear with shoulder stiffness. This study also highlights the remedial potential of miR-29a precursor for alleviating the shoulder disorder.

Glucocorticoid excess escalates osteoclastic resorption, accelerating bone mass loss and microarchitecture damage, which ramps up osteoporosis development. MicroRNA-29a (miR-29a) regulates osteoblast and chondrocyte function; however, the action of miR-29a to osteoclastic activity in the glucocorticoid-induced osteoporotic bone remains elusive. In this study, we showed that transgenic mice overexpressing an miR-29a precursor driven by phosphoglycerate kinase exhibited a minor response to glucocorticoid-mediated bone mineral density loss, cortical bone porosity and overproduction of serum resorption markers C-teleopeptide of type I collagen and tartrate-resistant acid phosphatase 5b levels. miR-29a overexpression compromised trabecular bone erosion and excessive osteoclast number histopathology in glucocorticoid-treated skeletal tissue. Ex vivo, the glucocorticoid-provoked osteoblast formation and osteoclastogenic markers (NFATc1, MMP9, V-ATPase, carbonic anhydrase II and cathepsin K) along with F-actin ring development and pit formation of primary bone-marrow macrophages were downregulated in miR-29a transgenic mice. Mechanistically, tumor necrosis factor superfamily member 13b (TNFSF13b) participated in the glucocorticoid-induced osteoclast formation. miR-29a decreased the suppressor of cytokine signaling 2 (SOCS2) enrichment in the TNFSF13b promoter and downregulated the cytokine production. In vitro, forced miR-29a expression and SOCS2 knockdown attenuated the glucocorticoid-induced TNFSF13b expression in osteoblasts. miR-29a wards off glucocorticoid-mediated excessive bone resorption by repressing the TNFSF13b modulation of osteoclastic activity. This study sheds new light onto the immune-regulatory actions of miR-29a protection against glucocorticoid-mediated osteoporosis.

Augmented reality (AR) is an emerging technology that allows users to interact with simulated environments, including those emulating scenes in the real world. Most current AR technologies involve the placement of virtual objects within these scenes. However, difficulties in modeling real-world objects greatly limit the scope of the simulation, and thus the depth of the user experience. In this study, we developed a process by which to realize virtual environments that are based entirely on scenes in the real world. In modeling the real world, the proposed scheme divides scenes into discrete objects, which are then replaced with virtual objects. This enables users to interact in and with virtual environments without limitations. An RGB-D camera is used in conjunction with simultaneous localization and mapping (SLAM) to obtain the movement trajectory of the user and derive information related to the real environment. In modeling the environment, graph-based segmentation is used to segment point clouds and perform object segmentation to enable the subsequent replacement of objects with equivalent virtual entities. Superquadrics are used to derive shape parameters and location information from the segmentation results in order to ensure that the scale of the virtual objects matches the original objects in the real world. Only after the objects have been replaced with their virtual counterparts in the real environment converted into a virtual scene. Experiments involving the emulation of real-world locations demonstrated the feasibility of the proposed rendering scheme. A rock-climbing application scenario is finally presented to illustrate the potential use of the proposed system in AR applications.

Fucoxanthin is a carotenoid with many pharmaceutical properties that is found in brown seaweed. However, the effects of fucoxanthin on corneal innervation and intense eye pain have not been extensively examined. To clarify the protective roles and underlying mechanisms of fucoxanthin on ocular lesions, we investigated the beneficial effects and mechanisms by which fucoxanthin ameliorates ultraviolet B (UVB)-induced corneal denervation and trigeminal pain. Treatment with fucoxanthin enhanced the expression of nuclear factor erythroid 2-related factor 2 in the cornea. Inhibition of typical denervation and epithelial exfoliation in the cornea were observed in rats treated with fucoxanthin following UVB-induced nerve disorders. Moreover, the active phosphorylated form of p38 MAP kinase (pp38) and the number of glial fibrillary acidic protein (GFAP)-positive neural cells were significantly reduced. Decreased expression of neuron-selective transient receptor potential vanilloid type 1 (TRPV1) in the trigeminal ganglia neurons was also demonstrated in rats treated with fucoxanthin after UVB-induced keratitis. Symptoms of inflammatory pain, including difficulty in opening the eyes and eye wipe behaviour, were also reduced in fucoxanthin-treated groups. Pre-treatment with fucoxanthin may protect the eyes from denervation and inhibit trigeminal pain in UVB-induced photokeratitis models.

OBJECTIVES:Although betel quid (BQ) is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature regarding the dose-response, BQ types, HNC sites, and BQ cessation. The current study was conducted to fill these insufficiencies. MATERIALS AND METHODS:A hospital-based case-control study was conducted to evaluate the association between BQ and HNC. In-person interview was conducted to collect data on BQ chewing. The current analysis included 487 men newly diagnosed with HNC and 617 male controls who were frequency-matched to the cases by age. The association between BQ and HNC was assessed using multivariable unconditional logistic regression. RESULTS:Ever BQ chewing was associated with an increased HNC risk regardless of the BQ types. A non-linear positive association between BQ and HNC was observed, with a steep rise in HNC risk for the first 5 pack-years or 200,000 minutes of BQ consumption. Every year of BQ cessation was associated with a 2.9% reduction in HNC risk; however, the risk did not reduce to the level of non-BQ chewers even after 20 years of BQ cessation. Eliminating BQ chewing may prevent 51.6% of HNCs, 62.6% of oral cancers, and 41.3% of pharyngeal cancers in Taiwan. CONCLUSION:Our results supported the positive association between BQ and HNC. BQ cessation is effective in reducing HNC risk and should be encouraged. Because BQ cessation may not reduce the HNC risk to the level of non-BQ chewers, it is important to prevent the initiation of BQ chewing.

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