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With the advent of semiconductor spintronics, spin-polarized electron–hole plasmas could occur in semiconductors, leading to spin-dependent many-body effects. To understand these many-body effects, spin-dependent bandgap renormalization (BGR) often needs to be calculated quantitatively, which requires to know the fractional contribution of electrons (k) to the total BGR induced by the electron–hole plasma. However, the measurement of the k value is challenging because BGR is usually submerged or partially offset by the strong band-filling effect. Facing this challenge, we develop a new experimental technique which could measure spin-dependent many-body effects without the influence from the band-filling effect. The presented technique is employed in intrinsic bulk GaAs, with a dynamic model developed to extract the k value from the measured data. It is found that the k value in bulk GaAs increases with increasing concentration of the photoinjected electron–hole plasma but is consistently much less than the reported value in GaAs quantum wells. These results reveal obviously different many-body interactions in bulk GaAs and its quantum wells. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) rapidly spreads worldwide and causes more suffering. The relation about the aggravation of inguinal pain and COVID-19 was unclear in patients with total hip arthroplasty (THA). This study aimed to evaluate the risk of groin pain aggravation in short-term THA patients after COVID-19. Methods: Between 2020 and 2022, 129 patients with THA who were affected COVID-19 were enrolled. A short-standardized questionnaire was administered during follow-up to inquire about the aggravation of groin ache before and after SARS-COV-2 affection. Furthermore, we evaluated the potential association between the presence of increased pain and various factors, including age, gender, body mass index, diagnosis, and length of hospital stay. Results: The case-crossover study revealed an increased risk of inguinal soreness aggravation when comparing 8 weeks after COVID-19 with 12 weeks before COVID-19 (Relative risk [RR], 9.5; 95% Confidence intervals [CI], 2.259–39.954). For COVID-19 positive patients, multivariate analysis showed length of stay was an independent factor significantly associated with increased risk of aggravation of groin pain (Odds ratio [OR], 1.26; 95%CI, 1.03–1.55, p = 0.027). Conclusion: This study confirms the association between COVID-19 and the exacerbation of soreness in the groin region in THA patients and extended length of stay is a possible contributing factor. This study expands the current literature by investigating the risk of aggravation of inguinal pain in patients with THA after COVID-19, providing valuable insights into postoperative outcomes in this specific population. Trial registration This retrospective study was approved by the Institutional Review Board of Shanghai general hospital (No.2023-264). [ABSTRACT FROM AUTHOR]

Abstract Vasoactive intestinal peptide receptor 1 (VIPR1) is observed to express differently in human malignancies. Here, we aim to reveal clinical significance and transcriptional regulation mechanism of VIPR1 in hepatocellular carcinoma (HCC). Using immunohistochemistry, pyrosequencing, quantitative real-time PCR (qPCR), decitabine (DAC)/4-phenylbutyricacid (PBA) treatment and chromatin immunoprecipitation (ChIP), we found the low expression of VIPR1 was correlated with poor histological differentiation and poor survival. The promoter region of VIPR1 was methylated and DNA methylation inhibited VIPR1 gene transcription. Deacetylation of H3K27 in the promoter of VIPR1 inhibited the transcription of VIPR1 in HCC. In conclusion, low expression of VIPR1 had an adverse prognostic impact on HCC, and such expression is at least partially mediated by epigenetic modification. Highlights • Low expression of VIPR1 was correlated with poor survival in HCC patients. • The frequency of genetic alteration in VIPR1 is very low in HCC. • DNA methylation inhibited VIPR1 transcription. • H3K27 deacetylation inhibited the transcription of VIPR1. [ABSTRACT FROM AUTHOR]

In this work, the indentation-induced incipient plasticity of Ni 3 Al crystal is investigated by performing molecular dynamics (MD) simulations. Simulation results reveal that the incipient plasticity of Ni 3 Al is originated from the homogeneous nucleation of the 1/6〈1 1 2〉-type Shockley partial dislocation. The critical load, critical contact pressure, dislocation nucleation site and active slip system are significantly affected by crystallographic orientation, model size, indenter radius and temperature. The choice of interatomic potential has significant implications for the indentation behavior of Ni 3 Al. Some benchmarks for evaluating the credibility of interatomic potentials are presented. The pop-in phenomena are correlated with dislocation generation, multiplication and reactions. The formation mechanisms of complex stacking faults (CSFs), antiphase boundaries (APBs) and superlattice intrinsic stacking faults (SISFs) are clarified. The highest indentation modulus is obtained in (1 1 1) indentation followed by the (1 1 0) and (1 0 0) cases. The indentation modulus and the depth of nucleation sites increase with increasing indenter radius but the maximum shear stress decreases. The maximum shear stress and indentation modulus decrease linearly with increasing temperature, reflecting the stress-assisted and thermally activated nature of dislocation nucleation. [ABSTRACT FROM AUTHOR]

• Few-layer NiTe 2 nanosheets are prepared by combining the convenient chemical synthesis and liquid phase exfoliation. • Two-dimensional semi-metallic NiTe 2 exhibits saturable absorption properties, which has been seldom reported. • Er-doped and Tm-doped mode-locked fiber lasers are realized using NiTe 2 -based tapered fiber saturable absorber, respectively. Two-dimensional transition metal dichalcogenides (TMDs) have been widely used in ultrafast optics. However, the traditional TMDs such as MoS 2 and WS 2 have narrow operating band and slow carrier recovery time, limiting their practical application. Among various kinds of TMDs, nickel ditelluride (NiTe 2) is a special type-II Dirac semi-metallic TMD material developed recently, showing great potential in ultrafast pulse generation due to its broadband optical response, ultrafast carrier recovery time, strong light-matter interaction and high chemical stability. Nevertheless, there has been no research reported on the NiTe 2 based saturable absorber (SA) and its application in the mode-locked laser at the 1.5 and 2 μm regions. In this work, few-layer NiTe 2 nanosheets were prepared and SA device was further fabricated by depositing them on a tapered fiber. The saturable absorption property of NiTe 2 SA was confirmed by using a balanced twin-detector measurement system. With the use of NiTe 2 SA, the Er-doped mode-locked fiber laser with a central wavelength of 1567.3 nm and a pulse width of 1.07 ps was achieved. Moreover, the Tm-doped mode-locked fiber laser with a central wavelength of 1966.08 nm was also obtained based on the NiTe 2 SA. These results show that NiTe 2 is a promising SA material for ultrafast pulse laser. [ABSTRACT FROM AUTHOR]

• Two-dimensional PdTe 2 is a novel saturable absorption material which has been rarely reported. • Few-layer PdTe 2 nanosheets are prepared by the simple and effective ultrasonic liquid exfoliation method. • Yb-doped mode-locked fiber laser with a pulse width of 887.2 ps is realized using PdTe 2 /PVA as the saturable absorber. In this work, two-dimensional few-layer palladium ditelluride (PdTe 2) nanosheets are produced by the simple and effective ultrasonic liquid exfoliation method and used as novel saturable absorber in an Yb-doped mode-locked fiber laser. The results show that the prepared flexible PdTe 2 /PVA composite film has a modulation of 3.7% and a saturation intensity of 77.6 MW/cm2. The obtained Yb-doped mode-locked fiber laser based on the film shows a pulse width of 887.2 ps with a repetition and central wavelength of 8.921 MHz and 1069 nm, respectively. So far, there has been few reports on PdTe 2 as saturable absorbers to realize mode-locked fiber lasers. The results suggest that two-dimensional PdTe 2 has great potential applications in nonlinear optics and ultrafast photonics. [ABSTRACT FROM AUTHOR]

In this paper, we propose a genetic algorithm based design procedure for a radial-basis function neural network. A Hierarchical Rank Density Genetic Algorithm (HRDGA) is used to evolve the neural network's topology and parameters simultaneously. Compared with traditional genetic algorithm based designs for neural networks, the hierarchical approach addresses several deficiencies highlighted in literature. In addition, the rank-density based fitness assignment technique is used to optimize the performance and topology of the evolved neural network to deal with the confliction between the training performance and network complexity. Instead of producing a single optimal solution, HRDGA provides a set of near-optimal neural networks to the designers so that they can have more flexibility for the final decision-making based on certain preferences. In terms of searching for a near-complete set of candidate networks with high performances, the networks designed by the proposed algorithm prove to be competitive, or even superior, to three other traditional radial-basis function networks for predicting Mackey–Glass chaotic time series. [ABSTRACT FROM AUTHOR]

In this paper, we propose a genetic algorithm based design procedure for a multi-layer feed-forward neural network. A hierarchical genetic algorithm is used to evolve both the neural network's topology and weighting parameters. Compared with traditional genetic algorithm based designs for neural networks, the hierarchical approach addresses several deficiencies, including a feasibility check highlighted in literature. A multi-objective cost function is used herein to optimize the performance and topology of the evolved neural network simultaneously. In the prediction of Mackey-Glass chaotic time series, the networks designed by the proposed approach prove to be competitive, or even superior, to traditional learning algorithms for the multi-layer Perceptron networks and radial-basis function networks. Based upon the chosen cost function, a linear weight combination decision-making approach has been applied to derive an approximated Pareto-optimal solution set. Therefore, designing a set of neural networks can be considered as solving a two-objective optimization problem. [ABSTRACT FROM AUTHOR]

Lenticular printing is widely used for outdoor advertisements, giant posters, and stage backgrounds. Current lenticular printing technology has a number of limitations, including a small number of viewpoints, serious crosstalk among viewpoints, and weak stereoscopic perception. In this study, we developed low-crosstalk super multi-view lenticular printing using triplet lenticular lens. Based on the super multi-view vision principle and the optical transmission characteristics of the cylindrical lens, the optical formula of the lenticular lens were derived. The viewing distance is 6 m, the viewing zone length is 3 m, and the number of viewpoints is 59. According to the above viewing requirements, the parameters of the lenticular lens were designed, including the radius of the curvature, and the thickness and the pitch. The light intensity distributions of 59 viewpoints in the viewing zone were simulated using optical software (Zemax and LightTools). The viewpoint width is 50 mm, which is less than a normal adults' pupillary distance. Triplet cylindrical lenses were arranged in a circular arc to reduce crosstalk among viewpoints; the crosstalk of 59 viewpoints is from 3.9% to 4.8%. Finally, simulation results were verified experimentally. The results show that super multi-view lenticular printing can meet the requirements of auto-stereoscopic perception. [ABSTRACT FROM AUTHOR]

The phase diagrams of continuous binary nanoalloys are important in providing guidance for material designs and industrial applications. However, experimental determination of the nano-phase diagram is scarce since calorimetric measurements remain quite challenging at the nanoscale. Based on the size-dependent cohesive energy model, we developed a unified nano-thermodynamic model to investigate the effects of the size, shape, and segregation on the phase diagrams of continuous binary nanoalloys. The liquidus/solidus dropped in temperature, two-phase zone was narrowed, and the degree of surface segregation decreased with decrease in the size or increase in the shape factor. The congruent melting point of Cu-Au nanoalloys with and without segregation is linearly shifted to higher Au component and lower temperature with decreasing size or increasing shape factor. By reviewing surface segregated element of different binary nanoalloys, two segregation rules based on the solid surface energy and atomic size have been identified. Moreover, the established model can be employed to describe other physicochemical properties of nanoalloys, e.g. the cohesive energy, catalytic activation energy, and order-disorder transition temperature, and the validity is supported by available other theoretical prediction, experimental data and molecular dynamic simulations results. This will help the experimentalists by guiding them in their attempts to design bimetallic nanocrystals with the desired properties. [ABSTRACT FROM AUTHOR]

With structural miniaturization down to the nanoscale, the detectable parameters of materials no longer remain constant but become tunable. For GaN nanocrystals example, the band gap increases while the dielectric constant, Young's modulus and melting temperature decrease with decreasing the solid size. Herein, we developed the models to describe the size and shape dependences of these seemingly uncorrelated parameters for GaN nanocrystals, based on our established thermodynamic model for cohesive energy of metallic nanocrystals. Consistency between our theoretical predictions and the corresponding experimental or simulated results confirms the accuracy of the developed models and indicates the essentiality of cohesive energy in describing the effects of size and shape on the physicochemical properties of different low-dimensional systems. [ABSTRACT FROM AUTHOR]

Transition metal-free half-metallicity recently has been the subject of intense research activity due to its potential in spintronics application. By employing density functional theory calculations, we revealed that F-intercalated GaN bilayers exhibit robust p orbital-based half-metallicity against the intercalant concentration and biaxial strain of −10% to 10%. The stable half-metallicity results from a spontaneous phase transition through Stoner instability and can be attributed to unusually high density of states near the Fermi level due to the quasi-flat bands. These findings provide a strategy to design transition-metal free half-metallic materials for futuristic spintronic applications. [ABSTRACT FROM AUTHOR]

Although the vapor-liquid-solid growth of semiconductor nanowire is a non-equilibrium process, the equilibrium phase diagram of binary alloy provides important guidance on the growth conditions, such as the temperature and the equilibrium composition of the alloy. Given the small dimensions of the alloy seeds and the nanowires, the known phase diagram of bulk binary alloy cannot be expected to accurately predict the behavior of the nanowire growth. Here, we developed a unified model to describe the size- and dimensionality-dependent equilibrium phase diagram of Au-Ge binary eutectic nanoalloys based on the size-dependent cohesive energy model. It is found that the liquidus curves reduce and shift leftward with decreasing size and dimensionality. Moreover, the effects of size and dimensionality on the eutectic composition are small and negligible when both components in binary eutectic alloys have the same dimensionality. However, when two components have different dimensionality (e.g. Au nanoparticle-Ge nanowire usually used in the semiconductor nanowires growth), the eutectic composition reduces with decreasing size. [ABSTRACT FROM AUTHOR]

Objectives: To quantify intra-tumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) from computed tomography (CT) images. Methods: We developed a quantitative ITH measurement—ITHscore—by integrating local radiomic features and global pixel distribution patterns. The associations of ITHscore with tumor phenotypes, genotypes, and patient's prognosis were examined on six patient cohorts (n = 1399) to validate its effectiveness in characterizing ITH. Results: For stage I NSCLC, ITHscore was consistent with tumor progression from stage IA1 to IA3 (p < 0.001) and captured key pathological change in terms of malignancy (p < 0.001). ITHscore distinguished the presence of lymphovascular invasion (p = 0.003) and pleural invasion (p = 0.001) in tumors. ITHscore also separated patient groups with different overall survival (p = 0.004) and disease-free survival conditions (p = 0.005). Radiogenomic analysis showed that the level of ITHscore in stage I and stage II NSCLC is correlated with heterogeneity-related pathways. In addition, ITHscore was proved to be a stable measurement and can be applied to ITH quantification in head-and-neck cancer (HNC). Conclusions: ITH in NSCLC can be quantified from CT images by ITHscore, which is an indicator for tumor phenotypes and patient's prognosis. Key Points: • ITHscore provides a radiomic quantification of intra-tumor heterogeneity in NSCLC. • ITHscore is an indicator for tumor phenotypes and patient's prognosis. • ITHscore has the potential to be generalized to other cancer types such as HNC. [ABSTRACT FROM AUTHOR]

• Novel hybrid self-supervised visual representation learning method tailored for H&E-stained histopathological images. • Generative and discriminative self-supervised learning can complement and enhance each other. • Good rationality by leveraging domain-specific knowledge in histopathology. • Good versatility for different kinds of computational histopathology tasks. Visual representation extraction is a fundamental problem in the field of computational histopathology. Considering the powerful representation capacity of deep learning and the scarcity of annotations, self-supervised learning has emerged as a promising approach to extract effective visual representations from unlabeled histopathological images. Although a few self-supervised learning methods have been specifically proposed for histopathological images, most of them suffer from certain defects that may hurt the versatility or representation capacity. In this work, we propose CS-CO, a hybrid self-supervised visual representation learning method tailored for H&E-stained histopathological images, which integrates advantages of both generative and discriminative approaches. The proposed method consists of two self-supervised learning stages: cross-stain prediction (CS) and contrastive learning (CO). In addition, a novel data augmentation approach named stain vector perturbation is specifically proposed to facilitate contrastive learning. Our CS-CO makes good use of domain-specific knowledge and requires no side information, which means good rationality and versatility. We evaluate and analyze the proposed CS-CO on three H&E-stained histopathological image datasets with downstream tasks of patch-level tissue classification and slide-level cancer prognosis and subtyping. Experimental results demonstrate the effectiveness and robustness of the proposed CS-CO on common computational histopathology tasks. Furthermore, we also conduct ablation studies and prove that cross-staining prediction and contrastive learning in our CS-CO can complement and enhance each other. Our code is made available at https://github.com/easonyang1996/CS-CO. [ABSTRACT FROM AUTHOR]

Mn-doped La(Fe,Si) 13 compounds have been demonstrated as excellent candidates for magnetic refrigeration applications. However, the origins of Mn-dependent magnetic properties are still unclear. Here, by employing density functional theory calculations and Monte Carlo simulations, the changes in magnetic moment, total magnetic exchange coupling constant J total , atomic local environment, and Curie temperature T C of Mn-doped La(Fe,Si) 13 compounds were investigated. Mn atoms were found to prefer 96i sites and anti-parallelly couple with Fe atoms. The reduction of total magnetic moments during Mn substitution originates from the decreasing magnetic moments of Fe and anti-ferromagnetic coupling between Mn and Fe. Moreover, Mn dopants lead to the decrease in J total and T C , and the analysis of atomic local environment indicates that the weakening of J total can be mainly attributed to the shrinkage of the intra-icosahedral bond between Fe-I and Fe-II. This work offers a theoretical comprehension of the fundamental magnetic properties of Mn-doped La(Fe,Si) 13 compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert -butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 μg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage. • PTP is an isoquinoline alkaloid with anti-inflammatory and antioxidant properties. • PTP significantly ameliorated chondrocyte inflammation and ferroptosis. • Repression of chondrocyte ferroptosis was mediated by activating the Nrf2 pathway. • PTP exerts these effects on chondrocytes to protect the articular cartilage. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn't been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods: LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA. [ABSTRACT FROM AUTHOR]

The rapid decline of Arctic sea ice has been reminding us the significant impacts caused by global warming. However, the other side of the coin is that this opens a window to utilize the Arctic sea routes in the summer seasons, bringing remarkable economic benefits for ocean transportation between Asia and Europe. However, commercial vessels with low ice classes must tackle substantial environmental challenges in the Arctic sea routes, particularly those caused by variable sea ice, even in the melting seasons. Therefore, the science-based support for shipping safety in the Arctic sea routes is being given more prominence. Emerging satellite remote sensing technology plays a critical role in environmental monitoring in the Arctic. This paper reviews state-of-the-art satellite observations on monitoring sea ice and potential applications on supporting shipping activities in the Arctic Ocean. Moreover, we introduced a recently developed system based on satellite observations to support the safe transportation of Chinese cargo vessels in the Arctic northern sea route, demonstrating the efforts by both the science and business communities to promote the development of the polar silk road. [ABSTRACT FROM AUTHOR]

Objectives: Aseptic loosening (AL) is the most common reason of total hip arthroplasty (THA) failure and revision surgery. Osteolysis, caused by wear particles released from implant surfaces, has a vital role in AL. Although previous studies suggest that wear particles always lead to osteoblast programmed death in the process of AL, the specific mechanism remains incompletely understood and osteoblast ferroptosis maybe a new mechanism of AL. Materials and Methods: CoCrMo nanoparticles (CoNPs) were prepared to investigate the influence of ferroptosis in osteoblasts and calvaria resorption animal models. Periprosthetic osteolytic bone tissue was collected from patients who underwent AL after THA to verify osteoblast ferroptosis. Results: Our study demonstrated that CoNPs induced significant ferroptosis in osteoblasts and particles induced osteolysis (PIO) animal models. Blocking ferroptosis with specific inhibitor Ferrostatin‐1 dramatically reduced particle‐induced ferroptosis in vitro. Moreover, in osteoblasts, CoNPs significantly downregulated the expression of Nrf2 (nuclear factor erythroid 2‐related factor 2), a core element in the antioxidant response. The overexpression of Nrf2 by siKeap1 or Nrf2 activator Oltipraz obviously upregulated antioxidant response elements (AREs) and suppressed ferroptosis in osteoblasts. Furthermore, in PIO animal models, the combined utilization of Ferrostatin‐1 and Oltipraz dramatically ameliorated ferroptosis and the severity of osteolysis. Conclusions: These results indicate that CoNPs promote osteoblast ferroptosis by regulating the Nrf2‐ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the shape evolution and thermal stability of Ag nanoparticles (NPs) on spherical SiO2 substrates were investigated by means of in situ transmission electron microscopy (TEM) imaging and differential scanning calorimetry (DSC). The initial Ag NPs at room temperature were semispherical-like, with an average size of 9nm in half-height width, well-dispersed on spherical SiO2 substrates. No obvious shape change was observed when the semispherical NPs of Ag were heated at temperature lower than 550°C. The shape of the semispherical Ag NPs changed gradually into a spherical one in the temperature range of 550–700°C, where surface diffusion and surface premelting took place. When the heating temperature was increased up to 750°C, the spherical Ag NPs were found to desquamate from the substrates due to the decreases of the contact area and the binding force between Ag NPs and SiO2 substrates. A possible mechanism for the desquamation of Ag NPs from the SiO2 sphere surface is proposed according to the results of in situ TEM observation and DSC analysis. [Copyright &y& Elsevier]

Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1β, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1β-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-ɑ. Furthermore, we revealed that LDC067 inhibited IL-1β-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA. • CDK9 is upregulated in osteoarthritis cartilage and is correlated with the severity of OA. • The specific inhibitor of CDK9, LDC067 attenuates the catabolism and hypertrophic changes of chondrocytes in vitro. • LDC067 suppresses the activation of the NF-κB signaling pathway. • LDC067 ameliorates OA cartilage destruction in vivo and may be a novel therapeutic agent. [ABSTRACT FROM AUTHOR]

Macrophytes are of key importance to the structure and ecological services of shallow lakes and are sensitive to anthropogenic and natural perturbations. Ongoing eutrophication and hydrological regime change affect macrophytes through changes in water transparency and water level, which lead to a dramatic decrease in bottom light availability. Here an integrated dataset (2005–2021) of multiple environmental factors is used to demonstrate the driving forces and recovery potential of the macrophyte decline in East Taihu Lake by using a critical indicator, which is the ratio of the Secchi disk depth to the water depth (SD/WD). The macrophyte distribution area showed a remarkable decrease from 136.1 ± 9.7 km2 (2005–2014) to 66.1 ± 6.5 km2 (2015–2021). The macrophyte coverage in the lake and in the buffer zone decreased by 51.4% and 82.8%, respectively. The structural equation model and correlation analysis showed that the distribution and coverage of macrophytes decreased with the decrease in the SD/WD over time. Moreover, an extensive hydrological regime change, which caused a sharp decrease in SD and an increase in the water level, is likely to be the driving force that brought about the decline of macrophytes in this lake. The proposed recovery potential model shows that the SD/WD has been low in recent years (2015–2021), and that this SD/WD cannot ensure the growth of submerged macrophytes and is unlikely to ensure the growth of floating-leaved macrophytes, especially in the buffer zone. The approach developed in the present study provides a basis for the assessment of macrophyte recovery potential and the management of ecosystems in shallow lakes that suffer from macrophyte loss. [Display omitted] • Macrophyte dynamics and environmental changes were studied in East Taihu Lake. • Decline in macrophytes was the result of sharp decrease in the SD/WD. • The SD/WD was mainly controlled by hydrological regime changes. • We develop the first conceptual model to assess macrophyte recovery potential. [ABSTRACT FROM AUTHOR]

Abstract Farm ponds, which are sometimes numerous and widely distributed in agricultural regions, have faced widespread degradation in recent decades. Although conservation strategies for these biodiversity hotspots have gradually increased, appropriate approaches for developing country contexts are lacking. Farm ponds provided hydrologic, biogeochemical, and socioeconomic benefits to southern China for thousands of years, but they are facing contemporary threats and management challenges, including (1) inadequate planning in terms of construction and conservation regulations; (2) rural nonpoint source and mini-point source pollution; (3) climate change induced abnormalities in the hydroperiod and disturbance to wildlife; (4) invasive species; and (5) inadequate social and political capacity to consider ecological conservation. Because farm ponds function as wetland complexes that are embedded within or integral to larger ecosystems, their conservation requires collaborative efforts over scales ranging from within-pond to regional. We highlight approaches that build public awareness and involve inventory maps as a basis. Policies that integrate top-down regulation and bottom-up engagement and emphasize sustainable management and utilization are recommended to ensure the effectiveness and continuous improvement of conservation programs. Techniques that involve interconnected smart sensors, volunteering and citizen science, and integrated process-based modeling are preferred when conducting comprehensive descriptions of the pond landscape, numerical assessments on their ecosystem services, and associated conservation cost analyses. Nature-based solutions are increasingly recognized as an important opportunity for coping with water-related crises. This paper presents the first synthetic perspective on the ecological roles of farm ponds in agriculturally dominated developing countries. The analytical framework and conservation suggestions are referential to sustainable rural development and the management of other small, scattered wetlands. Graphical abstract Unlabelled Image Highlights • Farm ponds are small, scattered wetlands with a long history in southern China. • They provided hydrologic, biogeochemical, biodiversity and socioeconomic functions. • Their ever-increasing degradation threats and management challenges are evaluated. • Policies and approaches are presented to form a collaborative conservation framework. • It is a first synthetic analysis of ponds' ecological roles in developing countries. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anti-inflammatory effectiveness of celecoxib and its effect on the rehabilitation of joint function after total knee arthroplasty.Methods: 72 patients presented between 2016 and 2017 and were divided into two groups. The experimental group was given 200 mg celecoxib twice daily with tramadol hydrochloride 50 mg twice daily (as required); the control group was given tramadol hydrochloride 50 mg twice daily for 6 weeks from the first day after total knee arthroplasty. Skin temperature around the knee was measured 1 day before surgery, on postoperative days 1 and 3, and at weeks 1, 2, and 6. Inflammatory markers (white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6) were measured preoperatively, on postoperative day 3, and at weeks 1 and 6. Knee Society Score was recorded preoperatively and at postoperative weeks 1, 2, and 6.Results: Except for preoperative skin temperature, the recorded skin temperatures of the experimental group were significantly different compared to those of the control group (p = 0.001, 0.024, 0.030, 0.041, 0.047, respectively). Levels of C-reactive protein were significantly different at the 1st and the 6th week after surgery, differing by 19.3 ± 4.64 mg/L (p < 0.001) and 2.6 ± 0.92 mg/L (p = 0.006). Levels of interleukin-6 showed a significant difference of 6.61 ± 2.36 pg/mL (p = 0.007) at the 1st week after surgery. Until the 6th week after surgery, the erythrocyte sedimentation rate in the experimental group and the control group differed by 17 ± 4.6 mm/h (p = 0.001).Conclusions: Celecoxib has a significant inhibitory effect on postoperative aseptic inflammation. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) has traditionally been defined as a non-inflammatory disease. Recently, many studies have demonstrated that OA also has an inflammatory component. BRD4, a member of the Bromodomain and Extra-Terminal Domain family, has emerged as an important regulator of some chronic inflammatory diseases. JQ1, an antagonist of BRD4, modulates transcription of several genes. Our study demonstrated that BRD4 is up-regulated in articular cartilage of OA. BRD4 inhibition attenuated the inflammation and catabolism of chondrocytes and suppressed NF-κB signalling pathway activation. In addition, BRD4 inhibition abolished the transcriptional activity of High Mobility Group Protein B1 (HMGB1). We identified HMGB1 as a direct target of BRD4. Genetic and pharmacological inhibition of BRD4 suppressed IL-1β-induced expression and translocation of HMGB1. Chromatin immunoprecipitation (ChIP) showed the enrichment of BRD4 around the HMGB1 upstream non-promoter region, which diminished with JQ1 treatment. Finally, haematoxylin & eosin and Safranin o/Fast Green staining demonstrated that JQ1 attenuates cartilage destruction in mice with anterior cruciate ligament transection without significant toxic effects. These studies highlighted the importance of BRD4 in the chronic inflammatory reactions of OA, which, as far as we know, was the first report of this finding, and suggested that BRD4 might be a novel potential therapeutic target for the treatment of OA. [ABSTRACT FROM AUTHOR]

The off-flavor compound 2-methylisoborneol (2-MIB) is generally associated with the proliferation and metabolism of filamentous cyanobacteria in shallow freshwater ecosystems. Here field monitoring in East Taihu Lake from July to October 2021, along with cultural experiments, was conducted to determine the impact of submerged macrophytes on the growth and 2-MIB production of filamentous cyanobacteria. Pseudanabaena sp. was identified as the 2-MIB producer with the highest detection rate (100%) and correlation coefficient (R =0.68, p < 0.001). The 2-MIB concentration and algal growth in the macrophyte-dominated zones were markedly decreased compared with those in the phytoplankton-dominated zone. Five submerged macrophytes classified into flat-leaf type (Vallisneria natans and Potamogeton crispus) and thin-leaf type (Hydrilla verticillata , Ceratophyllum demersum , and Myriophyllum spicatum) exhibited strong inhibition effects against Pseudanabaena sp.: Overall inhibition efficiencies (IEs) of 92.7% ± 6.8% and 92.7% ± 8.4% for cell growth and 2-MIB production were achieved, respectively. Moreover, the thin-leaf macrophytes exhibited significant higher IEs for cell growth (94.0% vs. 84.7%) and 2-MIB production (99.4% vs. 82.6%) than the flat-leaf macrophytes and can be selected as pioneer species in controlling odor problems. Nutrient uptake, increasing water clarity, shading effects, and allelopathic effects of the submerged macrophytes were found to be the dominant inhibition mechanisms. [Display omitted] • Pseudanabaena was first identified as the 2-MIB producer in East Taihu Lake. • All submerged macrophytes are effective in the inhibitory process of Pseudanabaena. • The shading effects and allelopathic effects play important role in the experiment. • The thin-leaf types are the optimal submerged macrophytes to minimize odor problem. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of body mass index (BMI) and hip anatomy on direct anterior approach (DAA) total hip replacement.Subjects and Methods: The study is a retrospective analysis of 124 cases of DAA total hip replacement from 2009 to 2012. The BMI, the ratio of the greater trochanter (GT) and anterior superior iliac spine (ASIS) bilaterally (GT/ASIS), and the vertical distance between the ASIS and GT (AGVD) were obtained from medical records. All cases were categorized into three groups (43, 49, and 32 cases in each group, respectively) based on BMI (BMI <18.5, BMI 18.5-25, and BMI >25) or divided into two groups based on GT/ASIS (≤1.17 or >1.17) or AGVD (≤86 or >86 mm). Operating time, intraoperative bleeding, and surgical complications were compared between different groups.Results: A longer average operating time, more intraoperative bleeding, and a higher rate of complications were observed in the group with the highest BMI. The complications included a case of intraoperative femur fracture, a wound hematoma, and a lateral femoral cutaneous nerve injury. The group with higher GT/ASIS had a shorter average operating time, less bleeding, and a lower complication rate than the group with lower GT/ASIS. Moreover, the group with higher AGVD showed a shorter average operating time, less bleeding, and a lower complication rate compared with the group with lower AGVD.Conclusion: Our study suggests that lower BMI and larger GT/ASIS and AGVD are associated with a shorter operating time, less bleeding, and a lower complication rate in DAA total hip replacement. These findings are valuable for clinicians to make the appropriate choice of surgery types for different individuals. [ABSTRACT FROM AUTHOR]

• The Ti 3 C 2 /CPNC heterostructure is designed by intercalating Ti 3 C 2 nanosheets with CoP nanocages, in which Ti 3 C 2 prevent the aggregation of CoP and CoP also restrain the recombination of Ti 3 C 2. • The Ti 3 C 2 /CPNC provides abundant actives sites for effective adsorption-diffusion-conversion of LiPSs. • The Ti 3 C 2 /CPNC with remarkable lithiophilicity and high conductivity can accomplish uniform Li deposition to inhibit the growth of dendrites. • The Li–S full cell harvests excellent electrochemical performance even at a high sulfur loading of 5.3 mg cm−2 and a negative to positive electrode capacity ratio of 1.7:1. The practical application of lithium–sulfur (Li-S) batteries has been hampered by the shuttle effect of lithium polysulfides (LiPSs) and seriously uncontrollable Li dendrite growth. Herein, we report an elaborate heterostructure (Ti 3 C 2 /CPNC), composed of Ti 3 C 2 nanosheets-encapsulated CoP nanocages with abundant lithiophilic/sulfiphilic sites for suppressing polysulfide shuttling and dendritic growth in Li-S batteries. Functioning as a separator mediator, the Ti 3 C 2 /CPNC heterostructure affords a synergistic effect of strong chemical interactions and fast conversion kinetics toward LiPSs. A half cell with the Ti 3 C 2 /CPNC interlayer exhibits a remarkable cycling stability with a capacity decay of only 0.039 % per cycle at 1C after 1150 cycles. As a Li host, the Ti 3 C 2 /CPNC heterostructure with remarkable lithiophilicity and high conductivity regulates the uniform plating/stripping of Li. The integrated Li–S full cell harvests an excellent electrochemical performance, even at a high sulfur loading of 5.3 mg cm−2 with a negative to positive (N/P) electrode capacity ratio of 1.7:1. This work demonstrates the potential application of bifunctional mediators for fabricating Li–S full batteries with outstanding electrochemical performance. [ABSTRACT FROM AUTHOR]

As a kind of semiconductors, tellurium has attracted much attention due to its superior optical, electrical, and thermoelectric properties. In particular, a lot of research on low-dimensional tellurium has been performed in recent years, but with relatively few work on its applications in ultrafast photonics. In this work, a femtosecond fiber laser was realized using the prepared tellurium nanowires as the saturable absorber. Tellurium nanowires were synthesized by the hydrothermal method and then deposited on the tapered optical fiber to form the tellurium saturable absorber (Te-SA). The saturable absorption property of Te-SA was tested by the two-arm balance detection method, the saturation intensity and modulation depth were determined to be 8.9 MW/cm2 and 27.0%, respectively. Then, Te-SA was applied in the erbium-doped fiber laser and a stable mode-locked fiber laser with a pulse width of 621 fs was achieved. The results indicate the great potential application of tellurium nanowires in ultrafast photonics. • Tellurium nanorods are prepared by a green and safe hydrothermal method. • The saturable absorber based on the tellurium nanorods shows strong nonlinear optical absorption property. • A mode-locked Er-doped fiber laser with of a pulse width of 621 fs was realized based on the Te-SA. [ABSTRACT FROM AUTHOR]

Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, is transiently expressed in the arterial wall in response to injury, indicating that it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration. Recent studies showed that it is aberrantly upregulated in most human solid tumors, yet its role in osteosarcoma remains unclear. In this study, the authors investigated the role of CTHRC1 in human osteosarcoma tumorigenesis. The authors used lentivirus-mediated short hairpin RNA (shRNA) against CTHRC1 to limit its endogenous expression in U2OS and SW1353 cells. Interestingly, they found that depletion of CTHRC1 significantly inhibited cell proliferation and colony formation in U2OS and SW1353 cells. Flow cytometry assay showed that knockdown of CTHRC1 increased the cell percentage of G0/G1 phase, resulting in cell cycle arrest in U2OS cells. Moreover, CTHRC1 silencing induced the cell cycle arrest by a decrease in the cell percentage in G0/G1 phase and increased in G2/M phase in SW1353 cells. In addition, crystal violet staining suggested CTHRC1 silencing inhibited migration of U2OS and SW1353 cells. These results demonstrated that CTHRC1 might play an important role in osteosarcoma progression. [ABSTRACT FROM AUTHOR]

Transition metal salen complex MoO2-salen was successfully tethered onto amino-functionalized graphene oxide (designated as MoO2-salen-GO), which was tested in the of various alkenes using tert-butylhydroperoxide or H2O2 as oxidant. Characterization results showed that dioxomolybdenum(VI) complex was successfully grafted onto the amino-functionalized graphene oxide and the structure of the graphene oxide was well preserved after several stepwise synthesis procedures. Catalytic tests showed that heterogeneous catalyst MoO2-salen-GO was more active than its homogeneous analogue MoO2-salen in the of cyclooctene due to site isolation. In addition, the MoO2-salen-GO catalyst could be reused three times without significant loss of activity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Oxovanadium(iv) and iron(iii) salen complexes grafted onto amino-modified graphene oxide (NH2–GO) have been synthesized via a stepwise procedure and the prepared materials were used as heterogeneous catalysts in the aerobic oxidation of styrene. The structures of these materials have been thoroughly investigated using different characterization techniques such as XRD, N2 adsorption–desorption, TEM, FT-IR, diffuse reflectance UV-visible spectroscopy, ICP-AES, TEM, TG, Raman, and XPS. The results of XRD, N2 adsorption–desorption and TEM revealed that the structures of the prepared catalysts were well preserved. In addition, the results of FT-IR, diffuse reflectance UV-visible spectroscopy, ICP-AES, TG, Raman and XPS suggested that the oxovanadium(iv) and iron(iii) complexes had been incorporated onto amino-modified graphene oxide (GO). It was found that the heterogeneous oxovanadium(iv) catalyst was more active than its homogeneous analogue in the epoxidation of styrene, using acetonitrile as solvent and air as the oxidant in combination with the sacrificial co-reductant isobutyraldehyde, due to site-isolation. Furthermore, the tethered vanadium catalyst was quite stable and could be recycled many times. [ABSTRACT FROM AUTHOR]

Purpose: Suture fixation is mostly used in arthroscopic treatment of tibial eminence avulsion fractures. However, no clinical studies of metal cable fixation have been reported. We hypothesised that cable fixation can provide equal stability and clinical outcome compared with Ethibond sutures. Methods: Between 2007 and 2008, we treated 42 patients of adult type III tibial eminence avulsion fractures. Twenty-three patients were male, and 19 were female. All patients were confirmed by radiographs, MRI, and arthroscopy during surgery. Ligament injury and meniscus tears were excluded from this study. Twenty-two patients were treated with No. 2 Ethibond suture fixation (group I), and 20 were treated with cable fixation under arthroscopy (group II). Follow-up assessments included imaging evaluation, Lysholm knee score, International Knee Documentation Committee (IKDC) classification, and the Lachman test. Results: Bone union was found in radiographic evaluation in all patients within 3 months. At the last follow-up, there was neither extension nor flexion limitation in any patient. There were no significant differences in the Lysholm score between the two groups at follow-up. All 42 patients were classified by the IKDC as normal or nearly normal. Stability based on the Lachman test showed two patients of grade II laxity in group I. At the final follow-up, all 42 patients had returned to their pre-injury activities. Conclusions: Cable fixation to treat type III tibial eminence avulsion fracture can provide a clinical outcome equal to that of Ethibond sutures. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

We aimed to identify RNA N6-methyladenosine methylation associated genes in osteoarthritis (OA), and to explore possible regulatory mechanisms of these RNA methylation associated genes. Bioinformatics analyses, including differential expression analysis, functional enrichment analysis, verification analysis, and box plot analysis, were conducted based on different datasets from OA and non-OA patients. Gene expression at mRNA and protein levels was determined by quantitative reverse transcription PCR, western blot and immunofluorescence. Interleukin 1β (IL-1β)-treated SW1353 cells was used as cell model. Lentiviral vector was used for over-expression METTL3 in vitro. CCK-8 assay kit was used to determine cell viability and inflammatory cytokines (IL-1α, IL-6, IL-8, IL-10 and TNF-α) was detected using ELISA kits. Bioinformatics analysis showed that METTL3 expression was decreased in OA group, which was confirmed in clinical samples. Expression of METTL3 was also reduced in IL-1β-treated cells. Levels of inflammatory cytokines were obviously reduced in the METTL3 overexpression group, while IL-1β treatment reversed such decrease caused by METTL3 overexpression (p < 0.05). Both METTL3 overexpression and IL-1β treatment promoted expression of p65 protein and p-ERK (p < 0.01). Additionally, increased expression of MMP1 and MMP3 , and decreased expression of MMP13 , TIMP-1 , and TIMP-2 at both mRNA and protein levels were observed in the METTL3 overexpression group when compared with the control group (p < 0.01). Expression of m6A methylation gene METTL3 was reduced in OA. METTL3 is involved in OA probably by regulating the inflammatory response. METTL 3 overexpression may affect extracellular matrix degradation in OA by adjusting the balance between TIMPs and MMPs. • METTL3 and YTHDC2 were identified as m6A methylation-related genes in OA. • METTL3 may be involved in OA by regulating the inflammatory response. • METTL3 overexpression may affect ECM degradation in OA. [ABSTRACT FROM AUTHOR]

Abstract: Silica–silver core–shell composite particles with uniform thin silver layers were successfully synthesized by a facile and one-step ultrasonic electrodeposition method. By electrolysis of the slurry consisting of preformed silica spheres and silver perchlorate without any additives, the homogenous composite particles can be prepared. The average size of single silver crystals in the composite is about 12nm and the thickness of silver layer is 14±2nm. Moreover, the continuity of Ag distribution, the surface roughness and the thickness of silver layer are controllable by adjusting the current density (I), the concentration of electrolyte (C) and the reaction time (t). Optical properties of the composite particles with different silver content were also investigated. [Copyright &y& Elsevier]

Different groups of adatoms induced different magnetic and electronic properties. • The physical properties of 2D GaN after adsorption were explored by the first-principles calculation. • Groups III-V and VII adatoms introduce magnetic feature with spin-polarized properties. • A semiconducting state presents in the groups IIIA, IVA and VIA atoms adsorbed 2D GaN. • A half-metallic state appears in 2D GaN after adsorption of VA and VIIA atoms. We explore a first-principles study of the structural, electronic, magnetic, and optoelectronic properties of two-dimensional (2D) gallium nitride (GaN) adsorbed by the groups IIIA-VIIA atoms. Our calculations reveal that the chemisorption occurs for all selected adatoms and the adsorption energy of C is the highest because of its special adsorption configuration. The electronic structure studies indicate that the adatoms introduce magnetic feature with spin-polarized properties except for the group VIA atoms. Moreover, a semiconducting state presents in the groups IIIA, IVA and VIA atoms adsorbed 2D GaN, while a half-metallic state appears in 2D GaN after the adsorption of VA and VIIA atoms, which makes the latter higher work functions. Such regular modifications in physical properties of 2D GaN induced by adsorption could potentially allow use of this material in diverse electronic, optoelectronic, and spintronic applications. [ABSTRACT FROM AUTHOR]

• EsA attenuates inflammation and catabolism of chondrocytes. • EsA restrains RANKL-induced osteoclast formation. • Treatment with EsA suppresses NF-κB and MAPK signalling pathway activation in vitro. • EsA protects OA cartilage in vivo and may be a novel therapeutic target. Osteoarthritis is a relatively common disorder of articular deterioration related to cartilage damage, subchondral bone remodelling, inflammation and metabolism. Agents that can inhibit cartilage degradation and osteoclastogenesis are required for the prevention and treatment of osteoarthritis. Esculentoside A, the highest concentration triterpene saponin isolated from the root of Phytolacca esculenta, has commonly been used for the treatment of chronic bronchitis. However, the role esculentoside A plays in ameliorating osteoarthritis has not been reported. We found that esculentoside A suppresses the expression of IL-1β-induced inflammatory and metabolic factors (IL-6, IL-8, TNF-α, MMP2, MMP3 and MMP13). In addition, esculentoside A restrains osteoclast formation by inhibiting the marker gene expression of NFATc1 and c-Fos. Our results indicate that esculentoside A markedly suppresses IL-1β-induced NF-κB and MAPK signalling pathway activation in chondrocytes, and inhibits RANKL-induced osteoclast precursor generation. Finally, treatment with esculentoside A inhibits the progressive cartilage degeneration and osteoclastogenesis in osteoarthritis mouse models. In summary, these results demonstrate that esculentoside A could be a latent therapeutic reagent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]