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Objectives: TANK-binding kinase 1 (TBK1) is pivotal in autoimmune and inflammatory diseases, yet its role in osteoarthritis (OA) remains elusive. This study sought to elucidate the effect of the TBK1 inhibitor BX795 on OA and to delineate the underlying mechanism by which it mitigates OA. Methods: Interleukin-1 Beta (IL-1β) was utilized to simulate inflammatory responses and extracellular matrix degradation in vitro. In vivo, OA was induced in 8-week-old mice through destabilization of the medial meniscus surgery. The impact of BX795 on OA was evaluated using histological analysis, X-ray, micro-CT, and the von Frey test. Additionally, Western blot, RT-qPCR, and immunofluorescence assays were conducted to investigate the underlying mechanisms of BX795. Results: Phosphorylated TBK1 (P-TBK1) levels were found to be elevated in OA knee cartilage of both human and mice. Furthermore, intra-articular injection of BX795 ameliorated cartilage degeneration and alleviated OA-associated pain. BX795 also counteracted the suppression of anabolic processes and the augmentation of catabolic activity, inflammation, and senescence observed in the OA mice. In vitro studies revealed that BX795 reduced P-TBK1 levels and reversed the effects of anabolism inhibition, catabolism promotion, and senescence induction triggered by IL-1β. Mechanistically, BX795 inhibited the IL-1β-induced activation of the cGAS–STING and TLR3–TRIF signaling pathways in chondrocytes. Conclusions: Pharmacological inhibition of TBK1 with BX795 protects articular cartilage by inhibiting the activation of the cGAS–STING and TLR3–TRIF signaling pathways. This action attenuates inflammatory responses and cellular senescence, positioning BX795 as a promising therapeutic candidate for OA treatment. The translational potential of this article: This study furnishes experimental evidence and offers a potential mechanistic explanation supporting the efficacy of BX795 as a promising candidate for OA treatment.

Abstract Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines. Graphical Abstract

The journal retracts the article “Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis” [...]

Abstract Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1β-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment. Clinical trial registration: Not applciable. Graphical Abstract

Aims: Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods: In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results: DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion: We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273.

Aims: Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods: After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results: In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion: Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132.

BackgroundIntracerebral hemorrhage (ICH) is one of the most serious complications in patients with chronic kidney disease undergoing long-term hemodialysis. It has high mortality and disability rates and imposes a serious economic burden on the patient's family and society. An early prediction of ICH is essential for timely intervention and improving prognosis. This study aims to build an interpretable machine learning-based model to predict the risk of ICH in patients undergoing hemodialysis.MethodsThe clinical data of 393 patients with end-stage kidney disease undergoing hemodialysis at three different centers between August 2014 and August 2022 were retrospectively analyzed. A total of 70% of the samples were randomly selected as the training set, and the remaining 30% were used as the validation set. Five machine learning (ML) algorithms, namely, support vector machine (SVM), extreme gradient boosting (XGB), complement Naïve Bayes (CNB), K-nearest neighbor (KNN), and logistic regression (LR), were used to develop a model to predict the risk of ICH in patients with uremia undergoing long-term hemodialysis. In addition, the area under the curve (AUC) values were evaluated to compare the performance of each algorithmic model. Global and individual interpretive analyses of the model were performed using importance ranking and Shapley additive explanations (SHAP) in the training set.ResultsA total of 73 patients undergoing hemodialysis developed spontaneous ICH among the 393 patients included in the study. The AUC of SVM, CNB, KNN, LR, and XGB models in the validation dataset were 0.725 (95% CI: 0.610 ~ 0.841), 0.797 (95% CI: 0.690 ~ 0.905), 0.675 (95% CI: 0.560 ~ 0.789), 0.922 (95% CI: 0.862 ~ 0.981), and 0.979 (95% CI: 0.953 ~ 1.000), respectively. Therefore, the XGBoost model had the best performance among the five algorithms. SHAP analysis revealed that the levels of LDL, HDL, CRP, and HGB and pre-hemodialysis blood pressure were the most important factors.ConclusionThe XGB model developed in this study can efficiently predict the risk of a cerebral hemorrhage in patients with uremia undergoing long-term hemodialysis and can help clinicians to make more individualized and rational clinical decisions. ICH events in patients undergoing maintenance hemodialysis (MHD) are associated with serum LDL, HDL, CRP, HGB, and pre-hemodialysis SBP levels.

Currently, cloud storage servers are controlled by a third-party administrator. This semi-trusted approach gives rise to security concerns. Therefore, in cloud computing, some protocols use a key manager to encrypt the user’s private data before uploading the data to the cloud. However, the security concerns that arise from the use of a key manager are not yet solved. In this respect, in this paper, a provably secure user cloud data access control protocol (DAC) is proposed based on existing cloud storage. Empirical tests confirm that the proposed approach is highly secure against adaptive selective ciphertext attacks and has excellent resistance to message attacks. A comprehensive performance evaluation, including time measurements, is conducted and the protocol is compared to other protocols, revealing the efficient file upload and download processes of the proposed approach. The results demonstrate the protocol’s strong security, practicality, and operational efficiency.

We experimentally studied the supercontinuum induced by femtosecond filamentation in different liquid media. Using a Mach–Zehnder interferometer, we determined the relative filamentation thresholds (Pth) of these media. Research has shown that the value of the filamentation threshold is greater than that of Pcr (critical power for self-focusing), which can mainly be attributed to the strong dispersion effect. Changing the focal length of the focusing lens affects filamentation dynamics, thereby affecting the measured results regarding the filamentation threshold. With shorter focal lengths, the linear focusing (i.e., geometrical focusing) regime dominates, and the measured values of Pth for different liquid media are almost the same; as the focal length becomes larger, self-focusing starts to play a role, making the values of Pth for different media different from each other. This study presents an efficient method for investigating the femtosecond filamentation phenomenon in liquid media, helpful to provide further insights into the physical mechanism of supercontinuum generation via femtosecond filamentation in liquid media.

BackgroundHand osteoarthritis (OA) is a chronic progressive disease characterized by disabling pain in the hand, with a high clinical burden. This study is designed to assess the epidemiological patterns of hand OA from 1990 to 2019 and analyze its secular trends based on sex, age, and socio-demographic index (SDI) at global, regional, and national levels.MethodsData on the incidence and disability-adjusted life years (DALYs) of hand OA were extracted from the 2019 Global Burden of Disease (GBD), and their respective age-standardized rates (ASRs) were calculated. The estimated annual percentage changes (EAPCs) in ASR were calculated to assess the prevalent trends of the incidence and DALYs of hand OA over the recent three decades. The relationship between ASR and SDI was analyzed by Pearson's correlation analysis.ResultsThe incidence of hand OA increased from 371.30 million in 1990 to 676.02 million in 2019, increasing by 82.07%, whereas its age-standardized incidence rate (ASIR) decreased, with a downward trend [EAPC = −0.34; 95% confidence interval: −0.39–−0.28]. With the changes in age, the incidence of hand OA exhibited a unimodal distribution before 70 years of age, peaking at 50–54 years, while its incidence had an upward trend in the >70 years age groups. Overall, hand OA-related DALYs increased in the recent 30 years. Meanwhile, its annual age-standardized DALY rate decreased, with EAPCs of −0.35 (95% CI, −0.38 –−0.32). The DALYs increased with age. In 2019, the ASIR and age-standardized DALY rate were positively associated with the SDI regions. The incidence and DALYs presented predominance in female patients. The burden of hand OA over the recent three decades displayed obvious geographical diversity.ConclusionThe incident cases of hand OA increased globally from 1990 to 2019, while the ASIR and age-standardized DALY rate decreased. However, in many countries and regions, there was a rising trend of ASR related to incidence and DALYs. In addition, the prevalence revealed geographical, sex, and age diversity. Thus, governments and medical institutions should reallocate medical resources based on the epidemiological characteristics of hand OA.

Cancer is one of the primary causes of death worldwide, and its morbidity and mortality rates are increasing rapidly. However, standard treatment modalities (surgery, radiotherapy, chemotherapy, and immunotherapy) often fail to achieve a satisfactory therapeutic effect. Extracellular vesicles (EVs) are natural nano-sized lipid bilayer vesicles secreted from cells. Owing to their advantages of low toxicity, high biocompatibility, low immunogenicity, and inherent targeting, EVs can be exploited as drug delivery vectors for cancer treatment. In this review, we summarize the research progress of EV-based drug delivery systems in cancer treatment by focusing on four aspects: sources, cargo types, cargo loading methods and modification strategies. Finally, current challenges and future perspectives are discussed.

Femtosecond (fs) and nanosecond (ns) laser pulses have their own advantages and disadvantages in laser-induced breakdown spectroscopy (LIBS). This paper investigated fs + ns (FN) dual-pulse (DP) LIBS, utilizing the respective advantages of two laser pulses in LIBS. Compared to traditional single ns LIBS, applying a smaller energy fs pulse could effectively improve the LIBS emission. Firstly, this study discussed the spectra of FN DP LIBS with overlapping pulse time—that is, the FN DP inter-pulse delay (DID) was 0 μs. The results showed that the spectra were increased to three times that of a single ns LIBS. Subsequently, the DID between the two pulses was optimized. The results showed that as the DID between the two pulses increased, the spectral emission first increased and then decreased, ultimately remaining unchanged. The optimized DID was approximately 2 μs. Finally, using this optimized DID, the variation of spectral intensity with ns laser energy was discussed in DP LIBS. The spectral enhancement ratio increased from 3 with 0 μs DID to 6 with 2 μs DID. The investigation provides a reference in the application of FN DP LIBS element analysis.

Progressive bone loss during aging makes osteoporosis one of the most common and life impacting conditions in geriatric populations. The bone homeostasis is maintained through persistent remodeling mediated by bone-forming osteoblast and bone-resorbing osteoclast. Inflammaging, a condition characterized by increased pro-inflammatory markers in the blood and other tissues during aging, has been reported to be associated with skeletal stem/progenitor cell dysfunction, which will result in impaired bone formation. However, the role of age-related inflammation and metabolites in regulation of osteoclast remains largely unknown. In the present study, we observed dichotomous phenotypes of anti-inflammatory metabolite itaconate in responding to inflammaging. Itaconate is upregulated in macrophages during aging but has less reactivity in responding to RANKL stimulation in aged macrophages. We confirmed the inhibitory effect of itaconate in regulating osteoclast differentiation and activation, and further verified the rescue role of itaconate in lipopolysaccharides induced inflammatory bone loss animal model. Our findings revealed that itaconate is a crucial regulatory metabolite during inflammaging that inhibits osteoclast to maintain bone homeostasis.

Increasing the emission intensity of laser-induced breakdown spectroscopy (LIBS) is an effective way to improve the sensitivity of LIBS technology to elements analysis in liquid samples. In this work, the influence of the distance from lens to sample surface (DFLS) on the spectral emission of femtosecond laser-induced plasma of NaCl water film was studied by measuring Na atomic line. The results showed that the emission intensity of the spectral line presented the phenomenon of double peaks with an increase in the DFLS. The position for the highest spectral intensity was not geometric focal point of focusing lens, but was located in front of the geometric focal point. In addition, we carried out quantitative analysis on Na element with different concentrations, showing a calibration curve of Na element, and calculating limit of detection (LOD) and relative standard deviation (RSD) for different DFLSs. Subsequently, the changes in the LOD and RSD with the DFLS are discussed. With the increase of the DFLS, the LOD and RSD were greatly reduced. At the DFLS of 99.0 mm, the line intensity was highest, and the LOD and RSD were better. Therefore, it can be confirmed that femtosecond LIBS of water film can be optimized by changing the DFLS, the experiment shows great potential in real-time water quality monitoring.

Abstract The roadway deformation process is closely associated with the accumulation and dissipation of energy. Understanding the characteristics of energy dissipation in surrounding rock is critical to revealing the development process and the disaster mechanisms of the roof accidents in underground coal mines. This paper presents a triaxial compression experiment to analyze energy characteristics of mudstone taken from Huangyanhui Coal Mine. A numerical study is performed to study the energy distribution under different roof strengths. The results suggest that the instability of the roadway is an irreversible energy dissipation process with high nonlinearity and complexity. The roadway support principle, based on the energy balance theory, is proposed to explain the energy distribution. The safety control of roadways with thick and soft roofs should consider the following three aspects: (a) optimize the layout of the roadway, avoid placing it in the stress concentration zone, and reduce the strain energy of the surrounding rock accumulation from the source; (b) improve the ability of the supporting structure to adapt to the deformation of the surrounding rock and avoid the failure of the supporting structure because of excessive force; and (c) set weak structures in the surrounding rock, that dissipate part of the energy, thus reducing the load acting on the support. The results of field application monitoring show that roadway severe deformation was effectively controlled using pressure relief boreholes (PRB), and the average floor heave speed of the roadway decreased from the original 2.0 to 0.98 mm/d. Therefore, PRB provides a new approach for roadway control.

Abstract Background Flavonoids are a class of plant and fungus secondary metabolites and are the most common group of polyphenolic compounds in the human diet. In recent studies, flavonoids have been shown to induce browning of white adipocytes, increase energy consumption, inhibit high-fat diet (HFD)-induced obesity and improve metabolic status. Promoting the activity of brown adipose tissue (BAT) and inducing white adipose tissue (WAT) browning are promising means to increase energy expenditure and improve glucose and lipid metabolism. This review summarizes recent advances in the knowledge of flavonoid compounds and their metabolites. Methods We searched the following databases for all research related to flavonoids and WAT browning published through March 2019: PubMed, MEDLINE, EMBASE, and the Web of Science. All included studies are summarized and listed in Table 1. Result We summarized the effects of flavonoids on fat metabolism and the specific underlying mechanisms in sub-categories. Flavonoids activated the sympathetic nervous system (SNS), promoted the release of adrenaline and thyroid hormones to increase thermogenesis and induced WAT browning through the AMPK-PGC-1α/Sirt1 and PPAR signalling pathways. Flavonoids may also promote brown preadipocyte differentiation, inhibit apoptosis and produce inflammatory factors in BAT. Conclusion Flavonoids induced WAT browning and activated BAT to increase energy consumption and non-shivering thermogenesis, thus inhibiting weight gain and preventing metabolic diseases.

The study used linearly and circularly polarized femtosecond pulsed lasers to irradiate a Ta2O5/SiO2 film. Firstly, the damage thresholds of the film for linearly and circularly polarized femtosecond pulsed lasers were measured in 1-on-1 mode. The results showed that the damage threshold (1.70 J/cm2) under a circularly polarized laser was higher than that (1.68 J/cm2) under a linearly polarized laser. For femtosecond lasers, the multi-photon ionization cross-section under circular polarization was lower than that under linear polarization. The lower ionization rate under circular polarization led to a higher damage threshold compared to the case under linear polarization. Secondly, the damage morphology of the film irradiated by linearly and circularly polarized femtosecond lasers was observed by microscope. The damage caused by linearly polarized laser was more evident than that caused by the circularly polarized laser. Finally, the damage thresholds induced by linearly and circularly polarized femtosecond pulsed lasers were measured in S-on-1 (S = 2, 5, and 10) mode. For the same S value (2, 5, or 10), the damage threshold under the circularly polarized laser was higher than that under the linearly polarized laser. The damage thresholds under two polarized laser pulses decreased with an increase in the number of laser shots, indicating that repeated laser pulses had a cumulative effect on the damage of the film.

Carbon quantum dots have promising advantages such as high stability, low cost and environment-friendliness, but their broad emission band limits their application in displays. Here Yuan et al. synthesize these dots showing tunable emission color, high fluorescence and a narrow FWHM of only 30 nanometers.

Increasing sample temperature is an effective method for improving emission intensity of laser-induced breakdown spectroscopy (LIBS). An increase in the sample temperature requires only simple modification to LIBS system, and does not require sample pretreatment. In addition, the formation and decay of laser-induced plasma (LIP) are a dynamic physical process. Time-resolved spectroscopy can enrich the dynamic information of LIBS and increase data dimension. The further analysis of the time-resolved LIBS data has the potential to understand the physical process. In this study, a beam of nanosecond laser was used to excite brass sample to produce plasma. The time-resolved spectroscopy of the LIP was measured at different sample temperatures. The results indicated that increasing sample temperature improved optical emission intensity in LIBS, and increased the plasma persistence. We also obtained plasma temperature and electron density at different sample temperatures. The time-resolved plasma temperature and electron density in the case with higher sample temperature were higher than those in the case with lower sample temperature. Moreover, the decay of electron density at higher sample temperature was faster than that at lower sample temperature.

The influence of distance between sample surface and focal point on optical emission spectroscopy of laser-induced silicon plasma by a nanosecond Nd:YAG laser operating at the wavelength of 1064 nm was investigated in air. Our results show that the emission intensity of Si (I) 390.6 nm line and N (II) 399.5 nm line depends strongly on the distance between sample surface and focal point. When the surface of ablated sample is away from the focal point of focusing lens, the neutral atomic line (Si(I) signal to be measured) is much higher than the ionic line (interference signal N (II)). Therefore, we can improve the intensity of Si (I) signal to be measured, and reduce the intensity of interference signal N (II). The presented result is mainly based on the reduction of interaction between the plasma plume and the ambient air, leading to much weaker collisions.

Cancer is one of the leading causes of death worldwide and a major global health problem. In recent decades, the rates of both mortality and morbidity of cancer have rapidly increased for a variety of reasons. Despite treatment options, there are serious side effects associated with chemotherapy drugs and multiple forms of drug resistance that significantly reduce their effects. There is an accumulating amount of evidence on the pharmacological activities of baicalein (e.g., anti-inflammatory, antioxidant, antiviral, and antitumor effects). Furthermore, there has been great progress in elucidating the target mechanisms and signaling pathways of baicalein’s anti-cancer potential. The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammalian target of rapamycin (mTOR) activities, to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9). In this review, we focused on the relevant biological mechanisms of baicalein involved in inhibiting various cancers, such as bladder cancer, breast cancer, and ovarian cancer. Moreover, we also summarized the specific mechanisms by which baicalein inhibited the growth of various tumors in vivo. Taken together, baicalein may be developed as a potential, novel anticancer drug to treat tumors.

We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/β-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.

Previous studies showed that SDF-1α is a catabolic factor that can infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity. Inhibiting the SDF-1α/CXCR4 signalling pathway can attenuate the pathogenesis of osteoarthritis (OA). Recent studies have also shown that SDF-1α enhances chondrocyte proliferation and maturation. These results appear to be contradictory. In the current study, we used a destabilisation OA animal model to investigate the effects of SDF-1α/CXCR4 signalling in the tibial subchondral bone and the OA pathological process. Post-traumatic osteoarthritis (PTOA) mice models were prepared by transecting the anterior cruciate ligament (ACLT), or a sham surgery was performed, in a total of 30 mice. Mice were treated with phosphate buffer saline (PBS) or AMD3100 (an inhibitor of CXCR4) and sacrificed at 30 days post ACLT or sham surgery. Tibial subchondral bone status was quantified by micro-computed tomography (μCT). Knee-joint histology was analysed to examine the articular cartilage and joint degeneration. The levels of SDF-1α and collagen type I c-telopeptidefragments (CTX-I) were quantified by ELISA. Bone marrow mononuclear cells (BMMCs) were used to clarify the effects of SDF-1α on osteoclast formation and activity in vivo. μCT analysis revealed significant loss of trabecular bone from tibial subchondral bone post-ACLT, which was effectively prevented by AMD3100. AMD3100 could partially prevent bone loss and articular cartilage degeneration. Serum biomarkers revealed an increase in SDF-1α and bone resorption, which were also reduced by AMD3100. SDF-1α can promote osteoclast formation and the expression oftartrate resistant acid phosphatase (TRAP), cathepsin K (CK), and matrix metalloproteinase (MMP)-9 in osteoclasts by activating the MAPK pathway, including ERK and p38, but not JNK. In conclusion, inhibition of SDF-1α/CXCR4signalling was able to prevent trabecular bone loss and attenuated cartilage degeneration in PTOA mice.

In this paper, a fiber laser marking machine was used to pretreat an Al plate, and then a Au nanoparticle (Au NP) solution was dripped on the surface of the pre-treated plate to study the effect of the laser pretreatment assisted-nanoparticle-enhanced laser-induced breakdown spectroscopy technique on the emission and stability of the AlO molecular bands (B2P+ - X2P, Dn = 0) in the Al plasma. The results showed that laser pretreatment significantly improved the emission and stability of the AlO molecular bands. Therefore, this paper demonstrates the potential of laser pretreatment in improving analytical sensitivity in LIBS. [ABSTRACT FROM AUTHOR]