Metabolomic insights into pulmonary fibrosis: a mendelian randomization study.

BACKGROUND: This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets. METHODS: Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences. RESULTS: The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis. CONCLUSIONS: The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.

170†GHz quasi-optical sub-harmonic mixer with a back-to-back lenses packaging based on HDI.

The paper presents a 170 GHz quasi-optical sub-harmonic mixer with a 3D-printed back-to-back lenses packaging. The quasi-optical mixer is comprised by a pair of antiparallel GaAs Schottky diodes, a patch antenna for receiving local oscillator (LO) pump signal, a symmetric-slit patch antenna for receiving radio frequency (RF) signal, dual 3D-printed lenses and a matching network. The quasi-optical mixer with a pair of antiparallel GaAs Schottky diodes is designed on a multilayer build-up printed circuit board (PCB) utilizing commercially low-cost and high-density interconnect (HDI) technology. The LO and RF antennas are placed on the front and back of the multilayer build-up substrate, respectively, thus significantly simplifying the quasi-optical design. Furthermore, dual 3D-printed lenses placed back-to-back are proposed for LO and RF antennas radiation gain enhancement and mechanical robustness. Additionally, the buried planar reflectors in the substrate maintain effective radiation isolation between the antennas. For facilitating coupling efficiency of signal power into the Schottky diodes and signal isolation between the LO pump signal and RF signal, a compact matching network with low-loss quasi-coaxial via transition structure is integrated in the mixer circuit. The measured single-sideband conversion loss is from 11.3 to 15.4 dB in an operation range of 160 to 180 GHz. The measured radiation patterns agree well with the simulated results.

Image restoration algorithm for terahertz FMCW radar imaging.

The terahertz frequency modulation continuous-wave (THz FMCW) imaging technology has been widely used in non-destructive testing applications. However, THz FMCW real-aperture radar usually has a small depth of field and poor lateral resolution, thus restricting the high-precision imaging application. This paper proposes a 150-220 GHz FMCW Bessel beam imaging system, effectively doubling the depth of field and unifying the lateral resolution compared to the Gaussian beam quasi-optical system. Moreover, a THz image restoration algorithm based on local gradients and convolution kernel priors is proposed to eliminate further the convolution effect introduced by the Bessel beam, thereby enhancing the lateral resolution to 2 mm. It effectively improves the image under-restoration or over-restoration caused by the mismatch between the ideal and actual point spread function. The imaging results of the resolution test target and semiconductor device verify the advantages of the proposed system and algorithm.

Connection between Osteoarthritis and Nitric Oxide: From Pathophysiology to Therapeutic Target.

Osteoarthritis (OA), a disabling joint inflammatory disease, is characterized by the progressive destruction of cartilage, subchondral bone remodeling, and chronic synovitis. Due to the prolongation of the human lifespan, OA has become a serious public health problem that deserves wide attention. The development of OA is related to numerous factors. Among the factors, nitric oxide (NO) plays a key role in mediating this process. NO is a small gaseous molecule that is widely distributed in the human body, and its synthesis is dependent on NO synthase (NOS). NO plays an important role in various physiological processes such as the regulation of blood volume and nerve conduction. Notably, NO acts as a double-edged sword in inflammatory diseases. Recent studies have shown that NO and its redox derivatives might be closely related to both normal and pathophysiological joint conditions. They can play vital roles as normal bone cell-conditioning agents for osteoclasts, osteoblasts, and chondrocytes. Moreover, they can also induce cartilage catabolism and cell apoptosis. Based on different conditions, the NO/NOS system can act as an anti-inflammatory or pro-inflammatory agent for OA. This review summarizes the studies related to the effects of NO on all normal and OA joints as well as the possible new treatment strategies targeting the NO/NOS system.

Ultra-wideband signal generation and fusion algorithm for high-resolution terahertz FMCW radar imaging.

The terahertz frequency modulated continuous wave (THz FMCW) imaging has proved to be a novel nondestructive testing (NDT) technology for non-metal materials, and the large bandwidth is usually required to meet high range resolution demands in many applications such as multilayer sample under test (SUT). However, broadband THz hardware is difficult to design. In this paper, an ultra-wideband THz FMCW generation method is proposed, which provides frequency modulation bandwidths of up to 386 GHz by time-division multiplexing. Furthermore, an ultra-wideband signal fusion algorithm (USFA) is also proposed and significantly improves the range resolution to 0.46 mm in air. Results from the artificially constructed multilayer structure demonstrate the superiority and effectiveness of our method quantitatively.

High range resolution wideband terahertz FMCW radar with a large depth of field.

Terahertz frequency modulation continuous wave (THz FMCW) imaging technology has been widely used in non-destructive testing (NDT) applications of non-metallic materials. However, THz FMCW real-aperture radar usually has a narrow bandwidth and small depth of field, thus restricting the application of THz FMCW NDT. In this paper, a wideband THz signal (220-500 GHz) generation method is proposed by time-division multiplexing. Moreover, a dual-band quasi-optical design with a large depth of field is proposed based on the THz Bessel beam, and a high-quality range profile is obtained. Especially, a signal fusion extended Fourier analysis algorithm without prior knowledge is proposed to further enhance the range profile accuracy, which improves the range resolution to 0.28 mm (λ/3, center frequency 360 GHz). The effectiveness and advantages of the proposed system are verified by artificially constructing composite materials.

RUNX1 promotes MAPK signaling to increase tumor progression and metastasis via OPN in head and neck cancer.

Tumor progression and metastasis are still major burdens for head and neck squamous cell carcinoma (HNSCC). Runt-related transcription factor 1 (RUNX1) is involved in aggressive phenotypes in several cancers, while the molecular role of RUNX1 underlying cancer progression and metastasis of HNSCC remains largely unknown. In our study, RUNX1 expression was increased with disease progression in patients with HNSCC. The silencing of RUNX1 significantly decelerated the malignant progression of HNSCC cells, reduced osteopontin (OPN) expression in vitro and weakened the tumorigenicity of HNSCC cells in vivo. Moreover, we demonstrated that RUNX1 activated the mitogen-activated protein kinase signaling by directly binding to the promoter of OPN in tumor progression and metastasis of HNSCC. Our results may provide new insight into the mechanisms underlying the role of RUNX1 in tumor progression and metastasis and reveal the potential therapeutic target in HNSCC.

A Convolutional Neural Network-Based Method for Corn Stand Counting in the Field.

Accurate corn stand count in the field at early season is of great interest to corn breeders and plant geneticists. However, the commonly used manual counting method is time consuming, laborious, and prone to error. Nowadays, unmanned aerial vehicles (UAV) tend to be a popular base for plant-image-collecting platforms. However, detecting corn stands in the field is a challenging task, primarily because of camera motion, leaf fluttering caused by wind, shadows of plants caused by direct sunlight, and the complex soil background. As for the UAV system, there are mainly two limitations for early seedling detection and counting. First, flying height cannot ensure a high resolution for small objects. It is especially difficult to detect early corn seedlings at around one week after planting, because the plants are small and difficult to differentiate from the background. Second, the battery life and payload of UAV systems cannot support long-duration online counting work. In this research project, we developed an automated, robust, and high-throughput method for corn stand counting based on color images extracted from video clips. A pipeline developed based on the YoloV3 network and Kalman filter was used to count corn seedlings online. The results demonstrate that our method is accurate and reliable for stand counting, achieving an accuracy of over 98% at growth stages V2 and V3 (vegetative stages with two and three visible collars) with an average frame rate of 47 frames per second (FPS). This pipeline can also be mounted easily on manned cart, tractor, or field robotic systems for online corn counting.

Upregulation of secreted phosphoprotein 1 affects malignant progression, prognosis, and resistance to cetuximab via the KRAS/MEK pathway in head and neck cancer.

Acquired resistance is a barrier to cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Secreted phosphoprotein 1 (SPP1) is involved in various biological processes, including immune responses, cancer progression, and prognosis in many cancers, while little is known in HNSCC. Bioinformatics methods were used to identify candidate genes and further in vivo and in vitro experiments were performed to examine and validate the function of SPP1. We found that SPP1 was upregulated and has been found to have an oncogenic role in HNSCC. We further confirmed that overexpression of SPP1 affected proliferation, migration, invasion, and survival, and inhibited apoptosis, whereas silencing of SPP1 yielded opposite results to those of SPP1 overexpression. In addition, activation of the KRAS/MEK pathway contributed to the SPP1-induced malignant progression of HNSCC and resistance to cetuximab. Furthermore, SPP1 knockdown or an MEK inhibitor overcame this cetuximab-resistance pattern. Taken together, our findings for the first time identify the role of SPP1 in tumor promotion, prognostic prediction, and potential therapeutic targeting, as well as resistance to cetuximab in HNSCC.

Automatic Non-Destructive Growth Measurement of Leafy Vegetables Based on Kinect.

Non-destructive plant growth measurement is essential for plant growth and health research. As a 3D sensor, Kinect v2 has huge potentials in agriculture applications, benefited from its low price and strong robustness. The paper proposes a Kinect-based automatic system for non-destructive growth measurement of leafy vegetables. The system used a turntable to acquire multi-view point clouds of the measured plant. Then a series of suitable algorithms were applied to obtain a fine 3D reconstruction for the plant, while measuring the key growth parameters including relative/absolute height, total/projected leaf area and volume. In experiment, 63 pots of lettuce in different growth stages were measured. The result shows that the Kinect-measured height and projected area have fine linear relationship with reference measurements. While the measured total area and volume both follow power law distributions with reference data. All these data have shown good fitting goodness (R² = 0.9457-0.9914). In the study of biomass correlations, the Kinect-measured volume was found to have a good power law relationship (R² = 0.9281) with fresh weight. In addition, the system practicality was validated by performance and robustness analysis.

Nutritional Quality Assessment of Miscellaneous Cassava Tubers Using Principal Component Analysis and Cluster Analysis.

Cassava is a staple crop in developing countries because its starchy roots provide essential dietary carbohydrates. The aim of this research was to conduct a comprehensive inquiry and scientific evaluation of the nutritional value of cassava tubers. Eight nutritional characteristics were examined in native and imported cassava variants: starch, reduced sugar, anthocyanins, protein, dietary fiber, quinic acid, vitamin C, and dry matter content. Principal component analysis (PCA) was conducted to minimize the dimensionality of the nutritional markers. A scientific assessment technique was developed to calculate a composite score for the various cassava samples. Analysis of the data revealed noticeable variance among the samples' nutritional indicators, suggesting varying degrees of association. Starch had a substantial positive link with lower sugar, protein, and dry matter content (p < 0.01). Anthocyanins and quinic acid interacted favorably (p < 0.05), and a positive link between protein and dry matter content was observed (p < 0.05); however, protein and dietary fiber interacted negatively (p < 0.05). The contribution rate of the top three PCA factors was over 76%, demonstrating that these factors incorporated the primary information acquired from the eight original nutritional indices, while maintaining excellent representativeness and impartiality. The experimental results showed a preliminary nutritional grade for 22 cassava tuber samples. The top five types were Guangxi Muci, Gui Cassava 4, Glutinous Rice Cassava, Huifeng 60, and Dongguan Hongwei. In the cluster analysis, the levels of similarity between the data showed that the 22 types of cassava tubers could be grouped into five categories, each with their own set of nutrients. This study promotes the directed breeding of cassava species and offers a theoretical foundation for creating and using various cassava varieties. Furthermore, this work lays the groundwork for a systematic and dependable technique for the quality assessment, comprehensive evaluation, and reasonable classification of cassava species and similar crops.

Magnetic Soft Microrobot Design for Cell Grasping and Transportation.

Manipulating cells at a small scale is widely acknowledged as a complex and challenging task, especially when it comes to cell grasping and transportation. Various precise methods have been developed to remotely control the movement of microrobots. However, the manipulation of micro-objects necessitates the use of end-effectors. This paper presents a study on the control of movement and grasping operations of a magnetic microrobot, utilizing only 3 pairs of electromagnetic coils. A specially designed microgripper is employed on the microrobot for efficient cell grasping and transportation. To ensure precise grasping, a bending deformation model of the microgripper is formulated and subsequently validated. To achieve precise and reliable transportation of cells to specific positions, an approach that combines an extended Kalman filter with a model predictive control method is adopted to accomplish the trajectory tracking task. Through experiments, we observe that by applying the proposed control strategy, the mean absolute error of path tracking is found to be less than 0.155 mm. Remarkably, this value accounts for only 1.55% of the microrobot's size, demonstrating the efficacy and accuracy of our control strategy. Furthermore, an experiment involving the grasping and transportation of a zebrafish embryonic cell (diameter: 800 µm) is successfully conducted. The results of this experiment not only validate the precision and effectiveness of the proposed microrobot and its associated models but also highlight its tremendous potential for cell manipulation in vitro and in vivo.

Exploring the role and mechanism of Astragalus membranaceus and radix paeoniae rubra in idiopathic pulmonary fibrosis through network pharmacology and experimental validation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragalus membranaceus (AM) and Radix paeoniae rubra (RPR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AM and RPR remain unclear. Utilizing network pharmacology analysis, differentially expressed genes (DEGs) associated with IPF were obtained from the GEO database. Targets of AM and RPR were identified using the TCM Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction. A protein-protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes analysis were conducted using Metascape. Additionally, a component-target-pathway network and a Sankey diagram were employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vivo studies were conducted based on network pharmacology. A total of 117 common targets between DEGs of IPF and drug targets were identified and included in the PPI network, in which AKT1, MAPK3, HSP90AA1, VEGFA, CASP3, JUN, HIF1A, CCND1, PTGS2, and MDM2 were predicted as key targets. These 117 targets were enriched in the PI3K-AKT pathway, HIF-1 signaling pathway, apoptosis, and microRNAs in cancer. Astragaloside III, (R)-Isomucronulatol, Astragaloside I, Paeoniflorin, and ß-sitosterol were selected as the main active components. Docking scores ranged from - 4.7 to - 10.7 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vivo studies have indeed shown that AM and RPR can alleviate the pathological lung fibrotic damage caused by bleomycin treatment. The treatment with AM and RPR resulted in a reduction of mRNA levels for key targets AKT1, HSP90AA1, CASP3, MAPK3, and VEGFA. Additionally, the protein expression levels of AKT1, HSP90AA1, and VEGFA were also reduced. These results support the therapeutic potential of AM and RPR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects.

Analysis of the anatomical distribution of HPV genotypes in head and neck squamous papillomas.

Squamous papillomas (SPs) of the head and neck are usually benign lesions associated with human papilloma virus (HPV) infection. However, the reported HPV detection rates vary widely, especially with respect to anatomical distribution. The etiology of SPs in the head and neck remains unclear; analyzing HPV genotypes of SPs based on anatomical sites could assist in clarifying the pathogenesis of SPs in the head and neck. Therefore, the aim of this study was to review the prevalence, subtypes, and anatomical distribution of HPV in head and neck SPs at a hospital in China; we also investigated whether p16, a marker of HPV infection in oropharyngeal carcinoma, could serve as a surrogate marker for HPV in head and neck SPs. The presence of HPV DNA of 23 types (5 low-risk HPV and 18 high-risk HPV types) was detected via real-time PCR. p16 immunohistochemistry was performed using SP sections. Age, sex, anatomical location, and HPV subtype were recorded for each case. In total, 105 SPs were identified, including 47 in the larynx, 42 in the pharynx, 6 in the external auditory canal (EAC), 5 in the oral cavity, and 5 in the nasal cavity. HPV was found in 57 (54.3%) cases, with the highest positivity rate in the larynx (46/47; 97.9%). Only 5/42 (11.9%) patients showed HPV positivity in the pharynx. HPV incidence was highly dependent on the anatomical site. SPs in the larynx and EAC were more likely to carry HPV than those in other anatomical sites. High-risk HPV infections were rarely associated with SPs in the head and neck region. The sensitivity and specificity of p16 immunohistochemistry for HPV infection were 88% and 96%, respectively. There may be an association between p16 and HPV infection in head and neck SPs, but further studies are needed to validate this assertion.

Licochalcone B confers protective effects against LPS-Induced acute lung injury in cells and mice through the Keap1/Nrf2 pathway.

BACKGROUND: Acute lung injury (ALI) is a severe and often fatal pulmonary disease. Current treatments for ALI and acute respiratory distress syndrome (ARDS) are limited. Natural product metabolites have shown promise as therapeutic alternatives. However, the effects of Licochalcone B (LCB) on ALI are largely unknown. METHODS: We investigated the effects of LCB on lipopolysaccharide-challenged mice and human pulmonary microvascular endothelial cells. Cell viability, apoptosis, and ROS production were assessed. Lung tissue histopathology and oxidative stress and inflammation markers were evaluated. Protein expression levels were measured. RESULTS: LCB had no cytotoxic effects on cells and increased cell viability. It reduced apoptosis and ROS levels in cells. In mice with ALI, LCB decreased lung tissue weight and improved oxidative stress and inflammation markers. It also enhanced expression levels of Nrf2, HO-1, and NQO1 while reducing Keap1. CONCLUSION: LCB protects against LPS-induced acute lung injury in cells and mice. The Keap1/Nrf2 pathway may be involved in its protective effects. LCB shows potential as a strategy to alleviate ALI caused by LPS.

[Effectiveness of sagittal top compression reduction technique in treatment of thoracolumbar vertebral fractures].

Objective: To investigate the effectiveness of sagittal top compression reduction technique in the treatment of thoracolumbar vertebral fractures. Methods: A retrospective analysis was conducted on the clinical data of 59 patients with thoracolumbar vertebral fractures who met the selection criteria and were admitted between November 2018 and January 2022. Among them, 34 patients were treated with sagittal top compression reduction technique (top pressure group), and 25 patients were treated with traditional reduction technique (traditional group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, fracture segment, cause of injury, AO classification of thoracolumbar vertebral fractures, thoracolumbar injury classification and severity (TLICS) score, American Spinal Injury Association (ASIA) grading, surgical approach, preoperative vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, segmental kyphosis angle, visual analogue scale (VAS) score, and Oswestry disability index (ODI). The operation time, intraoperative blood loss, and incidence of complications between the two groups were recorded and compared. After operation, VAS score and ODI were used to evaluate effectiveness, and X-ray and CT examinations were performed to measure imaging indicators such as vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, and segmental kyphosis angle. Results: There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). No complication such as dural sac, nerve root, or vascular injury was found during operation, and all incisions healed by first intention. Patients in both groups were followed up 6-48 months, with an average of 20.6 months. No loosening, breakage, or failure of internal fixation occurred during follow-up. The imaging indicators, VAS score, and ODI of the two groups significantly improved at 1 week and last follow-up when compared to preoperative ones ( P<0.05). At last follow-up, the VAS score and ODI further significantly improved when compared to 1 week after operation ( P<0.05). At 1 week after operation and last follow-up, the vertebral body index, segmental kyphosis angle, injured vertebra angle, and ODI in the top pressure group were significantly better than those in the traditional group ( P<0.05). There was no significant difference in VAS score and height ratio of the anterior margin of injured vertebra between the two groups at 1 week after operation ( P>0.05), but the two indicators in the top pressure group were significantly better than those in the traditional group at last follow-up ( P<0.05). Conclusion: The treatment of thoracolumbar vertebral fractures with sagittal top compression reduction technique can significantly improve the quality of vertebral reduction, and is superior to traditional reduction techniques in relieving pain and improving spinal function.

Induction of Apoptosis by Metabolites of Rhei Radix et Rhizoma (Da Huang): A Review of the Potential Mechanism in Hepatocellular Carcinoma.

Liver cancer is a global disease with a high mortality rate and limited treatment options. Alternations in apoptosis of tumor cells and immune cells have become an important method for detailing the underlying mechanisms of hepatocellular carcinoma (HCC). Bcl-2 family, Caspase family, Fas and other apoptosis-related proteins have also become antagonistic targets of HCC. Da Huang (Rhei Radix et Rhizoma, RR), a traditional Chinese herb, has recently demonstrated antitumor behaviors. Multiple active metabolites of RR, including emodin, rhein, physcion, aloe-emodin, gallic acid, and resveratrol, can successfully induce apoptosis and inhibit HCC. However, the underlying mechanisms of these metabolites inhibiting the occurrence and development of HCC by inducing apoptosis is complicated owing to the multi-target and multi-pathway characteristics of traditional Chinese herbs. Accordingly, this article reviews the pathways of apoptosis, the relationship between HCC and apoptosis, the role and mechanism of apoptosis induced by mitochondrial endoplasmic reticulum pathway and death receptor pathway in HCC and the mechanism of six RR metabolites inhibiting HCC by inducing apoptosis.

Growth parameter acquisition and geometric point cloud completion of lettuce.

The plant factory is a form of controlled environment agriculture (CEA) which is offers a promising solution to the problem of food security worldwide. Plant growth parameters need to be acquired for process control and yield estimation in plant factories. In this paper, we propose a fast and non-destructive framework for extracting growth parameters. Firstly, ToF camera (Microsoft Kinect V2) is used to obtain the point cloud from the top view, and then the lettuce point cloud is separated. According to the growth characteristics of lettuce, a geometric method is proposed to complete the incomplete lettuce point cloud. The treated point cloud has a high linear correlation with the actual plant height (R 2 = 0.961), leaf area (R 2 = 0.964), and fresh weight (R 2 = 0.911) with a significant improvement compared to untreated point cloud. The result suggests our proposed point cloud completion method have has the potential to tackle the problem of obtaining the plant growth parameters from a single 3D view with occlusion.

Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling.

Osteoarthritis (OA) is a deteriorating disease of cartilage tissues mainly characterized as low-grade inflammation of the joint. Innate immune molecule surfactant protein D (SP-D) is a member of collectin family of collagenous Ca2+-dependent defense lectins and plays a vital role in the inflammatory and innate immune responses. The present study investigated the SP-D-mediated innate/inflammatory bioregulation in OA and explored the underlying molecular mechanism. Transcriptome analysis revealed that SP-D regulated genes were strongly enriched in the inflammatory response, immune response, cellular response to lipopolysaccharide (LPS), PI3K-Akt signaling, Toll-like receptor (TLR) signaling, and extracellular matrix (ECM)-receptor interaction pathways. Knockdown of the SP-D gene by the recombinant adeno-associated virus promoted the macrophage specific markers of CD68, F4/80 and TLR4 in the articular cartilage in vivo. SP-D alleviated the infiltration of synovial macrophages and neutrophils, and inhibited TLR4, TNF-α and the phosphorylation of PI3K, Akt and NF-κB p65 in cartilage. SP-D suppressed cartilage degeneration, inflammatory and immune responses in the rat OA model, whilst TAK-242 strengthened this improvement. In in vitro conditions, SP-D pre-treatment inhibited LPS-induced overproduction of inflammation-correlated cytokines such as IL-1ß and TNF-α, and suppressed the overexpression of TLR4, MD-2 and NLRP3. SP-D prevented the LPS-induced degradation of ECM by down-regulating MMP-13 and up-regulating collagen II. Blocking of TLR4 by TAK-242 further enhanced these manifestations. We also demonstrated that SP-D binds to the TLR4/MD-2 complex to suppress TLR4-mediated PI3K/Akt and NF-κB signaling activation in chondrocytes. Taken together, these findings indicate that SP-D has chondroprotective properties dependent on TLR4-mediated PI3K/Akt and NF-κB signaling and that SP-D has an optimal bioregulatory effect on the inflammatory and innate responses in OA.