Genome sequence of a traditional medicinal edible fungus Calvatia gigantea CGMCC5.9.

The Calvatia gigantea is commonly used traditional medicinal edible fungus, which has multiple pharmacological effects. This paper reports the high-quality draft genome assembly of Calvatia gigantea CGMCC5.9, which consists of 39 scaffolds with 36.6 Mb (GC content, 48.37%), an N50 of 1,467,728 bp.

Relative corneal refractive power shift and inter-eye differential axial growth in children with myopic anisometropia treated with bilateral orthokeratology.

PURPOSE: To investigate the relationship between relative corneal refractive power shift (RCRPS) and axial length growth (ALG) in bilateral myopic anisometropes treated with orthokeratology. METHODS: A total of 102 children with myopic anisometropia in this prospective interventional study were randomly assigned to the spectacle group and orthokeratology group. Axial length (AL) and corneal topography was measured at baseline and the 12-month follow-up visit. ALG was defined as the difference between the two measurements, and RCRPS profiles were calculated from two axial maps obtained. RESULTS: In the orthokeratology group, the ALG in the more myopic eye (0.06 ± 0.15 mm) was significantly smaller than that in the less myopic eye (0.15 ± 0.15 mm, p < 0.001), and the interocular difference in AL significantly decreased following 1-year treatment, from 0.47 ± 0.32 to 0.38 ± 0.28 mm (p < 0.001). However, in the spectacle group, the ALG was similar between the two eyes, and the interocular difference in AL did not change significantly over one year (all p > 0.05). The interocular difference in ALG in the orthokeratology group was significantly correlated with the interocular difference in RCRPS (dRCRPS, ß=-0.003, p < 0.001) and the interocular difference in baseline AL (ß=-0.1179, p < 0.001), with R2 being 0.6197. CONCLUSION: Orthokeratology was effective in decreasing the magnitude of anisometropia. The interocular variation in RCRPS is an important factor accounting for the reduction of interocular ALG difference in anisomyopic children post-orthokeratology. These results provide insight into establishing eye-specific myopia control guidelines during orthokeratology treatment for myopic anisometropes.

Comparison of two different orthokeratology lenses and defocus incorporated soft contact (DISC) lens in controlling myopia progression.

BACKGROUND: To compare axial elongation in 8-11-year-old myopes wearing orthokeratology (OK) lenses with different back optic zone diameters (BOZD), defocus incorporated soft contact (DISC) lenses, and single-vision soft contact lenses (SCLs). METHODS: A total of 122 children (aged 8-11 years) with spherical equivalent refraction (SER) between - 1.00 D and - 4.00 D were enrolled in this prospective study and randomly assigned to four groups: 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, DISC, and single-vision SCLs. Children in each group were further divided into subgroups stratified by the average baseline SER: low myopic eyes (SER: - 1.00 D to - 2.50 D) and moderate myopic eyes (SER: - 2.50 D and over). Axial length (AL) was measured at baseline and after one year. RESULTS: The 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, and DISC groups exhibited significantly slower AL elongation than the SCL group. The proportion of slow progressors (AL elongation ≤ 0.18 mm/year) in the first three groups was 42%, 23%, and 29%, respectively. Furthermore, one-year AL elongation was significantly smaller in the 5.0 mm-BOZD OK group compared with the 6.2 mm-BOZD OK group. Regardless of SER, children in the 5.0 mm-BOZD OK and DISC groups showed comparably slower AL elongation than those in the SCL group. However, fitting with 6.2 mm-BOZD OK lenses significantly retarded AL elongation in moderate myopic eyes, but not in low myopic eyes. CONCLUSIONS: Overall, 5.0 mm-BOZD OK lenses, 6.2 mm-BOZD OK lenses, and DISC lenses were effective in retarding AL elongation in 8-11-year-old myopes compared with single-vision SCLs, but for children with SER less than - 2.50 D, fitting with 5.0 mm-BOZD OK lenses and DISC lenses yielded better myopia control efficacy compared to wearing single-vision SCLs or 6.2 mm-BOZD OK lenses.

Integrated omic profiling of the medicinal mushroom Inonotus obliquus under submerged conditions.

BACKGROUND: The Inonotus obliquus mushroom, a wondrous fungus boasting edible and medicinal qualities, has been widely used as a folk medicine and shown to have many potential pharmacological secondary metabolites. The purpose of this study was to supply a global landscape of genome-based integrated omic analysis of the fungus under lab-growth conditions. RESULTS: This study presented a genome with high accuracy and completeness using the Pacbio Sequel II third-generation sequencing method. The de novo assembled fungal genome was 36.13 Mb, and contained 8352 predicted protein-coding genes, of which 365 carbohydrate-active enzyme (CAZyme)-coding genes and 19 biosynthetic gene clusters (BCGs) for secondary metabolites were identified. Comparative transcriptomic and proteomic analysis revealed a global view of differential metabolic change between seed and fermentation culture, and demonstrated positive correlations between transcription and expression levels of 157 differentially expressed genes involved in the metabolism of amino acids, fatty acids, secondary metabolites, antioxidant and immune responses. Facilitated by the widely targeted metabolomic approach, a total of 307 secondary substances were identified and quantified, with a significant increase in the production of antioxidant polyphenols. CONCLUSION: This study provided the comprehensive analysis of the fungus Inonotus obliquus, and supplied fundamental information for further screening of promising target metabolites and exploring the link between the genome and metabolites.

Cartilage organoids for cartilage development and cartilage-associated disease modeling.

Cartilage organoids have emerged as powerful modelling technology for recapitulation of joint embryonic events, and cartilage regeneration, as well as pathophysiology of cartilage-associated diseases. Recent breakthroughs have uncovered "mini-joint" models comprising of multicellular components and extracellular matrices of joint cartilage for development of novel disease-modifying strategies for personalized therapeutics of cartilage-associated diseases. Here, we hypothesized that LGR5-expressing embryonic joint chondroprogenitor cells are ideal stem cells for the generation of cartilage organoids as "mini-joints" ex vivo "in a dish" for embryonic joint development, cartilage repair, and cartilage-associated disease modelling as essential research models of drug screening for further personalized regenerative therapy. The pilot research data suggested that LGR5-GFP-expressing embryonic joint progenitor cells are promising for generation of cartilage organoids through gel embedding method, which may exert various preclinical and clinical applications for realization of personalized regenerative therapy in the future.

The relationship between baseline axial length and axial elongation in myopic children undergoing orthokeratology.

PURPOSE: To investigate the correlation between the baseline axial length (AL) and axial elongation in myopes undergoing orthokeratology (ortho-k). METHODS: This was a retrospective study. During the 1-year follow-up, 1176 children (aged 8-14 years) were included and divided into an ortho-k group (n = 588) and a single-vision spectacle group (n = 588). The ortho-k group participants (8-11 years of age) who completed the 3-year follow-up (n = 150) were further divided into three subgroups stratified by their baseline AL: subgroup 1 (AL < 24.5 mm), subgroup 2 (24.5 ≤ AL < 26 mm) and subgroup 3 (AL ≥ 26 mm). AL was measured at baseline and during the annual visit. RESULTS: The ortho-k group exhibited slower 1-year axial elongation (39% reduction) than the spectacle group. The 1-year axial elongation was negatively correlated with initial age in both groups. A negative association between 1-year axial elongation and baseline AL was observed in the ortho-k group but not in the spectacle group. However, this relationship only existed in ortho-k participants 8-11 years of age. For the younger ortho-k participants who completed the 3-year follow-up, the annual axial elongation was significantly higher in subgroup 1 for the first and second years but not in the third year compared with subgroups 2 and 3. CONCLUSION: Axial elongation was negatively correlated with baseline AL in the ortho-k group. Children aged 8-11 years with longer baseline AL (≥24.5 mm) demonstrated slower annual axial elongation during the first 2 years of ortho-k treatment, which may provide insight into establishing individual guidelines for controlling myopia using ortho-k in children with different baseline characteristics.

The effect of back optic zone diameter on relative corneal refractive power distribution and corneal higher-order aberrations in orthokeratology.

PURPOSE: To compare axial elongation, relative corneal refractive power (RCRP) distribution within the pupillary diameter, and corneal higher-order aberrations (HOAs) in myopic children wearing orthokeratology (ortho-k) lenses with different back optic zone diameters (BOZD). METHODS: Children aged 8-11 years were fitted with 5.0 or 6.2 mm-BOZD ortho-k lenses (groups A and B, respectively). Axial length (AL) and corneal topography were measured at baseline and during the annual visit. RCRP and corneal HOAs were compared between the two groups after one-year treatment. Multivariate linear regression analysis was performed to determine the association between AL elongation and RCRP parameters, corneal HOAs, and other variables between the groups. RESULTS: After one-year treatment, axial elongation was slower in group A than in group B, with a difference of 0.15 mm. Children in group A showed smaller treatment zone size, smaller 3/4X value (describing the distance from the apex RCRP profile rising to its three-quarter-peak level), greater RCRP sum value within the pupillary area, and higher increases in corneal total HOAs and horizontal coma (Z31). AL elongation was significantly correlated with baseline age, baseline spherical equivalent refraction (SER), treatment zone size, and 3/4X value. CONCLUSIONS: Ortho-k lenses designed with smaller BOZD increased myopia control efficacy, induced a steeper distribution of the RCRP profile within the pupillary diameter, and induced greater increases in corneal total HOAs and horizontal coma (Z31). Lens-induced RCRP profile within pupillary diameter, rising to its three-quarter-peak level at a smaller distance, may show a better myopia control effect.

Bistable insulin response: The win-win solution for glycemic control.

To satisfy both the safety and rapidity of glycemic control, muscles' insulin response must be bistable, as theoretically predicted. Here, we test the bistability hypothesis by combining cellular experiments (to measure the threshold values in vitro) with mathematical modeling (to test the relevance of bistability in vivo). We examine bistability in C2C12 myotubes by both single-cell analysis (FÓ§rster resonance energy transfer) and cultured cells analysis (immunoblot). These technologies demonstrate bistable insulin response, with typical switch-on and switch-off thresholds of approximately 300 and 100 pM, respectively. Our mathematical model demonstrates the indispensability of bistability in interpreting experimental data, reveals fine details of plasma glucose-insulin dynamics, and explains unclear phenomena. These results suggest that the body's ability to simultaneously avoid both hypoglycemia and hyperglycemia is mediated by bistability. The switch-on threshold is a promising biomarker for metabolic complications due to its deep quantitative connection with body composition, which is easy to measure.

Copper regulation of immune response and potential implications for treating orthopedic disorders.

Copper is an indispensable trace metal element in human body, and copper deficiency is rare in clinic. However, diseases associated with serum copper deficiency, such as leukopenia, neutropenia, arthritis, osteoporosis, and bone defects, are well known. Copper ions can also achieve the effect of fighting pathogenic bacteria through the "contact killing" characteristic. Copper ion is also an important cofactor of bone matrix synthase, plays an important role in the pathophysiology of orthopedic diseases. The present review highlights the biological functions of copper in immunity, bone diseases and stem cells, as well as potential drug development targeting copper status for diagnostics and therapeutics of copper-associated bone diseases.

Alleviation of osteoarthritis by intra-articular transplantation of circulating mesenchymal stem cells.

This study aimed to evaluate the efficacy of intra-articular delivery of peripheral blood derived mesenchymal stromal cells (PB-MSCs) on the progression of trauma-induced osteoarthritis (OA) in mice. Adult male C57BL/6J mice subjected to destabilization of the medial meniscus surgeries (DMM) were randomly divided into four groups: sham surgery group; vehicle control group (treated with saline), PBMSC-treated group, or adipose tissue derived MSCs (AD-MSC)-treated group (n = 4 per group). PB-MSCs and AD-MSCs were harvested and cultured following previously established protocols, and pre-labeled with BrdU for 48 h before transplantation. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3-5) were intra-articular injected into the right knee joints thrice post-surgery. The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations. PB-MSCs administration significantly reduced subchondral bone volume comparing to the vehicle control group. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which was comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of the PB-MSCs treated group comparing to that of the vehicle control group. Co-expression of BrdU and Sox9 indicated that injected PB-MSCs differentiated in chondrocytes in situ, along with reduced levels of IL-6 within peripheral sera of PB-MSCs- and AD-MSCs-treated mice. Therefore, administration of PB-MSCs or AD-MSCs attenuated trauma-induced OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs are ideal cell source for treating cartilage-associated diseases.

The treatment zone decentration and corneal refractive profile changes in children undergoing orthokeratology treatment.

BACKGROUND: To confirm the association between treatment-zone (TZ) decentration and axial length growth (ALG) in children who underwent orthokeratology; and to explore the association between TZ decentration and relative corneal refractive power (RCRP) profile, which was known to be significantly associated with ALG retardation. METHODS: Four hundred myopic children of age 12 years participated in the study, with 200 wearing orthokeratology lenses and the other 200 wearing single-vision spectacle as the controls. Cycloplegic refraction was performed at baseline. Axial length was measured at baseline and 12 months after initial lens wear, and ALG was defined as the difference. In the ortho-k group, TZ decentration and the RCRP map were calculated from the topography map obtained at the 12-month visit. RCRP were summed within various chord radii from the cornea center, and the association to TZ decentration, spherical equivalent (SE), ALG were analyzed with linear regressions. RESULTS: Compared to the controls, children wearing orthokeratology lenses had significantly smaller ALG over 1 year (0.1 ± 0.15 mm vs. 0.32 ± 0.17 mm, p < 0.001). ALG was significantly and negatively associated with summed RCRP within the central cornea of 2 mm in radius. The mean TZ decentration was 0.62 ± 0.25 mm, and the mean direction was 214.26 ± 7.39 degrees. ALG was negatively associated with the TZ decentration magnitude (p < 0.01), but not the direction (p = 0.905). TZ decentration caused an asymmetrical distribution of the RCRP with the nasal side plus power shifting towards the corneal center. For chord radius ranging 1-2 mm, the association between TZ decentration and the summed RCRP were significant, and the proportion of variance accountable increased with chord radius. For chord radius beyond 1.5 mm, the association between baseline spherical equivalent (SE) and summed RCRP was significant. The portion of variance accountable by SE increased and peaked in 2.5 mm chord radius. CONCLUSIONS: A larger TZ decentration was associated with a larger summed RCRP in the central cornea. It may be one of the possible reasons why TZ decentration is beneficial to retarding myopia progression.

Comprehensive identification of protein orthologs in the family Ascoviridae facilitates an understanding of phylogenomics, protein conservation, and phosphorylation.

Analysis of orthology is important for understanding protein conservation, function, and phylogenomics. In this study, we performed a comprehensive analysis of gene orthology in the family Ascoviridae based on identification of 366 protein homologue groups and phylogenetic analysis of 34 non-single-copy proteins. Our findings revealed 90 newly annotated proteins, five newly identified core proteins for the family Ascoviridae, and 14 core proteins for the genus Ascovirus. A phylogenomic tree of 11 Ascoviridae members was constructed based on a concatenation of 35 of the 45 ortholog groups. In combination with phosphoproteomic results and conservation estimations, 30 conserved phosphorylation sites on 17 phosphoproteins were identified from a total of 176 phosphosites on 57 phosphoproteins from Heliothis virescens ascovirus 3h (HvAV-3h), providing potential research targets for investigating the role of these protein in the regulation of viral infection. This study will facilitate genome annotation and comparison of further Ascoviridae members as well as functional genomic investigations.

Cranial Bone Transport Promotes Angiogenesis, Neurogenesis, and Modulates Meningeal Lymphatic Function in Middle Cerebral Artery Occlusion Rats.

BACKGROUND: Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model. METHODS: CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function. RESULTS: CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats. CONCLUSIONS: This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.

An enhanced cascade-based deep forest model for drug combination prediction.

Combination therapy has shown an obvious curative effect on complex diseases, whereas the search space of drug combinations is too large to be validated experimentally even with high-throughput screens. With the increase of the number of drugs, artificial intelligence techniques, especially machine learning methods, have become applicable for the discovery of synergistic drug combinations to significantly reduce the experimental workload. In this study, in order to predict novel synergistic drug combinations in various cancer cell lines, the cell line-specific drug-induced gene expression profile (GP) is added as a new feature type to capture the cellular response of drugs and reveal the biological mechanism of synergistic effect. Then, an enhanced cascade-based deep forest regressor (EC-DFR) is innovatively presented to apply the new small-scale drug combination dataset involving chemical, physical and biological (GP) properties of drugs and cells. Verified by the dataset, EC-DFR outperforms two state-of-the-art deep neural network-based methods and several advanced classical machine learning algorithms. Biological experimental validation performed subsequently on a set of previously untested drug combinations further confirms the performance of EC-DFR. What is more prominent is that EC-DFR can distinguish the most important features, making it more interpretable. By evaluating the contribution of each feature type, GP feature contributes 82.40%, showing the cellular responses of drugs may play crucial roles in synergism prediction. The analysis based on the top contributing genes in GP further demonstrates some potential relationships between the transcriptomic levels of key genes under drug regulation and the synergism of drug combinations.

The treatment zone size and its decentration influence axial elongation in children with orthokeratology treatment.

BACKGROUND: To investigate whether the treatment zone size (TZS) and treatment zone decentration (TZD) will affect the axial elongation in myopic children undergoing orthokeratology treatment. METHODS: A self-controlled retrospective study was conducted on 352 children who met the inclusion criteria. Axial length was measured before and at 12 months after the initial lens wear. Corneal topography was measured at baseline and at each follow-up after lens wear. The Corneal topography obtained from the 12-month visit was used to quantify TZS and TZD for each subject. Cycloplegic refraction was required for all children before fitting the orthokeratology lenses. RESULTS: Axial elongation was significantly associated with age, baseline spherical equivalent (SE), TZS, and TZD with univariate linear regression. In groups with both small and large TZS, axial elongation was significantly decreased with large TZD (both P < 0.01). In groups with both small and large TZD, axial elongation was significantly decreased with small TZS (P = 0.03 for small TZD, P = 0.01 for large TZD). Age, SE, and TZD were significantly associated with axial elongation in multiple regression (all P < 0.01). CONCLUSION: Relatively smaller TZS and larger TZD may be beneficial in slowing myopia progression in children with orthokeratology treatment.

Sox11 Modified Tendon-Derived Stem Cells Promote the Repair of Osteonecrosis of Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.

Dynamic regulation of mitochondrial-endoplasmic reticulum crosstalk during stem cell homeostasis and aging.

Cellular therapy exerts profound therapeutic potential for curing a broad spectrum of diseases. Adult stem cells reside within a specified dynamic niche in vivo, which is essential for continuous tissue homeostatic maintenance through balancing self-renewal with lineage selection. Meanwhile, adult stem cells may be multipotent or unipotent, and are present in both quiescent and actively dividing states in vivo of the mammalians, which may switch to each other state in response to biophysical cues through mitochondria-mediated mechanisms, such as alterations in mitochondrial respiration and metabolism. In general, stem cells facilitate tissue repair after tissue-specific homing through various mechanisms, including immunomodulation of local microenvironment, differentiation into functional cells, cell "empowerment" via paracrine secretion, immunoregulation, and intercellular mitochondrial transfer. Interestingly, cell-source-specific features have been reported between different tissue-derived adult stem cells with distinct functional properties due to the different microenvironments in vivo, as well as differential functional properties in different tissue-derived stem cell-derived extracellular vehicles, mitochondrial metabolism, and mitochondrial transfer capacity. Here, we summarized the current understanding on roles of mitochondrial dynamics during stem cell homeostasis and aging, and lineage-specific differentiation. Also, we proposed potential unique mitochondrial molecular signature features between different source-derived stem cells and potential associations between stem cell aging and mitochondria-endoplasmic reticulum (ER) communication, as well as potential novel strategies for anti-aging intervention and healthy aging.

Hydroxysafflor yellow A promotes osteogenesis and bone development via epigenetically regulating ß-catenin and prevents ovariectomy-induced bone loss.

In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxysafflor yellow A (HSYA), one of the essential compounds of Safflower, has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteogenesis through epigenetic control and ovariectomy-induced bone loss in vivo has not been explored. Therefore, the study aimed to explore the function and mechanism of HSYA on bone formation and development. We found HSYA could enhance the cell viability and promote osteogenesis of hBMSCs in vitro. Mechanistically, HSYA could increase the expression of ß-catenin leading to its accumulation in the nucleus and activation of downstream targets to promote osteogenesis. Besides, RNA-seq and quantitative RT-PCR and western blot showed KDM7A was significantly increased by HSYA. The occupancy of H3K27me2 on ß-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA promoted bone development in chick embryos and prevented ovariectomy (OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA could promote osteogenesis and bone development via epigenetically regulating ß-catenin and prevent ovariectomy-induced bone loss.

Asiatic acid protects articular cartilage through promoting chondrogenesis and inhibiting inflammation and hypertrophy in osteoarthritis.

Natural small molecules have become attractive in osteoarthritis (OA) treatment. This study aims to investigate the effect of asiatic acid (AA) on OA development in vitro and in vivo. Chondrocytes were pretreated with AA at optimized concentrations and subsequently treated with interleukin-1 beta (IL-1ß). Inflammatory mediator nitric oxide (NO) was measured by Griess method. The mRNA expression level of inflammatory markers nitric oxide synthase (iNOS) and cyclooxygenase 2 (Cox2), as well as chondrogenic or hypertrophic markers including SRY-box transcription factor 9 (Sox9), Aggrecan, Collagen 2a1 (Col II), and Matrix metalloproteinase-13 (Mmp13) were measured by using real-time PCR analysis. The nuclear factor-kappa B (NF-κB) signaling activity was determined by dual luciferase assay and Western blot analysis. Surgery-induced OA animal model was constructed, and AA was administrated to study its effect on OA pathogenesis. AA induced a dose-dependent inhibitory effect up to -67.4% on NO production. AA could repress iNOS and Cox2 protein expression levels (-77.2% and -73.4%, respectively) in IL-1ß induced chondrocytes. AA increased the formation of cartilage extracellular matrix components including glycosaminoglycans (GAGs) and collagen type II. AA also mRNA expression of chondrogenesis marker including Aggrecan, Sox9, Col II and Fibronectin (402.87%, 151.04%, 314.15% and 187.76%, respectively) as well as hypertrophic marker Mmp13 (-67.8%). AA repressed the chondrocyte inflammation by directly inhibiting NF-κB signaling activity, which was revealed by the inhibition effect of AA on IκBα phosphorylation (-105.4%) and NF-κB/p65 translocation (-60.9%) induced by IL-1ß. Furthermore, In vivo OA study indicated the protective effect of AA on OA progression by preventing articular cartilage from degeneration and destruction. AA treatment could significantly reduce OA score (16.125 vs 5.25) and repress mRNA expression level of Mmp13 and Col X (23.5, vs 2.375 and 18.125 vs 94.5). Taken together, our findings suggest that AA could effectively rescue IL-1ß induced chondrocytes and protected cartilage in OA progression, which shed light on a potential novel therapeutic strategy of OA treatment.

The Association between Fourier Parameters and Clinical Parameters in Myopic Children Undergoing Orthokeratology.

Purpose: To explore how Fourier parameters are associated with axial length growth (ALG) and clinical parameters in children who underwent orthokeratology.Materials and Methods: A total of 267 children received orthokeratology. Baseline cycloplegic autorefraction was performed. Axial length was measured at baseline and one year after the lens dispatch, and the difference was defined as ALG. Corneal topography was performed at the same two visits. Central treatment zone (CTZ) was identified from the difference between the two tangential maps, and its center distance to corneal center was defined as decentration. A relative refractive corneal power (RCRP) map was derived by subtracting the center value from every point on the one-year axial map. It was decomposed into 3 Fourier components: a mean (F0), a single-cycle sinewave (F1), and a double-cycle sinewave (F2). Linear regressions were used to reveal the association between ALG and these parameters.Results: At baseline, the age was 10.18 ± 1.48 year, spherical equivalent (SE) was - 3.10 ± 1.15D, astigmatism was 1.17 ± 0.58D, and axial length was 24.69 ± 0.81 mm. The mean ALG was 0.181 ± 0.22 mm. In multiple regression, ALG was negatively associated with F1 (p < .001), not F0 and F2. Amplitude-wise, F0 and F1 were correlated with decentration (p < .01) and SE (p < .01), and F2 was associated with astigmatism (p < .001). Direction-wise, F1 was correlated with decentration (p < .001) and F2 was associated with astigmatism (p < .001).Conclusions: Among Fourier parameters, F0 and F1 were negatively associated with ALG in myopic children undergoing orthokeratology. Their associations to SE and CTZ decentration may partially explain the effect on ALG retardation.