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Sijie Chen,1,* Longsheng Huang,2,* Guihua Liu,2 Jie Kang,3 Qinfang Qian,2 Jingrong Wang,4 Rong Wang,1 Lizhen Zheng,1 Haijun Wang,5 Ping Ou2 1College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 2Child Health Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of TCM Syndrome Research Base, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, 350122, People’s Republic of China; 4Child Health Center, Fujian Branch of Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou, Fujian Province, 350011, People’s Republic of China; 5School of Public Health, Peking University, Beijing, 100089, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Ou, Child Health Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86-13905916211, Email fyxwktz2021@126.comPurpose: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes.Patients and Methods: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Běnshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus.Results: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups.Conclusion: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.Keywords: acupuncture, autism, behavioral abnormalities, RNA-sequencing

Osteoporotic fracture with increase of aging population became an urgent orthopedic problem. Bisphosphonates were widely recommended as effective clinical treatment drugs. Combination of biodegradable Mg-based implants and merits of bisphosphonates was suggested for osteoporotic fracture healing. Considering the mild and sustained drug release, a novel one-step electrodeposition synthesis of drug loaded coating was proposed in this study. In comparison to conventional soaking method, encapsulated zoledronate coating by one-step electrodeposition method could modulate drug release in first diffusion-controlled and later degradation-controlled manner. The in vitro cell response to zoledronate loaded coating showed enhanced proliferation and osteogenic differentiation of osteoblasts and no significant inhibition on osteoclasts, which could improve bone-forming and decrease bone resorption due to osteoporosis.

Highlights Nanoparticles hold considerable promise for controlling the local pharmacokinetics of therapeutic agents during osteoarthritis therapy. The advantages of nanoparticles, the bioactive design, the transports and interactions within cartilage, and therapeutic mechanisms are discussed. This review proposes future strategies to design more intelligent and multi-functional nanomaterials as delivery systems for cartilage therapy., Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of “smart” bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.

Purpose Corticosteroid (CS) therapy for infectious and rheumatological diseases showed to decrease serum magnesium (Mg++) level and induce muscle atrophy in patients. The present study investigated the effects of Mg++ supplementation on preventing CS-induced muscle atrophy in an animal model, which provided experimental data for potential clinical translation. Methods Twelve 24-week-old male Sprague–Dawley rats were treated with lipopolysaccharide (LPS) and CS methylprednisolone (MPS) to induce muscle atrophy, with half of the rats also given daily 50 mg/kg Mg++ oral supplementation. Additional six rats without LPS + CS treatments were used as normal controls. After treatment for 6 weeks, serum was collected for Mg++ quantification, animal dual-energy X-ray absorptiometry (DXA) was performed for tissue composition, and the extensor digitorum longus (EDL) was collected for muscle functional test and histology including muscle fiber size, intramuscular fat infiltration and fiber typing. In vitro myotube atrophy model was used to study the in vitro effect associated with in vivo muscle atrophy. Results LPS + CS treatments induced hypomagnesemia while the serum Mg++ level was in normal range after Mg++ supplementation. DXA showed 53.0% lower fat percent and 29.7% higher lean mass in LPS + CS + Mg group when compared to LPS + CS group. Muscle functional test showed 22.2% higher specific twitch force and 40.3% higher specific tetanic force in LPS + CS + Mg group when compared to LPS + CS group. Histological analysis showed 4.1% higher proportion of muscle fibers area to total area and 63.6% lower intramuscular fat infiltration in EDL sections in LPS + CS + Mg group when compared to LPS + CS group. LPS + CS + Mg group had 33.0% higher area proportion and 29.4% higher cross-sectional area (CSA) of type IIb muscle fiber. Myoblast culture results showed that Mg++ supplementation group had larger myotube diameter. The mRNA expressions of the muscle atrophy marker genes MuRF1 and MAFbx were lower in Mg++ supplementation group both in vitro and in vivo. Conclusion The current study demonstrated that Mg++ supplementation successfully alleviated CS-associated muscle atrophy in rats at both functional and morphology levels, indicating a translational potential for patients undergoing CS therapy. This study provided the evidence for the first time that Mg++ supplementation could prevent muscle atrophy—an adverse effect of CS therapy, currently also adopted for treating coronavirus disease 2019 (COVID-19).

Entomopathogenic fungus as biological control agent plays a crucial role in the integrated management of insect pests. Metarhizium anisopliae Ma6 has been identified as a highly pathogenic strain against Phyllotreta striolata (Fabricius) (Coleoptera: Chrysomelidae), one of the most economically important and dominant insect pests damaging Brassica plants. The infection of M. anisopliae Ma6 on P. striolata was observed under stereomicroscopy and scanning electron microscopy (SEM), and biochemical defense responses of P. striolata adults after infection were investigated. The changes in total amino acids and free fatty acids, and the activities of protective enzymes, including catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), in P. striolata adults were measured. In stereomicroscopy and SEM observations, a large number of mycelia were observed on the body surface of P. striolata on the 5th day after treatment by M. anisopliae. Many conidia were germinated and covered the body of P. striolata on the 7th day after treatment. The free fatty acid, total amino acid, CAT, POD, and SOD activities all showed an increased and then decreased trend. These results suggest that entomopathogenic fungal infection triggers the defense response of hosts, which induces changes in nutrients and antioxidant enzymes in P. striolata adults. Our findings provide useful information for understanding the potential for using M. anisopliae Ma6 as a biocontrol agent.

Magnesium (Mg) and its alloys have been intensively explored as the next generation of metallic bone substitutes in past decades, but their rapid corrosion rate in physiological environments is still a great hindrance for further therapeutic applications. In the present study, we attempt to design biodegradable poly(l-lactic acid) (PLLA) coatings on pure Mg substrates (99.99 wt %) with tunable surface morphologies through dip-coating in combination with mixed nonsolvent induced phase separation (Dip-coating-mNIPS) method to regulate their corrosion behavior and biocompatibility. We applied the mixtures of ethanol and hexane as the coagulation baths, and changed the composition of mixed nonsolvent and the concentration of polymer solution to obtain PLLA coatings with different pore sizes and morphologies. Standard electrochemical measurements and immersion tests demonstrated that all PLLA coatings could effectively enhance the corrosion resistance of Mg substrates but that the corrosion behaviors varied among coatings with different surface and inner structures. A systematic investigation of cellular response through MTT assay, LIVE/DEAD staining, cell distribution, and cell attachment indicated that PLLA-coated Mg substrates could enhance cytocompatibility in comparison to pure Mg. In addition, the cellular behaviors were affected by the corrosion activity as well as the surface properties of different PLLA coatings. Our findings illustrated that through the Dip-coating-mNIPS method, the structure of the PLLA membrane on Mg substrates could easily be controlled to regulate the corrosion behaviors and further improve the biocompatibility. This presents great potential in designing functional polymer coatings on Mg-based orthopedic implants to meet specific clinical requirements.

Magnesium (Mg) and its alloys show excellent potential as orthopedic implantable materials, with their in vivo degraded Mg ions (Mg

Fruit bagging is a commonly used cultivation measure to protect citrus fruit from insects and adverse environments. The present study aimed to comprehensively investigate the effects of bagging on the physiochemical characteristics of grapefruit. The grapefruit were bagged at approximately 110–120 d after anthesis with a one-layer kraft paper bag with black coating inside (SL), a double-layer kraft paper bag with one black paper as the inner layer (DL), and a three-layer kraft paper bag with two black papers as inner layers (TL), respectively. Ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) technique was used to identify a total of 19 flavonoids, 2 phenylpropanoids, 9 coumarins, and 5 limonoids. By using UPLC, 50 carotenoids were identified. Gas chromatography–mass spectrometry was used to identify 3 soluble sugars, 3 organic acids, and 11 amino acids. In the quantitated components in the peel (albedo and flavedo), the chlorophylls and the carotenoids components (such as luteoxanthin, violaxanthin, 9-cis-violaxanthin, xanthophyll, zeaxanthin and β-carotene) were significantly downregulated by bagging, causing the surface color of bagged fruit to turn yellow earlier but paler than that of the unbagged control, particularly in the three-layer kraft bag treatment. Unlike the peel, the color and the carotenoid content of the juice sacs were less affected. The physiochemical compounds other than pigments, including soluble sugars, organic acids, amino acids, flavonoids, coumarins and limonoids, were minimally affected by bagging treatments. Our results indicated that bagging at approximately 110–120 d after anthesis exerted influence mainly on peel color, but less on sugars, acids, amino acids, flavonoids, limonoids and coumarins of grapefruit.

Magnesium (Mg) and its alloys show excellent potential as orthopedic implantable materials, with their in vivo degraded Mg ions (Mg2+) known to promote the growth of new bone. However, the swift co...

In this study, perforated cannulated magnesium (Mg) hip stents were fabricated via modified Mg injection molding and conventional machining, respectively. Additionally, the stent canal was filled with paraffin to simulate injection of biomaterials. The microstructure, mechanical performance, corrosion behavior, and biocompatibility were comparably studied. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process. After immersion in SBF, machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents. Corrosion resistance was improved via paraffin-filling. Consistently, the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones, which was improved by paraffin-filling treatment as well. These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required, which could be enhanced by designing canal-filling injection of biomaterials as well.

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Here, we demonstrated that magnesium (Mg) nail implantation into the marrow cavity degraded gradually accompanied with about 4-fold increase of new bone formation and over 5-fold of new vessel formation as compared with DO alone group in the 5 mm femoral segmental defect rat model at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. CGRP concentration-dependently promoted endothelial cell migration and tube formation. Meanwhile, CGRP promoted the phosphorylation of focal adhesion kinase (FAK) at Y397 site and elevated the expression of vascular endothelial growth factor A (VEGFA). Moreover, inhibitor/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation. We revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.

In this paper, the effect of binder decay rather than a change in the pigments on the blurring of ancient wall paintings was researched. The simulated wall paintings were prepared by brushing an aqueous solution containing gelatine and ochre grains on the surface of cylindrical compressed soil samples. Then, the dried samples were calcined at 650 °C for 2 h to obtain the simulated wall paintings with the degraded binder gelatine. Next, the calcined samples were brushed with a certain amount of acetone solution containing an ionic liquid ([BMIm]PF6) to obtain the corresponding repaired samples. Based on the results from various characterization methods (UV–vis, FTIR, XRD, XPS, SEM, TG), the following conclusions were drawn. The degradation of the binder caused by calcination increases the surface roughness of the painting layer, resulting in enhanced scattering. In this case, because scattering decrease the light absorption by the pigments, even if unchanged pigment exists in the painting layer, its colour can become blurred. The filling of the ionic liquid into the pores caused by gelatine decay in the painting layer can decrease the scattering, and the blurred colour can be restored to some extent. As typical examples, this principle was successfully applied to restore the blurred colour of an ancient Chinese wall painting (Tang Dynasty) and a pottery (Eastern Han Dynasty).

Displaced fractures of patella often require open reduction surgery and internal fixation to restore the extensor continuity and articular congruity. Fracture fixation with biodegradable magnesium (Mg) pins enhanced fracture healing. We hypothesized that fixation with Mg pins and their degradation over time would enhance healing of patellar fracture radiologically, mechanically, and histologically. Transverse patellar fracture surgery was performed on thirty-two 18-weeks old female New Zealand White Rabbits. The fracture was fixed with a pin made of stainless steel or pure Mg, and a figure-of-eight stainless steel band wire. Samples were harvested at week 8 or 12, and assessed with microCT, tensile testing, microindentation, and histology. Microarchitectural analysis showed that Mg group showed 12% higher in the ratio of bone volume to tissue volume at week 8, and 38.4% higher of bone volume at week 12. Tensile testing showed that the failure load and stiffness of Mg group were 66.9% and 104% higher than the control group at week 8, respectively. At week 12, Mg group was 60.8% higher in ultimate strength than the control group. Microindentation showed that, compared to the Control group, Mg group showed 49.9% higher Vickers hardness and 31% higher elastic modulus at week 8 and 12, respectively. At week 12, the new bone of Mg group remodelled to laminar bone, but those of the control group remained woven bone-like. Fixation of transverse patellar fracture with Mg pins and its degradation enhanced new bone formation and mechanical properties of the repaired patella compared to the Control group., Graphical abstract Image 1, Highlights • Kirschner wires (K-wire) with tension band wire is widely used fixation implants for repairing of displaced patellar fractures. • Fixation of patellar fracture with Mg pins enhanced new bone formation and mechanical properties of the repaired patella. • With a stainless steel tension band wire, Mg pins may be an alternative to K-wire for fixation of patellar fractures.

Targeting delivery system has been widely used in packaging drugs for medical therapies attributed to its high efficiency and efficacy. A Traditional Chinese Medicine (TCM) formula consisting of Herba Epimedii has previously been shown to effectively treat postmenopausal osteoporosis. We have subsequently found that icaritin, which was a flavonoid isolated from both Herba Epimedii and its serum metabolites after oral administration, inhibited the adipogenic capacity of bone mesenchymal stem cells (BMSCs) while promoted their osteogenesis. However, previous pharmacokinetic analyses have shown that icaritin had a short half-life in blood and only trace amounts of the molecule reach the bone tissue. To overcome this limitation, we developed a bone-targeting liposome containing an oligopeptide of eight aspartate residues (Asp8), which had previously been shown to specifically target the bone, encapsulating icaritin. In vivo, we found that the Asp8-icaritin-liposome enhanced bone formation in ovariectomized mice compared to an icaritin-liposome control lacking the Asp8 moiety. Through in vitro mechanistic studies we further found that icaritin inhibited adipogenesis through an Akt/GSK-3β/β-catenin signaling pathway. Taken together, our study shows that Asp8-liposome as a bone-targeting delivery system is effective to carry an osteogenic phytomolecule for facilitating and enhancing its therapeutic effects on the prevention of estrogen depletion-induced osteoporosis.

Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s). The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON) in rats with pulsed injections of lipopolysaccharide (LPS) and methylprednisolone (MPS). Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg) and three intraperitoneal injections of MPS (100 mg/kg) with a time interval of 24 hour, and then, MPS (40 mg/kg) was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19) mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT) showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction. Conclusion: The present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON. The translational potential of this article: The present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON. Keywords: Animal model, Corticosteroid, Osteonecrosis

One of the effective strategies for prevention of steroid-associated osteonecrosis (SAON) is to inhibit bone resorption and fat formation and promote bone formation at osteonecrotic sensitive skeletal sites. We identified a novel phytomolecule that showed positive effects on osteogenesis, anti-bone resorption and anti-adipogenesis in vitro and also developed a bone-targeting delivery system (BTDS) for in vivo experimental study. The study investigated if our innovative synthesized BTDS carrying this phytomolecule would be able to effectively prevent SAON in a rat model. SAON was induced by combined injections of lipopolysaccharide and methylprednisolone. SAON rats were divided into four groups, one SAON untreated control group and three SAON treatment groups with different types of delivery systems (Asp8-liposome-icaritin, liposome-icaritin and Asp8-liposome) for two weeks. SAON lesions were identified and osteoclasts activity, osteogenesis and adipogenesis at these sites were evaluated by immunohistochemistry. Ex vitro study was also designed to evaluate the osteogenic and adipogenic potential of the isolated bone marrow stromal cells (BMSCs) via real-time PCR and histochemical staining. Our results showed that as a bone surface-specific BTDS, Asp8-liposome-icaritin effectively prevented steroids-treated rats from SAON with significantly decreased osteocytes apoptosis, down-regulated osteoclatsogenesis and up-regulated osteogenesis. However, both liposome-icaritin and Asp8-liposome treatment did not show significant efficacy for SAON prevention. In summary, this proof-concept-study showed for the first time that the innovative Asp8-liposome-icaritin BTDS was effective for prevention of SAON in terms of bone resorption prevention, adipogenesis suppression, and bone-formation enhancement.

Background/Objective: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial to investigate the safety and efficacy of Chinese herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH). Methods: Patients of both genders, aged between 18 and 65 years, with diseases such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid arthritis indicated for CS treatment and who did not show magnetic resonance imaging of ONFH at baseline were recruited into the study and then randomised into either XLGB group (n = 129) with daily oral administration of XLGB or placebo group (n = 146). Results: Magnetic resonance imaging revealed a total of 30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and 14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p

Fading and showing mechanisms of ancient color paintings based on light scattering induced by particles were proposed. To confirm the mechanisms, simulated and application experiments were carried out to restore an ancient blurred color painting. Loading TiO2 particles (500–1000 nm) onto a piece of colored paper could result in blurring of the color of the paper, which is attributed to light scattering caused by air voids between the particles. Filling air voids with ionic liquid (a non-volatile solution with a high refractive index) could highlight the color by reducing scattering. These results were experimentally testified by the combination of a fluorescence probe and multi-angle reflectance spectra, in which scattering decreased the incident optical path in the painting layer while the incident optical path was increased by filling the air voids with ionic liquid. As a practical example, the proposed method was applied to highlight an ancient Chinese painting with blurred color. This investigation is very useful to restore faded color paintings.

Constructing methods for cleaning stains on paper artworks that meet the requirements of preservation of cultural relics are still challenging. In response to this problem, a novel electrochemical cleaning method and the preparation of corresponding electrodes were proposed. For this purpose, the conductive graphene (rGO)/polyacryamide (PAM)/montmorillonite (MMT) composite hydrogel as cathode and PbO2-based material as anode were prepared and characterized. The electrochemical cleaning efficiencies of real sample and mimicking paper artifacts were evaluated, and the effects of the electrochemical cleaning on paper itself were detected. Based on the above experiments, the following results were obtained. The composite hydrogel with attractive mechanical properties is mainly based on the hydrogen bond interactions between PAM chains and MMT. The results of cleaning efficiency revealed that the black mildew stains together with the yellowish foxing stains were almost completely eliminated within 6 min at 8 mA/cm2, and various stains formed by tideline, foxing, organic dyes and drinks could be thoroughly removed at 4 mA/cm2 within 5 min. In addition, the proposed cleaning method has advantages in local selectivity, easy control of cleaning course, and reusability, which represents a potential utility of this approach.

Summary As the most common form of joint disorder, osteoarthritis (OA) imposes a tremendous burden on health care systems worldwide. Without effective cure, OA represents a unique opportunity for innovation in therapeutic development. In contrast to traditional treatments based on drugs, proteins, or antibodies, stem cells are poised to revolutionize medicine as they possess the capacity to replace and repair tissues and organs such as osteoarthritic joints. Among different types of stem cells, mesenchymal stem cells (MSCs) are of mesoderm origin and have been shown to generate cells for tissues of the mesoderm lineage, thus, raising the hope for them being used to treat diseases such as OA. However, given their ability to differentiate into other cell types, MSCs have also been tested in treating a myriad of conditions from diabetes to Parkinson's disease, apparently of the ectoderm and endoderm lineages. There are ongoing debates whether MSCs can differentiate into lineages outside of the mesoderm and consequently their effectiveness in treating conditions from the ectoderm and endoderm lineages. In this review, we discuss the developmental origin of MSCs, their differentiation potential and immunomodulatory effects, as well as their applications in treating OA. We suggest further investigations into new therapies or combination therapies that may provide more effective treatment for bone and joint diseases. Furthermore, cell-based therapy and its associated safety and effectiveness should be carefully evaluated before clinical translation. This review provides updated information on recent approval of clinical trials and related applications of MSCs, and discusses additional efforts on cell-based therapy for treating OA and other joint and bone diseases.

Background/objectives For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.

Visual analytic methods are a growing area of research that targets the effective description of weapon system, which capitalizing on displaying of various indicators information of weapon system simulation. We provide a method which can display all kinds of indicators and architectural features of simulation results in the same screen. First of all, the simulation data of multidimensional information index system and the corresponding dimension is mapped into the two-dimensional matrix. Secondly, the index system of two-dimensional graphs and planar map simulation data are fused by computation. Finally, distinguish the architectural features by drawing the influence range of the indicators to the systems. The method can analyze the correlation between indicators, similarity comparisons system features, and describe some kind of index and the system characteristics of the correlation degree. Because of the above characteristics of the method, we can adjust the index system, using visualization method to display the comprehensive characteristic of the weapon equipment system, and select the weapon equipment system in accordance with the specific conditions of the system.

Periosteum can improve tendon-bone healing when applied to wrap the tendon graft in both animal studies and clinical trials. As magnesium (Mg) ions can significantly elevate the levels of relevant cytokines involving in the osteogenic differentiation of periosteum-derived stem cells, the Mg-pretreated periosteum may be an innovative approach for enveloping the tendon graft. To test this hypothesis, we compared the effects of Mg-pretreated periosteum (M − P) and the stainless steel (SS)-pretreated periosteum (SS–P) in ACL reconstruction. We firstly found that the released Mg ions from the Mg implants were partially accumulated in periosteum, resulting in higher Mg/Ca ratio in the M − P compared to the SS-P. Additionally, the M − P showed significantly higher expression levels of calcitonin gene-related peptide (CGRP) and periostin than the SS-P due to the decrease in Cathepsin K (CTSK). Elevation of CGRP and periostin was beneficial for the osteogenic differentiation of periosteum-derived stem cells. More importantly, we demonstrated that the M − P remarkably increased the formation of fibrocartilage at the interface between the periosteum and tendon. Collectively, M − P group demonstrated significantly prevented peri-tunnel bone loss, more osseous ingrowth into the tendon graft and higher maximum load to failure as compared to the SS-P group. In summary, our study warrants further investigations for translating the current proof-of-concept findings to optimize the delivery of CGRP, periostin, and cells as novel practical therapeutic strategy for enhancing tendon-bone interface healing in patients undergoing ACL reconstruction.

Background/Objectives: Decalcification of bone specimens is necessary for routine paraffin embedding and sectioning. Ethylenediaminetetraacetic acid (EDTA), a chelating agent for decalcification, maintains bone tissue integrity and histological features but requires long decalcification period, especially for cortical bone with dense mineral matrix. We hypothesised that the application of a newly commercially available ultrasound (US) decalcifier would accelerate decalcification of thick cortical bone specimen in EDTA efficiently and that the working temperature at 30–45°C would not affect histological and immunohistochemical analysis. Comparison was made with traditional decalcification method with regards to quality of tissue morphology and antigenicity. Methods: A fresh human cadaveric femoral shaft was sectioned into 5-mm-thick transverse sections. After fixation, the bone slices were divided into two groups: Ultrasound decalcification group (US DeCal), in which bone sections (n = 3) were placed in a US decalcifier (50 W at a frequency of 40kHz) with EDTA solution, and normal decalcification group (Normal DeCal), in which bone sections (n = 3) were decalcified in EDTA without US. The mineral content of the bone sections was measured with micro-computed tomography and dual-energy X-ray absorptiometry at different time points. Rate of calcium extraction was quantified by measuring the calcium concentration in EDTA solution using inductively coupled plasma optical emission spectrometry. After decalcification, the paraffin sections of the decalcified bone were stained with haematoxylin and eosin or immunohistochemical staining of sclerostin. Results: Samples in US DeCal contained 2.9 ± 2.8% of the mineral content at Day 6 and were completely decalcified at Day 8. However, sections in Normal DeCal retained 36.3 ± 5.1% and 24.3 ± 4.8% at Day 6 and Day 8, respectively, and took six times longer to complete decalcification. The concentration of calcium in the EDTA solution of the US DeCal group was 70% higher than that of the Normal DeCal group (p

In an established steroid-associated osteonecrosis (SAON) rabbit model we found recently that blockage Src by siRNA could improve reconstructive repair of osteonecrosis via enhancing osteogenesis and inhibiting bone resorption. The current study investigated if blocking Src was able to prevent steroid-associated osteoporosis (SAOP) in the same SAON animal model. Rabbits were treated with pulsed lipopolysaccharide (LPS) and corticosteroid methylprednisolone (MPS). At 2, 4, and 6 weeks after induction, Src siRNA, control siRNA and saline were intramedullary injected into proximal femur, respectively. Two fluorescent dyes xylenol orange and calcein green were injected before sacrificing the animals for in vivo labeling of the newly formed bone. At week 6 after induction, proximal femora of rabbits were dissected for micro-CT and histological analysis. Results showed significant bone loss in the metaphysis of femoral head in the control rabbits after SAON induction. Src siRNA treatment was able to prevent steroid-associate bone loss in trabecular bone and increase cortical bone thickness at femoral neck. Histomorphometry showed that Src siRNA increased the osteoblastic bone formation and decreased the eroded bone surfaces suggesting decreased osteoclastic bone resorption. This was the first study to report bone loss after SAON induction in rabbit model that could be prevented by knocking down Src by siRNA., Graphical abstract, Highlights • Significant bone loss was found after pulsed treatment of LPS and MPS in rabbits. • Src siRNA could prevent trabecular bone loss and increase cortical bone thickness. • Src siRNA increased osteoblastic bone formation and decreased osteoclastic bone resorption. • Knocking down Src by siRNA could be a potential therapeutic strategy for preventing steroid-associated osteoporosis.

Background/Objective: Epimedii Folium is the most important osteogenic herb formulated for the traditional Chinese Medicine Xian Ling Gu Bao (XLGB) capsule. The present study compared XLGB capsules containing two different Epimedium species, i.e., either Epimedium pubescens (XEP) or Epimedium koreanum (XEK), with the focus being on the chemical constituents and antiosteoporotic efficacy. Methods: Ultra performance liquid chromatography was used to demonstrate the different chemical constituents. Biomechanical tests, histological, and cytological evaluation were performed to characterise and compare the bone mineral density, bone strength, microstructure of bone tissue, and biological activity between XEP and XEK using an established ovariectomised (OVX) rat model. Results: Six flavonoids with different contents between XEK and XEP were identified. As compared with the OVX group, significantly higher bone mineral density, elastic-modulus, and compressive strength were found in both the XEK group and XEP group (p