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Introduction: Guilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. Methods: This was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1꞉1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC–MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. Results: At weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P

Summary: Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.

Summary: Parkinson’s disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. The oligomeric α-synuclein (O-αS) is the most toxic form of α-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that LRRK2 G2019S mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both in vivo and in vitro. Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both LRRK2 G2019S and O-αS. We also demonstrated that nuclear factor κB (NF-κB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of LRRK2 kinase activity may be a viable strategy for suppressing neuroinflammation in PD.

Dielectric capacitors with high energy storage performances are exceedingly desired for the next-generation advanced high/pulsed power devices that demand miniaturization and integration. However, poor energy-storage density (Urec) and low efficiency (η) resulted from the large remanent polarization (Pr) and low breakdown strength (BDS), have been the major challenge for the application of dielectric capacitors. Herein, a high-entropy strategy with superparaelectric relaxor ferroelectrics (SP-RFE) was adopted to achieve extremely low Pr and high BDS in BaTiO3 system, simultaneously. Due to the high BDS ∼800 kV/cm and low Pr ∼0.58 μC/cm2, high-entropy SP-RFE (La0.05Ba0.18Sr0.18K0.115Na0.115Ca0.18Bi0.18)TiO3 (LBSKNCBT) MLCCs exhibited high Urec ∼6.63 J/cm3 and excellent η ∼ 96%. What's more, LBSKNCBT MLCCs with high-entropy and SP-RFE characteristic also possess a good temperature and frequency stability. In a word, this work offers an excellent paradigm for achieving good energy-storage properties of BaTiO3-based dielectric capacitors to meet the demanding requirements of advanced energy storage applications.

Phytoremediation of heavy metal-polluted soils assisted by plant-associated endophytes, is a suitable method for plant growth and manganese (Mn) removal in contaminated soils. This investigation was conducted to evaluate the Mn-resistant endophytic resources of the Mn hyperaccumulator Arabis paniculata and their functions in the phytoremediation of Mn2+ toxicity. This study isolated an endophytic bacterium with high Mn resistance and indole-3-acetic acid (IAA) production form A. paniculata and identified it as Bacillus sp. AP10 using 16 S rRNA gene sequencing analysis. The effects of Bacillus sp. AP10 on the alleviation of Mn2+ toxicity in Arabidopsis thaliana seedlings and the molecular mechanisms were further investigated using biochemical tests and RNA-seq analysis. Under Mn2+ stress, Bacillus sp. AP10 increased the biomass, chlorophyll content and the translocation factor (TF) values of Mn in the aerial parts, while decreased the malondialdehyde (MDA) content of A. thaliana seedlings compared with that of control plants. The differentially expressed genes (DEGs) and enrichment analysis showed that Bacillus sp. AP10 could significantly increase the expression of key genes involved in cell-wall loosening, which may improve plant growth under Mn stress. Superoxide dismutase (SOD)-encoding genes were detected as DEGs after AP10 treatment. Moreover, AP10 regulated the expression of genes responsible for phenylpropanoid pathway, which may promote antioxidant flavonoids accumulation for reactive oxygen species (ROS) scavenging to improve Mn tolerance. The activation of ATP-binding cassette (ABC) transporter gene expression especially ABCB1 after AP10 stimulation, explained the elevation of metal ion binding or transport related to enhanced Mn accumulation in plants. Futhermore, AP10 might alleviate Mn toxicity through enhancing abscisic acid (ABA) responsive gene expression and ABA biosynthesis. These findings provide new insights into the functions and regulatory mechanism of Bacillus sp. AP10 in promoting plant growth, and tolerance, improving Mn accumulation and alleviating Mn2+ toxicity in plants. The application of Bacillus sp. AP10 as potential phytoremediators may be a promising strategy in Mn2+ contaminated fields. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Woven lattice truss sandwich panels (WLTSPs) structure has excellent anti-stripping ability and energy absorption effect. The warp and weft distributions have an effect on the WLTSPs. Foam-filling technique and different heights of WLTSPs were double studied by the testing. Through the compression test and lateral compression test reveal the deformation, damage, failure and energy absorption. In the compression testing, the foam-filling can effectively increase peak force (PF) and energy absorption (EA), especially the weft distribution along the length direction-the specific energy absorption per unit mass of foam (△SEA) is 7.086 J/g. The foam filling transforms the piles from compression-shear coupled damage to progressive damage. In the lateral compression testing, when the WLTSPs at a low height the foam filling leads the load-displacement curve changes from brittleness to ductility. Foam filling improves the PF of PB by up to 459% at the height of 80 mm and restrain the decrease of bearing capacity with the increased height. The failure modes of the WLTSPs includes bending failure to progressive failure, concave, and the end fracture compression.

A higher prevalence of depression occurs in patients with lung cancer, while poor prognosis of lung cancer is often associated with depression. Excessive inflammatory response is one of the factors in the presumptive etiology of depression, and the inflammatory microenvironment also plays a key role in tumor genesis, which may indicate a common factor between the lung and the brain. Recently, a new hypothesis, called lung-brain axis, has been proposed because critical pulmonary disorders, such as acute lung injury and acute respiratory distress syndrome appear to be responsible for mood disorder and poor cognitive outcomes. Thus, lung cancer and depression might influence each other through the lung-brain axis. Findings throughout the literature suggest that activation of the interleukin (IL)-6 pathway can activate glial M1 and A1 phenotype activity, which triggers the activity of indoleamine 2,3-dioxygenase (IDO), thereby depleting tryptophan and reducing 5-hydroxytryptamine (5-HT) synthesis. The activation of IL-6 can also inhibit the expression of the 5-HT transporter through the IL-6-JAK/STAT signaling pathway. These changes are major neuropathological aspects of depression. The pathway, as mentioned above, can also promote lung cancer since increased IDO inhibits T lymphocyte proliferation and induces lymphocyte apoptosis. Therefore, the up-regulation of IDO caused by IL-6 may be the common cause for both the development of depression and lung cancer. The purpose of this review is to analyze the inflammatory mechanism and the role of the lung-brain axis in these two disease entities. The review aims to confirm the hypothesis of the lung-brain axis and promote our understanding of the interaction between the lung and the brain.

Summary: Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Here, we demonstrated that the protein from GCs in ovarian hyperandrogenism phenotype mouse group exhibits lower palmitoylation level compared with that in the control group. Using S-palmitoylation-enriched quantitative proteomics, we identified heat shock protein isoform α (HSP90α) with lower S-palmitoylation levels in ovarian hyperandrogenism phenotype group. Mechanistically, S-palmitoylation of HSP90α modulates the conversion of androgen to estrogens via the androgen receptor (AR) signalling pathway, and its level is regulated by PPT1. Targeting AR signaling by using dipyridamole attenuated ovarian hyperandrogenism symptoms. Our data help elucidate ovarian hyperandrogenism from perspective of protein modification and provide new evidence showing that HSP90α S-palmitoylation modification might be a potential pharmacological target for ovarian hyperandrogenism treatment.

In view of most current studies on text sentiment classification focus on the deep learning model to obtain the sentimental characteristics of English text. Chinese text sentiment analysis is rarely involved, and only the context information of the statement is considered, but the syntax information of the statement is rarely considered. In this paper, a novel sentiment classification model is proposed (Dependency Tree Graph Convolutional Network, DTGCN) combined Chinese syntactically dependent tree with graph convolution. Firstly, the Bi-GRU (Bi-directional Gated Recurrent Unit) model is used to learn the contextual feature representation of a given text. Secondly, the syntax-dependent tree structure of a given text is constructed, then obtain its adjacency matrix according to the syntax-dependent tree, with the initial features extracted from the bidirectional gate control network, input into the graph convolutional neural network (GCN) to extract the sentimental features of the text; the obtained sentimental characteristics are then input into the classifier SoftMax for text sentimental polarity classification. Finally, the data set is compared with the mainstream neural network model. The experimental results show that the accuracy of the proposed DTGCN model proposed on the data set is 90.51% and the recall rate is 90.34%. Compared with the benchmark models (LSTM, CNN, TextCNN and Bi-GRU), the proposed DTGCN model shows a 4.45% advantage in accuracy. It shows that the proposed DTGCN model can effectively use the grammatical information of Chinese text to mine the hidden relationship in statements, it can improve the accuracy of Chinese text sentiment classification. In addition, the proposed DTGCN model not only improves the performance of sentiment classification in the essay, it also provides a new research method for social network public opinion identification.

Ovarian functional deterioration in women with climacteric disorders increases the prevalence of type 2 diabetes (T2D). Therefore, we revealed that paeoniflorin (PF), an ingredient of paeony root (PR), which is a constituent of Kami-shoyo-san (KS), promotes glucose uptake by increasing estradiol secretion from adipocytes. Adipocytes differentiated from 3T3-L1 cells were incubated in culture medium containing the extracts of KS, PR, KS excluding PR (KS-PR), or PF for 5 d at 37 °C and 5% CO2. The estradiol and glucose concentrations in the medium were determined using enzyme-linked immunosorbent assay (ELISA). Next, PF (1 or 10 mg/kg) was subcutaneously injected into ovariectomized mice (12-week-old, ICR strain) once daily for 19 d to perform the glucose tolerance test and determine blood estradiol and adiponectin levels. The release of estradiol from 3T3-L1 adipocytes was significantly increased by KS, PR, KS-PR, and PF, and the increased estradiol level caused by KS was significantly decreased by excluding PF from KS (KS-PR). Glucose concentration in the medium was significantly decreased by KS and PF. In in vivo experiments, the 10 mg/kg PF-treated group showed significantly suppressed blood glucose levels at 0 and 30 min after d-glucose loading by intraperitoneal injection. These findings indicate that KS, which includes PR-containing PF as the main ingredient, may have the potential to prevent T2D caused by ovarian dysfunction in menopausal women by increasing estradiol secretion from adipocytes.

Juglone (5 - hydroxy - 1, 4 - naphthalene diketone) is a kind of natural naphthoquinone, present in the roots, leaves, nut-hulls, bark and wood of walnut trees. Recent studies have found that Juglone has special significance in the treatment of cancer, which plays a significant role in the resistance of cancer cell proliferation, induction of cancer cell apoptosis, induction of autophagy, anti-angiogenesis and inhibition of cancer cell migration and invasion, etc. Additionally, its derivatives also play a tumor suppressive effect. In conclusion, Juglone and its derivatives have been identified as effective anticancer drugs. This paper reviews action mechanisms of Juglone and its derivatives in cancer treatment.

Oleanolic acid (OA, 3 β - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.

Nanoparticles of four noble metal doped titanium dioxide (i.e., Pd/TiO2, Ag/TiO2, Pt/TiO2 and Cu/TiO2) were synthesized and investigated for their effectiveness to degrade polybrominated diphenyl ethers (PBDEs) under UV light. All the investigated noble metal additives can greatly enhance the performance of TiO2 to degrade 2,2′,4′,4′-tetrabromodiphenyl ether (BDE-47). However, the debromination pathways of BDE-47 in Ag/TiO2 and Cu/TiO2 systems are just contrary to those in Pd/TiO2 and Pt/TiO2 systems, and there was an induction period in the former systems but not in the latter systems. The hydrogenation experiment suggests a direct H-atom transfer mechanism in Pd/TiO2 and Pt/TiO2 systems, while in Ag/TiO2 and Cu/TiO2 systems, electron transfer is still the dominant mechanism. Electronic method was applied to explain why BDE-47 exhibit different debromination pathways based on different degradation mechanism. In addition, oxygen was proved to be able to capture both electrons and H atoms, and thus can greatly inhibit the degradation of PBDEs in all investigated systems. Finally, the merit and demerit of each metal doped TiO2 were discussed in detail, including the reactivity, stability and the generation of byproducts. We proposed our study greatly enhance our understanding on the mechanisms of PBDE degradation in various metal doped TiO2 systems. Keywords: Polybrominated diphenyl ethers, Debromination pathways, Photocatalytic degradation, Mechanisms, Titanium dioxide

Antibiotic resistance genes (ARGs), prevalent across multiple environmental media, threaten human health worldwide and are considered emerging environmental contaminants. Earthworm gut, a niche for bacteria to survive, represents a potential reservoir for ARGs in soil. However, the compositions of ARGs in the earthworm gut microbiota remain elusive, especially under field conditions. In this study, we applied high-throughput quantitative PCR to profile the ARGs in the gut microbiota of earthworms after chronic exposure to fertilizers. To elucidate the factors that impact the ARGs composition, the bacterial community of gut microbiota, mobile genetic elements (MGEs), soil (nutrients, heavy metals, and antibiotics) and the properties of gut content (pH and nutrients) were analyzed. A total of 98 subtypes among 9 major types of ARGs, and 3 different MGEs were detected in the gut microbiota of earthworms. Organic fertilizer (sewage sludge and chicken manure) application significantly increased the diversity and abundance of ARGs. Of the 1123 identified operational taxonomic units (OTUs) at 97% similarity cutoff, most of them were assigned to Firmicutes (55.5%) and Proteobacteria (33.6%) in earthworm gut microbiota. Long-term organic fertilization slightly changed the microbiota composition, but did not impact the diversity. Partial redundancy analysis (pRDA) revealed that bacterial community, combined with environmental factors (soil and gut content properties) and MGEs, explained 72% of the variations of ARGs in the earthworm gut. Furthermore, the co-occurrence pattern between ARGs and MGEs indicated that horizontal gene transfer via MGEs may occur in the earthworm gut. These findings improve the current understanding of the dynamics of soil fauna-associated ARGs and the gut microbiota of earthworms may be an underappreciated hotspot for ARGs in the environment. Keywords: Antibiotic resistome, Gut microbiota, Soil fauna, Sewage sludge, Chicken manure

In this data article, we present the structural and PXRD data of the lanthanide complexes constructed by bis-tridentate ligand tppz (2,3,5,6-tetra-2-pyridinylpyrazine). Detailed structure, luminescence and sensing properties were discussed in “highly luminescent lanthanide complexes constructed by bis-tridentate ligand and as sensor for Et2O” (Zheng et al., 2018). The data includes the structure of Tb-complex, PXRD of Tb-complex, and also detailed structure information listed in Tables 1–3.

In this data article, we present the FT-IR and PXRD data of the lanthanide complexes constructed by 4-iodo-3-methylbenzoic acid (IMBA) and 4,7-dimethyl-1,10-phenanthroline (dmp). Detailed structure analysis, luminescence and sensing properties were discussed in our previous study, “Highly Luminescent Lanthanide Complexes as Bifunctional Sensor for Et2O and Fe2+” (Zhao et al., 2018). Also, the data include the bond lengths and angles of [Ln2(IMBA)6(dmp)2] (Ln=Eu3+, 1a; Ln=Gd3+, 1b; Ln=Tb3+, 1c).

The Urban Heat Island (UHI) effect occurs when an urban area experiences higher temperatures than its rural surrounding because of heat being absorbed by built structures and heat being released by anthropogenic sources. UHIs can cause adverse effects to human health and increase energy consumption used for cooling buildings. Therefore, it is important to monitor accurately the UHI effect. The intensity of UHIs are usually monitored using satellite imagery, airborne sensors, and surface temperature sensors. Satellite imagery can cover a large area but requires a clear sky to obtain good images. Moreover, airborne sensors are expensive and also require a clear sky to obtain good data. A large network of surface temperature sensors is required to monitor the UHI of an entire region, which can also be expensive. In this paper, we present a three-step algorithm to monitor UHI intensity using data from Global Navigation Satellite Systems (GNSS). The advantages of using GNSS data to monitor the UHI effect are the increased availability of observation data, high temporal resolution and high geographical resolution. The first step of the algorithm is the calculation of a priori environmental parameters (i.e., water vapour partial pressure, troposphere height, surface pressure, and the vertical profile of refractivity) from radiosonde data. The second step is the calculation of temperature from GNSS data. The last step is the UHI intensity computation. The algorithm presented in this paper has been tested and validated using publicly available GNSS and meteorological data from Los Angeles, California, USA. The validation of the algorithm is done by comparing the UHI intensity estimated from the algorithm with temperature data obtained from weather stations. In the validation, the proposed algorithm can achieve an accuracy of 1.71 °C at 95 % confidence level.

Fracture nonunion, a serious bone fracture complication, remains a challenge in clinical practice. Although the molecular pathogenesis of nonunion remains unclear, a better understanding may provide better approaches for its prevention, diagnosis and treatment at the molecular level. This review tries to summarise the progress made in studies of the pathogenesis of fracture nonunion. We discuss the evidence supporting the concept that the development of nonunion is related to genetic factors. The importance of several cytokines that regulate fracture healing in the pathogenesis of nonunion, such as tumour necrosis factor-α, interleukin-6, bone morphogenetic proteins, insulin-like growth factors, matrix metalloproteinases and vascular endothelial growth factor, has been proven in vitro, in animals and in humans. Nitric oxide and the Wnt signalling pathway also play important roles in the development of nonunion. We present potential strategies for the prevention, diagnosis and treatment of nonunion, and the interaction between genetic alteration and abnormal cytokine expression warrants further investigation. The translational potential of this article: A better understanding of nonunion molecular pathogenesis may provide better approaches for its prevention, diagnosis and treatment in clinical practice. Keywords: Cytokine, Gene, Molecular pathogenesis, Nonunion

Background/Objective: As a widely used absorbable suture with antibacterial property, triclosan- coated polyglactin suture (Vicryl Plus) has been extensively utilized to reduce the occurrence rate of surgical site infections (SSIs) in orthopaedic surgery. However, the potential toxicity and side-effects of triclosan raised increasing concerns about its biological safety. This study aimed to investigate the antimicrobial activity and biocompatibility of quaternised chitosan-coated Vicryl suture (HV) both in vitro and in vivo. Methods: In this study, a modified chitosan derivate, (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), was coated over the surface of the absorbable Vicryl suture. Two standard bacteria strains, Staphylococcus epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate bacterial adhesion and biofilm formation on the sutures at 6, 24 and 48 h in vitro. Additionally, human skin-derived fibroblasts cells were used to test the cytocompatibility of the sutures. Furtherly, sutures contaminated with methicillin-resistant S. aureus were implanted subcutaneously in SD rats in order to confirm the in vivo antibacterial performance and biocompatibility. Results: We found that HACC-coated Vicryl suture (HV) exhibited significant anti-bacterial effects on the two tested strains. The bacterial attachment and biofilm formation on the surface of the HV sutures were found to be comparable to that of Vicryl Plus sutures (VP). Moreover, all the four tested sutures presented good cytocompatibility with human skin-derived fibroblasts cells. Histology and immunohistochemistry results indicated that the infections and inflammations were significantly inhibited around the HV and VP sutures. Conclusion: In general, the present study demonstrated that the quaternised chitosan coating is a flexible and cost-effective alternative strategy to prevent the suture related surgical site infections in orthopaedic practices.

Background/Objective: Plasma-sprayed titanium coating (TC) with rough surfaces has been successfully applied in hip or knee prostheses. This study aimed to investigate the osteoconduction and osseointegration of Type I collagen covalently immobilised on TC (TC-AAC) compared with those of TC. Methods: In vitro, the migration of human mesenchymal stem cells (hMSCs) on TC and TC-AAC was observed by scanning electron microscopy and visualised fluorescent live/dead assay. In vivo, a rabbit model with femur condyle defect was employed, and implants of TC and TC-AAC were embedded into the femur condyles. Results: Collagen immobilised on TC could promote hMSCs' migration into the porous structure of the TC. Micro computed tomography images showed that bone trabeculae were significantly more abundant around TC-AAC implants than around TC implants. Fluorescence micrographs indicated more active new-bone formation around implants in the TC-AAC group than in the TC group. The measurement of bone–implant contact on histological sections indicated significantly greater osteointegration around TC-AAC implants than around TC ones. Conclusion: Immobilised Type I collagen could improve the osteoconduction and osseointegration of TC implants.

The research project entitled “rapid prototyping of custom-made bone-forming tissue engineering constructs” (RAPIDOS) is one of the three unique projects that are the result of the first coordinated call for research proposals in biomaterials launched by the European Union Commission and the National Natural Science Foundation of China in 2013 for facilitating bilateral translational research. We formed the RAPIDOS European and Chinese consortium with the aim of applying technologies creating custom-made tissue engineered constructs made of resorbable polymer and calcium phosphate ceramic composites specifically designed by integrating the following: (1) imaging and information technologies, (2) biomaterials and process engineering, and (3) biological and biomedical engineering for novel and truly translational bone repair solutions. Advanced solid free form fabrication technologies, precise stereolithography, and low-temperature rapid prototyping provide the necessary control to create innovative high-resolution medical implants. The use of Chinese medicine extracts, such as the bone anabolic factor icaritin, which has been shown to promote osteogenic differentiation of stem cells and enhance bone healing in vivo, is a safe and technologically relevant alternative to the intensely debated growth factors delivery strategies. This unique initiative driven by a global consortium is expected to accelerate scientific progress in the important field of biomaterials and to foster strong scientific cooperation between China and Europe.

In this study, we investigated the hypothesis that regulatory T cells (Treg) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. Treg numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of Treg were determined in vitro. Our data revealed that the suppressive function of Treg from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, Treg numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of Treg from primary T cells and enhanced preexisting Treg function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of Treg by AT. In conclusion, AT significantly increased Treg numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.