Fatigue-related changes in intermuscular electromyographic coherence across rotator cuff and deltoid muscles in individuals with and without subacromial pain.

Neuromuscular fatigue induces superior migration of the humeral head in individuals with subacromial pain. This has been attributed to weakness of rotator cuff muscles and overactive deltoid muscles. Investigation of common inputs to motoneuron pools of the rotator cuff and deltoid muscles offers valuable insight into the underlying mechanisms of neuromuscular control deficits associated with subacromial pain. This study aims to investigate intermuscular coherence across the rotator cuff and deltoid muscles during a sustained submaximal isometric fatiguing contraction in individuals with and without subacromial pain. Twenty symptomatic and 18 asymptomatic young adults participated in this study. Surface EMG was recorded from the middle deltoid (MD) and infraspinatus (IS). Intramuscular EMG was recorded with fine-wire electrodes in the supraspinatus (SS). Participants performed an isometric fatiguing contraction of 30° scaption at 25% MVC until endurance limit. Pooled coherence of muscle pairs (SS-IS, SS-MD, IS-MD) in the 2-5 Hz (delta), 5-15 Hz (alpha) and 15-35 Hz (beta) frequency bands during the initial and final 30s of the fatigue task were compared. SS-IS and SS-MD delta-band coherence increased with fatigue in the asymptomatic group, but not the symptomatic group. In the alpha and beta bands, SS-IS and SS-MD coherence increased with fatigue in both groups. IS-MD beta-band coherence was greater in the symptomatic than the asymptomatic group. Individuals with subacromial pain failed to increase common drive across rotator cuff and deltoid muscles and have altered control strategies during neuromuscular fatigue. This may contribute to glenohumeral joint instability and subacromial pain experienced by these individuals.

The completed mitochondrial genomes of Globodera vulgaris reveals new insights into the genus Globodera phylogeny.

Due to the highly conserved structure, animal mitochondrial genome (mtDNA) is widely used in classification, evolution, phylogeny, population genetic structure and other fields. We reported on the five circle multipartite mtDNAs of a newly described species of Globodera, Globodera vulgaris (Gv) from potatoes in China. The results showed that the mtDNA of Gv was obtained through second- and third-generation sequencing, with a total length of 42,995 bp. It contained 12 protein-coding genes, two rRNA genes and 17 tRNA genes, which were distributed in different subgenomic circles. Comparison of the differences in mtDNA among Gv, G. rostochiensis, G. pallida and G. ellingtonae showed that the size and arrangement of the genes in the mtDNA of the genus Globodera were variable and not conserved. The codon usage bias of the mitochondrial protein-coding gene of Gv showed that Gv might have originated from locally and more primitive group of existing Globodera. Based on the cytochrome c oxidase subunits I genes (COX1) and the nicotinamide adenine dinucleotide dehydrogenase subunits I genes (ND1), and the results showed that Gv was clustered with Globodera spp. according to the COX1 and ND1 in scmtDNA-V, while Gv was clustered with Meloidogyne spp. according to ND1 in scmtDNA-III. The results of this study provided a new basis for understanding the multipartite structure of mtDNA as a phylogenetic and taxonomic feature of the genus Globodera. The number of subgenomic circles is a diagnostic feature of species and the arrangement order and size of mitochondrial protein-coding genes also have important application value in species identification within the genus.

Aromatic Ketones as Mild Presodiating Reagents toward Cathodes for High-Performance Sodium-Ion Batteries.

Chemical presodiation (CP) is an effective strategy to enhance energy density of sodium ion batteries. However, the sodiation reagents reported so far are basically polycyclic aromatic hydrocarbons (PAHs) wth low reductive potential (~0.1 V vs. Na+ /Na), which could easily cause over-sodiation and structural deterioration of the presodiated cathodes. In this work, Aromatic ketones (AKs) are rationally designed as mild presodiating reagents by introducing a carbonyl group (C=O) into PAHs to balance the conjugated and inductive effect. As the representatives, two compounds 9-Fluorenoneb (9-FN) and Benzophenone (BP) manifest favorable equilibrium potential of 1.55 V and 1.07 V (vs. Na+ /Na), respectively. Note that 9-FN demonstrates versatile presodiating capability toward multiple Na uptake hosts (tunneled Na0.44 MnO2 , layered Na0.67 Ni0.33 Mn0.67 O2 , polyanionic Na4 Fe2.91 (PO4 )2 P2 O7 , Na3 V2 (PO4 )3 and Na3 V2 (PO4 )2 F3 ), enabling greatly improved initial charging capacity of the cathode to balance the irrevisible capacity of the anode. Our results indicate that the Aromatic ketones are competitive presodiating cathodic reagents for high-performance sodium-ion batteries, and will inspire more studies and application attempts in the future.

Proteomics Analysis of Serum Reveals Potential Biomarkers for Heart Failure Patients with Phlegm-Blood Stasis Syndrome.

Heart failure (HF), a complex clinical syndrome, has become a global burden on health and economics around the world. Phlegm-blood stasis syndrome, one of the Traditional Chinese Medicine (TCM) syndrome differentiation, is the core pathogenesis dynamically throughout the occurrence, development, and prognosis of HF. Biomarkers having high sensitivity and specificity are highly demanded to facilitate the accurate differentiation of HF patients with phlegm-blood stasis syndrome. In the present study, serum samples were collected from 20 healthy controls and 40 HF patients (20 with and 20 without phlegm-blood stasis syndrome). We implemented data-independent acquisition mass spectrometry (DIA-MS) for discovery and parallel reaction monitoring (PRM) for validation of biomarkers for heart failure with phlegm-blood stasis syndrome. A total of 84 different proteins were found in the HF with phlegm-blood stasis syndrome (HF-TY) group compared with healthy controls. 37 candidate proteins were selected for the PRM assay, and five validated proteins with high sensitivity and specificity, including insulin-like growth factor-binding protein 4 (IGFBP4), ß-2-microglobulin (B2M), dystroglycan (DAG1), immunoglobulin J chain (JCHAIN), and kallikrein B1 (KLKB1), were considered potential biomarkers for heart failure patients with phlegm-blood stasis syndrome. Newly identified biomarkers might provide insights into the diagnosis and treatment of HF with TCM syndrome differentiation.

Three cases of late-onset post CAR-T therapy isolated CNS relapse in R/R large B-cell lymphoma.

CD19-chimeric antigen receptor T-cell (CAR T-cell) therapy has improved the outcomes of relapsed/refractory large B cell lymphoma significantly. However, about 50% of patients relapsed post-CAR-T therapy. Late relapse composed of 1/3 to 1/2 of CAR-T cell therapy failure, with no previous reports of isolated relapse in immune-privileged sites. Here, we report the first case series of late-onset post CAR-T cell therapy isolated central nervous system (CNS) relapses, in systemic relapsed/refractory large B cell lymphoma patients. With these cases, we suggest that additional CNS prophylaxis should be administrated for primary refractory patients on CAR-T cell therapy with previous neurological involvements, multiple extra-nodular lesions, and high CNS-IPI score pre-CAR, as well as early disappearance of circulating CAR-T cells post infusion.

A robot-aided visuomotor wrist training induces motor and proprioceptive learning that transfers to the untrained ipsilateral elbow.

BACKGROUND: Learning of a visuomotor task not only leads to changes in motor performance but also improves proprioceptive function of the trained joint/limb system. Such sensorimotor learning may show intra-joint transfer that is observable at a previously untrained degrees of freedom of the trained joint. OBJECTIVE: Here, we examined if and to what extent such learning transfers to neighboring joints of the same limb and whether such transfer is observable in the motor as well as in the proprioceptive domain. Documenting such intra-limb transfer of sensorimotor learning holds promise for the neurorehabilitation of an impaired joint by training the neighboring joints. METHODS: Using a robotic exoskeleton, 15 healthy young adults (18-35 years) underwent a visuomotor training that required them to make continuous, increasingly precise, small amplitude wrist movements. Wrist and elbow position sense just-noticeable-difference (JND) thresholds and spatial movement accuracy error (MAE) at wrist and elbow in an untrained pointing task were assessed before and immediately after, as well as 24 h after training. RESULTS: First, all participants showed evidence of proprioceptive and motor learning in both trained and untrained joints. The mean JND threshold decreased significantly by 30% in trained wrist (M: 1.26° to 0.88°) and by 35% in untrained elbow (M: 1.96° to 1.28°). Second, mean MAE in untrained pointing task reduced by 20% in trained wrist and the untrained elbow. Third, after 24 h the gains in proprioceptive learning persisted at both joints, while transferred motor learning gains had decayed to such extent that they were no longer significant at the group level. CONCLUSION: Our findings document that a one-time sensorimotor training induces rapid learning gains in proprioceptive acuity and untrained sensorimotor performance at the practiced joint. Importantly, these gains transfer almost fully to the neighboring, proximal joint/limb system.

Left atrial dysfunction can independently predict exercise capacity in patients with chronic heart failure who use beta-blockers.

BACKGROUND: Beta-blockers are first-line clinical drugs for the treatment of chronic heart failure (CHF). In the guidelines for cardiac rehabilitation, patients with heart failure who do or do not receive beta-blocker therapy have different reference thresholds for maximal oxygen uptake (VO2max). It has been reported that left atrial (LA) strain can be used to predict VO2max in patients with heart failure, which can be used to assess exercise capacity. However, most existing studies included patients who did not receive beta-blocker therapy, which could have a heterogeneous influence on the conclusions. For the vast majority of CHF patients receiving beta-blockers, the exact relationship between LA strain parameters and exercise capacity is unclear. METHODS: This cross-sectional study enrolled 73 patients with CHF who received beta-blockers. All patients underwent a thorough resting echocardiogram and a cardiopulmonary exercise test to obtain VO2max, which was used to reflect exercise capacity. RESULTS: LA reservoir strain, LA maximum volume index (LAVImax), LA minimum volume index (LAVImin) (P < 0.0001) and LA booster strain (P < 0.01) were all significantly correlated with VO2max, and LA conduit strain was significantly correlated with VO2max (P < 0.05) after adjusting for sex, age, and body mass index. LA reservoir strain, LAVImax, LAVImin (P < 0.001), and LA booster strain (P < 0.05) were significantly correlated with VO2max after adjusting for left ventricular ejection fraction, the ratio of transmitral E velocity to tissue Doppler mitral annulus e' velocity (E/e'), and tricuspid annular plane systolic excursion. LA reservoir strain with a cutoff value of 24.9% had a sensitivity of 74% and specificity of 63% for the identification of patients with VO2max < 16 mL/kg/min. CONCLUSION: Among CHF patients receiving beta-blocker therapy, resting LA strain is linearly correlated with exercise capacity. LA reservoir strain is a robust independent predictor of reduced exercise capacity among all resting echocardiography parameters. CLINICAL TRIAL REGISTRATION: This study is a part of the Baduanjin-Eight-Silken-Movement with Self-efficacy Building for Patients with Chronic Heart Failure (BESMILE-HF) trial NCT03180320 (ClinicalTrials.gov, registration date: 08/06/2017).

Genetic characterization of a novel HIV­1 CRF01_AE/ CRF07_BC recombinant form found among men who have sex with men in Baoding City, Hebei Province, China.

Large numbers of unique recombinant forms (URF) of human immunodeficiency virus (HIV-1) have been found among sexual transmission populations in China. Here, we report a novel second-generation URF of HIV-1 named BD201AQ that was isolated from an HIV-1-positive man who was infected through homosexual transmission in Baoding City, Hebei Province, China. Phylogenetic analysis based on the near-full-length genome (NFLG) sequence indicated that BD201AQ formed a monophyletic branch that did not cluster with other HIV-1 subtypes. Recombination analysis showed that the NFLG of BD201AQ had 12 segments, six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. These findings indicate that the constant emergence of novel recombinant forms should receive more attention and that more measures should be taken to monitor the molecular epidemiological characteristics of HIV-1 and to prevent the spread of HIV-1 infections.

Effectiveness and Safety of Four Aerobic Exercise Intensity Prescription Techniques in Rehabilitation Training for Patients with Coronary Heart Disease.

Methods: A retrospective study was conducted on all patients with CHD who were admitted to CR and completed cardiopulmonary exercise tests (CPET) in Guangdong Hospital of traditional Chinese medicine. According to the risk stratification method of CHD, all participants were divided into three groups: low, moderate, and high risk. The training target heart rates (HRt) of each participant were calculated according to the formula of heart-rate-reserve (HRR), maximum-heart-rate (MHR), target-heart-rate (THR), and anaerobic threshold (AT) method provided in the guideline. Among them, the HRR method using the maximum-heart-rate obtained by the age formula was named "HRR method A," and that using the actual measured peak heart rate was named "HRR method B." For the three groups, the effectiveness and safety indexes at the target-heart-rate zone set by the different formulas above are counted and compared using CPET data. Results: A total of 324 patients were included in the analysis. There was no significant difference between the target-heart-rate set by the HRR method A and AT method among the three groups (P > 0.05). The mean value of HRt set by other methods was lower than the AT heart rate (P < 0.05). The HRt set by the THR method was close to the AT, while that set by the MHR method was the lowest. The frequency of patients whose HRt was set by the MHR method was lower than the AT one, which was the highest. None of the participants had serious adverse events. There were no risks of ECG abnormalities in the low- and moderate-risk groups. The HRR method A had the highest incidence of various risks of ECG abnormalities, while the MHR method had the lowest one, and the safety of the THR method is close to that of the AT method (P < 0.05). Conclusion: The heart rate calculated by HRR method A is more consistent with the actual AT. All four techniques are safe in low- and moderate-risk patients. In high-risk patients, using HRR method A has certain risks. It is recommended to use the MHR method for safety reasons, but its effectiveness is low. If considering both effectiveness and safety, the THR method can be conservatively selected at the beginning of the CR program.

Traditional Baduanjin exercise through the eyes of patients with chronic heart failure: A qualitative content analysis study.

Objective: Baduanjin (eight silken movements) is a traditional Chinese exercise that can be used as cardiac rehabilitation therapy for patients with chronic heart failure (CHF) especially when other forms of rehabilitation are scarce or unaffordable. This study explores the experiences of Chinese patients with CHF who undertook Baduanjin exercise at home as part of a pilot trial in Guangzhou, China. Methods: We conducted seven qualitative interviews with participants who had participated in the intervention arm of a pilot randomized controlled trial (RCT) (n = 8). For data collection, we used a semi-structured interview guide with both open-ended, and follow-up questions. We audio recorded the interviews, transcribed them verbatim, and then analyzed them with content analysis. Results: Participants' experiences of doing Baduanjin were classified into three categories: (1) improving practice (2) factors facilitating good exercise adherence, and (3) feeling good. Participants reported that the exercises were easy but that the correct Baduanjin execution and coordination between the mind, movements, and breathing were only achievable through practice. In addition, the training benefits which they perceived were the predominant motivation for patients to keep practicing. Finally, trust in Baduanjin, personal attitudes toward health, flexibility in practice times, as well as social support helped the participants to achieve good adherence to home-based training. Conclusion: This study's findings indicate that Baduanjin could be a cardiac rehabilitation exercise modality for patients with CHF in China, especially in a home-based setting.

Successful treatment of a 3-year-old girl with generalized pustular psoriasis using secukinumab monotherapy.

We report a case of a 3-year-old girl with generalized pustular psoriasis (GPP) and a compound heterozygous mutation within the IL36 receptor antagonist (IL36RN) gene at c.28C>T and c.115+6T>C, who was successfully treated using secukinumab monotherapy. The first dose of secukinumab (150 mg) was administered subcutaneously, followed by 75 mg of secukinumab subcutaneously once weekly for 4 weeks and then 75 mg every 4 weeks. The total course of treatment was 4 months, with a total of 8 doses. A PASI score of 75 and 100 was achieved at weeks 1 and 2, respectively, and maintained for 11 months of follow-up, without disease recurrence or adverse events.

A robot-aided visuomotor wrist training induces gains in proprioceptive and movement accuracy in the contralateral wrist.

Proprioceptive training is a neurorehabilitation approach known to improve proprioceptive acuity and motor performance of a joint/limb system. Here, we examined if such learning transfers to the contralateral joints. Using a robotic exoskeleton, 15 healthy, right-handed adults (18-35 years) trained a visuomotor task that required making increasingly small wrist movements challenging proprioceptive function. Wrist position sense just-noticeable-difference thresholds (JND) and spatial movement accuracy error (MAE) in a wrist-pointing task that was not trained were assessed before and immediately as well as 24 h after training. The main results are: first, training reduced JND thresholds (- 27%) and MAE (- 33%) in the trained right wrist. Sensory and motor gains were observable 24 h after training. Second, in the untrained left wrist, mean JND significantly decreased (- 32%) at posttest. However, at retention the effect was no longer significant. Third, motor error at the untrained wrist declined slowly. Gains were not significant at posttest, but MAE was significantly reduced (- 27%) at retention. This study provides first evidence that proprioceptive-focused visuomotor training can induce proprioceptive and motor gains not only in the trained joint but also in the contralateral, homologous joint. We discuss the possible neurophysiological mechanism behind such sensorimotor transfer and its implications for neurorehabilitation.

Development of a lipid metabolism-related gene model to predict prognosis in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly heterogeneous disease, making prognosis prediction challenging. Altered energy metabolism to satisfy uncontrolled proliferation and metastasis has become one of the most important markers of tumors. However, the specific regulatory mechanism and its effect on prognosis have not been fully elucidated. AIM: To construct a prognostic polygene signature of differentially expressed genes (DEGs) related to lipid metabolism. METHODS: First, 9 tissue samples from patients with pancreatic cancer were collected and divided into a cancer group and a para-cancer group. All patient samples were subjected to metabolomics analysis based on liquid tandem chromatography quadrupole time of flight mass spectrometry. Then, mRNA expression profiles and corresponding clinical data of pancreatic cancer were downloaded from a public database. Least absolute shrinkage and selection operator Cox regression analysis was used to construct a multigene model for The Cancer Genome Atlas. RESULTS: Principal component analysis and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) based on lipid metabolomics analysis showed a clear distribution in different regions. A Euclidean distance matrix was used to calculate the quantitative value of differential metabolites. The permutation test of the OPLS-DA model for tumor tissue and paracancerous tissue indicated that the established model was consistent with the actual condition based on sample data. A bar plot showed significantly higher levels of the lipid metabolites phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), phosphatidylethanol(PEtOH), phosphatidylmethanol (PMeOH), phosphatidylserine (PS) and diacylglyceryl trimethylhomoserine (DGTS) in tumor tissues than in paracancerous tissues. According to bubble plots, PC, PE, PEtOH, PMeOH, PS and DGTS were significantly higher in tumor tissues than in paracancerous tissues. In total, 12.3% (25/197) of genes related to lipid metabolism were differentially expressed between tumor tissues and adjacent paracancerous tissues. Six DEGs correlated with overall survival in univariate Cox regression analysis (P < 0.05), and a 4-gene signature model was developed to divide patients into two risk groups, with patients in the high-risk group having significantly lower overall survival than those in the low-risk group (P < 0.05). ROC curve analysis confirmed the predictive power of the model. CONCLUSION: This novel model comprising 4 lipid metabolism-related genes might assist clinicians in the prognostic evaluation of patients with pancreatic cancer.

Intensity level and cardiorespiratory responses to Baduanjin exercise in patients with chronic heart failure.

AIMS: Baduanjin (eight silken movements), a traditional Chinese exercise, is an alternative to the most common cardiac rehabilitation programmes due to their scarcity and unaffordability in China. The aim of this study was to measure the intensity and energy expenditure during Baduanjin and to determine the relative oxygen consumption (VO2 ) and heart rate (HR) responses of Baduanjin compared with maximal capacity in patients with chronic heart failure. METHODS AND RESULTS: Twenty participants (age: 65 ± 10 years, male: n = 17) with New York Heart Association II-III volunteered for this study. Participants were examined during two separate sessions, with 1-2 weeks between sessions. During session one, a symptom-limited cardiopulmonary exercise testing was performed on a cycle ergometer for measurement of maximal exercise capacity. Additionally, participants were taught Baduanjin exercise from a professional coach and were required to do it at home until the second session when their technique was confirmed by the coach. During session two, participants performed one 9 min round of Baduanjin with continuous measurement of VO2 and HR. Measurements obtained during the Baduanjin were compared with data obtained during cardiopulmonary exercise testing. While performing Baduanjin, the mean VO2 and HR were 7.1 ± 1.2 mL/kg/min and 86.1 ± 15.2 b.p.m., respectively. Compared with the cardiopulmonary exercise test, the VO2 was 44% of their VO2max and 67% of their HRmax , categorizing Baduanjin as a moderate-intensity exercise. The average energy expenditure during Baduanjin was 23.3 ± 4.4 kcal. Additionally, the VO2 and HR responses during Baduanjin both exhibited a bimodal pattern. CONCLUSIONS: The results suggest that Baduanjin is a moderate-intensity aerobic exercise that could be an effective and safe exercise modality for home-based cardiac rehabilitation.

Downregulation of MiR-218-5p Protects Against Oxygen-Glucose Deprivation/Reperfusion-Induced Injuries of PC12 Cells via Upregulating N-myc Downstream Regulated Gene 4 (NDRG4).

BACKGROUND Cerebral ischemia is a major player of acute ischemic stroke (AIS) and mainly caused by blood vessels obstruction-induced reduced blood flow. Furthermore, miR-218-5p level was elevated in patients with AIS compared with controls. The present study investigated the biochemical mechanisms underlying the role of miR-218-5p in AIS in vitro. MATERIAL AND METHODS PC12 cells were chosen to establish oxidative-glucose deprivation/re-oxygenation (OGD/R) injury model. The interaction between miR-218-5p and N-myc downstream regulated gene 4 (NDRG4) was evaluated by Luciferase reporter assay. The levels of NDRG4, endothelial nitric oxide synthase (eNOS) and protein related to cell apoptosis were quantitatively analyzed with real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. Inflammatory cytokines, myeloperoxidase (MPO) and oxidative stress status were measured using specific commercial assay kits. Further, the cells apoptosis was analyzed with flow cytometry assay. RESULTS MiR-218-5p level was notably increased in OGD/R injured PC12 cells and directly targeted NDRG4. MiR-218-5p inhibitor significantly inhibited inflammatory cytokines release, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and monocyte chemotactic protein 1 (MCP-1). In addition, miR-218-5p downregulation ameliorated nitric oxide (NO) and eNOS levels and suppressed the inducible nitric oxide synthase (iNOS) expression and cell apoptosis. However, NDRG4 silencing abolished all corrective effects of miR-218-5p inhibitor in OGD/R injured PC12 cells. CONCLUSIONS Downregulation of miR-218-5p protect against OGDR-induced injuries of PC12 cells through reducing inflammatory cytokines secretion, oxidative stress status, apoptosis rate and maintenance of endovascular homeostasis via upregulating NDRG4. MiR-218-5p may serve as a novel effective biomarker to monitor AIS progression.

The Protective Effect of Mycosporine-Like Amino Acids (MAAs) from Porphyra yezoensis in a Mouse Model of UV Irradiation-Induced Photoaging.

The objective of this research was to extract and prepare mycosporine-like amino acids (MAAs) and investigate the mechanism by which they act against UV-induced skin photoaging in Institute of Cancer Research (ICR ) mice. MAAs such as porphyra-334 and shinorine were extracted from Porphyra yezoensis, separated, and purified using column chromatography with SA-2 cation exchange resin. The effects of MAAs on the activity of endogenous antioxidant enzymes, namely total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were analyzed in mouse skin tissue. Pathological changes of skin tissue caused by ultraviolet radiation and the arrangement of collagen were observed by Hematoxylin-Eosin (HE) staining and scanning electron microscopy (SEM). Interleukin 1ß (IL-1ß), IL-6, and IL-10 were detected using the quantitative real-time reverse transcription-polymerase chain reaction (qPCR) and Enzyme Linked Immunosorbent Assay (ELISA). The concentration and expression of these proinflammatory cytokines was associated with the presence of nuclear factor (NF)-κB. The results show that MAA compounds from Porphyra yezoensis could suppress UV-induced photoaging of skin by inhibiting the reduction of endogenous antioxidant enzymes. Compared to the control group, the concentrations of SOD, GSH-Px, and CAT increased significantly in skin tissue homogenate following the external administration of MAAs (p < 0.05, p < 0.01), while the content of MDA decreased significantly (p < 0.05). Meanwhile, the administration of MAAs was associated with down-regulations in the concentration and mRNA expression of NF-κB, IL-1ß, IL-6, and IL-10. The results suggest that MAAs could protect skin from photodamage by increasing antioxidant enzyme activities and inhibiting inflammation.

Bioactive Scaffolds for Regeneration of Cartilage and Subchondral Bone Interface.

The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo. Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration.

Preparation and adsorption characteristics of an ion-imprinted polymer for fast removal of Ni(II) ions from aqueous solution.

A novel Ni(II) ion-imprinted polymer (IIP) was synthesized by bulk polymerization for fast removal of Ni(II) ions from aqueous solution. Effects of preparation conditions on adsorption performance were investigated. Diphenylcarbazide (DPC) and N,N-azobisisobutyronitrile (AIBN) were used as ligand and initiator, respectively. Various monomers, solvents, cross-linking agents and molar ratios of template, monomer and cross-linking agent for polymerization were studied to obtain the largest adsorption capacity. The prepared Ni(II)-IIPs were characterized using Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive X-ray spectroscopy (EDX) and thermogravimetric analysis (TGA). The elution process has no influence on the three-dimension network structure observed on the surfaces of Ni(II)-IIPs. Ni(II) ions could be eluted from IIPs successfully with HCl solution. Effects of operating time, pH and initial concentration of Ni(II) in aqueous solution on adsorption performance were investigated too. The adsorption equilibrium was reached within 30min. The maximum adsorption capacity of Ni(II)-IIPs was 86.3mgg-1 at pH 7.0 with initial Ni(II) concentration of 500mgL-1. The adsorption by Ni(II)-IIPs followed a pseudo-second-order kinetic and Freundlich isotherm models. The selectivity coefficients for all Ni(II)/interfering ions are larger than one because of the imprinting effect. The Ni(II)-IIPs also showed high reusability and stability.

Europium-doped mesoporous silica nanosphere as an immune-modulating osteogenesis/angiogenesis agent.

Although much research has gone into the design of nanomaterials, inflammatory response still impedes the capacity of nanomaterial-induced tissue regeneration. In-situ incorporation of nutrient elements in silica-based biomaterials has emerged as a new option to endow the nanomaterials modulating biological reactions. In this work, europium-doped mesoporous silica nanospheres (Eu-MSNs) were successfully synthesized via a one-pot method. The nanospheres (size of 280-300 nm) possess uniformly spherical morphology and mesoporous structure, and well distributed Eu elements. The nanospheres show distinct fluorescent property at 615 nm for potential bio-labeling. Noticeably, the Eu-MSNs stimulate pro-inflammatory response of macrophages and induce a modulated immune microenvironment, which further activates the osteogenic differentiation of bone marrow stromal cells (BMSCs) as well as angiogenic activity of human umbilical vein endothelial cells (HUVECs). During the process, osteogenesis-related genes (e.g. ALP, OCN, OPN and COL-I) of BMSCs, and angiogenesis-related genes (e.g. CD31, MMP9, VEGFR1/2, and PDGFRα/ß) of HUVECs were significantly upregulated by Eu-MSNs modulating immune environment of macrophages. The in vivo study further demonstrated that the Eu-MSNs could not only stimulate osteogenesis by accelerating the new bone formation at critical-sized cranial defect site, but also support the blood vessel formation as well as collagen deposition and re-epithelialization at chronic skin wound sites, showing an improved angiogenesis activity when comparing with MSNs alone. Given the easy handling characteristics and extensive application potential, the results suggest that Eu-MSNs could be used as immunity-modulated osteogenesis/angiogenesis agent for skin and bone regeneration.

3D-printed bioceramic scaffolds with antibacterial and osteogenic activity.

Bacterial infection poses a significant risk with the wide application of bone graft materials. Designing bone grafts with good antibacterial performance and excellent bone-forming activity is of particular significance for bone tissue engineering. In our study, a 3D printing method was used to prepare ß-tricalcium phosphate (ß-TCP) bioceramic scaffolds. Silver (Ag) nanoparticles were uniformly dispersed on graphene oxide (GO) to form a homogeneous nanocomposite (named Ag@GO) with different Ag-to-graphene oxide mass ratios, with this being synthesized via the liquid chemical reduction approach. Ag@GO nanocomposites were successfully modified on the ß-TCP scaffolds by a simple soaking method to achieve bifunctional biomaterials with antibacterial and osteogenic activity. The prepared scaffolds possessed a connected network with triangle pore morphology and the surfaces of the ß-TCP scaffolds were uniformly modified by the Ag@GO nanocomposite layers. The Ag content in the scaffolds was controlled by changing the coating times and concentration of the Ag@GO nanocomposites. The antibacterial activity of the scaffolds was assessed with Gram-negative bacteria (Escherichia coli, E. coli). The results demonstrated that the scaffolds with Ag@GO nanocomposites presented excellent antibacterial activity. In addition, the scaffolds coated with Ag@GO nanocomposites conspicuously accelerated the osteogenic differentiation of rabbit bone marrow stromal cells by improving their alkaline phosphatase activity and bone-related gene expression (osteopontin, runt-related transcription factor 2, osteocalcin and bone sialoprotein). This study demonstrates that bifunctional scaffolds with a combination of antibacterial and osteogenic activity can be achieved for the reconstruction of large-bone defects while preventing or treating infections.