Age-associated declined function of endothelial progenitor cells and its correlation with plasma IL-18 or IL-23 concentrations in patients with ST-segment elevation myocardial infarction.

Background: ST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood. Method: This study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients. Result: GRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function. Conclusion: In patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

Noninvasive serum N-glycans associated with ovarian cancer diagnosis and precancerous lesion prediction.

BACKGROUND: Ovarian cancer (OC) is one of the most common gynecological tumors with high morbidity and mortality. Altered serum N-glycome has been observed in many diseases, while the association between serum protein N-glycosylation and OC progression remains unclear, particularly for the onset of carcinogenesis from benign neoplasms to cancer. METHODS: Herein, a mass spectrometry based high-throughput technique was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasms and different stages of OC. To elucidate the alterations of glycan features in OC progression, an orthogonal strategy with lectin-based ELISA was performed. RESULTS: It was observed that the initiation and development of OC was associated with increased high-mannosylationand agalactosylation, concurrently with decreased total sialylation of serum, each of which gained at least moderately accurate merits. The most important individual N-glycans in each glycan group was H7N2, H3N5 and H5N4S2F1, respectively. Notably, serum N-glycome could be used to accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared to CA125 and HE4. Furthermore, bioinformatics analysis based discriminative model verified the diagnostic performance of serum N-glycome for OC in two independent sets. CONCLUSIONS: These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring.

Biodistributions and Imaging of Poly(ethylene glycol)-Conjugated Silicon Quantum Dot Nanoparticles in Osteosarcoma Models via Intravenous and Intratumoral Injections.

Osteosarcoma is a malignant tumor with relatively high mortality rates in children and adolescents. While nanoparticles have been widely used in assisting the diagnosis and treatment of cancers, the biodistributions of nanoparticles in osteosarcoma models have not been well studied. Herein, we synthesize biocompatible and highly photoluminescent silicon quantum dot nanoparticles (SiQDNPs) and investigate their biodistributions in osteosarcoma mouse models after intravenous and intratumoral injections by fluorescence imaging. The bovine serum albumin (BSA)-coated and poly(ethylene glycol) (PEG)-conjugated SiQDNPs, when dispersed in phosphate-buffered saline (PBS), can emit red photoluminescence with the photoluminescence quantum yield more than 30% and have very low in vitro and in vivo toxicity. The biodistributions after intravenous injections reveal that the SiQDNPs are mainly metabolized through the livers in mice, while only slight accumulation in the osteosarcoma tumor is observed. Furthermore, the PEG conjugation can effectively extend the circulation time. Finally, a mixture of SiQDNPs and indocyanine green (ICG), which complement each other in the spectral range and diffusion length, is directly injected into the tumor for imaging. After the injection, the SiQDNPs with relatively large particle sizes stay around the injection site, while the ICG molecules diffuse over a broad range, especially in the muscular tissue. By taking advantage of this property, the difference between the osteosarcoma tumor and normal muscular tissue is demonstrated.

In situ effects of microplastics on the decomposition of aquatic macrophyte litter in eutrophic shallow lake sediments, China.

The toxicity of microplastics (MPs) to aquatic organisms has been extensively studied recently. However, few studies have investigated the effects of MPs in sediments on aquatic ecosystem functioning. In the present study, we conducted an in situ experiment to explore the concentration-dependent effects (0.025%, 0.25%, 2.5%) and size-dependent effects (150-300 µm and 500-1000 µm) of polypropylene microplastics (PP MPs) on Vallisneria natans litter decomposition dynamics, in particular, the process associated with macroinvertebrates, microorganisms, as well as microalgae and/or cyanobacteria. The results showed that exposure to high concentrations and large sizes of PP MPs can accelerate leaf litter biomass loss and nutrition release. Moreover, microbial respiration, microalgal and/or cyanobacteria chlorophyll-a were also significantly affected by PP MPs. However, PP MPs have no effect on the abundance of associated macroinvertebrate during the experiment, despite the collection of five macroinvertebrate taxa from two functional feeding groups (i.e., collectors and scrapers). Therefore, our experiment demonstrated that PP MPs may enhance leaf litter decomposition through effected microbial metabolic activity, microalgal and/or cyanobacteria biomass in the sedimentary lake. Overall, our findings highlight that PP MPs have the potential to interfere with the basic ecological functions such as plant litter decomposition in aquatic environments.

Tizoxanide as a novel theraputic candidate for osteoarthritis.

Osteoarthritis (OA) is a frequently seen degenerative joint disease in the elderly. Its pathogenesis is highly related to the local inflammatory reaction and autophagy. Tizoxanide (Tiz), the main active metabolite of nitazoxanide, has proved its anti-inflammatory properties in several diseases. However, the exact role of Tiz in OA remains to explore. In this study, we investigated the anti-arthritic effects and the underlying molecular mechanisms of Tiz on rat OA. The results showed that Tiz could attenuate the IL-1ß-induced inflammatory disorders, cartilage matrix damage and autophagy reduction in rat chondrocytes. Moreover, employment of autophagy inhibitor 3-methyladenine (3-MA) could antagonize the protective effects of Tiz in IL-1ß-treated rat chondrocytes. Additionally, Tiz also inhibited the IL-1ß-induced PI3K/AKT/mTOR and P38/JNK phosphorylation in chondrocytes. In vivo, intra-articular injection of Tiz could significantly alleviate the progression of cartilage damage in rat OA model. Briefly, our study demonstrated the therapeutic potential of Tiz in OA, suggesting that Tiz administration might serve as a promising strategy in OA therapy.

Biodegradable germanium nanoparticles as contrast agents for near-infrared-II photoacoustic imaging.

Photoacoustic (PA) imaging using contrast agents with strong near-infrared-II (NIR-II, 1000-1700 nm) absorption enables deep penetration into biological tissue. Besides, biocompatibility and biodegradability are essential for clinical translation. Herein, we developed biocompatible and biodegradable germanium nanoparticles (GeNPs) with high photothermal stability as well as strong and broad absorption for NIR-II PA imaging. We first demonstrate the excellent biocompatibility of the GeNPs through experiments, including the zebrafish embryo survival rates, nude mouse body weight curves, and histological images of the major organs. Then, comprehensive PA imaging demonstrations are presented to showcase the versatile imaging capabilities and excellent biodegradability, including in vitro PA imaging which can bypass blood absorption, in vivo dual-wavelength PA imaging which can clearly distinguish the injected GeNPs from the background blood vessels, in vivo and ex vivo PA imaging with deep penetration, in vivo time-lapse PA imaging of a mouse ear for observing biodegradation, ex vivo time-lapse PA imaging of the major organs of a mouse model for observing the biodistribution after intravenous injection, and notably in vivo dual-modality fluorescence and PA imaging of osteosarcoma tumors. The in vivo biodegradation of GeNPs is observed not only in the normal tissue but also in the tumor, making the GeNPs a promising candidate for clinical NIR-II PA imaging applications.

Optical-Concentrating Solar Distillation Based on Three-Dimensional Copper Foam Cubes Coated with CuS Nanoparticles and Agarose Gel.

Solar distillation by interfacial evaporation is a promising method for relieving the freshwater crisis. However, the solar-to-water generation rate inside an enclosed system is usually lower than the solar-to-vapor evaporation rate in an open system due to the lower mass transfer rate. In this work, we demonstrate high rate solar distillation based on a three-dimensional copper foam (CF) cube, which offers five surfaces for absorbing direct and reflected sunlight to achieve optical concentration. The CF surface was first oxidized into black CuO and then dip-coated with a mixture of CuS nanoparticles (CuSNPs) and agarose gel (AG) for enhancing near-infrared (NIR) absorption and water transport. The open interconnected pores within the CF cube provide a large surface area for evaporation and steam escape. In an open space, the CuSNPs/AG-coated oxidized CF cube with the five surfaces illuminated by sunlight can achieve the solar-to-vapor evaporation rate equal to 5.83 kg m-2 h-1. When the same CF cube was placed in an enclosed distillation chamber with the five chamber surfaces illuminated by sunlight, the solar-to-water generation rate is equal to 4.14 kg m-2 h-1, which is 5.34 times higher than the case with only the top chamber surface illuminated. Lastly, when real seawater was used for distillation, although the solar-to-water generation rate was decreased by about 30%, the distillation efficiency was consistent after repeated cycles and no obvious salt accumulation was observed on the light absorbing surface. This work presents an efficient and reliable method of optical concentration for enhancing the solar distillation rate in an enclosed system.

High-Reliability Perovskite Quantum Dots Using Atomic Layer Deposition Passivation for Novel Photonic Applications.

In this study, we propose highly stable perovskite quantum dots (PQDs) coated with Al2O3 using atomic layer deposition (ALD) passivation technology. This passivation layer effectively protects the QDs from moisture infiltration and oxidation as well as from high temperatures and any changes in the material characteristics. They exhibit excellent wavelength stability and reliability in terms of current variation tests, long-term light aging tests, and temperature/humidity tests (60°/90%). A white-light system has been fabricated by integrating a micro-LED and red phosphor exhibiting a high data transmission rate of 1 Gbit/s. These results suggest that PeQDs treated with ALD passivation protection offer promising prospects in full-color micro-displays and high-speed visible-light communication (VLC) applications.

Luminescence-guided and visibly transparent solar concentrators based on silicon quantum dots.

In this work, we demonstrate a new tapered prism-shaped luminescent solar concentrator (LSC), which guides most of the luminescence toward one edge instead of four, for the solar window application. Only one Si photovoltaic (PV) strip attached to the light-emitting sidewall is needed to collect the luminescence, which further reduces PV material cost and avoids electrical mismatch. To achieve high visible transmission and mitigate reabsorption, colloidal silicon quantum dots (SiQDs) with ultraviolet-selective absorption and large Stokes shift are used as the fluorophores. With the SiQD concentration equal to 8 mg mL-1, the SiQD-LSC as a solar window can attain a power conversion efficiency (PCE) equal to 0.27%, while ensuring high average visible transmission (AVT = 86%) and high color rendering index (CRI = 94 with AM1.5G as the incident spectrum). When adjusted to front-facing, the Si PV strip can harvest not only the direct sunlight but also the concentrated SiQD fluorescence guided from the LSC. As a result, the overall solar window PCE can be increased to 1.18%, and the PCE of the front-facing Si PV strip alone can be increased by 7% due to the luminescence guided from the SiQD-LSC.

Procyanidin B2 ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degeneration and inflammation. Procyanidin B2 (PCB2), a natural flavonoid compound, exhibits potential anti-inflammatory and anti-oxidative effects against several diseases. However, its curative effects on OA remain unclear. PURPOSE: Herein, we explored the anti-arthritic effects of PCB2 on OA onset and progress and its potential mechanism. METHODS: CCK-8 assays and EdU staining were used to assess the cytotoxic effects and cell proliferation activity of PCB2. Flow cytometry was used to detect apoptosis in chondrocytes. ELISA, qPCR, and western blotting, were applied to explore the expression of apoptosis and senescence-associated secretion phenotype (SASP) factors. The Nrf2/NF-κB signaling cascade was explored using immunofluorescence and western blotting. Additionally, we silenced the Nrf2 gene using siRNAs to verify its function in PCB2 regulation of senescence and apoptosis phenotypes. Safranin O-Fast Green (SO) and immunohistochemical staining were used to explore the effects of PCB2 on OA model rats. RESULTS: PCB2 dampened interleukin (IL)-1ß-triggered expression of SASP factors in vitro. Additionally, PCB2 diminished IL-1ß-triggered destruction of the extracellular matrix (ECM) via downregulating the expression of MMPs, while upregulating the expression of collagen II and aggrecan. In addition, PCB2 treatment reduced IL-1ß-induced apoptosis of chondrocytes. Mechanistically, PCB2 could attenuated chondrocyte senescence in vitro via the Nrf2/NF-κB pathway. Moreover, PCB2 exhibited anti-apoptotic properties via the Nrf2/BAX/Bcl-2 pathway. PCB2 alleviated knee cartilage degeneration in an OA rat model. CONCLUSIONS: Our results suggest that PCB2 may be used as a therapeutic agent for OA.

State-of-the-Art ß-Ga2O3 Field-Effect Transistors for Power Electronics.

Due to the emergence of electric vehicles, power electronics have become the new focal point of research. Compared to commercialized semiconductors, such as Si, GaN, and SiC, power devices based on ß-Ga2O3 are capable of handling high voltages in smaller dimensions and with higher efficiencies, because of the ultrawide bandgap (4.9 eV) and large breakdown electric field (8 MV cm-1). Furthermore, the ß-Ga2O3 bulk crystals can be synthesized by the relatively low-cost melt growth methods, making the single-crystal substrates and epitaxial layers readily accessible for fabricating high-performance power devices. In this article, we first provide a comprehensive review on the material properties, crystal growth, and deposition methods of ß-Ga2O3, and then focus on the state-of-the-art depletion mode, enhancement mode, and nanomembrane field-effect transistors (FETs) based on ß-Ga2O3 for high-power switching and high-frequency amplification applications. In the meantime, device-level approaches to cope with the two main issues of ß-Ga2O3, namely, the lack of p-type doping and the relatively low thermal conductivity, will be discussed and compared.

Recent Advances In Silicon Carbide Chemical Mechanical Polishing Technologies.

Chemical mechanical polishing (CMP) is a well-known technology that can produce surfaces with outstanding global planarization without subsurface damage. A good CMP process for Silicon Carbide (SiC) requires a balanced interaction between SiC surface oxidation and the oxide layer removal. The oxidants in the CMP slurry control the surface oxidation efficiency, while the polishing mechanical force comes from the abrasive particles in the CMP slurry and the pad asperity, which is attributed to the unique pad structure and diamond conditioning. To date, to obtain a high-quality as-CMP SiC wafer, the material removal rate (MRR) of SiC is only a few micrometers per hour, which leads to significantly high operation costs. In comparison, conventional Si CMP has the MRR of a few micrometers per minute. To increase the MRR, improving the oxidation efficiency of SiC is essential. The higher oxidation efficiency enables the higher mechanical forces, leading to a higher MRR with better surface quality. However, the disparity on the Si-face and C-face surfaces of 4H- or 6H-SiC wafers greatly increases the CMP design complexity. On the other hand, integrating hybrid energies into the CMP system has proven to be an effective approach to enhance oxidation efficiency. In this review paper, the SiC wafering steps and their purposes are discussed. A comparison among the three configurations of SiC CMP currently used in the industry is made. Moreover, recent advances in CMP and hybrid CMP technologies, such as Tribo-CMP, electro-CMP (ECMP), Fenton-ECMP, ultrasonic-ECMP, photocatalytic CMP (PCMP), sulfate-PCMP, gas-PCMP and Fenton-PCMP are reviewed, with emphasis on their oxidation behaviors and polishing performance. Finally, we raise the importance of post-CMP cleaning and make a summary of the various SiC CMP technologies discussed in this work.

Development and reliability and validity test of the Fear of Cancer Scale (FOCS).

OBJECTIVE: To develop a Fear of Cancer Scale (FOCS) for non-cancer populations. METHODS: FOCS was developed by classical measurement theory. A total of 15 college students were invited to conduct semi-structured interviews. Seven experts were invited for expert consultation. A total of 2012 Chinese college students who had completed the electronic questionnaire on WJX.cn platform was included. The reliability and validity of FOCS were verified. Multiple linear regression analysis was adopted to explore the influencing factors of cancer fear among college students and further verify the validity of FOCS. RESULTS: There were 17 items in the FOCS, including two subscales - direct fear (8 items), and indirect fear (9 items). FOCS had good validity and reliability. Multiple linear regression showed that GAD-7 score, CSDS score, negative coping score, positive coping score, guardian's highest education, gender, life satisfaction, nationality and major were the influencing factors of cancer fear (p < .05). CONCLUSIONS: The 17-item FOCS was a reliable and valid measure to examine the level of cancer fear in non-cancer populations.

Development and validation of a computed tomography-based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer.

OBJECTIVES: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. METHODS: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). RESULTS: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759-0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647-0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206-0.546, p < 0.001), Resec4 (0.199, 0.040-1.000, p < 0.001), and TCIA (0.303, 0.098-0.944, p = 0.001). CONCLUSIONS: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. KEY POINTS: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.

Laser-Induced Plasmonic Nanobubbles and Microbubbles in Gold Nanorod Colloidal Solution.

In this work, we studied the initiated plasmonic nanobubbles and the follow-up microbubble in gold nanorod (GNR) colloidal solution induced by a pulsed laser. Owing to the surface plasmon resonance (SPR)-enhanced photothermal effect of GNR, several nanobubbles are initiated at the beginning of illumination and then to trigger the optical breakdown of water at the focal spot of a laser beam. Consequently, microbubble generation is facilitated; the threshold of pulsed laser energy is significantly reduced for the generation of microbubbles in water with the aid of GNRs. We used a probing He-Ne laser with a photodetector and an ultrasonic transducer to measure and investigate the dynamic formations of nanobubbles and the follow-up microbubble in GNR colloids. Two wavelengths (700 nm and 980 nm) of pulsed laser beams are used to irradiate two kinds of dilute GNR colloids with different longitudinal SPRs (718 nm and 966 nm). By characterizing the optical and photoacoustic signals, three types of microbubbles are identified: a single microbubble, a coalesced microbubble of multiple microbubbles, and a splitting microbubble. The former is caused by a single breakdown, whereas the latter two are caused by discrete and series-connected multiple breakdowns, respectively. We found that the thresholds of pulsed energy to induce different types of microbubbles are reduced as the concentration of GNRs increases, particularly when the wavelength of the laser is in the near-infrared (NIR) region and close to the SPR of GNRs. This advantage of a dilute GNR colloid facilitating the laser-induced microbubble in the NIR range of the bio-optical window could make biomedical applications available. Our study may provide an insight into the relationship between plasmonic nanobubbles and the triggered microbubbles.

A universal strategy of glyconanoparticle preparation using a bifunctional linker for lectin sensing and cell imaging.

Glyconanoparticles (G-NPs), biofunctional nanomaterials that can fully combine the unique properties of nanoparticles (NPs) with the bioactivities of carbohydrates, have become an appealing nanoplatform in analytical chemistry and biomedical research. However, there is currently a lack of an efficient and universal method for facile immobilization of reducing carbohydrates on NPs while maintaining their structure integrity, greatly limiting the preparation and application of G-NPs. Herein, a new and universal strategy for preparing carbohydrate-functionalized gold nanoclusters (Au NCs) was developed by using S-(3-(methoxyamino)propyl) thioacetate (MPTA) as a new bifunctional linker. MPTA with an N-methoxyamine group (-NHOMe) and a thioacetyl group (-SAc) was synthesized by a two-step strategy and then grafted onto Au NCs by an efficient click reaction. Subsequently, reducing carbohydrates could be readily immobilized onto MPTA-functionalized Au NCs (MPTA-Au NCs) by a reducing end ring-closure reaction under mild conditions. The obtained G-NPs showed average size of 1.9 ± 0.42 nm and strong fluorescence at 610 nm. Carbohydrates grafted on G-NPs still retained their structure integrity and specific recognition ability toward their receptor proteins. Notably, the affinity between G-NPs and proteins was increased by 1300 times compared with free carbohydrates with an association constant of (1.47 ± 0.356) × 106 M-1. The prepared fluorescent G-NPs were also successfully applied to lectin sensing and targeted breast cancer cell imaging with good performance. These results indicated that the intact immobilization of reducing carbohydrates (whether naturally or chemically accessed) on NPs could be easily achieved using MPTA, providing a simple, efficient, and universal strategy for G-NP preparation.

Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.

Diabetes Mellitus (DM) is a significant risk factor for cardiovascular disease (CVD), which is leading cause of deaths in DM patients. However, there are limited effective medical therapies for diabetic CVD. Vascular endothelial injury caused by DM is a critical risk factor for diabetic CVD. Previous study has indicated that Angiotensin-(1-7) (Ang-(1-7)) may prevent diabetic CVD, whereas it is not clear that Ang-(1-7) whether attenuates diabetic CVD through suppressing vascular endothelial injury. In this study, we found that Ang-(1-7) alleviated high glucose (HG)-induced endothelial injury in bEnd3 cells. Moreover, Ang-(1-7) ameliorated HG-induced endothelial injury through downregulating chloride channel 3 (CIC-3) via Mas receptor. Furthermore, HG-induced CIC-3 enhanced reactive oxygen species (ROS) and cytokine production and reduced the level of nitric oxide (NO), while Ang-(1-7) preserved the impact of HG-induced CIC-3 on productions of ROS, cytokine and NO through inhibiting CIC-3 via Mas receptor. Summarily, the present study revealed that Ang-(1-7) alleviated HG-induced vascular endothelial injury through the inhibition of CIC-3, suggested that Ang-(1-7) may preserve diabetic CVD through suppressing HG-induced vascular endothelial injury.

Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits.

BACKGROUND: Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough. METHODS: In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo. RESULTS: In vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/ß-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair. CONCLUSION: Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.

Hypofunction of Circulating Endothelial Progenitor Cells and Aggravated Severity in Elderly Male Patients With Non-ST Segment Elevation Myocardial Infarction: Its Association With Systemic Inflammation.

Background: Aging patients easily suffer from non-ST segment elevation myocardial infarction (NSTEMI). Our previous studies revealed declined function of endothelial progenitor cells (EPCs) in the elderly. However, the impact of aging on EPC function and severity in male NSTEMI patients and its possible mechanism is unclear until now. Methods: We measured the circulating EPC function including migration, proliferation, and adhesion in aging or young male patients with NSTEMI. The GRACE and TIMI risk score were evaluated. Plasma levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) were also detected in all patients. Results: Compared with the young group, the old male patients with NSTEMI had higher GRACE score and TIMI score and decreased function of circulating EPCs. EPC function was negatively correlated with GRACE score and TIMI score. IL-6 and IL-17 level were higher in the old group than those in the young group. There was a significant negative correlation between EPC function and IL-6 or IL-17. Moreover, IL-6 and IL-17 positively correlated with GRACE and TIMI score. Age was positively related with GRACE or TIMI score and plasma level of IL-6 or IL-17, but inversely correlated with EPC function. Conclusions: The current study firstly illustrates that the age-related decrement in EPC function is related to the severity of NSTEMI in male patients, which may be connected with systemic inflammation. These findings provide novel insights into the pathogenetic mechanism and intervention target of aging NSTEMI.

Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study.

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1ß-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.