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Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

Background There have been no effective treatments for slowing or reversing Alzheimer’s disease (AD) until now. Growing preclinical evidence, including this study, suggests that mesenchymal stem cells-secreted exosomes (MSCs-Exos) have the potential to cure AD.Aims The first three-arm, drug-intervention, phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos (ahaMSCs-Exos) in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups, intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks, and underwent follow-up visits at weeks 16, 24, 36 and 48.Results No adverse events were reported. In the medium-dose arm, Alzheimer’s Disease Assessment Scale–Cognitive section (ADAS-cog) scores decreased by 2.33 (1.19) and the basic version of Montreal Cognitive Assessment scores increased by 2.38 (0.58) at week 12 compared with baseline levels, indicating improved cognitive function. Moreover, the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36. There were no significant differences in altered amyloid or tau deposition among the three arms, but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated, and a dose of at least 4×108 particles could be selected for further clinical trials.Trial registration number NCT04388982.

Abstract Background Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. Methods First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. Results The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. Conclusions Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Abstract Background We used multimodal compositional magnetic resonance imaging (MRI) techniques, combined with clinical outcomes, to differentiate the alternations of composition in repair cartilage with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) in knee osteoarthritis (KOA) patients. Methods Eighteen patients participated a phase I/IIa clinical trial. All patients were divided randomly into three groups with intra-articular injections of haMPCs: the low-dose (1.0 × 107 cells), mid-dose (2.0 × 107), and high-dose (5.0 × 107) groups with six patients each. Compositional MRI examinations and clinical evaluations were performed at different time points. Results Significant differences were observed in quantitative T1rho, T2, T2star, R2star, and ADC measurements in patients of three dose groups, suggesting a possible compositional changes of cartilage with the treatment of allogeneic haMPCs. Also significant reduction in WOMAC and SF-36 scores showed the symptoms might be alleviated to some extent with this new treatment. As regards sensibilities of multi-parametric mappings to detect compositional or structural changes of cartilage, T1rho mapping was most sensitive to differentiate difference between three dose groups. Conclusions These results showed that multi-compositional MRI sequences might be an effective tool to evaluate the promotion of the repair of cartilage with allogeneic haMPCs by providing information of compositional alterations of cartilage. Trial registration Clinicaltrials, NCT02641860. Registered 3 December 2015.

Abstract Objective Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA). Methods Patients with Kellgren–Lawrence grade 1–3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected. Results Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group. Conclusions Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months. Trial registration ClinicalTrials.gov Identifier: NCT02162693. Registered 13 June 2014.

Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

Background There have been no effective treatments for slowing or reversing Alzheimer's disease (AD) until now. Growing preclinical evidence, including this study, suggests that mesenchymal stem cells-secreted exosomes (MSCs-Exos) have the potential to cure AD. Aims The first three-arm, drug-intervention, phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos (ahaMSCs-Exos) in patients with mild to moderate AD. Methods The eligible subjects were assigned to one of three dosage groups, intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks, and underwent follow-up visits at weeks 16, 24, 36 and 48. Results No adverse events were reported. In the medium-dose arm, Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog) scores decreased by 2.33 (1.19) and the basic version of Montreal Cognitive Assessment scores increased by 2.38 (0.58) at week 12 compared with baseline levels, indicating improved cognitive function. Moreover, the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36. There were no significant differences in altered amyloid or tau deposition among the three arms, but hippocampal volume shrank less in the medium-dose arm to some extent. Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated, and a dose of at least 4×108 particles could be selected for further clinical trials. [ABSTRACT FROM AUTHOR]

Thermal energy storage technology plays an important role on improving energy usage flexibility for the end users. The spherical stacking latent thermal energy storage devices inherits the advantages of direct thermal energy usage efficiency and simplified practical applications that received widely attentions. However, due to dispersed and multi-layer structural arrangement, the non-ignorable dynamic heat transfer process poses difficulties in the device design and operation control. In this study, an improved analytical model for predicting the transient heat transfer process of spherical stacking devices is developed. After verification, the parameter sensitivity analysis of the device is conducted by using the model. The results show that the dynamic change trend of thermal resistance is distinct for the melting and the solidification process. The developed model can dynamically predict the outlet temperature of heat transfer fluid and the heat transfer efficiency in a good agreement, and the prediction error of outlet temperature during solidification can reach −2.49 %–4.70 %. The correlation between sphere radius and heat transfer rate is negative and reaches a kind of high correlation above 0.8 for solidification process. The inlet temperature and the mass flow rate of heat transfer fluid are the most influential parameters for melting process.

Life-threatening systemic fungal infections caused by Candida albicans are significant contributors to clinical mortality, particularly among cancer patients and immunosuppressed individuals. The evasion of the immune response facilitated by fungal surface components enables fungal pathogens to evade macrophage attacks and to establish successful infections. This study developed a mesoporous silica nanoplatform, i.e., MSNP-EAP1Ab, which is composed of mesoporous silica nanoparticles grafted with the antibody of C. albicans surface adhesin Eap1. The activity of MSNP-EAP1Ab against C. albicans immune escape and infection was then evaluated by using the cell interaction model and the mouse systemic infection model. During interaction between C. albicans cells and macrophages, MSNP-EAP1Ab significantly inhibited fungal immune escape, leading to the enhanced phagocytosis of fungal cells by macrophages, with phagocytosis rates increasing from less than 8% to 14%. Furthermore, after treatment of the C. albicans-infected mice, MSNP-EAP1Ab drastically prolonged the mouse survival time and decreased the kidney fungal burden from >30,0000 CFU/g kidney to C. albicans adhesin, offering a promising approach for combatting systemic fungal infections.

Aim: This study aimed to evaluate the safety and therapeutic potential of autologous human adiposederived mesenchymal stem cells (haMSCs) in patients with osteoarthritis. Materials & methods: Safety and efficacy of haMSCs were preclinically assessed in vitro and in BALB/c-nu nude mice. 18 patients were enrolled and divided into three dose groups: the low-dose, mid-dose and high-dose group (1 x 107, 2 x 107 and 5 x 107 cells, respectively), provided three injections and followed up for 96 weeks. Results & Conclusion: The preclinical study established the safety and efficacy of haMSCs. Intra-articular injections of haMSCs were safe and improved pain, function and cartilage volume of the knee joint, rendering them a promising novel treatment for knee osteoarthritis. The dosage of 5 x 107 haMSCs exhibited the highest improvement (ClinicalTrials.gov Identifier: NCT01809769). [ABSTRACT FROM AUTHOR]

Abstract Nuclear localization signals (NLS) are generally short peptides that act as a signal fragment that mediates the transport of proteins from the cytoplasm into the nucleus. This NLS-dependent protein recognition, a process necessary for cargo proteins to pass the nuclear envelope through the nuclear pore complex, is facilitated by members of the importin superfamily. Here, we summarized the types of NLS, focused on the recently reported related proteins containing nuclear localization signals, and briefly summarized some mechanisms that do not depend on nuclear localization signals into the nucleus. Video Abstract

Pork is the main meat consumed by Chinese people. In this study, the sensory quality of four muscles (loin, shoulder, belly, and ham) under three cooking methods (boiling, scalding, and roasting) was examined, and the edible quality and nutritional quality of fresh meat were determined at the same time. Principal component analysis, cluster analysis, correlation analysis, and analysis of the coefficient of variation were used to determine key quality indicators, from which comprehensive quality evaluation equations were established. The results showed that, when meat was boiled, the comprehensive quality evaluation model was Y=0.1537X1+0.1805X2+0.2145X3+0.2233X4+0.2281X5 (X1~X5 are a*, fat, odor, tenderness, and flavor, respectively) and the most suitable muscle was belly; when meat slices were scalded in a hot pot, the comprehensive quality evaluation model was Y=0.1541X1+0.1787X2+0.2160X3+0.2174X4+0.2337X5 (X1~X5 are a*, fat, odor, tenderness, and flavor, respectively) and the most suitable muscle was belly; when meat was roasted, the comprehensive quality evaluation model was Y=0.1539X1+0.1557X2+0.1572X3+0.1677X4+0.1808X5+0.1845X6 (X1~X6 are flavor, marbling, elasticity, cooked flesh color, tenderness, and flesh color, respectively), and the most suitable muscles were belly and shoulder.

Polycyclic aromatic hydrocarbons (PAHs) with high carcinogenicity and mutagenicity may be generated in roast duck during high-temperature roasting. Natural extracts with antioxidant effects may inhibit the formation of PAHs. The objective of this study was to compare the effects of green tea extract (GTE); extract of bamboo leaves (EBL); grape seed extract (GSE) and rosemary extract (RE) on PAHs in roast duck to obtain the optimum extract and present a guidance for reducing PAHs in roast duck. The total phenol content and antioxidant capacity of the four extracts were measured, and the PAH changes in the roast duck caused by the four extracts were detected. The total phenol content of GTE was the highest, 277 mg gallic acid equivalent (GAE)/g, while RE was the lowest at 85 mg GAE/g. The antioxidant capacity of RE was 1.9 mmol Trolox/g, which was significantly lower than that of the other three. The four extracts inhibited PAHs formation in roast duck to varying degrees: When the concentration was 25 g/kg, the best inhibitory effects on Benzo [a] pyrene (BaP) and PAH4 (BaP, BaA, BbF and CHR) were obtained from GTE, with inhibition rates of 75.8% and 79.7%, respectively, while the weakest inhibition rates, 32.7% and 43.6%, respectively, were from RE.