A multifunctional nanoplatform based on MoS2-nanosheets for targeted drug delivery and chemo-photothermal therapy

Synergistic tumor treatment has recently attracted more and more attention due to its remarkable therapeutic effect. Herein, a multifunctional drug delivery system based on hyaluronic acid (HA) targeted dual stimulation responsive MoS2 nanosheets (HA-PEI-LA-MoS2-PEG, HPMP) for active interaction with CD44 receptor positive MCF-7 cells is reported. Melanin (Mel), a new type of photothermal agent and doxorubicin (DOX) are both loaded onto the HPMP nanocomposite and can be released by mild acid or hyperthermia. The prepared HPMP nanocomposite has a uniform hydrodynamic diameter (104 nm), a high drug loading (944.3 mg.g-1 HPMP), a remarkable photothermal effect (photothermal conversion efficiency: 55.3%) and excellent biocompatibility. The DOX release from HPMP@(DOX/Mel) can be precisely controlled by the dual stimuli of utilizing the acidic environment in the tumor cells and external laser irradiation. Meanwhile, loading of Mel onto the surface can enhance the photothermal effect of the MoS2 nanosheets. In vitro experiments showed that the HPMP@(DOX/Mel) nanoplatform could efficiently deliver DOX into MCF-7 cells and demonstrated enhanced cytotoxicity compared to that of the non-targeted nanoplatform. In vivo experiments in a breast cancer model of nude mice further confirmed that the HPMP@(DOX/Mel) significantly inhibited tumor growth under near infrared (NIR) laser irradiation, which is superior to any single therapy. In summary, this flexible nanoplatform, based on multi-faceted loaded MoS2 nanosheets, exhibits considerable potential for efficient pH/NIR-responsive targeted drug delivery and chemo-photothermal synergistic tumor therapy

Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice (P=0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P<0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P=0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden

Research Progress on the Quality Formation Mechanism of Dry-Aged Meat

Dry-aging is the aerobic aging process where meat carcasses or primal cuts are hanged and aged for a period of time (28 to 55 days, or even longer) under specific environmental conditions of temperature (0–4 ℃), relative humidity (61%–85%), and air flow (0.5–2.0 m/s). Dry-aging in a breathable bag, dry-aging combined with ultraviolet irradiation treatment, and stepwise dry/wet-aging have been successively developed. Due to dehydration during dry-aging, the surface of meat shrinks to produce a hard ‘crust’, resulting in significant mass loss and trim loss. However, compared with wet-aging, dry-aging can significantly enhance meat flavor characteristics, imparting a strong ‘dry-aged flavor’ and unique roasted beef-like, roasted nutty and buttery aromas to aged meat. Dry-aging can be used effectively to improve the eating quality and economic value of low-marbled beef. In this paper, the key parameters of dry-aging are reviewed, the potential mechanism by which dry-aging improves meat quality, especially flavor, is discussed. Future prospects for the application and development of dry-aging are discussed as well. This review will provide theoretical support for the development of the meat industry and for exploring the market for high-quality meat

Identification of BAG5 as a Potential Biomarker for Parkinson’s Disease Patients With R492X PINK1 Mutation

Parkinson’s disease (PD) is a degenerative, progressive nervous system disorder with an unknown cause. PINK1 [phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1] causative mutations R492X may cause autosomal recessive early-onset parkinsonism. In this study, we utilized patient samples and cell line system to investigate roles of Bcl2-associated athanogene 5 (BAG5) in PD patients with R492X PINK1 mutation. We show that the expression levels of BAG5 in the skin tissues from PD patients with R492X PINK1 mutation are markedly lower than those from the healthy control subjects in a small cohort of patients, which has not been recognized before. In addition, we demonstrate that BAG5 physically binds to R492X mutated PINK1 protein. Furthermore, we reveal that BAG5 promotes the degradation of R492X mutated PINK1 protein via ubiquitin/proteasome-dependent pathway, suggesting that decreased level of BAG5 may lead to R492X mutated PINK1 protein accumulation. These findings suggest that BAG5 may serve as an early detection biomarker for PD patients with R492X PINK1 mutation and provide important new insights on how BAG5 affects R492X mutated PINK1 protein, highlighting therapeutic targets for this disease

Using economic evaluations to support acupuncture reimbursement decisions: current evidence and gaps

Hongchao Li and colleagues explore the global challenges of including economic evaluations in decisions about reimbursement for acupunctur

Genetic, phenotypic and ecological differentiation suggests incipient speciation in two Charadrius plovers along the Chinese coast

BackgroundSpeciation with gene flow is an alternative to the nascence of new taxa in strict allopatric separation. Indeed, many taxa have parapatric distributions at present. It is often unclear if these are secondary contacts, e.g. caused by past glaciation cycles or the manifestation of speciation with gene flow, which hampers our understanding of how different forces drive diversification. Here we studied genetic, phenotypic and ecological aspects of divergence in a pair of incipient shorebird species, the Kentish (Charadrius alexandrinus) and the White-faced Plovers (C. dealbatus), shorebirds with parapatric breeding ranges along the Chinese coast. We assessed divergence based on molecular markers with different modes of inheritance and quantified phenotypic and ecological divergence in aspects of morphometric, dietary and climatic niches.ResultsOur integrative analyses revealed small to moderate levels of genetic and phenotypic distinctiveness with symmetric gene flow across the contact area at the Chinese coast. The two species diverged approximately half a million years ago in dynamic isolation with secondary contact occurring due to cycling sea level changes between the Eastern and Southern China Sea in the mid-late Pleistocene. We found evidence of character displacement and ecological niche differentiation between the two species, invoking the role of selection in facilitating divergence despite gene flow.ConclusionThese findings imply that ecology can indeed counter gene flow through divergent selection and thus contributes to incipient speciation in these plovers. Furthermore, our study highlights the importance of using integrative datasets to reveal the evolutionary history and assist the inference of mechanisms of speciation

Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A “cytokine storm”, i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients

Application of Hydrogels in Cardiac Regeneration

Abstract Myocardial infarction (MI) is a leading cause of death globally. Due to limited cardiac regeneration, infarcted myocardial tissue is gradually replaced by cardiac fibrosis, causing cardiac dysfunction, arrhythmia, aneurysm, free wall rupture, and sudden cardiac death. Thus, the development of effective methods to promote cardiac regeneration is extremely important for MI treatment. In recent years, hydrogels have shown promise in various methods for cardiac regeneration. Hydrogels can be divided into natural and synthetic types. Different hydrogels have different features and can be cross-linked in various ways. Hydrogels are low in toxicity and highly stable. Since they have good biocompatibility, biodegradability, and transformability, moderate mechanical properties, and proper elasticity, hydrogels are promising biomaterials for promoting cardiac regeneration. They can be used not only as scaffolds for migration of stem cells, but also as ideal carriers for delivery of drugs, genetic materials, stem cells, growth factors, cytokines, and small molecules. In this review, the application of hydrogels in cardiac regeneration during or post-MI is discussed in detail. Hydrogels open a promising new area in cardiac regeneration for treating MI

Combine MCDM Methods and PSO to Evaluate Economic Benefits of High-Tech Zones in China

High-tech zones (HTZs), as important economic growth poles, have played a key role in China’s economic boom. A method based on multi-criteria decision-making (MCDM) and particle swarm optimization (PSO) is proposed to evaluate economic benefits of HTZs. MCDM involves analytic hierarchy process (AHP) and technique for order preference by similarity to an ideal solution (TOPSIS) as they are easy and simple to calculate. AHP is used to construct judgment matrix. Then, the judgment matrix is converted to a constraint optimization problem. PSO is adopted to optimize the problem and get weights of indicators. TOPSIS is used to make the evaluation. The results from 2012 to 2016 of 105 HTZs are obtained and hierarchical clustering analysis is applied to cluster results. The results have demonstrated that the rankings of Zhongguancun Technology Park and Wuhan East Lake HTZ have always been at the forefront, and the ranking of Kunshan New District has risen rapidly, while Shenyang HTZ has dropped significantly. According to the results, some targeted suggestions have been proposed for the development of HTZs

Lifelong reinforcement learning with temporal logic formulas and reward machines

Continuously learning new tasks using high-level ideas or knowledge is a key capability of humans. In this paper, we propose lifelong reinforcement learning with sequential linear temporal logic formulas and reward machines (LSRM), which enables an agent to leverage previously learned knowledge to accelerate the learning of logically specified tasks. For a more flexible specification of tasks, we first introduce sequential linear temporal logic (SLTL), which is a supplement to the existing linear temporal logic (LTL) formal language. We then utilize reward machines (RMs) to exploit structural reward functions for tasks encoded with high-level events, and propose an automatic extension of RMs and efficient knowledge transfer over tasks for continuous lifelong learning. Experimental results show that LSRM outperforms methods that learn the target tasks from scratch by taking advantage of the task decomposition using SLTL and the knowledge transfer over RMs during the lifelong learning process