Mesenchymal stem/stromal cell (MSC)-based therapeutics is already available for treatment of a range of diseases or medical conditions. Autologous or allogeneic MSCs obtained from self or donors have their own advantages and disadvantages in their medical practice. Therapeutic benefits of using autologous vs. allogeneic MSCs are inconclusive. Transplanted MSCs within the body interact with their physical microenvironment or niche, physiologically or pathologically, and such cells in a newly established tissue microenvironment may be impacted by the pathological harmful environmental factors to alter their unique biological behaviors. Meanwhile, a temporary microenvironment/niche may be also altered by the resident or niche-surrounding MSCs. Therefore, the functional plasticity and heterogeneity of MSCs caused by different donors and subpopulations of MSCs may result in potential uncertainty in their safe and efficacious medical practice. Acknowledging a connection between MSCs’ biology and their existing microenvironment, donor-controlled clinical practice for the long-term therapeutic benefit is suggested to further consider minimizing MSCs potential harm for MSC-based individual therapies. In this review, we summarize the advantages and disadvantages of autologous vs. allogeneic MSCs in their therapeutic applications. Among other issues, we highlight the importance of better understanding of the various microenvironments that may affect the properties of niche-surrounding MSCs and discuss the clinical applications of MSCs within different contexts for treatment of different diseases including cardiomyopathy, lupus and lupus nephritis, diabetes and diabetic complications, bone and cartilage repair, cancer and tissue fibrosis.

No abstract

Abstract. China is experiencing increasingly serious ambient ozone pollution, including the economically developed Pearl River Delta (PRD) region. However, the underlying reasons for the ozone increase remain largely unclear, leading to perplexity regarding formulating effective ozone control strategies. In this study, we quantitatively examine the impacts of meteorology and precursor emissions from within and outside of the PRD on the evolution of ozone during the past decade by developing a statistical analysis framework combining meteorological adjustment and source apportionment. We found that meteorological conditions mitigated ozone increase, and that their variation can account for a maximum of 15 % of the annual ozone concentration in the PRD. Precursor emissions from outside the PRD (“nonlocal”) have the largest contribution to ambient ozone in the region and show a consistently increasing trend, whereas emissions from within the PRD (“local”) show a significant spatial heterogeneity and play a more important role during ozone episodes over the southwest of the region. Under general conditions, the impact on the northeastern PRD is positive but decreasing, and in the southwest it is negative but increasing. During ozone episodes, the impact on the northeastern PRD is negative and decreasing, whereas in the southwestern PRD it is positive but decreasing. The central and western PRD are the only areas with an increasing local ozone contribution. The spatial heterogeneity in both the local ozone contribution and its trend under general conditions and during ozone episodes is well interpreted by a conceptual diagram that collectively takes ozone precursor emissions and their changing trends, ozone formation regimes, and the monsoonal and microscale synoptic conditions over different subregions of the PRD into consideration. In particular, we conclude that an inappropriate NOx∕VOC control ratio within the PRD over the past few years is most likely responsible for the ozone increase over southwest of this region, both under general conditions and during ozone episodes. By investigating the ozone evolution influenced by emission changes within and outside of the PRD during the past decade, this study highlights the importance of establishing a dichotomous ozone control strategy to tackle general conditions and pollution events separately. NOx emission control should be further strengthened to alleviate the peak ozone level during episodes. Detailed investigation is needed to retrieve appropriate NOx∕VOC ratios for different emission and meteorological conditions, so as to maximize the ozone reduction efficiency in the PRD.

No abstract

Antibiotic abuse is becoming increasingly serious and the potential for harm to human health and the environment has aroused widespread social concern. Aminoglycoside antibiotics (AGs) are broad-spectrum antibiotics that have been widely used in clinical and animal medicine. Consequently, their residues are commonly found in animal-derived food items and the environment. A simple, rapid, and sensitive detection method for on-site screening and detection of AGs is urgently required. In recent years, with the development of molecular detection technology, nucleic acid aptamers have been successfully used as recognition molecules for the identification and detection of AGs in food and the environment. These aptamers have high affinities, selectivities, and specificities, are inexpensive, and can be produced with small batch-to-batch differences. This paper reviews the applications of aptamers for AG detection in colorimetric, fluorescent, chemiluminescent, surface plasmon resonance, and electrochemical sensors for the analysis in food and environmental samples. This study provides useful references for future research.

No abstract

Doublecortin-like kinase 1 (DCLK1) is upregulated in many tumors and is a marker for tumor stem cells. Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy. However, the regulation of DCLK1 kinase activity is poorly understood, particularly the function of its autoinhibitory domain (AID), and, moreover, no physiological activators of DCLK1 have presently been reported. Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1. The C-terminal AID functions to block the ATP-binding site and is competitive with ATP. HPCAL1 binds directly to the AID in a Ca 2+ -dependent manner, which releases the autoinhibition. We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation. Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.

Comparison of Dscam1 structures reveals the detailed mechanism of Dscam1 isoform-specific recognition.