The Tibetan Plateau (TP), the highest and largest plateau in the world, with complex and competing cryospheric‐hydrologic‐geodynamic processes, is particularly sensitive to anthropogenic warming. The ...quantitative water mass budget in the TP is poorly known. Here we examine annual changes in lake area, level, and volume during 1970s–2015. We find that a complex pattern of lake volume changes during 1970s–2015: a slight decrease of −2.78 Gt yr−1 during 1970s–1995, followed by a rapid increase of 12.53 Gt yr−1 during 1996–2010, and then a recent deceleration (1.46 Gt yr−1) during 2011–2015. We then estimated the recent water mass budget for the Inner TP, 2003–2009, including changes in terrestrial water storage, lake volume, glacier mass, snow water equivalent (SWE), soil moisture, and permafrost. The dominant components of water mass budget, namely, changes in lake volume (7.72 ± 0.63 Gt yr−1) and groundwater storage (5.01 ± 1.59 Gt yr−1), increased at similar rates. We find that increased net precipitation contributes the majority of water supply (74%) for the lake volume increase, followed by glacier mass loss (13%), and ground ice melt due to permafrost degradation (12%). Other term such as SWE (1%) makes a relatively small contribution. These results suggest that the hydrologic cycle in the TP has intensified remarkably during recent decades.
Key Points
Lake area, level, and volume vary in three stages: slight decrease (1970s–1995), rapid increase (1996–2010), and recent slowdown (2011–2015)
Lake and groundwater storage both increased at similar rates in Tibetan Plateau's endorheic basin over 2003–2009
Increased precipitation contributes a major water supply (74%) for lake volume increase, followed by glacier melting (13%) in 2003–2009
The importance of mitochondria in energy metabolism, signal transduction and aging in post-mitotic tissues has been well established. Recently, the crucial role of mitochondrial-linked signaling in ...stem cell function has come to light and the importance of mitochondria in mediating stem cell activity is becoming increasingly recognized. Despite the fact that many stem cells exhibit low mitochondrial content and a reliance on mitochondrial-independent glycolytic metabolism for energy, accumulating evidence has implicated the importance of mitochondrial function in stem cell activation, fate decisions and defense against senescence. In this Review, we discuss the recent advances that link mitochondrial metabolism, homeostasis, stress responses, and dynamics to stem cell function, particularly in the context of disease and aging. This Review will also highlight some recent progress in mitochondrial therapeutics that may present attractive strategies for improving stem cell function as a basis for regenerative medicine and healthy aging.
Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed ...exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.
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CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, ...CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.
Extracellular vesicles (EVs) have emerged as a novel cell‐free strategy for the treatment of many diseases including cancer. As a result of their natural properties to mediate cell‐to‐cell ...communication and their high physiochemical stability and biocompatibility, EVs are considered as excellent delivery vehicles for a variety of therapeutic agents such as nucleic acids and proteins, drugs, and nanomaterials. Increasing studies have shown that EVs can be modified, engineered, or designed to improve their efficiency, specificity, and safety for cancer therapy. Herein, a comprehensive overview of the recent advances in the strategies and methodologies of engineering EVs for scalable production and improved cargo‐loading and tumor‐targeting is provided. Additionally, the potential applications of engineered EVs in cancer therapy are discussed by presenting prominent examples, and the opportunities and challenges for translating engineered EVs into clinical practice are evaluated.
Extracellular vesicles (EVs) are excellent delivery vehicles for various therapeutic agents. EVs are engineered to improve their efficiency, specificity, and safety for cancer therapy. A comprehensive overview of advanced strategies for engineering EVs is given. Additionally, potential applications of engineered EVs in cancer therapy and the challenges for translating them into clinical practice are discussed.
Fluoride (F⁻) has significant impacts on human health. High fluoride groundwater (up to 1.90 mg/L) has been found in upper confined aquifer underlying the first terrace of Weihe River during a ...hydrogeological investigation for water supply in 2005. To reveal the occurrence and hydrogeochemistry of high F⁻ groundwater, hydrogeochemical tools such as saturation index, ionic ratios and correlation analysis were used in this study. The study shows that the concentrations of most physiochemical parameters from phreatic water, influenced by intensive evaporation and anthropogenic activities such as unregulated sewage and excreta disposal and agricultural practices in the area, are higher than those of confined water. The F⁻ concentration in phreatic water is within the acceptable limits set by China and the World Health Organization (WHO), while that of upper confined water shows a decreasing trend northwestward as the Weihe River approaches, with F⁻ concentration in the first terrace beyond the national and the WHO standards. High F⁻ groundwater is observed in alkaline environment associated with high Na⁺, pH, HCO₃ ⁻ and low Ca²⁺ and Mg²⁺. The enrichment of F⁻ is controlled by geologic and hydrogeological conditions, fluorine-bearing minerals presented in alluvial formations and their dissolution/precipitation under the alkaline environment along groundwater flow. Ion exchange, human activities and the mixing of different recharge waters may influence the enrichment of F⁻ as well.
To improve the performance of metallic catalysts, alloying provides an efficient methodology to design state‐of‐the‐art materials. As emerging functional materials, rare‐earth metal compounds can ...integrate the unique orbital structure and catalytic behavior of rare earth elements into metallic materials. Such rare‐earth containing alloy catalysts proffer an opportunity to tailor electronic properties, tune charged carrier transport, and synergize surface reactivity, which are expected to significantly improve the performance and stability of catalysis. Despite its significance, there are only few reviews on rare earth containing alloys or related topics. This review summarizes the composition, synthesis, and applications of rare earth containing alloys in the field of catalysis. Subsequent to comprehensively summarizing and constructively discussing the existing work, the challenges and possibilities of future research on rare‐earth metal compound materials are evaluated.
Rare‐earth alloys are emerging catalytic materials in the field of energy conversion. They have unique electronic structures and spatial characteristics. The families of all rare‐earth‐alloy catalytic materials are reviewed, focusing on their synthesis, properties, structure, and applications.
DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson–Crick base‐pairing interactions between only four types of nucleotides, ...well‐designed DNA self‐assembly can be programmable and predictable. Stem‐loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA‐based structures. The oligonucleotides experience thermal annealing in a near‐neutral buffer containing a divalent cation (usually Mg2+) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA‐based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA‐based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA‐based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost.
DNA is an exquisite design of nature, which is endowed with unique properties to assemble into desired structures with multiple functions. Classical artificial DNA structures, including aptamers, origamis, and tetrahedrons are discussed, with a focus on advanced biomedical applications. Although far from maturity, the use of DNA‐based materials is a promising and cutting edge solution to the most challenging biomedical problems.
There has been no significant improvements for immune checkpoint inhibitors since its first use. Tumour-associated macrophages (TAMs) are critical mediators in the PD-1/PD-L1 axis, contributing to ...the immunosuppressive tumour microenvironment. This study aims to investigate the potential role of PD-L1 in regulating TAMs in glioblastoma. Gene expression data and clinical information of glioma patients were collected from TCGA (n = 614) and CGGA (n = 325) databases. Differentially expressed genes between PD-L1
and PD-L1
groups were identified and subjected to bioinformatical analysis. We found that PD-L1 was frequently expressed in gliomas with a grade-dependent pattern. Higher PD-L1 expression predicted shorter overall survival. Moreover, PD-L1 was positively correlated with immunosuppressive cells (macrophage, neutrophil and immature DC) and negatively correlated with cytocidal immune cells (CD8
T cell and Th1). Importantly, PD-L1 high expression was significantly correlated with M2-polarization of macrophages (M2-TAMs). We conclude that PD-L1 is an unfavourable prognostic marker for patients with glioblastoma; PD-L1-mediated immunosuppression may attribute to the infiltration and M2-polarization of TAMs.
•In-situ observation of evapotranspiration (ET) in a data scarce region.•ET from semi-arid alpine steppe was mainly controlled by precipitation.•Different drivers for evapotranspiration for different ...seasons.•ET and precipitation are nearly balanced in the closed basin of central TP.
Characterizing the water and energy flux in the alpine steppe ecosystem in Tibetan Plateau (TP) is of particular importance for elucidating hydrological cycle mechanisms in high altitude areas. In the present study, two years of actual evapotranspiration (ET) values from a semi-arid alpine steppe region (4947m above sea level) and their environmental and biophysical controls were investigated using the energy balance Bowen ratio energy balance (BREB) method. Seasonally, ET was much lower in frozen soil period and transition period mainly because of low soil water availability. However, ample soil water supplied by rainfall during the rainy period substantially increased ET. The available energy played an important role in controlling ET in the rainy period. Also, the leaf-level stomata closure and plant leaf development could impact the ET through changing bulk surface conductance (Gs) in rainy period. Similarly, the land–atmosphere energy exchange was dominated by latent heat flux (λE) in July, but was dominated by sensible heat flux (H) in December and May. Annual ET (plus sublimation) were 362.9mm and 353.4mm in the first and second observation year, respectively, which were close to the annual precipitation. On annual scale, the low Gs (3.30–3.62mms−1), decoupling factor (Ω, 0.25–0.27) and the ratio of ET to equilibrium evapotranspiration (ET/ETeq, 0.34–0.35) corroborated the overall water-limited conditions for the high-altitude alpine steppe. This research provides not only the ground truth data for future hydrological modeling in the data scarce region of TP but also the insights for elucidating how the environmental and biophysical stress factors control the land surface ET in high-altitude region.