Most current nanoparticle-based PET tracers are radiolabeled through metal chelators conjugated on the nanoparticle surface. Metal chelation usually requires sophisticated optimization and may impact ...the physical or chemical properties of nanoparticles, which leads to the changes in their distribution and pharmacokinetics in vivo. A chelator-free radiolabeling approach is thus highly desirable. Here, we report that zinc sulfide (ZnS) quantum dots (QDs) can be rapidly radiolabeled with 68Ga or 64Cu through cation exchange without chelators. The radiolabeling was accomplished in times as short as 5 min at 37 °C in aqueous solution, yielding a high labeling efficiency and radiochemical purity for both isotopes. Surface functionalization with targeting peptides was also readily achieved to enable or enhance the cellular uptake of QDs. In vivo PET imaging showed that 64Cu-labeled QDs had a much higher tumor uptake (7.3% ID g-1) than 64Cu-DOTA in a murine cancer model. Overall, this study presents a QD-based platform to achieve convenient and chelator-free radiolabeling, and improve PET imaging of solid tumors.
Myocardial ischemia/reperfusion injury (I/RI) is closely associated with energy substrate metabolism. Fibronectin 1 (Fn1) was markedly elevated in the heart of I/R pigs and ischemic patients, but its ...role in myocardial I/RI is controversial and the precise mechanism involved remains elusive. Herein, we tested whether blockage of Fn1 with its inhibitor (fibronectin tetrapeptide, RGDS) would alleviate myocardial I/RI. Wild-type (WT) mice were administered with RGDS once 3 h before I/R operation and once at 24 or 48 h postreperfusion, and sacrificed at 24 or 72 h post-I/R, respectively. Cardiac function was evaluated by echocardiography. Myocardial infarction size, apoptosis, fibrosis, and inflammation were examined via histological staining. Uptake of glucose and fatty acids were detected by positron emission tomography (PET) and computer tomography (CT) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and 18F-fluoro-6-thia-heptadecanoic acid (FTHA), respectively. Our results showed that administration of RGDS to mice remarkably limited the I/R-induced myocardial infarct size, myocyte apoptosis, inflammation, oxidative stress, and fibrosis and improved cardiac contractile dysfunction. These protective effects were associated with upregulation of the AMP/ATP ratio and the activation of LKB1-AMPK signaling, which subsequently increased AS160-GLUT4-mediated glucose and fatty acid uptake, improved mitochondrial dynamic imbalance, and inactivated TGF-β and NF-κB signals in the I/R heart. In conclusion, the current study identified that blocking Fn1 protects against myocardial I/RI likely through activating the LKB1-AMPK-dependent signals and highlights that inhibition of Fn1 may be a novel therapeutic option for treating ischemic heart diseases.
•Focus on the optimal scale of urban green space.•Comprehensively considering the ecological and socioeconomic benefits of urban green space and constructing an evaluation index system.•Calculating ...the optimal scale of urban green space in Xi'an under different benefit conditions.•Providing new perspectives and references for the future construction of Park Citiy and urban green space system planning.
With the acceleration of urbanization in China, urban problems have become increasingly serious, and have led to the concept of the Park City. This concept involves a consideration of the comprehensive value of green space in order to give full play to the maximum benefit of that green space and, thus, realize the sustainable development of the city. Therefore, an exploration of the optimal scale of urban green space will have theoretical and practical significance for the construction of the Park City and the rational allocation of urban land resources. Taking Xi'an as an example, the present paper comprehensively considers the socioeconomic and ecological benefits of urban green space, and calculates its optimal scale. The results indicate that: (i) in terms of the socioeconomic benefits alone, the per capita amount of green area in Xi’an needs to be larger than 11.08 m2, and there is no theoretical optimal size; (ii) in terms of ecological benefits alone, the per capita amount of green area in Xi’an needs to be greater than 22.98 m2; (iii) in terms of the combined socioeconomic and ecological benefits, the per capita amount of green area of Xi’an needs to be greater than 24.89 m2; (iv) the optimal scale for any city is more siginficantly impacted by the ecological effects than by the socioeconomic effects; (v) to satisfy the development and construction needs of various cities, with their individual characteristics, the optimal urban green space scale should be explored according to the target city’s developmental stage and land use situation. The methods and results of the present study are intended to provide a reference for the future construction of Park Cities in China, as well as the planning of green space systems in other cities globally, and to open new prospects for future research.
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•Correlations between conventional and unconventional reservoirs are revealed.•Differences between conventional and unconventional reservoirs are revealed.•Unified classification ...scheme is established for all different oil and gas reservoirs.
The discovery and large-scale exploration of unconventional oil/gas resources since 1980s have been considered as the most important advancement in the history of petroleum geology. It has not only changed the balance of supply and demand in the global energy market, but also improved our understanding of the formation mechanisms and distribution characteristics of oil/gas reservoirs. However, misconceptions widely exist in studies of different types of petroleum accumulations because of the lack of a unified genetic classification. Unconventional reservoir has been used in the literature as a general name for various oil/gas reservoirs that are formed under complex dynamic mechanisms as long as buoyancy is not the major controlling factor. On the other hand, different terms have been given to the reservoirs even with the same formation mechanism. This paper selected six representative basins in China as the major subject of the study, analyzed the drilling results of 80,762 reservoir layers from 12,237 exploration wells in these basins. By investigating the progress of unconventional oil/gas exploration in North America in the past 30 years and addressing the distribution characteristics of discovered 52,926 oil/gas reservoirs in 1,186 basins around the world, this study revealed the correlations and differences of formation and distribution characteristics between conventional and unconventional oil and gas reservoirs. It was found that there are five correlations between conventional and unconventional reservoirs, including sharing the same oil and gas source, occurring in strata with the same geological age, coexisting in the same sedimentary basins, being confined in the same petroleum systems, and being enriched in the same reservoir layers. It was also found that there are five differences between conventional and unconventional reservoirs, including differences in hydrocarbon compositions, spatial relations to source rocks, reservoir lithology and quality, distribution in geological settings, and reservoir formation mechanism. Then, the unified genetic classification scheme is put forward to clarify their differences and correlations. All kinds of conventional and unconventional oil and gas resource are classified into 3 categories and 6 subcategories according to their dynamic mechanisms of formation, reclassified into 15 types based on main controlling factors, and further divided into 49 styles considering their underground occurrences. The application results show that all different oil/gas reservoirs can find their corresponding positions in the classification scheme, and all the oil/gas reservoirs with the same genetic mechanism, major controlling factor and occurrence can find their particular position in this classification scheme.
The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically ...proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated.
Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function.
(1) Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2) the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3) the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly.
The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time.
Abstract
Background
Due to recent emergence, severe fever with thrombocytopenia syndrome (SFTS) is becoming one of the major public health problems in Shandong Province, China. The numbers of ...reported SFTS cases in general and the area with reported SFTS cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of SFTS in Shandong Province have not been investigated yet.
Methods
The surveillance data of SFTS in Shandong Province, China, during 2014–2018 were extracted from China Information System for Disease Control and Prevention (CISDCP). Geoda software was used to explore spatial autocorrelation analysis, and Satscan software was used to identify spatio-temporal clustering of cases. The results were presented in ArcMap.
Results
The annual average incidence was 0.567/100,000 in Shandong Province during 2014–2018. Results showed that the distribution of SFTS was not random but clustered in space and time. A most likely cluster including 15 counties was observed in the northeastern region of Shandong Province from January 1, 2015 to December 31, 2015 (Relative risk = 5.13, Log likelihood ratio = 361.266,
P
< 0.001).
Conclusions
The number of SFTS cases in Shandong Province increased overall. Geographic information system analysis coupled with spatial analysis illustrated regions with SFTS clusters. Our results provide a sound evidence base for future prevention and control programs of SFTS such as allocation of the health resources, surveillance in high-risk regions, health education, improvement of diagnosis and so on.
Allosteric transcription factors (aTFs) have proven widely applicable for biotechnology and synthetic biology as ligand-specific biosensors enabling real-time monitoring, selection and regulation of ...cellular metabolism. However, both the biosensor specificity and the correlation between ligand concentration and biosensor output signal, also known as the transfer function, often needs to be optimized before meeting application needs. Here, we present a versatile and high-throughput method to evolve prokaryotic aTF specificity and transfer functions in a eukaryote chassis, namely baker's yeast Saccharomyces cerevisiae. From a single round of mutagenesis of the effector-binding domain (EBD) coupled with various toggled selection regimes, we robustly select aTF variants of the cis,cis-muconic acid-inducible transcription factor BenM evolved for change in ligand specificity, increased dynamic output range, shifts in operational range, and a complete inversion-of-function from activation to repression. Importantly, by targeting only the EBD, the evolved biosensors display DNA-binding affinities similar to BenM, and are functional when ported back into a prokaryotic chassis. The developed platform technology thus leverages aTF evolvability for the development of new host-agnostic biosensors with user-defined small-molecule specificities and transfer functions.
The proteasome is the main complex responsible for maintaining intracellular protein homeostasis, impairment of which is associated with cardiac ischaemia/reperfusion (I/R) injury. The small molecule ...TCH-165 has been found to activate the 20S proteasome to remove disordered proteins in multiple myeloma and glioblastoma. However, the preventive effect of TCH-165 against I/R-mediated cardiac impairment in mice remains largely unknown. Here, a cardiac I/R model was established in mice. Heart function was assessed with echocardiography. Cardiac infarction, myocyte death, and superoxide level were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC)-Evans blue staining, terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL) assay and immunostaining, respectively. Our results showed that TCH-165 treatment markedly ameliorated I/R-mediated cardiac dysfunction and decreased the infarct size, apoptosis, and superoxide levels. Mechanistically, TCH-165 increased immunoproteasome subunit expression/activity, increasing pro-fission protein dynamin-1-like protein (DNM1L, also known as DRP1) degradation and the expression of the pro-fusion proteins mitofusin 1/2 (Mfn1/2) and thereby leading to mitochondrial fission/fusion balance. In vitro experiments confirmed that inhibition of proteasome activity by epoxomicin abolished the protective effect of TCH-165 against hypoxia/reoxygenation (H/R)-induced increases in cardiomyocyte apoptosis, superoxide production and mitochondrial fission. In summary, TCH-165 is a newly discovered inducer of immunoproteasome activity that exerts a preventive effect against cardiac I/R damage by targeting Drp1 degradation, indicating that it may be as a potential therapeutic candidate for ischaemic heart disease.
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The integration of geodesign with vulnerability analysis offers a novel approach to landscape, urban, and environmental planning challenges. The interdisciplinary nature, engaged processes, and ...advanced spatial analytics in geodesign provide important component pieces for identifying and addressing vulnerable places. A comparative case-study approach explores the geodesign process and its efficacy in addressing flooding issues in diverse settings. The objectives of this review include assessing geodesign processes in the development of vulnerability indices and assessments, exploring their effectiveness and limitations, and providing insights across different scales and contexts. The work seeks to contribute to the advancement of vulnerability assessment methodologies and their broader role in the fields of landscape design and urban and environmental planning. The findings of this study are expected to provide insights for researchers and practitioners looking to produce more effective, sustainable, and resilient planning and design outcomes.
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