Publications by authors named "Xuhui Wang"

120 Publications

Shield and sword nano-soldiers ameliorate rheumatoid arthritis by multi-stage manipulation of neutrophils.

J Control Release 2021 May 6. Epub 2021 May 6.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Rheumatoid arthritis (RA) is characterized by the outbreak of inflammation. Neutrophils, the main culprit of the outbreak of inflammation, are the first inflammatory cells to be recruited to inflamed joints and facilitate the recruitment of themselves by stimulating the release of chemokines. Here, based on neutrophils, a novel anti-inflammatory "shield and sword soldiers" strategy is established with LMWH-TOS nanoparticles (LT NPs). The hydrophilic fragment low molecular weight heparin (LMWH) acts as a shield which block the transvascular movement of neutrophils through inhibiting the adhesion cascade by binding to P-selectin on inflamed endothelium. Synergistically, MMP-9, which is secreted by the recruited neutrophils and degrade the main component of articular cartilage, is reduced by the hydrophobic fragment d-α-tocopheryl succinate (TOS), functioning as a sword. In collagen-induced arthritis (CIA) mouse model, LT NPs show significant targeting effect, and exhibit prominent therapeutic efficacy after enveloping the first-line anti-RA drug methotrexate. Our work proves that the multi-stage manipulation of neutrophils is feasible and effective, providing a new concept for RA treatment.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.008DOI Listing
May 2021

Unusual characteristics of the carbon cycle during the 2015-2016 El Niño.

Glob Chang Biol 2021 May 1. Epub 2021 May 1.

Department of Biology and Graduate Degree Program in Ecology, Colorado State University, Fort Collins, USA.

The 2015-2016 El Niño was one of the strongest on record, but its influence on the carbon balance is less clear. Using Northern Hemisphere atmospheric CO observations, we found both detrended atmospheric CO growth rate (CGR) and CO seasonal-cycle amplitude (SCA) of 2015-2016 were much higher than that of other El Niño events. The simultaneous high CGR and SCA were unusual, because our analysis of long-term CO observations at Mauna Loa revealed a significantly negative correlation between CGR and SCA. Atmospheric inversions and terrestrial ecosystem models indicate strong northern land carbon uptake during spring but substantially reduced carbon uptake (or high emissions) during early autumn, which amplified SCA but also resulted in a small anomaly in annual carbon uptake of northern ecosystems in 2015-2016. This negative ecosystem carbon uptake anomaly in early autumn was primarily due to soil water deficits and more litter decomposition caused by enhanced spring productivity. Our study demonstrates a decoupling between seasonality and annual carbon cycle balance in northern ecosystems over 2015-2016, which is unprecedented in the past five decades of El Niño events.
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http://dx.doi.org/10.1111/gcb.15669DOI Listing
May 2021

Rapid pH-responsive self-disintegrating nanoassemblies balance tumor accumulation and penetration for enhanced anti-breast cancer therapy.

Acta Biomater 2021 Apr 18. Epub 2021 Apr 18.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

The dilemma of tumor accumulation and deep penetration has always been a barrier in antitumor therapy. Stimuli-responsive size changeable drug delivery systems provide possible solutions. Nevertheless, the low size-shrinkage efficiency limited the antitumor effects. In this study, an instant pH-responsive size shrinkable nanoassemblies named self-aggregated DOX@HA-CD (SA-DOX@HA-CD) was formulated using small-sized hyaluronic acid modified carbon dots (HA-CD) as monomers, which could self-aggregate into raspberry-like structure via hydrophobicity force in neutral pH and rapidly disassemble into shotgun-like DOX-loaded CD monomer in simulated tumor microenvironment (pH 6.5), owing to the transformation in electrical charge and hydrophobicity/hydrophilicity of this system. The transmission electron microscopy showed that the clustered SA-DOX@HA-CD had a diameter of ~150 nm, and thoroughly disassembled into ~30 nm nanoparticles in response to acidic environment. The disassemble efficiency was approximately 100%. Attributed to this property, SA-DOX@HA-CD led to enhanced cellular internalization and accumulation in 4T1 cells in simulated tumor microenvironment, as well as deep tumor penetration in 3D tumor spheroid model. Besides, the imine bond between DOX and HA-CD endowed DOX with pH-responsive release profile in the acidic lysosome environment. Furthermore, in the orthotopic 4T1 tumor-bearing mouse model, SA-DOX@HA-CD demonstrated higher tumor accumulation than non-aggregated DOX-HA-CD. Meanwhile, in response to the acid tumor microenvironment, the dissociated DOX-HA achieved deep tumor penetration, which consequently resulted in 2.5-fold higher antitumor efficiency. The formulation of self-aggregated SA-DOX@HA-CD provides a simple and effective alternative to prepare pH-responsive size-shrinkable nanodrug delivery systems. STATEMENT OF SIGNIFICANCE: The heterogeneity of tumor vasculature and the high tumor interstitial pressure lead to the barriers in tumor accumulation and deep penetration, which calls for opposite properties (e.g. size) of drug delivery systems. To address this dilemma, various size changeable nanoparticles have been developed utilizing special features of tumor microenvironment, such as pH, enzyme and reactive oxygen species. Nevertheless, the current strategies face the problems of incomplete hydrolysis of chemical bonds or insufficient enzyme degradation, which result in only partial size shrinkage, hindering the tumor deep penetration effects. Here we developed a self-assembled nanocluster, which could respond to acidic pH rapidly and thoroughly disassemble into small nanodots due to the alteration of hydrophobicity/hydrophilicity/charge, leading to approximately 100% dissociation. This strategy provides a new concept for design of size changeable drug delivery systems.
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http://dx.doi.org/10.1016/j.actbio.2021.04.022DOI Listing
April 2021

Reply to: Disentangling biology from mathematical necessity in twentieth-century gymnosperm resilience trends.

Nat Ecol Evol 2021 Apr 5. Epub 2021 Apr 5.

CSIC, Global Ecology Unit CREAF-CSIC-UAB, Bellaterra, Barcelona, Catalonia, Spain.

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http://dx.doi.org/10.1038/s41559-021-01412-4DOI Listing
April 2021

Preparation of Carbon-Covered Phosphorus-Modified Alumina with Large Pore Size and Adsorption of Rhodamine B.

Nanomaterials (Basel) 2021 Mar 20;11(3). Epub 2021 Mar 20.

Department of Physics, The University of Texas at Arlington, 502 Yates Street, 108 Science Hall, Arlington, TX 76019, USA.

In this study, phosphorus-modified alumina with large pore size was synthesized through a coprecipitation method. The carbon-covered, phosphorus-modified alumina with large pores was prepared by impregnating with glucose and carbonizing to further improve the adsorption of organic dyes. The morphology and structure of these composites were characterized by various analysis methods, and Rhodamine B (RhB) adsorption was also examined in aqueous media. The results showed that the specific surface area and pore size of the phosphorus-modified alumina sample AP7 (prepared with a P/Al molar ratio of 0.07) reached 496.2 m·g and 21.9 nm, while the specific surface area and pore size of the carbon-covered phosphorus-modified alumina sample CAP7-27 (prepared by using AP7 as a carrier for glucose at a glucose/Al molar ratio of 0.27) reached 435.3 m·g and 21.2 nm. The adsorption experiment of RhB revealed that CAP7-27 had not only an equilibrium adsorption capacity of 198 mg·g, but also an adsorption rate of 162.5 mg·g in 5 min. These superior adsorption effects can be attributed to the similar pore structures of CAP7-27 with those of alumina and the specific properties with those of carbon materials. Finally, the kinetic properties of these composites were also studied, which were found to be consistent with a pseudo-second-order kinetic model and Langmuir model for isothermal adsorption analysis. This study indicates that the prepared nanomaterials are expected to be promising candidates for efficient adsorption of toxic dyes.
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http://dx.doi.org/10.3390/nano11030799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004047PMC
March 2021

Neuritin promotes angiogenesis through inhibition of DLL4/Notch signaling pathway.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar 31. Epub 2021 Mar 31.

Department of Biochemistry and Molecular Biology, Department of Basic Medical Sciences, School of Medicine, Shihezi University, Shihezi 832000, China.

Neuritin is a member of the neurotrophic factor family, which plays an important role in the promotion and development of the nervous system. Neuritin is also involved in angiogenesis. Neuritin was recently found to be a negative regulatory factor of the Notch 1 signaling pathway. Notch signaling pathway is known as a regulatory pathway of angiogenesis. Thus, neuritin may play a role in angiogenesis through the Notch signaling pathway. In the present study, we investigated the expressions of neuritin and Notch signaling pathway factors in the pulmonary vascular tissue. The results showed that neuritin expression was increased in the paraneoplastic vascular tissue and decreased in the lung cancer vascular tissue. The neuritin expression was increased with the increase of vascular tissue density, and a negative correlation between neuritin expression and delta-like ligand 4 (DLL4) was identified in vascular tissues of lung cancer. Overexpression of neuritin in human umbilical vein endothelial cells (HUVECs) inhibited the expressions of Notch signaling pathway-associated factors, including DLL4, NICD, and Hes-1, and promoted the migration and tubular formation of HUVECs. In conclusion, our results indicated that neuritin is involved in angiogenesis and may play a role in angiogenesis through the Notch signaling pathway. This study provides a theoretical basis for clinical anti-angiogenesis therapy.
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http://dx.doi.org/10.1093/abbs/gmab039DOI Listing
March 2021

Iron and copper micronutrients influences cadmium accumulation in rice grains by altering its transport and allocation.

Sci Total Environ 2021 Mar 2;777:146118. Epub 2021 Mar 2.

School of Environment and Resource, Southwest University of Science and Technology, Mianyang, Sichuan 621010, China.

Cadmium (Cd) contamination in rice paddy fields constitutes a serious health issue in some parts of China. Here we study the potential for remediation of Cd contaminated alkaline paddy soil with low iron (Fe) and high copper (Cu) background by altering the concentrations of Fe and Cu in the growing media, which has been only seldom considered. We assessed how these two micronutrients (Cu and Fe) affect the absorption and transport of Cd in rice. Adding Cu significantly increased rice biomass and grain yield by reducing root Cd influx and Cd upward transport which, consequently, lowered Cd concentrations in roots, culms and leaves. However, excessive Cu also promoted a relatively higher Cd allocation in grains, especially under Fe deficiency, likely because Cu significantly increased the proportion of bioavailable Cd in leaves. Contrastingly, Fe did not alleviate the toxic effects of Cd on rice growth and yield, but it significantly reduced Cd transfer towards grains, which might be attributed to a sharp decrease in the proportion of bioavailable Cd in leaves. Our results demonstrated that Cd remediation may be achieved through altering Fe and Cu inputs, such that Cd accumulation in rice grains is reduced.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146118DOI Listing
March 2021

Divergent responses of phenology and growth to summer and autumnal warming.

Glob Chang Biol 2021 Mar 8. Epub 2021 Mar 8.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Plant phenology is highly sensitive to climate change, and shifts in autumnal foliar senescence are critical for plant productivity and nutrient cycling. Global warming has delayed the timing of foliar senescence, but the response of autumnal foliar senescence to nonuniform seasonal warming remains poorly understood, with experimental evidence in trees especially scarce. We therefore conducted a field experiment on seasonally asymmetric warming on 2-year-old larch (Larix principis-rupprechtii) seedlings in two hydrologically contrasting years (wet 2018 and dry 2019). Autumnal and year-round warming significantly delayed the timing of foliar senescence by 6 and 7 d in 2018, the wet year, with corresponding temperature sensitivities of 6.73 ± 1.47 and 8.26 ± 1.00 d/°C, respectively. Interestingly, the dates of senescence did not change across the warming treatments in 2019, the dry year. However, there was no significant effect of summer warming on the timing of foliar senescence neither in the wet nor dry year. The delayed autumnal foliar senescence was responsible for an increase in biomass only in the wet year, 2018. In contrast, summer warming, but not autumnal warming, increased the mortality of the seedlings in both 2018 and 2019. These results suggest that the hydrological conditions substantially modify the response of autumnal phenology and growth to seasonal warming. Autumnal warming increases growth, whereas summer warming could cause carbon starvation/hydraulic failure, reduce growth, and lead to higher mortality. Our results suggest that the functioning, ecosystem services, and sustainability of forests in the future depend on the strength and pattern of nonuniform seasonal warming. This study can inspire new research in phenology and tree growth in experiments with asymmetric warming.
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http://dx.doi.org/10.1111/gcb.15586DOI Listing
March 2021

Global irrigation contribution to wheat and maize yield.

Nat Commun 2021 02 23;12(1):1235. Epub 2021 Feb 23.

Sino-French Institute of Earth System Sciences, Peking University, 100871, Beijing, China.

Irrigation is the largest sector of human water use and an important option for increasing crop production and reducing drought impacts. However, the potential for irrigation to contribute to global crop yields remains uncertain. Here, we quantify this contribution for wheat and maize at global scale by developing a Bayesian framework integrating empirical estimates and gridded global crop models on new maps of the relative difference between attainable rainfed and irrigated yield (ΔY). At global scale, ΔY is 34 ± 9% for wheat and 22 ± 13% for maize, with large spatial differences driven more by patterns of precipitation than that of evaporative demand. Comparing irrigation demands with renewable water supply, we find 30-47% of contemporary rainfed agriculture of wheat and maize cannot achieve yield gap closure utilizing current river discharge, unless more water diversion projects are set in place, putting into question the potential of irrigation to mitigate climate change impacts.
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http://dx.doi.org/10.1038/s41467-021-21498-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902844PMC
February 2021

Data-driven estimates of global litter production imply slower vegetation carbon turnover.

Glob Chang Biol 2021 04 1;27(8):1678-1688. Epub 2021 Feb 1.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Accurate quantification of vegetation carbon turnover time (τ ) is critical for reducing uncertainties in terrestrial vegetation response to future climate change. However, in the absence of global information of litter production, τ could only be estimated based on net primary productivity under the steady-state assumption. Here, we applied a machine-learning approach to derive a global dataset of litter production by linking 2401 field observations and global environmental drivers. Results suggested that the observation-based estimate of global natural ecosystem litter production was 44.3 ± 0.4 Pg C year . By contrast, land-surface models (LSMs) overestimated the global litter production by about 27%. With this new global litter production dataset, we estimated global τ (mean value 10.3 ± 1.4 years) and its spatial distribution. Compared to our observation-based τ , modelled τ tended to underestimate τ at high latitudes. Our empirically derived gridded datasets of litter production and τ will help constrain global vegetation models and improve the prediction of global carbon cycle.
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http://dx.doi.org/10.1111/gcb.15515DOI Listing
April 2021

PKA-Dependent Membrane Surface Recruitment of CI-AMPARs Is Crucial for BCP-Mediated Protection Against Post-acute Ischemic Stroke Cognitive Impairment.

Front Neurol 2020 16;11:566067. Epub 2020 Dec 16.

Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing, China.

Post-acute ischemic stroke cognitive impairment frequently occurs and seriously affects patients daily activities. Recruitment of GluA2-containing Ca-impermeable AMPA receptors (CI-AMPARs) to hippocampal synaptic membrane surfaces was shown to trigger synaptic plasticity. Currently, the effect of CI-AMPAR trafficking on acute ischemic stroke remains poorly understood. β-Caryophyllene (BCP) has been shown to ameliorate cognitive impairment. However, the mechanism has not been characterized. In this study, a 60-min temporary middle cerebral artery occlusion (MCAO) model was established to simulate the pathology of acute ischemic stroke. BCP reduced neurologic deficits, cerebral infarct volume, and pathological damage in MCAO mice and caused CI-AMPARs to translocate to synaptic membranes in the hippocampus; surface expression of CI-AMPARs was also decreased in MCAO mice. Furthermore, this study also showed that BCP treatment significantly activated the cAMP/PKA pathway, which is consistent with the synaptic membrane expression of CI-AMPARs. To better understand the underlying mechanisms, the PKA inhibitor H-89 was used to study the role of BCP in MCAO mice. Interestingly, H-89 treatment significantly disrupted the BCP-mediated facilitation of CI-AMPAR translocation to the synaptic membrane surface and substantially attenuated BCP-induced protection against acute ischemic stroke. Additionally, inhibition the cAMP/PKA pathway not only reduced BCP-induced inhibition of AMPAR-mediated excitatory postsynaptic currents in the hippocampal CA1 region but also decreased the effect of BCP-mediated protection against post-acute ischemic stroke cognitive impairment. Taken together, these data indicate that PKA-dependent synaptic membrane surface recruitment of CI-AMPARs is crucial for the neuroprotective effect of BCP against acute ischemic stroke and protection against post-acute ischemic stroke cognitive impairment.
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http://dx.doi.org/10.3389/fneur.2020.566067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772322PMC
December 2020

Diverging models introduce large uncertainty in future climate warming impact on spring phenology of temperate deciduous trees.

Sci Total Environ 2021 Feb 3;757:143903. Epub 2020 Dec 3.

Centre of Excellence PLECO (Plant and Vegetation Ecology), Department of Biology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.

Spring phenology influences terrestrial ecosystem carbon, water and energy exchanges between the biosphere and atmosphere. Accurate prediction of spring phenology is therefore a prerequisite to foresee the impacts of climate warming on terrestrial ecosystems. In the present study, we studied the model performance of four widely used process-based models of spring leaf unfolding, including both a one-phase model (not considering a chilling phase: the Thermal Time model) and three two-phase models (all accounting for a required chilling period: the Parallel model, the Sequential model, the Unified model). Models were tested on five deciduous tree species occurring across Europe. We specifically investigated the divergence of their phenology predictions under future climate warming scenarios and studied the differences in the chilling periods. We found that, in general, the two-phase models performed slightly better than the one-phase model when fitting to the observed data, with all two-phase models performing similarly. However, leaf unfolding projections diverged substantially among the two-phase models over the period 2070-2100. Furthermore, we found that the modeled end dates of the chilling periods in these models also diverged, with advances for both the Sequential and Parallel models during the period 2070-2100 (compared to the period 1980-2010), and delays in the Unified model. These findings thus highlight large uncertainty in the two-phase phenology models and confirm that the mechanism underlying the leaf unfolding process is not yet understood. We therefore urgently need an improved understanding of the leaf unfolding process in order to improve the representation of phenology in terrestrial ecosystem models.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143903DOI Listing
February 2021

Biophysical impacts of Earth greening largely controlled by aerodynamic resistance.

Sci Adv 2020 Nov 20;6(47). Epub 2020 Nov 20.

Department of Earth and Environment, Boston University, Boston, MA 02215, USA.

Satellite observations show widespread increasing trends of leaf area index (LAI), known as the Earth greening. However, the biophysical impacts of this greening on land surface temperature (LST) remain unclear. Here, we quantify the biophysical impacts of Earth greening on LST from 2000 to 2014 and disentangle the contributions of different factors using a physically based attribution model. We find that 93% of the global vegetated area shows negative sensitivity of LST to LAI increase at the annual scale, especially for semiarid woody vegetation. Further considering the LAI trends ( ≤ 0.1), 30% of the global vegetated area is cooled by these trends and 5% is warmed. Aerodynamic resistance is the dominant factor in controlling Earth greening's biophysical impacts: The increase in LAI produces a decrease in aerodynamic resistance, thereby favoring increased turbulent heat transfer between the land and the atmosphere, especially latent heat flux.
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http://dx.doi.org/10.1126/sciadv.abb1981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679158PMC
November 2020

Global Phosphorus Losses from Croplands under Future Precipitation Scenarios.

Environ Sci Technol 2020 11 3;54(22):14761-14771. Epub 2020 Nov 3.

State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan 430072, China.

Phosphorus (P) losses from fertilized croplands to inland water bodies cause serious environmental problems. During wet years, high precipitation disproportionately contributes to P losses. We combine simulations of a gridded crop model and outputs from a number of hydrological and climate models to assess global impacts of changes in precipitation regimes on P losses during the 21st century. Under the baseline climate during 1991-2010, median P losses are 2.7 ± 0.5 kg P ha year over global croplands of four major crops, while during wet years, P losses are 3.6 ± 0.7 kg P ha year. By the end of this century, P losses in wet years would reach 4.2 ± 1.0 (RCP2.6) and 4.7 ± 1.3 (RCP8.5) kg P ha year due to increases in high annual precipitation alone. The increases in P losses are the highest (up to 200%) in the arid regions of Middle East, Central Asia, and northern Africa. Consequently, in three quarters of the world's river basins, representing about 40% of total global runoff and home up to 7 billion people, P dilution capacity of freshwater could be exceeded due to P losses from croplands by the end of this century.
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http://dx.doi.org/10.1021/acs.est.0c03978DOI Listing
November 2020

Vegetation forcing modulates global land monsoon and water resources in a CO-enriched climate.

Nat Commun 2020 10 14;11(1):5184. Epub 2020 Oct 14.

Department of Geography, University of Georgia, Athens, GA, USA.

The global monsoon is characterised by transitions between pronounced dry and wet seasons, affecting food security for two-thirds of the world's population. Rising atmospheric CO influences the terrestrial hydrological cycle through climate-radiative and vegetation-physiological forcings. How these two forcings affect the seasonal intensity and characteristics of monsoonal precipitation and runoff is poorly understood. Here we use four Earth System Models to show that in a CO-enriched climate, radiative forcing changes drive annual precipitation increases for most monsoon regions. Further, vegetation feedbacks substantially affect annual precipitation in North and South America and Australia monsoon regions. In the dry season, runoff increases over most monsoon regions, due to stomatal closure-driven evapotranspiration reductions and associated atmospheric circulation change. Our results imply that flood risks may amplify in the wet season. However, the lengthening of the monsoon rainfall season and reduced evapotranspiration will shorten the water resources scarcity period for most monsoon regions.
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http://dx.doi.org/10.1038/s41467-020-18992-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560717PMC
October 2020

Providing Sports Venues on Mainland China: Implications for Promoting Leisure-Time Physical Activity and National Fitness Policies.

Authors:
Kai Wang Xuhui Wang

Int J Environ Res Public Health 2020 07 16;17(14). Epub 2020 Jul 16.

College of Landscape Architecture and Arts, Northwest A&F University, Yangling 712100, China.

Leisure-time physical activity (LTPA) has been well documented as having substantial health benefits. The 2014 Chinese Fitness Survey Report stated that a lack of physical activity (PA) spaces is the most important non-human factor, leading to 10% of leisure-time physical inactivity in people aged 20 and above. We investigated the provision of sports venues in China and discussed the development of sports venues and national fitness policies in the context of promoting LTPA and public health. We analyzed information from China's most recent sport venue census, the Sixth National Sports Venues Census, conducted in 2013. The number of sports venues increased between 2000 and 2013, with an inflection point around the year 2008. At the end of 2013, there were 12.45 venues for every 10,000 residents, and the per capita area was 1.46 m. However, numbers were still small compared with the United States and Japan. The percentages of full-time access, part-time access and membership venues were 51.5%, 14.3% and 34.2% respectively. Only half of sports venues were fully open to the public, meaning that the realized number and area per capita could be even lower. A lack of sports venues forces people who want to engage in PA to occupy other urban spaces that are not planned and designed for PA. Urban parks had 119,750 fitness station facilities (3.32% of the total), and 2366 urban fitness trails (19.24%), with a combined length of 6450 km (32.91%). On average, urban and rural areas had 13.17 and 10.80 venues per 10,000 persons, and 1.83 m and 0.97 m per capita. The urban-rural gap in sports venues exactly embodies some aspects of the "urban-rural dual structure" in China's society. Measures to promote PA should focus on new and existing sports venues. In the policy making process, Chinese governments need to pay attention to the potential impact of related, external factors such as the gap between the urban and the rural and the potential advantage of indoor venues against summer heat and air pollution.
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http://dx.doi.org/10.3390/ijerph17145136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400163PMC
July 2020

Removal of Phosphorus from Wastewater by Different Morphological Alumina.

Molecules 2020 Jul 7;25(13). Epub 2020 Jul 7.

College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.

In this work, an organic-free method was used to synthesize different morphological boehmite by controlling the crystallization temperature, and alumina adsorbents were obtained by baking the boehmites at 500 °C. The alumina adsorbents were characterized by X-ray diffraction (XRD), High resolution transmission electron microscope (HRTEM), Fourier transform infrared (FT-IR), N adsorption/desorption analysis, and their phosphorus adsorption properties were comparatively investigated by a series of experiments. The results showed that the self-prepared alumina adsorbents were lamellar and fibrous material, while the industrial adsorbent was a granular material. The lamellar alumina adsorbents had the largest specific surface area and showed better phosphorus adsorption capacity. The maximum adsorption capacity could reach up to 588.2 mg·g; and only 0.8 g·L of lamellar alumina adsorbent is needed to treat 100 mg·L phosphorus solution under the Chinese level 1 discharge standard (0.5 mg·L). Further investigation suggests that the lamellar alumina adsorbent kept high adsorption capacity in various solution environments.
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http://dx.doi.org/10.3390/molecules25133092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412428PMC
July 2020

On-Demand Autophagy Cascade Amplification Nanoparticles Precisely Enhanced Oxaliplatin-Induced Cancer Immunotherapy.

Adv Mater 2020 Aug 28;32(32):e2002160. Epub 2020 Jun 28.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu, 610064, P. R. China.

Chemoimmunotherapy-induced antitumor immune response is highly dependent on tumor autophagy. When tumor cells are treated with chemoimmunotherapy, timely overactivated autophagy can not only lead more tumor cells to death, but also participate in the endogenous antigen presentation and immune stimulators secretion of dying cells, thus plays a vital role. However, timely and accurately overactivated tumor autophagy during chemoimmunotherapy is of great difficulty. Here, an on-demand autophagy cascade amplification nanoparticle (ASN) is reported to boost oxaliplatin-induced cancer immunotherapy. ASN is prepared by self-assemble of autophagy-responsible C-TFG micelle and is followed by electrostatic binding of oxaliplatin prodrug (HA-OXA). After entering tumor cells, the HA-OXA shell of ASN first responds to the reduction microenvironment and releases oxaliplatin to trigger tumor immunogenic cell death and mildly stimulates tumor autophagy. Then, the exposed C-TFG micelle can sensitively respond to oxaliplatin-induced autophagy and release a powerful autophagy inducer STF-62247, which precisely transforms autophagy to "overactivated" condition, leading tumor cells to autophagic death and enhance subsequent tumor antigen processing of the dying cells. In CT26 tumor-bearing mice, ASN exhibits optimal immune stimulation and antitumor efficiency due to its on-demand autophagy induction ability.
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http://dx.doi.org/10.1002/adma.202002160DOI Listing
August 2020

Temporal trade-off between gymnosperm resistance and resilience increases forest sensitivity to extreme drought.

Nat Ecol Evol 2020 08 15;4(8):1075-1083. Epub 2020 Jun 15.

CSIC, Global Ecology Unit CREAF-CSIC-UAB, Bellaterra, Barcelona, Spain.

The frequency and intensity of droughts have increased over the decades, leading to increased forest decline. The response of forest to drought can be evaluated by both its sensitivity to drought (resistance) and its post-drought recovery rate (resilience). However, it remains uncertain how drought resistance and resilience of forests change over time under climate change. We assessed the spatiotemporal dynamics of forest resistance and resilience to drought over the past century (1901-2015) with global tree ring data records from 2,935 sites, in conjunction with plant trait data. We found that gymnosperms and angiosperms showed different spatial patterns of drought resistance and resilience, driven by variations in eco-physiological traits. Resistance and resilience also varied with drought seasonal timing. Surprisingly, we found that the trade-off between resistance and resilience for gymnosperms, previously reported only spatially, also occurred at the temporal scale. In particular, drought resilience markedly increased, but resistance decreased, for gymnosperms between 1950-1969 and 1990-2009, indicating that previous model simulations assuming invariant resistance may have underestimated the impacts of drought on gymnosperm-dominated forests under future climate change.
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http://dx.doi.org/10.1038/s41559-020-1217-3DOI Listing
August 2020

Accelerated terrestrial ecosystem carbon turnover and its drivers.

Glob Chang Biol 2020 Sep 7;26(9):5052-5062. Epub 2020 Jul 7.

School of Atmospheric Sciences, Sun Yat-sen University, Zhuhai, Guangdong, China.

The terrestrial carbon cycle has been strongly influenced by human-induced CO increase, climate change, and land use change since the industrial revolution. These changes alter the carbon balance of ecosystems through changes in vegetation productivity and ecosystem carbon turnover time (τ ). Even though numerous studies have drawn an increasingly clear picture of global vegetation productivity changes, global changes in τ are still unknown. In this study, we analyzed the changes of τ between the 1860s and the 2000s and their drivers, based on theory of dynamic carbon cycle in non-steady state and process-based ecosystem model. Results indicate that τ has been reduced (i.e., carbon turnover has accelerated) by 13.5% from the 1860s (74 years) to the 2000s (64 years), with reductions of 1 year of carbon residence times in vegetation (r ) and of 9 years in soil (r ). Additionally, the acceleration of τ was examined at biome scale and grid scale. Among different driving processes, land use change and climate change were found to be the major drivers of turnover acceleration. These findings imply that carbon fixed by plant photosynthesis is being lost from ecosystems to the atmosphere more quickly over time, with important implications for the climate-carbon cycle feedbacks.
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http://dx.doi.org/10.1111/gcb.15224DOI Listing
September 2020

Fabrication of Few-Layer Graphene-Supported Copper Catalysts Using a Lithium-Promoted Thermal Exfoliation Method for Methanol Oxidative Carbonylation.

ACS Appl Mater Interfaces 2020 Jul 26;12(27):30483-30493. Epub 2020 Jun 26.

Key Laboratory of Coal Science and Technology, Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, China.

Exfoliation of graphene oxide (GO) via thermal expansion is regarded as the most promising approach to obtain few-layer graphene (FLG) in bulk. Herein, we introduce an efficient strategy for improving the exfoliation process by adding a tiny amount of lithium nitrate in the precursors, which significantly enhances the removal of oxygen-containing functional groups and produces 1-2 layer graphene. FLG-supported highly dispersed Cu nanoparticles (NPs, ≈4.2 nm) can be further synthesized through exfoliating the mixture of GO, lithium nitrate, and copper(II) nitrate, which displayed superior catalytic activity and stability in the synthesis of dimethyl carbonate (DMC) using liquid methanol oxidative carbonylation. The characterization results demonstrate that during the thermal expansion process, lithium nitrate was decomposed to LiO and immediately reacted with CO released by the decomposition of GO to form stable LiCO, which promotes efficient charge transfer and produces Cu (0 < δ < 1) species in the Cu/Li-PGO catalyst. Density functional theory calculations prove that the presence of Cu markedly facilitates CO adsorption over the resulting catalyst and causes a decrease of the energy barrier of the rate-limiting step for DMC formation (CO insertion). These findings give a theoretical explanation of the enhanced catalytic performance of the Cu/Li-PGO catalyst. The present work provides a simple and practical avenue to the exfoliation of graphene and the dispersions of metal NPs on graphene sheets.
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http://dx.doi.org/10.1021/acsami.0c08366DOI Listing
July 2020

Three-dimensional change in temperature sensitivity of northern vegetation phenology.

Glob Chang Biol 2020 Sep 23;26(9):5189-5201. Epub 2020 Jun 23.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Understanding how the temperature sensitivity of phenology changes with three spatial dimensions (altitude, latitude, and longitude) is critical for the prediction of future phenological synchronization. Here we investigate the spatial pattern of temperature sensitivity of spring and autumn phenology with altitude, latitude, and longitude during 1982-2016 across mid- and high-latitude Northern Hemisphere (north of 30°N). We find distinct spatial patterns of temperature sensitivity of spring phenology (hereafter "spring S ") among altitudinal, latitudinal, and longitudinal gradient. Spring S decreased with altitude mostly over eastern Europe, whereas the opposite occurs in eastern North America and the north China plain. Spring S decreased with latitude mainly in the boreal regions of North America, temperate Eurasia, and the arid/semi-arid regions of Central Asia. This distribution may be related to the increased temperature variance, decreased precipitation, and radiation with latitude. Compared to spring S , the spatial pattern of temperature sensitivity of autumn phenology (hereafter "autumn S ") is more heterogeneous, only showing a clear spatial pattern of autumn S along the latitudinal gradient. Our results highlight the three-dimensional view to understand the phenological response to climate change and provide new metrics for evaluating phenological models. Accordingly, establishing a dense, high-quality three-dimensional observation system of phenology data is necessary for enhancing our ability to both predict phenological changes under changing climatic conditions and to facilitate sustainable management of ecosystems.
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http://dx.doi.org/10.1111/gcb.15200DOI Listing
September 2020

Causes of slowing-down seasonal CO amplitude at Mauna Loa.

Glob Chang Biol 2020 08 20;26(8):4462-4477. Epub 2020 Jun 20.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Changing amplitude of the seasonal cycle of atmospheric CO (SCA) in the northern hemisphere is an emerging carbon cycle property. Mauna Loa (MLO) station (20°N, 156°W), which has the longest continuous northern hemisphere CO record, shows an increasing SCA before the 1980s (p < .01), followed by no significant change thereafter. We analyzed the potential driving factors of SCA slowing-down, with an ensemble of dynamic global vegetation models (DGVMs) coupled with an atmospheric transport model. We found that slowing-down of SCA at MLO is primarily explained by response of net biome productivity (NBP) to climate change, and by changes in atmospheric circulations. Through NBP, climate change increases SCA at MLO before the 1980s and decreases it afterwards. The effect of climate change on the slowing-down of SCA at MLO is mainly exerted by intensified drought stress acting to offset the acceleration driven by CO fertilization. This challenges the view that CO fertilization is the dominant cause of emergent SCA trends at northern sites south of 40°N. The contribution of agricultural intensification on the deceleration of SCA at MLO was elusive according to land-atmosphere CO flux estimated by DGVMs and atmospheric inversions. Our results also show the necessity to adequately account for changing circulation patterns in understanding carbon cycle dynamics observed from atmospheric observations and in using these observations to benchmark DGVMs.
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http://dx.doi.org/10.1111/gcb.15162DOI Listing
August 2020

Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

Onco Targets Ther 2020 15;13:3129-3139. Epub 2020 Apr 15.

Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin 300192, People's Republic of China.

Purpose: This study aims to investigate the biological effect and molecular mechanism of Lamin B1(LMNB1) in lung cancer cells and its significance for the prognosis of lung adenocarcinoma(LUAD) patients.

Methods: In this study, Bioinformatics was performed to analyze the expression at mRNA level and prognosis effect of LMNB1 in LUAD from TCGA dataset. The immunohistochemistry(IHC) assay was conducted to analyzed the expression of LMNB1 at the protein level in LUAD tissues. The correlation between the expression of LMNB1 and the clinical factors in patients with LUAD was analyzed. Next, LMNB1 transfected into LUAD cell lines (A549 and PC-9) which was proved by Western blot. CCK8 assay, cloning formation assay, and xenograft assay were conducted to explore the effect and mechanism of LMNB1 on the proliferation of LUAD cell lines in vitro and in vivo.

Results: The results of the present study demonstrated that LMNB1 was highly expressed in LUAD tissues and related to tumor stage. High LMNB1 expression was related with more advanced clinicopathological factors such as low degree of differentiation (P=0.02), large tumor size (P<0.01), lymph node metastasis (P<0.01) and higher tumor stage (P<0.01). After knocking down LMNB1, the cell growth rate (P<0.01) and the number of colonies (P<0.01) were significantly reduced, and the level of the proliferating marker Ki67 (P<0.01) was significantly decreased. At the same time, in vivo experiments showed that the tumor volume and tumor of the mice were significantly reduced (P<0.01). Moreover, we found that knockdown LMNB1 can inhibit the proliferation of lung cancer cells by inhibiting AKT phosphorylation by Western blot.

Conclusion: In summary, LMNB1 play an of vital roles in the growth of LUAD cells, highlighting its potential as a therapeutic target for the treatment of LUAD patients.
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http://dx.doi.org/10.2147/OTT.S229997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167283PMC
April 2020

Survival stratification in childhood rhabdomyosarcoma of the extremities: a derivation and validation study.

Sci Rep 2020 03 30;10(1):5684. Epub 2020 Mar 30.

Department of Pediatric Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China.

The objective of this study was to estimate overall survival in children with extremity rhabdomyosarcoma (RMS). In addition, we attempted to construct a nomogram to predict the prognosis in such patients using a population-based cohort. The national Surveillance, Epidemiology, and End Results (SEER) registry was used to identify a cohort of childhood RMS patients. A total of 197 patients with RMS were ultimately included. Multivariable analysis identified age group, N classification, M classification, and treatment combinations as independent predictive factors for patient overall survival. Candidate variables such as age group, N classification, M classification, and treatment combinations were used to fit the model. For overall survival, the bootstrap-adjusted c-index was 0.76 (95% CI, 0.73-0.80) for the nomogram. Furthermore, we performed recursive partitioning analysis for risk stratification according to overall survival, and 3 prognostic subgroups were generated (low, intermediate and high risk). Finally, we evaluated multimodal treatment based on the risk stratification according to the nomogram and IRSG prognostic stratification model. With regard to the entire cohort, overall survival in patients who received surgery and radiation was superior to that in patients who received surgery or radiation (p = 0.001). Regarding RPA and IRSG prognostic stratification, we found that the differences remained significant (p < 0.05) in patients with low-intermediate risk. However, the difference disappeared in patients with high risk (p > 0.05). We performed a population-based analysis of data from the SEER registry in an effort to identify prognostic factors and develop a nomogram in children with extremity RMS. The nomogram appears to be suitable for the survival stratification of children with RMS and will help clinicians identify patients who may be at a reduced probability of survival and assist them in making treatment and surveillance decisions. More studies concerning overall survival in children with RMS are needed to confirm and update our findings.
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http://dx.doi.org/10.1038/s41598-020-62656-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105456PMC
March 2020

Deceleration of China's human water use and its key drivers.

Proc Natl Acad Sci U S A 2020 04 24;117(14):7702-7711. Epub 2020 Mar 24.

International Institute for Applied Systems Analysis, A-2361 Laxenburg, Austria.

Increased human water use combined with climate change have aggravated water scarcity from the regional to global scales. However, the lack of spatially detailed datasets limits our understanding of the historical water use trend and its key drivers. Here, we present a survey-based reconstruction of China's sectoral water use in 341 prefectures during 1965 to 2013. The data indicate that water use has doubled during the entire study period, yet with a widespread slowdown of the growth rates from 10.66 km⋅y before 1975 to 6.23 km⋅y in 1975 to 1992, and further down to 3.59 km⋅y afterward. These decelerations were attributed to reduced water use intensities of irrigation and industry, which partly offset the increase driven by pronounced socioeconomic development (i.e., economic growth, population growth, and structural transitions) by 55% in 1975 to 1992 and 83% after 1992. Adoptions for highly efficient irrigation and industrial water recycling technologies explained most of the observed reduction of water use intensities across China. These findings challenge conventional views about an acceleration in water use in China and highlight the opposing roles of different drivers for water use projections.
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http://dx.doi.org/10.1073/pnas.1909902117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148580PMC
April 2020

Integrated bioinformatics analysis identifies microRNA-376a-3p as a new microRNA biomarker in patient with coronary artery disease.

Am J Transl Res 2020 15;12(2):633-648. Epub 2020 Feb 15.

Department of Gerontology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092, P. R. China.

Introduction: Coronary artery disease (CAD) is a major global health problem with high incidence and mortality. Despite many advances in treatment, the prognosis of patients with CAD still remains poor. Therefore, this study aimed to identify potential biomarkers and targets associated with the progression of CAD.

Methods: Two gene expression profile datasets (GSE20681 and GSE12288), and two microRNA (miRNA) expression profile datasets (GSE59421 and GSE105449) were downloaded from the Gene Expression Omnibus (GEO) database; R language was used to screen out the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. In addition, five online bioinformatics tools (miRWalk et al.) were used to identify the target genes of DEMs, and miRNA-gene network was constructed using Cytoscape software. Moreover, CCK-8, flow cytometry assays were used to detect the cell proliferation and apoptosis in human umbilical vein endothelial cells (HUVECs). Meanwhile, the dual luciferase reporter system assay was used to explore the interaction of miR-376a-3p and NRIP1 in HUVECs.

Results: In the present study, 150 common DEGs and 5 common DEMs were screened using a Venn diagram in R language. First, a total of 6812 target genes were identified from the overlapping DEMs. Second, 26 overlapping dysregulated genes from 150 overlapping DEGs and 6812 miRNA target genes were identified. Meanwhile, 43 miRNA-gene regulatory pairs were obtained between the 5 common DEMs and 26 dysregulated genes. Downregulation of miR-376a-3p significantly inhibited the proliferation of HUVECs via inducing apoptosis. Moreover, overexpression of miR-376a-3p markedly inhibited the growth of HUVECs via downregulating NRIP1.

Conclusion: In this study, miR-376a-3p-NRIP1 pair might involve in the progression of CAD, implying that miR-376a-3p may be a therapeutic target for the treatment of CAD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061823PMC
February 2020

Elevated CO concentration affects the defense of tobacco and melon against lepidopteran larvae through the jasmonic acid signaling pathway.

Sci Rep 2020 03 4;10(1):4060. Epub 2020 Mar 4.

Institute of Agro-products Processing Science and Technolog, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, 832000, China.

The massive use of fossil fuels since the industrial revolution has led to a rapid increase in the concentration of carbon dioxide (CO) in the atmosphere. What effects elevated CO concentrations (ECO) have on the defense mechanisms plants employ against insects remains poorly understood. This study showed that ECO of 750 ± 20 mmol/mol, increased the photosynthetic rate and biomass gain of tobacco and melon plants. However, while mass gain of Spodoptera litura, a nocturnal moth in the Noctuidae family, was higher when feeding on tobacco plants under ECO, mass gain of Diaphania indica was reduced when feeding on melon plant at ECO compared to ambient CO2. Plants have many mechanisms to defend themselves against insects. Jasmonic acid (JA) is a crucial element of plant defense against lepidopteran insects. Our study showed that JA levels increased in tobacco plants under ECO but decreased in melon plants. It is speculated that ECO changes plant resistance to insects mainly by affecting the JA signaling pathway. Nutrient analysis suggested defensive metabolites rather than changes in the total nitrogen or protein content of the plants led to the changes in plant defense levels under ECO. In summary, ECO affects the interaction between plants and insects. The results may provide a theoretical basis for studying the changes in crop resistance to pests under ECO and predicting the impact of ECO on future agro-ecosystems.
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http://dx.doi.org/10.1038/s41598-020-60749-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055285PMC
March 2020

Targeting cancer-associated fibroblasts by dual-responsive lipid-albumin nanoparticles to enhance drug perfusion for pancreatic tumor therapy.

J Control Release 2020 05 26;321:564-575. Epub 2020 Feb 26.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is rich in cancer-associated fibroblasts (CAFs), which participate in the formation of tumor stroma. However, the dense tumor stroma of PDAC presents major barriers to drug delivery, resulting in an obstacle for PDAC therapy. Considering the special tumor microenvironment of PDAC, we constructed a novel nanoparticle which is responsive to the membrane biomarker FAP-α on CAFs and near-infrared (NIR) laser irradiation. Small sized albumin nanoparticle of paclitaxel (HSA-PTX) with strong tumor-penetration ability was encapsulated into the CAP-(a FAP-α responsive cleavable amphiphilic peptide) modified thermosensitive liposomes (CAP-TSL). Moreover, IR-780, a photothermal agent, was incorporated into CAP-TSL to afford CAP-ITSL. The designed HSA-PTX@CAP-ITSL increased the drug retention of HSA-PTX in solid tumor and HSA-PTX was released via FAP-α (specifically expresses on CAFs) triggered. Under sequential stimulation of NIR laser irradiation, IR-780 produced hyperthermia to kill tumor cells and expand the tumor interstitial space at the same time, which further promoted the release of small sized HSA-PTX in deep tumor regions. Consequently, the excellent antitumor efficacy of HSA-PTX@CAP-ITSL was demonstrated in Pan 02 subcutaneous and orthotopic tumor mouse models. Therefore, HSA-PTX@CAP-ITSL well combined chemotherapy with photothermal therapy, providing a promising drug delivery strategy for PDAC treatment.
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http://dx.doi.org/10.1016/j.jconrel.2020.02.040DOI Listing
May 2020

Autophagy inhibition changes the disposition of non-viral gene carriers during blood-brain barrier penetration and enhances TRAIL-induced apoptosis in brain metastatic tumor.

J Control Release 2020 05 26;321:497-508. Epub 2020 Feb 26.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address:

Non-viral gene delivery systems have proven to be a promising approach in the treatment of brain metastatic cancers but facing delivery difficulties. Due to the existence of blood-brain barrier, non-viral gene carriers must pass through brain capillary endothelial cells to accumulate at the brain tumor sites. However, during this process, most of them trap into brain capillary endothelial cells and fail to penetrate to the brain tumor sites. Autophagy is involved in dynamic disposition of both intracellular and extracellular components, which theoretically affects intracellular fate of non-viral gene carriers during BBB penetration. In the present study, R6dGR peptide-modified PEGylated polyethyleneimine that carry therapeutic gene encoding human tumor necrosis factor-related apoptosis-inducing ligand (PPR/pTRAIL) are established as model non-viral gene delivery system and applied in breast cancer brain metastasis therapy. Autophagy-mediated lysosome degradation pathway is found to be involved in the degradation of PPR/pTRAIL in brain capillary endothelial cells and prevents them from BBB penetration. Pre-inhibiting BBB autophagy level by wortmannin loaded liposomes (Wtmn-Lip) can increase brain accumulation of non-viral gene carrier PPR without damaging BBB tight junctions. Besides, Wtmn-Lip synergistically induces apoptosis with TRAIL via different signaling pathways. Herein, pre-treatment of Wtmn-Lip might solve delivery difficulties of non-viral gene carriers in the treatment of brain metastatic cancers.
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http://dx.doi.org/10.1016/j.jconrel.2020.02.042DOI Listing
May 2020