Abstract
Defective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. ...Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.
Layered transition metal oxide (NaxTMO2), being one of the most promising cathode candidates for sodium‐ion batteries (SIBs), have attracted intensive interest because of their nontoxicity, high ...theoretical capacities, and easy manufacturability. However, their physical and electrochemical properties of water sensitivity, sluggish Na+ transport kinetics, and irreversible multiple‐phase translations hinder the practical application. Here, a concept of surface lattice‐matched engineering is proposed based on in situ spinel interfacial reconstruction to design a spinel coating P2/P3 heterostructure cathode material with enhanced air stability, rate, and cycle performance. The novel structure and its formation process are verified by transmission electron microscopy and in situ high‐temperature X‐ray diffraction. The electrode exhibits an excellent rate performance with the highly reversible phase transformation demonstrated by in situ charging/discharging X‐ray diffraction. Additionally, even after a rigorous water sensitivity test, the electrode materials still retain almost the same superior electrochemical performance as the fresh sample. The results show that the surface spinel phase can play a vital role in preventing the ingress of water molecules, improving transport kinetics, and enhancing structural integrity for NaxTMO2 cathodes. The concept of surface lattice‐matched engineering based on in situ spinel interfacial reconstruction will be helpful for designing new ultra‐stable cathode materials for high‐performance SIBs.
The formation process and function mechanism for inhibiting phase transformation and enhancing air stability of surface lattice‐matched engineering based on in situ spinel interfacial reconstruction are studied. This strategy of designing heterostructure with in situ interfacial reconstruction will inspire the exploitation of new chemistries and materials.
The electrochemical properties of V2C and V2CT2 (T = O, S) MXenes with and without vacancy as anode materials for Na-ion and Li-ion batteries, have been studied using first-principles calculation. ...The present results indicate that the adsorption strength of Li-ion and Na-ion on V2CS2 are less than that of O-functionalized, together with a lower diffusion barrier. Simultaneously, V2CS2 monolayer exhibits lower open-circuit voltage (OCV) values of 0.72 and 0.49 V for Li- and Na-ion, respectively. Interestingly, the presence of atomic vanadium vacancy on V2CS2 monolayer exerts more prominent effects on enhancing adsorption strength than that of carbon vacancy for Li-ion and Na-ion, but with an exception for the diffusion of Li-ion and Na-ion on V2CS2 monolayer. The finding suggests that the V2CS2 monolayer is expected to be a potential candidate as anode material for Li-ion and Na-ion battery due to its lower open-circuit voltages and diffusion barriers.
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•The S-group decreased the adsorption ability of Li- and Na-ion on V2C than O-group.•The vacancy has no effects to Li- and Na-ion diffusion property on V2CS2 monolayer.•The S-group significantly reduces the high diffusion barrier of Na-ion.•The storage capacity of Li- and Na-ion reaches to 301.12 mAh/g for V2CS2 monolayer.
Cluster-based functional materials have made remarkable progress owing to their wonderful structures and distinctive physicochemical performances, one of on-going advancements of which is basically ...driven by synthetic chemistry of exploring and constructing novel nanosized gigantic polyoxometalate (POM) aggregates. In this article, an unprecedented nanoscale hexameric arsenotungstate aggregate Na
9
K
16
H
4
Er
0.5
K
0.5
(H
2
O)
7
Er
5
W
10
O
26
(H
2
O)
14
B-
α
-AsW
9
O
33
6
·102H
2
O (
1
) has been synthesized by the combined synthetic strategy of simultaneously using the arsenotungstate precursor and simple tungstate material in a highly acidic aqueous solution. The {Er
5
W
10
O
26
(H
2
O)
14
B-α-AsW
9
O
33
6
}
31−
polyanion in
1
consists of an intriguing dumbbell-shaped pentadeca-nuclear W-Er heterometal {Er
5
W
10
O
26
(H
2
O)
14
}
23+
cluster connecting six trilacunary B-α-AsW
9
O
33
9−
moieties, which has never been seen previously. Furthermore, through electropolymerization of
1
and pyrrole on the conductive substrate, a thickness-controllable and robust
1
-PPY (PPY = polypyrrole) hybrid film was successfully prepared, which represents the first POM-PPY film assembled from high-nuclear lanthanide (Ln) encapsulated POM and PPY hitherto. The
1
-PPY film-based electrochemical biosensor exhibits a favorable recognition performance for ochratoxin A in multiple media. This work not only provides a feasible combined synthetic strategy of the POM precursor and simple tungstate material for constructing complicated multi-Ln-inserted POM aggregates, but also offers a promising electrochemical platform constructed from POM-based conductive films for identifying trace biomolecules in complex environments.
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•Direct synthesis of ZnO nanosheets using facile precipitation at room temperature.•The nanosheets based sensor exhibits high response, fast response-recovery and good selectivity to ...acetone vapor.•The correlation between surface defect contents and sensor response was established: the more defects, the higher response.
Zinc oxide (ZnO) nanosheets were directly synthesized using a facile precipitation method at room temperature without any template, surfactant or organic solvent. X-ray diffraction (XRD) confirms that the ZnO nanosheets belong to hexagonal wurtzite structure. Scanning electron microscope (SEM) and transmission electron microscope (TEM) reveals the morphology and structure of the ZnO nanosheets, showing the predominantly exposed non-polar {100} planes and an average thickness of about 20nm. In order to regulate and control the intrinsic surface defect contents, improving the thermal stability, the samples were calcined at different temperatures (200°C, 400°C and 600°C respectively), showing that the sheet-like structures can be maintained below 400°C. Photoluminescence (PL) analysis shows that abundant intrinsic surface defects exist on the ZnO crystal surfaces. Gas sensors based on ZnO nanosheets calcinated at 200°C exhibits high response, fast response-recovery and good selectivity to 5–1000ppm acetone vapor at 300°C. The response value to acetone vapor is correlated with the surface defect contents, namely, the more defects, the higher sensor response. Thus, it is considered that the improved acetone sensing property, especially enhanced response value, is mainly originated from the increased intrinsic defect content on the surface of ZnO nanosheets. Developed precipitation method is facile for synthesis of ZnO nanosheets, which demonstrate an effective strategy for surface defect engineering to improve the metal oxide semiconductor gas sensing performance.
Cesium lead halide perovskite nanocrystals (NCs) have emerged as promising luminescent materials for a range of applications. However, the creation of highly luminescent violet-emitting CsPbCl3 NCs ...mostly relies on doping of a limited number of small-sized metal ions or post-synthetic surface treatment of NCs. Alkaline-earth (AE) metals (e.g., Ca2+, Sr2+, and Ba2+) have been proposed to be able to substitute Pb2+ in halide perovskites, yet it remains incompletely understood whether AE metal ions can be incorporated into the perovskite lattice or can be merely situated at the surface. Here, we explore the possibility of using AE metal ions for the suppression of the formation of trap centers, which leads us to develop a one-pot synthetic passivation strategy to boost the violet-emitting efficiency of CsPbCl3 NCs through the creation of a Ca2+/Sr2+ involved passivation layer. The photoluminescence quantum yield of violet emission reaches 77.1% by incorporating an optimal amount of Ca2+. A wide range of optical and structural characterizations, coupled with first-principles calculations, aid in clarifying the underlying mechanism for the AE-metal-dependent passivation of CsPbCl3 NCs. Specifically, based on the experimental and theoretical results, a model is proposed for the observed abnormal incorporation phenomenon of AE2+ ions in NCs (i.e., Ba2+ can be incorporated into the core of NCs, Ca2+/Sr2+ can only be at/near the surface, while Mg2+ can neither be in the core nor at the surface). We believe that the knowledge gained here may not only offer a new perspective to obtain high-efficiency violet-emitting perovskite NCs through a one-pot synthetic passivation but can also help elucidate the functions that AE2+ ions play in the optimization of perovskite optoelectronic devices.
Chemical agents in the rhizosphere soils of plants might have an influence on root-rot disease, which therefore might reveal the mechanism of root rot in
(
). With this hypothesis the alterations of ...phenolic acids (PAs) in the rhizosphere soils of
after pathogen infection were determined. The effects of PAs on the growth of
(
), a fungal pathogenic factor for
, as well as production of fusaric acid, a wilting agent for the plants, were also examined. The results indicate the presence of five PAs (ferulic acid, syringic acid,
-hydroxybenzoic acid,
-coumaric acid, and vanillic acid) in the rhizosphere soils of
, whose contents in the rhizosphere soils of healthy plants are higher than those of the diseased ones. Further we found that individual PA could inhibit the mycelium growth and spore production of
, but stimulate fusaric acid production as well, disclosing the double-edge sword role of PAs in the occurrence of root rot of
and paving the way for the intervention of
root rot via balancing PAs.
China has been suffered from the severe sulfur dioxide (SO2) pollution in the past decades. The spatiotemporal estimation and health effect assessment of SO2 using two-stage machine learning models ...have not been performed yet. In this study, a high-quality model named random forest coupled with spatiotemporal Kriging (RF-STK) model was developed to estimate the daily SO2 concentration across the entire China from May 2014 to May 2015 based on the satellite data and geographic covariates. Compared with other statistical methods, the RF-STK model showed the better explanatory performance, with the 10-fold cross-validation R2 = 0.62 (root-mean-square error (RMSE) = 10.36 μg/m3) for daily estimations. The annually mean population-weighted SO2 concentration was estimated to be 30.49 ± 10.83 μg/m3 (mean ± standard deviation). The SO2 levels displayed the remarkably seasonal variation with the peak in winter (47.27 ± 22.64 μg/m3), followed by ones in autumn (28.41 ± 10.41 μg/m3) and spring (25.92 ± 7.95 μg/m3), and in summer (21.33 ± 6.51 μg/m3). At the national scale, only 20.31% of the population lived in the safe regions (population-weighted SO2 concentration < 20 μg/m3). The higher population-weighted SO2 concentrations were mainly concentrated on some provinces of North China Plain (NCP) (e.g., Shanxi, Hebei, Shandong), followed by the provinces of Northeast China, and the lowest one in Hainan (8.31 ± 1.38 μg/m3). The mean all-cause mortalities due to excessive SO2 exposure were estimated to be 131,957 cases, accounting for 0.009% of the whole Chinese population. Among all of the diseases, the mortalities per year were in the order of respiratory disease (RD) (11913 cases) > cardiovascular disease (CVD) (11386 cases) > chronic obstructive pulmonary disease (COPD) (8112 cases) > cerebrovascular disease (CEVD) (2188 cases). The statistical modelling of SO2 at a national scale provided the valuable data for epidemiological research and air pollution prevention.
•The annually mean SO2 concentration was estimated to be 25.87 ± 10.83 μg/m3.•The highest population-weighted SO2 concentration occurs in NCP.•79.69% of the population suffered from the excessive SO2 exposure over China.•The all-cause mortalities induced by SO2 exposure in China reached 131,957 cases each year.
Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to ...thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.
The root of Polygonum multiflorum Thunb （PM） has been used in China to treat a variety of diseases, such as constipation, early graying of the hair and hyperlipemia. Recent evidence shows that PM ...causes idiosyncratic drug-induced liver injury （IDILI） in humans. In this study, we investigated the molecular basis of PM-induced liver injury in a rat model of IDILI based on a non-hepatotoxic dose of LPS. SD rats were orally administered 3 potentially hepatotoxic compounds of PM： cis-stilbene glucoside （cis-SG, 50 mg/kg）, trans-SG （50 mg/kg） or emodin （5 mg/kg）, followed by injection of LPS （2.8 mg/kg, iv）. Serum and liver histology were evaluated 7 h after LPS injection. Among the 3 compounds tested, cis-SG, but not emodin or trans-SG, induced severe liver injury in rats when combined with LPS. The levels of AST and ALT in plasma and inflammatory cytokines in both plasma and liver tissues were markedly elevated. The liver tissues showed increased injury, hepatocyte apoptosis, and macrophage infiltration, and decreased cell proliferation. Microarray analysis revealed a negative correlation between peroxisome proliferator-activated receptor-y （PPAR-y） and LPS/cis-SG-induced liver injury. Immunohistochemical staining and RT-PCR results further confirmed that cis-SG significantly inhibited activation of the PPAR-~ pathway in the liver tissues of LPS/cis-SG-treated rats. Pre-treatment with a PPAR-y agonist pioglitazone （500 g/kg, ig） reversed LPS/ cis-SG-induced liver injury, which was associated with inhibiting the nuclear factor kappa B （NF-KB） pathway. These data demonstrate that c/s-stilbene glucoside induces immunological idiosyncratic hepatotoxicity through suppressing PPAR-γ in a rat model of IDILl.
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