The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include ...immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.
The copper‐catalyzed enantioselective radical difunctionalization of alkenes from readily available alkyl halides and organophosphorus reagents possessing a P−H bond provides an appealing approach ...for the synthesis of α‐chiral alkyl phosphorus compounds. The major challenge arises from the easy generation of a P‐centered radical from the P−H‐type reagent and its facile addition to the terminal side of alkenes, leading to reverse chemoselectivity. We herein disclose a radical 1,2‐carbophosphonylation of styrenes in a highly chemo‐ and enantioselective manner. The key to the success lies in not only the implementation of dialkyl phosphites with a strong bond dissociation energy to promote the desired chemoselectivity but also the utilization of an anionic chiral N,N,N‐ligand to forge the chiral C(sp3)−P bond. The developed Cu/N,N,N‐ligand catalyst has enriched our library of single‐electron transfer catalysts in the enantioselective radical transformations.
Copper‐catalyzed chemo‐ and enantioselective radical 1,2‐carbophosphonylation of styrenes from readily available alkyl halides and dialkyl phosphites is developed. The key to the success of the strategy lies in not only the proper choice of phosphorus reagents to suppress the reverse chemoselectivity but also the utilization of a chiral N,N,N‐ligand to forge chiral C(sp3)−P bond.
Abstract
High-energy density lithium-rich layered oxides are among the most promising candidates for next-generation energy storage. Unfortunately, these materials suffer from severe electrochemical ...degradation that includes capacity loss and voltage decay during long-term cycling. Present research efforts are primarily focused on understanding voltage decay phenomena while origins for capacity degradation have been largely ignored. Here, we thoroughly investigate causes for electrochemical performance decline with an emphasis on capacity loss in the lithium-rich layered oxides, as well as reaction pathways and kinetics. Advanced synchrotron-based X-ray two-dimensional and three-dimensional imaging techniques are combined with spectroscopic and scattering techniques to spatially visualize the reactivity at multiple length-scales on lithium- and manganese-rich layered oxides. These methods provide direct evidence for inhomogeneous manganese reactivity and ionic nickel rearrangement. Coupling deactivated manganese with nickel migration provides sluggish reaction kinetics and induces serious structural instability in the material. Our findings provide new insights and further understanding of electrochemical degradation, which serve to facilitate cathode material design improvements.
Nickel-rich layered lithium transition-metal oxides, LiNi(1-x)M(x)O(2) (M = transition metal), have been under intense investigation as high-energy cathode materials for rechargeable lithium ...batteries because of their high specific capacity and relatively low cost. However, the commercial deployment of nickel-rich oxides has been severely hindered by their intrinsic poor thermal stability at the fully charged state and insufficient cycle life, especially at elevated temperatures. Here, we report a nickel-rich lithium transition-metal oxide with a very high capacity (215 mA h g(-1)), where the nickel concentration decreases linearly whereas the manganese concentration increases linearly from the centre to the outer layer of each particle. Using this nano-functional full-gradient approach, we are able to harness the high energy density of the nickel-rich core and the high thermal stability and long life of the manganese-rich outer layers. Moreover, the micrometre-size secondary particles of this cathode material are composed of aligned needle-like nanosize primary particles, resulting in a high rate capability. The experimental results suggest that this nano-functional full-gradient cathode material is promising for applications that require high energy, long calendar life and excellent abuse tolerance such as electric vehicles.
Soil organic carbon (SOC) plays an important role in soil fertility and carbon sequestration, and a better understanding of the spatial patterns of SOC is essential for soil resource management. In ...this study, we used boosted regression tree (BRT) and random forest (RF) models to map the distribution of topsoil organic carbon content at the northeastern edge of the Tibetan Plateau in China. A set of 105 soil samples and 12 environmental variables (including topography, climate and vegetation) were analyzed. The performance of the models was evaluated using a 10-fold cross-validation procedure. Maps of the mean values and standard deviations of SOC were generated to illustrate model variability and uncertainty. The results indicate that the BRT and RF models exhibited very similar performance and yielded similar predicted distributions of SOC. The two models explained approximately 70% of the total SOC variability. The BRT and RF models robustly predicted the SOC at low observed SOC values, whereas they underestimated high observed SOC values. This underestimation may have been caused by biased distributions of soil samples in the SOC space. Vegetation-related variables were assigned the highest importance in both models, followed by climate and topography. Both models produced spatial distribution maps of SOC that were closely related to vegetation cover. The SOC content predicted by the BRT model was clearly higher than that of the RF model in areas with greater vegetation cover because the contributions of vegetation-related variables in the two models (65% and 43%, respectively) differed significantly. The predicted SOC content increased from the northwestern to the southeastern part of the study area, average values produced by the BRT and RF models were 27.3gkg−1 and 26.6gkg−1, respectively. We conclude that the BRT and RF methods should be calibrated and compared to obtain the best prediction of SOC spatial distribution in similar regions. In addition, vegetation variables, including those obtained from remote sensing imagery, should be taken as the main environmental indicators and explicitly included when generating SOC maps in Alpine environments.
We propose a general variable bandwidth filter of arbitrary even order based on the sum-difference microring filter architecture. The filter bandwidth can be varied by tuning only the resonant ...frequencies of the microrings and thus do not require additional controls other than those used to tune the filter center frequency. In addition, we show that there exists a bandwidth tuning range over which the filter exhibits no extra insertion loss and no degradation in the filter shape. We demonstrated a <inline-formula><tex-math notation="LaTeX">4^{\text {th}}</tex-math></inline-formula>-order variable bandwidth filter in Silicon-on-Insulator, achieving a bandwidth tuning range from 0.3 nm to 1.35 nm with a maximum in-band ripple of 3 dB. The proposed variable bandwidth filter could serve as a key element in elastic optical networks which can support variable data bandwidth allocation on demand.
Low thermal conductivity is favorable for preserving the temperature gradient between the two ends of a thermoelectric material, in order to ensure continuous electron current generation. In ...high-performance thermoelectric materials, there are two main low thermal conductivity mechanisms: the phonon anharmonic in PbTe and SnSe, and phonon scattering resulting from the dynamic disorder in AgCrSe
and CuCrSe
, which have been successfully revealed by inelastic neutron scattering. Using neutron scattering and ab initio calculations, we report here a mechanism of static local structure distortion combined with phonon-anharmonic-induced ultralow lattice thermal conductivity in α-MgAgSb. Since the transverse acoustic phonons are almost fully scattered by the compound's intrinsic distorted rocksalt sublattice, the heat is mainly transported by the longitudinal acoustic phonons. The ultralow thermal conductivity in α-MgAgSb is attributed to its atomic dynamics being altered by the structure distortion, which presents a possible microscopic route to enhance the performance of similar thermoelectric materials.
Cathodes of lithium-rich layered oxides for high-energy Li-ion batteries in electrically powered vehicles are attracting considerable attention by the research community. However, current research is ...insufficient to account for their complex reaction mechanism and application. Here, the structural evolution of lithium–manganese-rich layered oxides at different temperatures during electrochemical cycling has been investigated thoroughly, and their structural stability has been designed. The results indicated structure conversion from the two structures into a core–shell structure with a single distorted-monoclinic LiTMO2 structure core and disordered-spinel/rock salt structure shell, along with lattice oxygen extraction and lattice densification, transition- metal migration, and aggregation on the crystal surface. The structural conversion behavior was found to be seriously temperature sensitive, accelerated with higher temperature, and can be effectively adjusted by structural design. This study clarifies the structural evolution mechanism of these lithium-rich layered oxides and opens the door to the design of similar high-energy materials with better cycle stability.
To explore the effects of micro ribonucleic acid (miR)-182 on the proliferation and apoptosis of neural cells in cerebral infarction rats and its underlying mechanism. The rat model of cerebral ...infarction was established, and neural cells were extracted accordingly. The cell proliferation ability was detected via cell counting kit-8 (CCK8) assay. In addition, the apoptosis rate was determined through flow cytometry and the activity of active caspase-3. Furthermore, the interaction between miR-182 and PI3K was explored via dual luciferase reporter assay, and the protein expression levels were observed via Western blotting. The neural cells in mouse brain tissues significantly decreased in the model group compared with that in the control group via HE stain. Additionally, the expression level of miR-182 was significantly increased in the model group compared with that in the control group. Furthermore, overexpression of miR-182 could inhibit the proliferation of neural cells through inducing cell apoptosis. Besides, the results of the luciferase reporter assay showed that the relative luciferase activity in neural cells could be inhibited by the transfection with miR-182 (P<0.05). Overexpression of miR-182 significantly reduced the protein expression levels of phosphatidylinositol 3-hydroxy kinase (PI3K) and p-AKT. MiR-182 induces apoptosis of neural cells through inhibiting the PI3K/AKT signaling pathway, which plays an important regulatory role in the apoptosis of neural cells in cerebral infarction rats.
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