Search

With triethylamine as a vinylene source, a convenient protocol for the regioselective synthesis of β,γ-nonsubstituted 2-arylquinolines from aldehydes and arylamines has been accomplished. The deaminative cyclization is also extended to long-chain tertiary alkylamines, enabling diverse alkyl groups to be concurrently installed into the pyridine rings. This process demonstrates a new conversion pathway for the simultaneous dual C(sp

Glioma is one of the most aggressive human cancers with limited therapeutic options. Though research has extensively examined immune components in those malignant tumors, the pathophysiological mechanism establishing their immunosuppressive microenvironment remains incompletely characterized. In this study, we report for the first time the unique presence of tumor-specific neutrophils (TSNs) in human glioblastoma (GBM) tumors. This newly defined neutrophil subtype exhibits the high expression of several immunosuppressive genes (e.g., CD274 and IDO1) and is strongly correlated with glioma grades and poor prognosis of patients. TSNs with comparable gene signatures are similarly present in the tumors but not bone marrow or spleen of mouse glioma models. Blockage of TSN recruitment by either Cxcl1-knockout in glioma cells or Cxcr2-deletion in host mice significantly enhances antitumor immunity and inhibits tumor progression. Surprisingly, we further discover the meninges as the key extratumoral source of generating TSNs in both human GBM patients and mouse glioma models. These results have therefore elucidated a novel mechanism designating the tumor microenvironment of gliomas and its essential link to meningeal immunity.

The highly tunable properties of multi-principal element alloys, commonly known as high-entropy alloys (HEAs), provide a remarkable potential for the development of superior materials for critical structural applications that involve extreme conditions. However, the optimization of the properties of HEAs has been primarily limited to behavior at either low or high temperatures. Here, we report on a non-equiatomic, heterostructured, high-entropy alloy FeNiCoAlTaB which possesses remarkable combinations of mechanical properties across a wide range of temperatures from 77 K to 1073 K. The current metastable alloy presents good ductility and superior engineering tensile strengths of 2.2 GPa, 1.4 GPa, 800 MPa, and 500 MPa at 77 K, 298 K, 873 K, and 1073 K, respectively. This behavior is achieved by a synergic sequence of individual mechanisms that are activated at different temperatures. The alloy even displays pseudoelasticity at 77 K with an applied load up to 2 GPa. This work provides a methodology for tailoring structural heterogeneity and metastability in the design and fabrication of multifunctional HEAs that will outperform known metals and alloys over a wide range of temperatures.

Refractory high-entropy alloys (RHEAs) are considered promising candidate materials for high-temperature structural applications that currently use superalloys. However, for most of the reported RHEAs, their poor ductility and negligible cold-workability at room temperature have hindered their use. Here, we report a new class of non-equiatomic NbTaTi-based RHEAs that can be cold-rolled to a reduction of over 90% from the as-cast state without surface treatment and/or intermediate annealing. This excellent cold-workability is facilitated by activation of a high-density of dislocations and deformation twins as well as by high diffusivity paths, such that these RHEAs can be rendered homogeneous at lower annealing temperatures for much shorter time durations. In addition, we report that the RHEAs retain their high strength at elevated temperatures and exhibit considerable ductility at cryogenic conditions, evading the traditional strength–ductility trade-off. This class of super-formable RHEAs provides a novel design pathway to fabricate high-temperature structural materials via an energy- and time-saving method.

Glioblastoma (GBM) is the most common brain tumor and is currently incurable. Primary GBM cultures are widely used tools for screening potentially therapeutic drugs; however, there is a lack of genomic and pharmacological characterization of these primary GBM cultures. Here, we collected 52 patient-derived glioma cell (PDGC) lines and characterized them through whole- genome sequencing (WGS), RNA-seq, and drug response screening. We identified three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Upon profiling the responses of PDGCs to 214 drugs, we found that the PN subtype PDGCs were sensitive to tyrosine kinase inhibitors, whereas the OXPHOS subtype PDGCs were sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably formed tumorsin vivoupon intracranial transplantation into immunodeficient mice, while most MES subtype PDGCs were incapable of tumorigenesisin vivo. In addition, profiling and follow-up investigations showed that the serum-free culture system used for PDGCs enriched and propagated rareMYC/MYCN- amplified glioma cells. Our study provides a resource for understanding primary glioma cell cultures and aiding clinical translation.SignificanceOur study provides a resource for patient-derived glioma cell lines (PDGCs) on transcriptome, genome, drug response, and tumorigenic abilities. PDGCs are categorized into PN, MES, and OXPHOS subtypes, with MES-subtype PDGCs incapable of tumorigenesisin vivo. Notably, the serum-free culture system for PDGCs enriches glioma cells withMYC/MYCNamplification.

With full knowledge of a material's atomistic structure, it is possible to predict any macroscopic property of interest. In practice, this is hindered by limitations of the chosen characterisation techniques. For example, electron microscopy is unable to detect the smallest and most numerous defects in irradiated materials. Instead of spatial characterisation, we propose to detect and quantify defects through their excess energy. Differential scanning calorimetry (DSC) of irradiated Ti measures defect densities 5 times greater than those determined using transmission electron microscopy (TEM). Our experiments also reveal two energetically-distinct processes where the established annealing model predicts one. Molecular dynamics (MD) simulations discover the defects responsible and inform a new mechanism for the recovery of irradiation-induced defects. The combination of annealing experiments and simulations can reveal defects hidden to other characterisation techniques, and has the potential to uncover new mechanisms behind the evolution of defects in materials., Comment: main: 17 pages and 6 figures, supplemental: 25 pages and 16 figures

High-entropy alloys (HEAs) with concentrated solid solutions are conceived to possess a rugged atomic and energy landscape in which dislocation motion necessarily proceeds to accommodate mechanical deformation. Fundamental questions remain as to how rough the energy landscape is and to what extent it can be influenced by the local ordering of their constituent elements. Here, we construct and report the potential energy landscape (PEL) governing screw dislocation motion in refractory HEAs that reveals a hierarchical and multilevel structure with a collection of small basins nested in large metabasin. This striking feature pertaining to HEAs exerts a trapping force and back stress on saddle point activations, retarding dislocation movement. By introducing chemical short-range order, the energy landscape is smoothed but skewed to different degrees that shifts the rate-liming process from kink-glide to kink-pair nucleation. The chemical disorder-roughened PEL in HEAs, analogous to structural disorder induced in metallic glasses, signifies the role of various barrier-hopping processes underlying the extraordinary mechanical behaviors of the two distinct groups of materials.

The aqueous zinc-ion batteries (ZIBs) have been considered as a promising energy storage device. However, the ion transfer at the Zn metal anode-electrolyte interface is limited by the sluggish kinetics resulting in high interface resistance. Herein, mesoporous TiO2 (m-TiO2) is coated on the Zn foil (Zn-TiO2) driving the ion's faster transfer to reduce interface resistance (70.1 Ω vs 799.3 Ω of bare Zn). The lower interface resistance is ascribed to shortening the ion transfer path provided by the mesoporous structure and the smaller Zn2+ absorption energy barrier of the surface of the Zn-TiO2 anode as well as the unobstructed ion transfer path at the crystal planes (100) of TiO2, which have been supported by the density functional theory (DFT) calculation and experiments. Therefore, the Zn-TiO2 anodes in the symmetrical cells display a low voltage hysteresis (36.5 mV) and long-term cycling stability (500 h at 4.4 mA cm-2). Especially, the Zn-TiO2/MnO2 full cells show superior cycling performance with a high capacity of 269.8 mAh g-1 after 50 cycles at 0.2 A g-1 and 210.9 mAh g-1 after 1000 cycles at 0.5 A g-1. The analysis of ion-transfer kinetics at the interface provides deep enlightenment and reference for the study of the metal anodes.

To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging, novel Au@Bi2S3 core shell nanobones (NBs) (Au@Bi2S3 NBs) with Au nanorods as cores were synthesized. The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal (PT) conversion efficiency, remarkable photoacoustic (PA) imaging and high computed tomography (CT) performance; these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging. Subsequently, poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs (Au@Bi2S3-PVP NBs) were successfully loaded with the anticancer drug doxorubicin (DOX), and a satisfactory pH sensitive release profile was achieved, thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells. Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy, including extremely low toxicity, good biocompatibility, high drug loading ability, precise tumor targeting and effective accumulation. Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy (PTT). As both a contrast enhancement probe and therapeutic agent, Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.

Multi-principal element alloys (MPEAs), commonly termed as medium- or high-entropy alloys containing three or more components in high concentrations, render a tunable chemical short-range order (SRO). Leveraging large-scale atomistic simulations, we probe the limit of Hall-Petch strengthening and deformation mechanisms in a model CrCoNi alloy and unravel chemical short-range ordering effects. It is found that, in the presence of SRO, the maximum strength is appreciably increased, and the strongest grain size drifts to a small value. Additionally, the propensity for faulting and deformation transformation is reduced and accompanied by the intensification of planar slip and strain localization. We reveal strikingly different deformation microstructures and dislocation patterns that prominently depend on crystallographic grain orientation and the number of slip planes activated during deformation. Grain of single planar slip attains the highest volume fraction of deformation-induced structure transformation, and grain with double active slip planes develops the densest dislocation network. These results advancing the fundamental understanding of deformation mechanisms and dislocation patterning in MPEAs suggest a mechanistic strategy for tuning mechanical behavior through simultaneously tailoring grain texture and local chemical order.

Multifunctional bismuth sulfide (Bi2S3) nanomaterials exhibit significant potential as nanomedicines for the diagnosis and treatment of cancer. These nanomaterials act as excellent photothermal agents and radiation sensitizers for the treatment of tumors, and they can also act as contrast agents for computed tomography (CT) imaging, photoacoustic imaging (PA), and other forms of imaging to provide real-time tumor monitoring and testing guidance. Compared with other nanomaterials, Bi2S3 nanomaterials can readily adapt to different applications by virtue of the fact that they can be easily functionalized. However, these nanomaterials have some limitations that cannot be ignored and need to be addressed, such as poor biocompatibility, toxicity, and low chemical stability. It is widely believed that appropriate functionalization of Bi2S3 nanomaterials could remedy such defects and significantly improve performance. This review summarizes the ways in which Bi2S3 nanomaterials can be functionalized and discusses their applications in cancer theranostics over the last few years, focusing particularly on imaging and therapy. We also discuss issues relating to how Bi2S3 nanomaterials can be analyzed, including how we might be able to use these systems to inhibit and treat tumors and how current limitations might be overcome to improve treatment efficacy. Finally, we hope to provide inspiration and guidance as to how we might create a more optimized multifunctional nano-system for the diagnosis and treatment of tumors.

Cerebral hyperperfusion syndrome (CHS) is a common complication after direct bypass surgery in patients with Moyamoya disease (MMD). Since preventive measures may be inadequate, we assessed whether the blood flow difference between the superficial temporal artery (STA) and recipient vessels (△BF) and the direct perfusion range (DPR) are related to CHS. We measured blood flow in the STA and recipient blood vessels before bypass surgery by transit-time probe to calculate △BF. Perfusion changes around the anastomosis before and after bypass were analyzed with FLOW800 to obtain DPR. Multiple factors, such as △BF, DPR, and postoperative CHS, were analyzed using binary logistic regression. Forty-one patients with MMD who underwent direct bypass surgery were included in the study. Postoperative CHS symptoms occurred in 13/41 patients. △BF and DPR significantly differed between the CHS and non-CHS groups. The optimal receiver operating characteristic (ROC) curve cut-off value was 31.4 ml/min for ΔBF, and the area under the ROC curve (AUC) was 0.695 (sensitivity 0.846, specificity 0.500). The optimal cut-off value was 3.5 cm for DPR, and the AUC was 0.702 (sensitivity 0.615, specificity 0.750). Postoperative CHS is caused by multiple factors. △BF is a risk factor for CHS while DPR is a protective factor against CHS.

High-entropy alloys containing multi-principal-element systems significantly expand the potential alloy design space, and offer the possibility of overcoming the strength-ductility trade-off in metallurgical research. However, the gain in ultra-high strength through traditional grain refinement and precipitation-strengthening mechanisms inevitably leads to a drastic loss of ductility. Here, we report on the design and fabrication of heterogeneous-lamella structured, aged bulk high-entropy alloy, which attains gigapascal tensile strength while retaining excellent ductility (UTS ~1.4 GPa, elongation ~30%; UTS ~1.7 GPa, elongation ~10%). Our work shows that the improved strength-ductility synergy arises due to various complementary strengthening mechanisms, including solid-solution, interfaces, precipitation and martensitic transformation, which influence the hardening and deformation processes at different strain levels. In particular, the hetero-deformation that is associated with the formation of microbands as well as the stress-induced martensite promotes additional hardening and hence high ductility. The strategy described here, that is leveraging the concept of heterogeneous microstructure design, provides a practical and novel method for fabricating high-performance structural materials.

Nanostructured materials with amorphous intergranular films (AIFs) have demonstrated superior strength and ductility. Their radiation tolerance is expected to be high as the large fraction of interfacial volume efficiently sinks radiation-induced defects. Here we demonstrate how a crystalline-amorphous system (nanocrystalline Cu with Zr-doped AIFs) responds to continuous irradiation with molecular dynamics simulations. We propose a diffusion model that well characterizes the cascade-driven mixing process, and reveal that the spread of Zr distribution scales linearly with the damage level. The exceptional radiation resistance is attributed to the interfaces acting as sustainable defect sinks, Zr mixing into the bulk to enhance local defect annihilation due to solute-interstitial dragging, and Zr impeding radiation-enhanced grain growth by restraining AIFs from migration and maintaining interface stiffness. These findings suggest that AIF-engineered systems hold promise as highly radiation-tolerant materials with strong structural stability and self-healing capability under radiation damage.

Reactive oxygen species (ROS) are by-products of aerobic metabolism and can also act as signaling molecules to participate in multiple regulation of biological and physiological processes. The occurrence, growth and metastasis of tumors, and even the apoptosis, necrosis and autophagy of tumor cells are all closely related to ROS. However, ROS levels in the body are usually maintained at a stable status. ROS produced by oxidative stress can cause damage to cell lipids, protein and DNA. In recent years, ROS have achieved satisfactory results on the treatment of tumors. Therefore, this review summarizes some research results of tumor treatments from the perspective of ROS in recent years, and analyzes how to achieve the mechanism of inhibition and treatment of tumors by ROS or how to affect the tumor microenvironment by influencing ROS. At the same time, the detection methods of ROS, problems encountered in the research process and solutions are also summarized. The purpose of this review is to provide a clearer understanding of the ROS role in tumor treatment, so that researchers might have more inspiration and thoughts for cancer prevention and treatment in the next stage.

By doping molybdenum (Mo) into bismuth oxide (Bi2O3), we synthesized novel Bi2MoO6 nanohybrids with a unique tremella-like crystal structure via a one-pot hydrothermal method. Such a porous tremella structure of Bi2MoO6 possesses a significantly larger surface area than the spherical structure of Bi2O3, which is favorable for the special functionalization and effective immobilization of molecules such as antibodies on the surface of the tremella flaps. As expected, Au nanoparticles grew easily and uniformly outside the surface of the flaps of the as-prepared Bi2MoO6 NTs (Au@Bi2MoO6 NTs), showing preferable conductivity and biocompatibility, and the anti-carcinoembryonic antigen (anti-CEA) was effectively immobilized outside the obtained Au@Bi2MoO6 NTs. Acting as a novel label-free immunosensing platform, the anti-CEA-immobilized Au@Bi2MoO6 NTs were used to fabricate an electrochemical immunosensor for the quantitative detection of CEA. The as-prepared Au@Bi2MoO6-based immunosensor linearly responded to CEA in a wide concentration range from 1 pg mL−1 to 1 μg mL−1 with a detection limit calculated to be 0.3 pg mL−1 (S/N = 3), significantly comparable to numerous existing immunosensors. Moreover, the minimum detection concentration of the designed immunosensor was about ten times smaller than that of many Bi and Mo-based sensors toward CEA detection, and the detection limit was lower, revealing higher sensitivity. The satisfactory selectivity and stability made the immunosensor potentially applicable for CEA detection in real samples.

Refractory multi-principal element alloys exhibiting promising mechanical properties such as excellent strength retention at elevated temperatures have been attracting increasing attention. Although their inherent chemical complexity is considered a defining feature, a challenge arises in predicting local chemical ordering, particularly in grain boundary regions with an enhanced structural disorder. In this study, we use atomistic simulations of a large group of bicrystal models to sample a wide variety of interfacial sites (grain boundary) in NbMoTaW and explore emergent trends in interfacial segregation and the underlying structural and chemical driving factors. Sampling hundreds of bicrystals along the [001] symmetric tilt axis and analyzing more than one hundred and thirty thousand grain boundary sites with a variety of local atomic environments, we uncover segregation trends in NbMoTaW. While Nb is the dominant segregant, more notable are the segregation patterns that deviate from expected behavior and mark situations where local structural and chemical driving forces lead to interesting segregation events. For example, incomplete depletion of Ta in low-angle boundaries results from chemical pinning due to favorable local compositional environments associated with chemical short-range ordering. Finally, machine learning models capturing and comparing the structural and chemical features of interfacial sites are developed to weigh their relative importance and contributions to segregation tendency, revealing a significant increase in predictive capability when including local chemical information. Overall, this work, highlighting the complex interplay between the local grain boundary structure and chemical short-range ordering, suggests tunable segregation and chemical ordering by tailoring grain boundary structure in multi-principal element alloys.

Twin boundary (TB) strengthening in nanotwinned metals experiences a breakdown below a critical spacing at which softening takes over. Here, we survey a range of nanotwinned materials that possess different stacking fault energies (SFEs) and understand the TB strengthening limit using atomistic simulations. Distinct from Cu and Al, the nanotwinned, ultralow SFE materials (Co, NiCoCr, and NiCoCrFeMn) intriguingly exhibit a continuous strengthening down to a twin thickness of 0.63 nm. Examining dislocation slip mode and deformation microstructure, we find the hard dislocation modes persist even when reducing the twin boundary spacing to a nanometer regime. Meanwhile, the soft dislocation mode, which causes detwinning in Cu and Al, results in phase transformation and lamellar structure formation in Co, NiCoCr, and NiCoCrFeMn. This study, providing an enhanced understanding of dislocation mechanism in nanotwinned materials, demonstrates the potential for controlling mechanical behavior and ultimate strength with broadly tunable composition and SFE, especially in multi-principal element alloys.

Novel highly hydrophilic and biocompatible bismuth nanospheres with gold nanoparticles growing outside (Bi@Au nano-acanthospheres, Bi@Au NASs) were synthesized through a simple procedure, which demonstrated to be a promising photothermal agent owing to the ultrahigh photothermal conversion efficiency (η = 46.6 %). The as-prepared Bi@Au NASs showed excellent blood compatibility and fairly low cytotoxicity to human lung cancer A549 cells, as well as efficient photothermal ablation (PTA) therapy induced by a near-infrared laser. Under the 808 nm laser radiation, the tumour temperature could be elevated by ∼25 °C high enough to kill the cancer cells. Moreover, the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded in Bi@Au NASs with a loading content as high as 16.78 % and released under a pH sensitive release profile, a characteristic beneficial for intravenous delivery of DOX into cancer cells for chemotherapy. The presence of the Bi element enabled Bi@Au NASs to act as a favourable computed tomography (CT) contrast medium for CT imaging-guided tumour treatment. Compared with cancer treatment through either photothermal therapy or chemotherapy, the chemo-photothermal synergistic therapy using Bi@Au NASs as both a photothermal agent and a drug carrier has efficiently enhanced the in vitro and in vivo therapeutic effects in cancer treatment.

The essence of Zn dendrite formation is ultimately derived from Zn nucleation and growth during the repeated Zn plating/stripping process. Here, the nucleation process of Zn has been analyzed using ex situ scanning electron microscopy to explore the formation of the initial Zn dendrite, demonstrating that the formation of tiny protrusions (the initial state of Zn dendrites) is caused by the inhomogeneity of Zn nucleation. Based on this, the uniform Zn nucleation is promoted by the Ni5Zn21 alloy coating (ZnNi) on the surface of Zn foil by electrodeposition, and the mechanism of ZnNi-promoted even nucleation is further analyzed with the assistance of density functional theory (DFT). The DFT results indicate that the ZnNi displays a stronger binding ability to Zn compared to the bare Zn, suggesting that Zn nuclei will preferentially form around ZnNi instead of continuing to grow on the surface of the initial Zn nuclei. Therefore, the designed Zn metal anode (Zn@ZnNi) can be ultra-stable for over 2200 h at a current density of 2 mA cm-2 in the symmetric cell. Even at a much higher current density of 20 mA cm-2, the extra-long life of over 2200 cycles (over 530 h) can be achieved. Moreover, the full cell with the Zn@ZnNi anode exhibits extra-long cycling performance for 500 cycles with a capacity of 207.7 mA h g-1 and 1100 cycles (148.5 mA h g-1) at a current density of 0.5 and 1 A g-1, respectively.

Ketamine has become a major substance of abuse worldwide. Nevertheless, The long-term effects of ketamine use on intrinsic spontaneous neural activity remain unknown.In the present study, rs-fMRI was used to explore whether chronic ketamine use changes the intrinsic spontaneous neural activity, and whether the intrinsic spontaneous neural activity changes in chronic ketamine users(CKUs) are associated with cognitive impairments observed in chronic ketamine users.28 CKUs and 30 healthy controls(HC) were enrolled. The fractional amplitude of low-frequency fluctuations (fALFF) was measured to evaluate the intrinsic spontaneous neural activity in multiple brain regions. Cognitive alterations were assessed using MATRICS Consensus Cognitive Battery (MCCB).CKUs showed higher fALFF in the right parahippocampal gyrus(PHG), right anterior cingulate cortex(ACC), left cerebellar vermis, left posterior cingulate cortex(PCC), bilateral caudate, and lower fALFF in the right middle occipital gyrus(MOG), left cuneus, right precuneus. The fALFF in the right PHG, left cerebellar vermis, bilateral caudate, right ACC of CKUs presented a negative correlation with the average quantity of ketamine use/day(g) and estimated total ketamine consumption. The fALFF in left PCC had a negative correlation with the average quantity of ketamine use/day(g). Speed of processing on MCCB presented a negative correlation with the fALFF in the right MOG.Our study found abnormal fALFF in multiple brain areas in CKUs, which indicated the changes of intrinsic spontaneous neural activity in multiple brain areas. The changes of fALFF were associated with the severity of ketamine use and cognitive impairment in CKUs.