In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for ...improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.
The biomimetic DS@HLipo targets the tumor site, where near‐infrared light‐induced membrane permeation triggers the “ultrafast” and “thorough” release of sunitinib for both antiangiogenic therapy and anti‐MDSC immunotherapy. The liberated doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) from the liposomes can then be more easily ingested by tumor cells for improved immunogenic chemotherapy.
Monolayer SnP3 is a novel two-dimensional (2D) semiconductor material with high carrier mobility and large optical absorption coefficient, implying its potential applications in the photovoltaic and ...thermoelectric (TE) fields. Herein, we report on the TE properties of monolayer SnP3 utilizing first principles density functional theory (DFT) together with semiclassical Boltzmann transport theory. Results indicate that it exhibits a low lattice thermal conductivity of ∼4.97 W m−1 K−1 at room temperature, mainly originating from its small average acoustic group velocity (∼1.18 km s−1), large Grüneisen parameters (∼7.09), strong dipole–dipole interactions, and strong phonon–phonon scattering. A large in-plane charge transfer is observed, which results in a non-ignorable bipolar effect on the lattice thermal conductivity. The exhibited mixed mode between in-plane and out-of-plane vibrations enhances the complexity of the phonon phase space, which enhances the possibility of phonon scattering processes and results in suppression of thermal conductivity. A highly twofold degeneracy appearing at the K point gives a high Seebeck coefficient. Our calculated figure of merit (ZT) for optimal p-type doping at 500 K can approach 3.46 along the armchair direction, which is better than the theoretical value of 1.94 reported in the well-known TE material SnSe. Our studies here shed light on monolayer SnP3 in use as a TE material and supply insights to further optimize the TE properties in similar systems.
High-entropy herringbone alloy
Eutectic high-entropy alloys have a dual phase structure that could be useful for optimizing a material’s properties. Shi
et al
. found that directional solidification ...of an aluminum-iron-cobalt-nickel eutectic high-entropy alloy created a herringbone-patterned microstructure that was extremely resistant to fracture (see the Perspective by An). The structure contained lamellae of hard and soft phases, and the cracks that formed in the hard phase were arrested at the boundary of the soft phase. This, along with stress transfer, allowed a tripling of the maximal elongation while retaining high strength. —BG
A herringbone pattern of hard and soft phases helps to improve fracture toughness in an eutectic high entropy alloy.
In human-made malleable materials, microdamage such as cracking usually limits material lifetime. Some biological composites, such as bone, have hierarchical microstructures that tolerate cracks but cannot withstand high elongation. We demonstrate a directionally solidified eutectic high-entropy alloy (EHEA) that successfully reconciles crack tolerance and high elongation. The solidified alloy has a hierarchically organized herringbone structure that enables bionic-inspired hierarchical crack buffering. This effect guides stable, persistent crystallographic nucleation and growth of multiple microcracks in abundant poor-deformability microstructures. Hierarchical buffering by adjacent dynamic strain–hardened features helps the cracks to avoid catastrophic growth and percolation. Our self-buffering herringbone material yields an ultrahigh uniform tensile elongation (~50%), three times that of conventional nonbuffering EHEAs, without sacrificing strength.
Recently, an air-stable layered semiconductor Bi2O2Se has been synthesized Nat. Nanotechnol., 2017, 12, 530; Nano Lett. 2017, 17, 3021. It possesses ultrahigh mobility, semiconductor properties, ...excellent environmental stability and easy accessibility. Here, we report on the thermal transport properties in monolayer (ML), bilayer (BL), and bulk forms of Bi2O2Se using density-functional theory and the Boltzmann transport approach. The results show that the ML exhibits better thermal transport properties than the BL and bulk. The intralayer opposite phonon vibrations greatly suppress the thermal transport and lead to an ultralow lattice thermal conductivity of ∼0.74 W m-1 K-1 in the ML, which has a large band gap of ∼2.12 eV, a low value of average acoustic group velocity of ∼0.76 km s-1, low-lying optical modes of ∼0.54 THz, strong optical-acoustic phonon coupling, and large Grüneisen parameters of ∼5.69. The size effect for all three forms is much less sensitive due to their short intrinsic phonon mean free path (MFP).
The design of CRISPR gRNAs requires accurate on-target efficiency predictions, which demand high-quality gRNA activity data and efficient modeling. To advance, we here report on the generation of ...on-target gRNA activity data for 10,592 SpCas9 gRNAs. Integrating these with complementary published data, we train a deep learning model, CRISPRon, on 23,902 gRNAs. Compared to existing tools, CRISPRon exhibits significantly higher prediction performances on four test datasets not overlapping with training data used for the development of these tools. Furthermore, we present an interactive gRNA design webserver based on the CRISPRon standalone software, both available via https://rth.dk/resources/crispr/ . CRISPRon advances CRISPR applications by providing more accurate gRNA efficiency predictions than the existing tools.
Based on first-principles calculations, we explore the electronic and phonon transport properties of a new-type two-dimensional (2D) hexagonal material XSe (X = Ge, Sn, and Pb), which can be prepared ...by atomic isovalent substitutions of the recently synthesized crystal Ge4Se3Te. Among them, 2D PbSe possesses a large Seebeck coefficient of ∼1150 μV/K and an ultralow lattice thermal conductivity of ∼0.50 W/mK at room temperature. Theoretical calculations prove that the antiparallel movements of the atoms could lead to the strong optical-acoustic phonon coupling with low values of acoustic group velocities of 0.81–2.03 km/s and large Grüneisen parameters of ∼4, which accordingly greatly suppresses the heat transport ability. Using our calculated transport parameters, large values of the thermoelectric (TE) figure of merit (ZT) of 1.76, 2.32, and 3.95 can be obtained at an effective temperature range (GeSe and SnSe at 700 K and PbSe at 500 K) under p-type doping for 2D GeSe, SnSe, and PbSe, respectively. Interestingly, after checking several series of 2D materials, we find that their lattice thermal conductivities are almost proportional to their values of the lowest optical phonon frequencies. Our work clearly shows the advantages of these novel 2D group-IV selenides as TE materials and may stimulate further experimental and theoretical studies in this field.
Metal‐phenolic networks (MPNs) are an emerging class of supramolecular surface modifiers with potential use in various fields including drug delivery. Here, the development of a unique MPN‐integrated ...core‐satellite nanosystem (CS‐NS) is reported. The “core” component of CS‐NS comprises a liposome loaded with EDTA (a metal ion chelator) in the aqueous core and DiR (a near‐infrared photothermal transducer) in the bilayer. The “satellite” component comprises mesoporous silica nanoparticles (MSNs) encapsulating doxorubicin and is coated with a Cu2+‐tannic acid MPN. Liposomes and MSNs self‐assemble into the CS‐NS through adhesion mediated by the MPN. When irradiated with an 808 nm laser, CS‐NS liberated the entrapped EDTA, leading to Cu2+ chelation and subsequent disassembly of the core‐satellite nanostructure. Photo‐conversion from the large assembly to the small constituent particles proceeded within 5 min. Light‐triggered CS‐NS disassembly enhanced the carrier and cargo penetration and accumulation in tumor spheroids in vitro and in orthotopic murine mammary tumors in vivo. CS‐NS is long circulating in the blood and conferred improved survival outcomes to tumor‐bearing mice treated with light, compared to controls. These results demonstrate an MPN‐integrated multistage nanosystem for improved solid tumor treatment.
Upon 808 nm laser irradiation, DiR‐mediated photothermal effect leads to the instability of “core” liposomes, and triggers EDTA release to chelate the Cu2+ from the metal phenolic networks. This effect disassembles the core‐satellite nanosystem to liberate the satellites for enhanced penetration and chemotherapy.
Carrying out emergency rescue in coordination with multiple organizations, is of great significance for the effectiveness and timeliness of emergency response. Therefore, this study aims to extend a ...novel practical tool for distinguishing the optimal combination of different emergency plans in multiple organizations. In a multi-granularity extended probabilistic linguistic term sets (MGEPLTSs) environment, we propose a new collaborative emergency decision-making (CEDM) approach in the inspiration of the best–worst method (BWM) and TOmada de Decisão Iterativa Multicritério (TODIM) method. Firstly, a combined multi-granularity and extended probabilistic linguistic term sets, namely MGEPLTSs, are proposed to quantify the preferences given by decision makers (DMs) to address the issues on potential ambiguity and uncertainty in actual CEDM. Then, the BWM is introduced to the MGEPLTSs environment to compute the index weights of the individual and collaborative performance evaluation for multi-plan combinations, by building the fuzzy mathematical programming model respectively. Finally, we develop the multi-granularity extended probabilistic linguistic TODIM method to calculate the overall dominance of indexes considering the psychological behavior of DMs, thereby achieving the ranking of multi-plan combinations. A CEDM case on COVID-19 epidemic is used to illustrate the feasibility of the proposed approach, and the sensitivity analysis and comparative analysis with other similar approaches are presented to demonstrate its effectiveness and superiority.
•A novel practical tool for distinguishing the optimal multi-plan combination is proposed.•An integrated BWM-TODIM approach with multi-granularity extended probabilistic linguistic term sets is developed.•The proposed method considers individual performance and collaborative performance.•A collaborative emergency decision-making case on COVID-19 epidemic is presented.
Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the ...Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
