ABSTRACT
BACKGROUND: Natural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell-related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell-related genes for predicting thyroid cancer (THCA). METHODS: The single-cell RNA sequencing (scRNA-seq) data from seven THCA samples (GSE184362) and bulk-RNA-seq data of 502 THCA patients (TCGA-THCA) were included. The scRNA-seq data was analyzed using the "Seurat" R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package "ConsensusClusterPlus". The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta-cohort. In the TCGA-THCA cohort, the "glmnet" R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The "maftools" R package was used to examine the somatic mutation landscape of THCA in both low- and high-risk groups. RESULTS: One-hundred and eighty-five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA-THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low-risk H-TMB+ group had a better prognosis, while the high-risk L-TMB+ group had the worst prognosis. CONCLUSION: Natural killer cell-related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.
Subject(s)
Thyroid Neoplasms , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/therapy , Immunotherapy , Killer Cells, Natural , Algorithms , Cluster Analysis , Tumor Microenvironment/geneticsABSTRACT
Optical modulation of high harmonic generation (HHG) is of fundamental interest in science and technology, which can facilitate understanding of HHG generation mechanisms and expand the potential optoelectronic applications. However, the current established works have neither shown the advanced modulation performance nor provided a deep understanding of modulation mechanisms. In this work, taking wurtzite zinc oxide (ZnO) single crystal as a prototype, we have demonstrated an all-optical intensity modulation of high-order HHG with a response time of less than 0.2 ps and a depth of more than 95%, based on the pump-probe configuration with two different pumping wavelengths. Besides the achieved excellent modulation performance, we have also revealed that the modulation dynamics in ZnO single crystal highly depend on the excitation conditions. Specifically, the modulation dynamics with the near-bandgap or above-bandgap excitation are attributed to the non-equilibrium interband carrier relaxations, while for mid-gap excitation, the modulation dynamics are dominated by the nonlinear frequency mixing process. This work may enhance the current understanding of the HHG modulation mechanism and enlighten novel device designs.
ABSTRACT
In order to explore the mechanism during the process of the non-synchronous vibration (NSV), the flow field formation development is investigated in this paper. Based on the fluid-structure interaction method, the vibration of rotor blades is found to be in the first bending mode with a non-integral order (4.6) of the rotation speed. Referring to the constant inter blade phase angle (IBPA), the appearances of frequency-locking and phase-locking can be identified for the NSV. A periodical instability flow emerges in the tip region with the mixture of separation vortex and tip leakage flow. Due to the nonlinearities of fluid and structure, the blade vibration exhibits a limit cycle oscillation (LCO) response. The separation vortex presenting a spiral structure propagates in the annulus, indicating a pattern as modal oscillation. A flow induced vibration is initiated by the spiral vortex in the tip. The large pressure oscillation caused by the movement of the spiral vortex is regarded as a main factor for the presented NSV. As the oscillation of blade loading occurs with blade rotating pass the disturbances, the intensity of the reverse leakage flow in adjacent channels also plays a crucial role in the blade vibration.
ABSTRACT
microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell proliferative and migrating/invasive potentials were further evaluated with the help of a CCK-8 and Transwell assays, respectively. Gain- and loss-of-function assays were also implemented to assess the role of miR-331-3p, SCARA5, and FAK pathway in PC cells. Lastly, xenograft nude mice were established to investigate the role of miR-331-3p in vivo. miR-331-3p negatively targeted SCARA5 and was highly expressed in CAFs-derived EVs, which accelerated the proliferative, migrating, and invasive potentials of PC cells. Meanwhile, over-expression of miR-331-3p enhanced the proliferative, migrating, and invasive properties of PC cells and promoted tumor growth in vivo by manipulating SCARA5/FAK axis, whereas SCARA5 countered the oncogenic effects of miR-331-3p. Overall, miR-331-3p in CAFs-derived EVs inhibits SCARA5 expression and activates the FAK pathway, thereby augmenting the progression of PC. Our study provides a potential therapeutic target for the treatment of PC.
Subject(s)
Carcinoma , Extracellular Vesicles , MicroRNAs , Pancreatic Neoplasms , Animals , Carcinoma/metabolism , Cell Proliferation , Extracellular Vesicles/metabolism , Fibroblasts/metabolism , Humans , Mice , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Scavenger Receptors, Class A/metabolism , Pancreatic NeoplasmsABSTRACT
The layered semiconductor Bi2 O2 Se is a promising new-type 2D material that holds layered structure via electrostatic forces instead of van der Waals (vdW) attractions. Aside from the huge success in device performance, the non-vdW nature in Bi2 O2 Se with a built-in interlayer electric field has also provided an appealing platform for investigating unique photoexcited carrier dynamics. Here, experimental evidence for the observation of excimers in multilayer Bi2 O2 Se nanosheets via transient absorption spectroscopy is presented. It is found that the excimer formation is the primary decay pathway of photoexcited excitons and three-stage excimer dynamics with corresponding time scales are established. Excitation-fluence-dependent excimer dynamics further suggest that the excimer is diffusive and its formation can be simply described as excitons relaxed to an excimer geometry. This work indicates the outstanding promise of unique excitonic processes in Bi2 O2 Se, which may motivate novel device designs.
ABSTRACT
Manipulating lattice vibrations is the cornerstone to achieving ultralow thermal conductivity in thermoelectrics. Although spatial control by novel material designs has been recently reported, temporal manipulation, which can shape thermoelectric properties under nonequilibrium conditions, remains largely unexplored. Here, taking SnSe as a representative, we have demonstrated that in the ultrafast pump-pump-probe spectroscopy, electronic and lattice coherences inherited from optical excitations can be exploited independently to manipulate phonon oscillations in a highly selective manner. Specifically, when the pump-pump delay time (tmod) is in the electronic coherence time range, the amplitude, frequency, and lifetime of all phonon modes are simultaneously following the optical cycle. While extending tmod into the lattice coherence time range, the amplitude of each coherent phonon mode can be selectively manipulated according to its intrinsic period without changing the frequency and lifetime. This work opens up exciting avenues to temporally and discriminatorily manipulate phononic processes in thermoelectric materials.
ABSTRACT
Layered tin selenide (SnSe) has recently emerged as a high-performance thermoelectric material with the current record for the figure of merit (ZT) observed in the high-temperature Cmcm phase. So far, access to the Cmcm phase has been mainly obtained via thermal equilibrium methods based on sample heating or application of external pressure, thus restricting the current understanding only to ground-state conditions. Here, we investigate the ultrafast carrier and phononic dynamics in SnSe. Our results demonstrate that optical excitations can transiently switch the point-group symmetry of the crystal from Pnma to Cmcm at room temperature in a few hundreds of femtoseconds with an ultralow threshold for the excitation carrier density. This nonequilibrium Cmcm phase is found to be driven by the displacive excitation of coherent Ag phonons and, given the absence of low-energy thermal phonons, exists in SnSe with the status of 'cold lattice with hot carriers'. Our findings provide an important insight for understanding the nonequilibrium thermoelectric properties of SnSe.
ABSTRACT
Nonlinear phononics has recently been demonstrated as a viable approach for dynamically modifying materials' properties. Conventionally, nonlinearity in the lattice dynamics is introduced via the "ionic" Raman scattering, in which infrared-active phonons (i.e., coherent ionic vibrations) serve as the intermediate state for transferring energy to Raman-active phonons. Here we report that it is also possible to achieve phononic nonlinearity through the "electronic" route, a process that relies on excited electronic states to initiate energy exchange among Raman-active phonons. Taking layered ReSe2 as a model system, we use coherent phonon spectroscopy with a pump energy larger than the band gap to follow lattice dynamics and observe the nonlinear coupling between both Raman-active intralayer atomic oscillations and interlayer breathing modes. In addition, we show that such nonlinear phononic coupling is highly dependent on the environment temperature. This work, which demonstrates a different and novel mechanism, may enrich the toolkit for controlling material properties by means of nonlinear phononics.
ABSTRACT
As a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal ß-WP2 crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the "spike-like" Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of ß-WP2. These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials.
ABSTRACT
Uniform stereo-complex microparticles ranging from nanometer to micrometer size are prepared by using stereo multiblock co-poly(rac-lactide)s (smb-PLAs) with different stereo-regularity. At comparable molecular weights, as the smb-PLA stereo-regularity decreases from 88% to 76%, the crystallinity of the microparticles decreases noticeably, as proved by DSC and WAXD. At the same time, the shape of the microparticles varies from the flower shape to the sphere shape and the particle size increases markedly from 700-2700 nm as shown by SEM. However, all insulin-loaded microparticles are of cake-shape and their sizes depend on the stereo-regularity. The crystallization of smb-PLAs facilitated by insulin is evidenced by the increase of T(m) and DeltaH(f) in DSC. The highest insulin-loading content of 14.2% and -entrapment efficiency of 82.8% are obtained from the smb-PLA with the highest stereo-regularity of 88%. Release studies in vitro show the least first-day release at about 25% followed by continuous release of another 70% of insulin over one month. Stereo-complex microparticles of smb-PLAs with lower stereo-regularity resulted in a relatively lower insulin-entrapment efficiency and -loading content, a larger first-day release, and also complete release of 90% of the total amount within one month. The release system follows a diffusion mechanism. By contrast, atactic PLA shows a very low entrapment efficiency of 16.7%. Structure of a stereo multiblock co-poly(rac-lactide).
Subject(s)
Insulin/administration & dosage , Insulin/metabolism , Polyesters/chemistry , Calorimetry, Differential Scanning/methods , Crystallization , Insulin/chemistry , Particle Size , Stereoisomerism , X-Ray Diffraction/methodsABSTRACT
Li3V2(PO4)3-LiVPO4F, LiFePO4-Li3V2(PO4)3, and LiFePO4-Li3V2(PO4)3-LiVPO4F composite cathode materials are synthesized through mechanically activated chemical reduction followed by annealing. X-ray diffraction (XRD) results reveal that the obtained products are pure phase, and the molar ratio of each phase in the composites is consistent with that in raw material. Transmission electron microscopy (TEM) images show that each phase coexists in the composites. The LiFePO4-Li3V2(PO4)3-LiVPO4F composites exhibit the best electrochemical performance. These composites can deliver a capacity of 164 mAh g(-1) at 0.1 C and possess favorable capacities at rates of 0.5, 1, and 5 C. The excellent electrochemical performance is attributed to the mutual modification and the synergistic effects.
ABSTRACT
VPO4/C nanosheets and microspheres are successfully synthesized via a hydrothermal method followed by calcinations. The XRD results reveal that the obtained products both have an orthorhombic VPO4 phase. The SEM and TEM images demonstrate that nanosheets and spherical morphology can be obtained by controlling the synthesis conditions. The samples are both uniformly coated by amorphous carbon. The electrochemical test results show that the sample with a nanosheet structure has a better electrochemical performance than the microsphere samples. The VPO4/C nanosheets can deliver an initial discharge capacity of 788.7 mAh g(-1) at 0.05 C and possessed a favorable capacity at the rates of 1, 2, and 4 C. The nanosheet structure can effectively improve the electrochemical performances of VPO4/C anode materials.
ABSTRACT
VOPO4 nanosheets are successfully synthesized using a hydrothermal method followed by calcination. The XRD results reveal that obtained products are crystallized in the orthorhombic VOPO4 phase. SEM and TEM images demonstrate that VOPO4 products possess unique nanosheet morphology. Electrochemical tests show that the VOPO4 nanosheets exhibit an excellent electrochemical performance as anode materials. They can deliver an initial discharge capacity of 1356 mA h g(-1) at 0.1 C, and possess a favorable capacity at rates of 0.2, 1, and 2 C. The synthesized VOPO4 can be used as a good anode material; furthermore, the nanosheet structure can effectively improve the electrochemical performance of this material.
ABSTRACT
Insulin has been encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres by solid-in-oil-in-oil (S/O/O) emulsion technique using DMF/corn oil as new solvent pairs. To get better encapsulation efficiency, insulin nanoparticles were prepared by the modified isoelectric point precipitation method so that it had good dispersion in the inner oil phase. The resulting microspheres had drug loading of 10% (w/w), while the encapsulation efficiency could be up to 90-100%. And the insulin release from the microspheres could last for 60 days. Microspheres encapsulated original insulin with the same method had lower encapsulation efficiency, and shorter release period. Laser scanning confocal microscopy indicated the insulin nanoparticle and original insulin had different distribution in microspheres. The results suggested that using insulin nanoparticle was better than original insulin for microsphere preparation by S/O/O method. Study about the secondary structure of insulin by Fourier transform infrared spectroscopy (FTIR) indicated high insulin structural integrity during the process. In vivo test showed insulin in microspheres retained its bioactivity. In addition, cytotoxicity evaluation by the MTT assay has proved that no extra toxicity was introduced into the microspheres during the emulsion process.
Subject(s)
Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Lactic Acid/chemistry , Nanoparticles , Polyglycolic Acid/chemistry , Animals , Corn Oil/chemistry , Delayed-Action Preparations , Dimethylformamide , Emulsions , Female , Formamides/chemistry , Hypoglycemic Agents/toxicity , Insulin/toxicity , Isoelectric Point , Microscopy, Confocal , Microspheres , Polylactic Acid-Polyglycolic Acid Copolymer , Protein Structure, Secondary , Rats , Rats, Wistar , Solvents/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
Model protein bovine serum albumin (BSA) was covalently grafted onto poly[(L-lactide)-co-carbonate] microsphere surfaces by "click chemistry." The grafting was confirmed by confocal laser scanning microscopy and X-ray photoelectron spectroscopy. The maximum amount of surface-grafted BSA was 45 mg x g(-1). The secondary structure of the grafted BSA was analyzed by FTIR and the results demonstrated that the grafting did not affect protein structure. This strategy can also be used on microspheres prepared from poly(L-lactide)/poly[(L-lactide)-co-carbonate] blend materials.