Thermoelectric materials have potential applications in energy harvesting and electronic cooling devices, and bismuth antimony telluride (BiSbTe) alloys are the state‐of‐the‐art thermoelectric ...materials that have been widely used for several decades. It is demonstrated that mixing SiC nanoparticles into the BiSbTe matrix effectively enhances its thermoelectric properties; a high dimensionless figure of merit (ZT) value of up to 1.33 at 373 K is obtained in Bi0.3Sb1.7Te3 incorporated with only 0.4 vol% SiC nanoparticles. SiC nanoinclusions possessing coherent interfaces with the Bi0.3Sb1.7Te3 matrix can increase the Seebeck coefficient while increasing the electrical conductivity, in addition to its effect of reducing lattice thermal conductivity by enhancing phonon scattering. Nano‐SiC dispersion further endows the BiSbTe alloys with better mechanical properties, which are favorable for practical applications and device fabrication.
A high figure of merit (ZT) up to 1.33 at 373 K is achieved by incorporating a tiny number of SiC particles to a traditional Bi0.3Sb1.7Te3 thermoelectric material. The existence of SiC nanoinclusions in the p‐type Bi0.3Sb1.7Te3 thermoelectric matrix reduces the electrical resistivity and increases the Seebeck coefficient, which leads to the remarkable ZT enhancement.
AgPbmSbTem+2 (abbreviated as LAST) has received tremendous attention as a promising thermoelectric material at medium temperature. It can be synthesized by a simple process combining mechanical ...alloying (MA) and spark plasma sintering (SPS). This work reveals that the thermoelectric figure of merit (ZT value) of LAST can be increased by 50%, benefiting from enhanced electrical conductivity and thermopower due to refined grains and from nanostructuring realized by repeating the milling and SPS processes. This modified process and further compositional optimization enables ZT values of the LAST alloys up to 1.54 at 723 K. This supports the potential of the LAST alloy as a promising medium‐temperature thermoelectric material and reveals the validity of ZT enhancement by a simple microstructural refining and nanostructuring method.
A high thermoelectric figure of merit (ZT) of up to 1.54 at a relatively low temperature (723 K) is obtained in n‐type AgPbmSbTem+2 system bulk materials fabricated by a simple process. Simultaneous enhancement of electrical conductivity and thermopower is achieved by optimizing mesostructures and tuning carrier density via controlling Pb compositions
This article introduces a three-degree-of-freedom (3DOF) model-based adaptive fractional-order dynamic surface control (AFODSC) system for a synchronous position control of a gantry table. First, the ...3DOF model of the gantry table is investigated considering the rotational dynamics caused by inter-axis mechanical coupling and synchronous error. Then, a new fractional-order dynamic surface control (FODSC) approach is introduced using a fractional-order low-pass filter to provide an extra degree of freedom for the existing dynamic surface control (DSC) method. Because it is arduous to know the system uncertainty, the AFODSC is further elaborated by incorporating an adaptive mechanism and an uncertainty observation into the FODSC. In the proposed AFODSC, a modified dendritic neuron model observer (DNMO) is proposed to identify uncertainties, whereas an exponential compensator is designed to compensate for the observation error. Multiple adaptation laws are derived to adapt the parameters of DNMO on the basis of the Lyapunov stability theorem. Experimental results confirm that the proposed AFODSC system demonstrates favorable position tracking and synchronization accuracies for the gantry table compared with the conventional DSC system.
The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is ...unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their ...biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity.
Abstract
Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three ...cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%–24.3%) and 95% (95% CI: 85.4%–100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.
•2205/X65 bimetallic plate was produced by explosive welding.•Microstructural inhomogeneity of 2205/X65 bimetallic sheet was investigated.•Mechanical inhomogeneity of 2205/X65 bimetallic sheet was ...studied.•Distribution of alloy elements across 2205/X65 interface was studied.•Weak positions of 2205/X65 sheet in bending process were revealed.
In this study, microstructural inhomogeneity and mechanical properties of explosive welded 2205 stainless steel/X65 pipe steel bimetallic sheets were investigated. The explosion-bonded 2205/X65 bimetallic sheets had good shear strength. The tensile shear fracture primarily occurred in the interior of X65 material and primarily exhibited dimple morphology. Fine crystal grains in the 0.5–2μm range were found all over the narrow localized melted zone near the 2205/X65 interface, whereas a coarse columnar crystal structure growing along the perpendicular direction to the interface formed in the wider localized melted zone. Quasi-cleavage fracture morphology was observed in the coarse columnar crystal region after the stratified tensile test. The junction of the three regions near the interface with large differences in morphology was the weak point in the bimetallic sheet, where Y-shaped cracking easily occurred under a loading force. Stratified tensile test and micro-hardness tests for the explosively welded bimetallic sheet showed that severe hardening occurred in the 2205 cladding, and the most severe metal hardening occurred near the interface. Tests for 45° face bending and root bending tests were conducted under extreme conditions. The results showed that voids were prone to appeared in the peninsula and island morphologies near the interface.
CP-Ti/X65-pipe-steel bimetallic sheet was fabricated by explosive welding and hot rolling (W&R). Trace of the wavy CP-Ti/X65 interface formed from explosive welding was observed along the straight ...CP-Ti/X65 interface of bimetallic sheet fabricated by W&R. The microstructure and component analysis showed the following. (i) The cross-section of the X65 zone consisted of a 2–5μm-wide Ti diffusion layer next to the interface, a 150–200μm-wide decarbonization layer, and the rest area with a banded structure morphology. (ii) There were numerous voids and a slight C element enrichment at the interface. (iii) The section of the CP-Ti zone consisted of a 10–50μm-wide Fe diffusion zone next to the interface, a residual adiabatic shear band zone next to Fe diffusion zone, and the rest region composed of the α-Ti microstructure. The micro-hardness profile across CP-Ti/X65 interface was measured. The variation patterns of the mechanical properties of the bimetallic sheet in the thickness direction were obtained from stratified tensile tests. The shear test proved that the CP-Ti/X65 bimetallic sheet produced by W&R had acceptable shear bond strength. The microstructure and alloy element distribution across the TA1/X65 interfaces of as-welded, heat treated and extruded TA1/X65 bimetallic sheets were studied and compared.
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•Big-size TA1/X65 sheet is achieved by explosive welding & hot rolling.•Periodic characteristic of microstructure across TA1/X65 interface is studied.•Mechanical inhomogeneity of TA1/X65 bimetallic sheet is studied.•Variation of chemical composition across TA1/X65 interface is studied.•Proposal abound for improving performance of TA1/X65 bimetallic sheet is given.
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Triple-negative breast cancer (TNBC) is characterized by elevated metastasis, low survival, and poor response to therapy. Although many specific and effective agents for treating TNBC ...have been investigated, promising therapeutic options remain elusive. Here, we screened the inhibitory activities of three main components of Lithospermum erythrorhizon Sieb. et Zucc (shikonin, acetylshikonin, and β,β-dimethylacrylshikonin) on TNBC cells. The results revealed that shikonin potently decreased the viabilities of TNBC MDA-MB-231 and 4T1 cells but showed less cytotoxicity to normal mammary epithelial MCF-12A cells. Additionally, shikonin reversed the epithelial-to-mesenchymal transition (EMT) in MDA-MB-231 and 4T1 cells. Shikonin depressed cell migration and invasion, upregulated E-cadherin levels, downregulated N-cadherin, vimentin, and Snail levels, and reorganized the cytoskeletal proteins F-actin and vimentin. Shikonin reversed EMT by inhibiting activation of β-catenin signaling through attenuating β-catenin expression, nuclear accumulation, binding to T-cell factor consensus oligos, and transcription of its targeted EMT-related genes. Moreover, shikonin upregulated glycogen synthase kinase 3β (GSK-3β) levels, leading to enhanced phosphorylation and decreased levels of β-catenin. Furthermore, shikonin administration significantly inhibited lung metastasis of MDA-MB-231 cells in NOD/SCID mice accompanied by low systemic toxicity. Histological analysis confirmed that shikonin elevated levels of E-cadherin, phosphorylated β-catenin, and GSK-3β, and decreased levels of vimentin and β-catenin in pulmonary metastatic foci. These results indicated that shikonin potently inhibits TNBC metastasis by targeting the EMT via GSK-3β-regulated suppression of β-catenin signaling, which highlights the importance of shikonin as a potential candidate for novel anticancer therapeutics against TNBC.
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