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Pb(Zr,Ti)O3-based ceramics are the mainstream materials for commercial multilayer piezoelectric ceramic actuators, but to date, large strains at low electric fields have not been well solved. Herein, 0.95Pb(Zr0.56Ti0.44)O3–0.05(Bi0.5Na0.5)TiO3–xBaZrO3 (PZT–BNT–xBZ) ceramics with efficient ferroelectric domain wall motion were designed and realized by reducing lattice distortion and changing the domain structure. It is found that the introduction of BaZrO3 (BZ) weakens the tetragonal phase distortion of PZT, contributing to a reduction in the mechanical stress that impedes the migration of domain walls. Moreover, the domain structures could be modified by adjusting the BZ content, where short and broad striped domains are constructed with high amplitude characteristics to enhance the domain wall motion. A large strain of 0.39% is accordingly achieved at an electric field as low as 40 kV/cm for the sample with x = 0.03, accompanied by excellent temperature stability over the temperature range of 30–210 °C. This study delves into the synergistic effects of reducing lattice distortion and changing domain structure on domain wall motion and provides an effective strategy to improve the strain of PZT-based piezoelectric ceramics.

Abstract Intrinsically safe solenoids drive solenoid valves in coal mining equipment. The low power consumption of these solenoids limits the response time of the solenoid valves. Additionally, the low viscosity and high susceptibility to dust contamination of the emulsion fluid often lead to leakage and sticking of hydraulic valves. This study proposes a low-power-driven, large-flux, fast-response three-stage valve structure with an internal displacement feedback device to address these issues. The critical parameters of the valve were optimized using a novel multi-objective optimization algorithm. A prototype was manufactured based on the obtained parameters and subjected to simulation and experimental verification. The results demonstrate that the valve has an opening time of 21 ms, a closing time of 12 ms, and a maximum flow rate of approximately 225 L/min. The driving power of this structure is less than 1.2 W. By utilizing this valve for hydraulic cylinder control, a positioning accuracy of ± 0.15 mm was achieved. The comparative test results show that the proposed structural control error fluctuation is smaller than that of the 3/4 proportional valve.

Abstract Moiré structures formed by twisting three layers of graphene with two independent twist angles present an ideal platform for studying correlated quantum phenomena, as an infinite set of angle pairs is predicted to exhibit flat bands. Moreover, the two mutually incommensurate moiré patterns among the twisted trilayer graphene (TTG) can form highly tunable moiré quasicrystals. This enables us to extend correlated physics in periodic moiré crystals to quasiperiodic systems. However, direct local characterization of the structure of the moiré quasicrystals and of the resulting flat bands are still lacking, which is crucial to fundamental understanding and control of the correlated moiré physics. Here, we demonstrate the existence of flat bands in a series of TTGs with various twist angle pairs and show that the TTGs with different magic angle pairs are strikingly dissimilar in their atomic and electronic structures. The lattice relaxation and the interference between moiré patterns are highly dependent on the twist angles. Our direct spatial mappings, supported by theoretical calculations, reveal that the localization of the flat bands exhibits distinct symmetries in different regions of the moiré quasicrystals.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Royal Jelly (RJ) is a natural substance produced by honeybees, serving not only as nutrition for bee brood and queens but also as a functional food due to its health-promoting properties. Despite its well-known broad-spectrum antibacterial activity, the precise molecular mechanism underlying its antibacterial action has remained elusive. In this study, we investigated the impact of RJ on the bacteria model MG1655 at its half-maximal inhibitory concentration, employing LC–MS/MS to analyze proteomic changes. The differentially expressed proteins were found to primarily contribute to the suppression of gene expression processes, specifically transcription and translation, disrupting nutrition and energy metabolism, and inducing oxidative stress. Notably, RJ treatment led to a marked inhibition of superoxide dismutase and catalase activities, resulting in heightened oxidative damage and lipid peroxidation. Furthermore, through a protein–protein interaction network analysis using the STRING database, we identified CRP and IHF as crucial host regulators responsive to RJ. These regulators were found to play a pivotal role in suppressing essential hub genes associated with energy production and antioxidant capabilities. Our findings significantly contribute to the understanding of RJ's antibacterial mechanism, highlighting its potential as a natural alternative to conventional antibiotics. The identification of CRP and IHF as central players highlights the intricate regulatory networks involved in RJ's action, offering new targets for developing innovative antimicrobial strategies.

Abstract Direct solar-to-hydrogen conversion from pure water using all-organic heterogeneous catalysts remains elusive. The challenges are twofold: (i) full-band low-frequent photons in the solar spectrum cannot be harnessed into a unified S 1 excited state for water-splitting based on the common Kasha-allowed S 0 → S 1 excitation; (ii) the H+ → H2 evolution suffers the high overpotential on pristine organic surfaces. Here, we report an organic molecular crystal nanobelt through the self-assembly of spin-one open-shell perylene diimide diradical anions (:PDI2-) and their tautomeric spin-zero closed-shell quinoid isomers (PDI2-). The self-assembled :PDI2-/PDI2- crystal nanobelt alters the spin-dependent excitation evolution, leading to spin-allowed S 0 S 1 → 1 (TT) → T 1 + T 1 singlet fission under visible-light (420 nm~700 nm) and a spin-forbidden S 0 → T 1 transition under near-infrared (700 nm~1100 nm) within spin-hybrid chromophores. With a triplet-triplet annihilation upconversion, a newly formed S 1 excited state on the diradical-quinoid hybrid induces the H+ reduction through a favorable hydrophilic diradical-mediated electron transfer, which enables simultaneous H2 and O2 production from pure water with an average apparent quantum yield over 1.5% under the visible to near-infrared solar spectrum.

Abstract The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo. Mechanistically, 15a induces a viral mimicry response by promoting the expression of endogenous retroviral elements in breast cancer cells, thus increasing the intracellular level of double-stranded RNA to activate the RIG-I–MAVS pathway. This in turn promotes the production of interferons and chemokines and augments the expression of interferon-stimulated genes and PD-L1. The combination of 15a and an anti-PD-L1 antibody had an additive effect in vivo. These findings indicate that this DNMT/HDACi has immunomodulatory functions and enhances the effectiveness of immune checkpoint blockade therapy. A novel dual DNMT and HDAC inhibitor induces viral mimicry, which induces the accumulation of dsRNA to activate tumoral IFN signalling and cytokine production to enhance the immune response in breast cancer.

ABSTRACTThe short-term power load forecasting provides an essential foundation for the dispatching management of the power system, which is crucial for enhancing economy and ensuring operational stability. To enhance the precision of the short-term power load forecasting, this paper proposes a hybrid prediction algorithm based on sparrow search algorithm (SSA), convolutional neural network (CNN) and long short-term memory (LSTM). First, feature datasets are constructed based on date information, meteorological data, similar days. The CNN performs effective feature extraction on the data and feeds the results into the LSTM for time series data analysis. Second, eight key parameters are optimized by SSA for improving the prediction precision of the CNN-LSTM prediction model. Simulation results show that the R2 of the proposed model exhibits a substantial enhancement in comparison to other models, reaching 0.9919 and presents a remarkable decrease in MAPE resulting in a value of 1.2%. Furthermore, RMSE and MAE have decreased to 1.17MW and 0.97MW respectively. Therefore, the proposed method has the ability to improve the prediction accuracy, due to the advantages in data mining of CNN, good time series data fitting ability of LSTM, and excellent optimization ability of SSA.

Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100 nm and/or 1 μm) and Cd for 25 days.The results showed that PS at 100 nm caused more severe oxidative damage and cell apoptosis than PS at 1 μm. Combined exposure to PS at both 100 nm and 1 μm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100 nm vs. 1 μm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100 nm PS+1μm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.

Solar energy utilization in buildings is crucial for energy conservation and carbon reduction. Previous studies have shown the promise of heat-pipe-ring (HPR) embedded building façades as effective modules for solar energy utilization and energy conservation in air-conditioning systems. However, research on their thermal characteristics as building-attached solar collectors is limited. This paper fills this gap by combining experimental data and numerical simulations using self-developed Fortran programs. Regression analysis of HPR modules in building integration solar systems (BISS) determines thermal efficiency and thermal loss coefficient. Results indicate the advantage of selective Cr coating in minimizing energy losses, with less pronounced impact from glass covers. Optimal HPR module designs for building-attached solar systems (BASS) in different Chinese climate regions are established, achieving yearly averaged thermal efficiencies ranging from 62.6 % to 73.5 %. The study further presents the thermal performance of HPR modules in BASS on a typical summer day in each city within each climate zone. These findings offer practical insights for selecting HPR modules in BASS systems tailored to diverse regions, promoting the integration of renewable solar energy into building applications.

Photonic neuromorphic computing has emerged as a promising avenue toward building a high-speed, low-latency, and energy-efficient non-von-Neumann computing system. Photonic spiking neural network (PSNN) exploits brain-like spatiotemporal processing to realize high-performance neuromorphic computing. Linear weighting and nonlinear spiking activation are two fundamental functions of a SNN. However, the nonlinear computation of PSNN remains a significant challenge. Therefore, this perspective focuses on the nonlinear computation of photonic spiking neurons, including numerical simulation, device fabrication, and experimental demonstration. Different photonic spiking neurons are considered, such as vertical-cavity surface-emitting lasers, distributed feedback (DFB) lasers, Fabry–Pérot (FP) lasers, or semiconductor lasers embedded with saturable absorbers (SAs) (e.g., FP-SA and DFB-SA). PSNN architectures, including fully connected and convolutional structures, are developed, and supervised and unsupervised learning algorithms that take into account optical constraints are introduced to accomplish specific applications. This work covers devices, architectures, learning algorithms, and applications for photonic and optoelectronic neuromorphic computing and provides our perspective on the challenges and prospects of photonic neuromorphic computing based on semiconductor lasers.

Abstract Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) – in which the current flows perpendicularly to the substrate surface direction – are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.

Abstract Background Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. Methods CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. Results AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. Conclusion Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM. Graphical Abstract

Many designs of in-memory logic computing using ReRAM have been proposed and even a few of them have been experimentally demonstrated. However, the ability to cascade and extend the designed circuits is limited. In this work, we elaborate a design called time-sum-logic based on 2T1R memristor arrays and implement arithmetic computing circuits using memristors by integrating both time and space dimension. The core method of our design is to use sum of minterms to transfer logic to time sequence by 2T1R memristor arrays. This method is extensible by extending the number of layers to realize multi-bit arithmetic computing. Remarkably, cascading between different layers is elaborated carefully and pipelines are adopted to manage the sequence of memristors’ writing and reading and lower the complexity and latency. In this way, the proposed circuits will be more efficient and can support high data throughout. Based on our design, 4-bit full adder and $4\times 4$ multiplier are designed with pipelines, and n-bit full adders and m $\times $ n multipliers could be easily constructed. The low latency and high efficiency confirm the advantages we have illustrated and show a promised application prospect.

Abstract Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of the P23-45 RNAPs with other RNAPs suggest that, despite the extensive functional differences, the two P23-45 RNAPs originate from an ancient gene duplication in an ancestral phage. Our findings demonstrate striking adaptability of RNAPs that can be attained within a single virus species.

Abstract Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood–brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/β-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain–blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/β-catenin pathway. Graphical Abstract

Stabilizing the CMOS-compatible low-temperature Au-free GaN Ohmic contact is a critical work that determines the performance and yield of GaN power HEMTs in mass production. The instability of this contact has been puzzling the industry and academia for years. In this work, an overlooked factor, fluorine injection, is unambiguously verified to widely exist during dielectric etching and can easily destroy the low-temperature GaN Ohmic contact formation. The injection depth is confirmed to be over 30 nm with a fluorine peak concentration of 1023 at/cm3 in vicinity of the surface. Traditional method of partial AlGaN recessing with a pretty tiny processing window is proven unfriendly for production and vulnerable to the fluorine injection. Two methods to get rid of the fluorine are proposed. The first one is to over-etch the AlGaN barrier to the GaN channel to fully remove the fluorine ions. The second is to deposit an etch-stop blocking layer of Al2O3, which is also compatible with CMOS process.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

In this paper, an integrated device which realized the dual-mode integration of power amplifier (PA) and radio frequency (RF) switch based on GaN dual-gate (DG) structure is designed and fabricated. The integrated device provides two working modes and meets the performance requirements of PA and RF switch. In the transmit (Tx) mode, the integrated device is used as PA. At the frequency of 3.6 GHz, compared with the conventional GaN HEMT (high electron mobility transistor) as PA, due to the field modulation effect of the dual-gate structure, the current collapse is effectively suppressed, and the output power density $(P_{out})$ of the integrated device is increased from 6.90 W/mm to 7.85 W/mm, and the power added efficiency (PAE) is increased from 44.3% to 51.1%. In the receive (Rx) mode, the integrated device is used as RF switch. Compared with conventional RF switch, the isolation of integrated devices is significantly improved. At the frequency of 3.6GHz, the isolation is improved from 19.4 dB to 41.0 dB; At the frequency of 40 GHz, the isolation is improved from 3.0 dB to 29.7 dB. The integrated device provides a novel function integration scheme for RF frontends, with great potential for improving the integration and dimension of future communication systems.

In order to improve the off-state and breakdown characteristics of double-channel GaN HEMTs, an ultra-thin barrier layer was chosen as the second barrier layer. The strongly polarized and ultra-thin AlN sub-barrier and the InAlN sub-barrier are great candidates. In this article, the two epitaxial structures, AlGaN/GaN/AlN/GaN (sub-AlN) HEMTs and AlGaN/GaN/InAlN/GaN (sub-InAlN) HEMTs, were compared to select a more suitable sub-barrier layer. Through TEM images of the InAlN barrier layer, the segregation of In components can be seen, which decreases the mobility of the second channel. Thus, the sub-AlN HEMTs have a higher output current density and transconductance than those of the sub-InAlN HEMTs. Because the high-quality AlN barrier layer shields the gate leakage current, a 294 V breakdown voltage was achieved by the sub-AlN HEMTs, which is higher than the 121 V of the sub-InAlN HEMTs. The current gain cut-off frequency (fT) and maximum oscillation frequency (fmax) of the sub-AlN HEMTs are higher than that of the sub-InAlN HEMTs from low to high bias voltage. The power-added efficiency (PAE) and output power density (Pout) of the sub-AlN HEMTs are 57% and 11.3 W/mm at 3.6 GHz and 50 V of drain voltage (Vd), respectively. For the sub-InAlN HEMTs, the PAE and Pout are 41.4% and 8.69 W/mm, because of the worse drain lag ratio. Thus, the Pout of the sub-AlN HEMTs is higher than that of the sub-InAlN HEMTs.