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Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies. [ABSTRACT FROM AUTHOR]

HfO2‐based ferroelectrics offer promises for next‐generation nonvolatile nanoscale devices owing to excellent CMOS compatibility and robust ferroelectricity at the nanoscale. However, fundamentally understanding the mechanism of polarization reversal and domain dynamics is challenging because the role of the spacer layer at the domain level in HfO2‐based ferroelectrics remains elusive. Here, it is realized that visualization of time‐resolved dynamics of nanoscale domain configurations in the epitaxial Hf0.5Zr0.5O2 thin films using phase‐field simulations. Scale‐free domain independent switchability (namely, irreducible stable polar domain down to 1 nm lateral size) and sharp domain walls that originate from weak interactions between adjacent domains characterized by the reduced gradient energy coefficient, which unravels the mesoscale mechanism of spacer layer in domain dynamics are demonstrated. Meanwhile, it is revealed that 180° polarization switching is dominated by the nucleation of a new domain with a high nucleation density, well described by the nucleation‐limited switching model. This study not only provides a fundamental mesoscale mechanism of the spacer layer, but also stimulates further studies on the manipulation of ultra‐scaled single domain state for designing high‐density and fast‐speed HfO2‐based ferroelectric memory. [ABSTRACT FROM AUTHOR]

Fluorite-structured HfO2 ferroelectrics exhibit remarkable ferroelectricity owing to the robust thickness scalability, rendering them promising for next-generation ferroelectric memories. Unlike the well-understood perovskite structured ferroelectrics, such as Pb(Zr,Ti)O3, the origin of ferroelectricity in HfO2 remains elusive, which impedes the experimental fabrication of pure and stable ferroelectric orthorhombic phase in films. This study seeks to elucidate its origin by analyzing the covalent nature of local chemical bonding and changes in orbital hybridization and by catching the typical feather of the half-unit-cell spacer/polar layer in the orthorhombic phase. Notably, we find that the differences in the hybridization intensity of the 2s orbitals of two types of O atoms (OI and OII) and 5d orbitals of Hf atoms play a crucial role in inducing ferroelectric distortion. Furthermore, we demonstrate that the intrinsic mechanisms of stress in enhancing the ferroelectricity of HfO2 originate from the modulation of orbital hybridization intensity of the Hf–O bonds. These insights provide a vital theoretical foundation for further exploration of ferroelectric phase transitions and property modulation in HfO2 and similar fluorite-structured ferroelectrics. [ABSTRACT FROM AUTHOR]

Introduction: Variability in microbial residues within soil aggregates are becoming progressively essential to the nutritive and sustainability of soils, and are therefore broadly regarded as an indispensable part of soil organic matter. It is unexplored how the widespread implementation of microbial fertilisers in agricultural production impacts soil organic nutrients, in particular the microbial residue fraction. Methods: We performed a three-year field experiment to verify the distinct impacts of microbial and organic fertilizers on carbon accumulation in soil microbial leftovers among aggregate fractions. Results: Microbial residual carbon was shown to decrease insignificantly during the application of microbial fertilizer and to rise marginally afterwards with the utilization of organic fertilizer. However, the combined effects of the two fertilizers had substantial impacts on the accumulation of microbial residual carbon. Changes in the structure of the fungi and bacteria shown in this study have implications for the short-term potential of microbial fertilizer shortages to permanent soil carbon sequestration. Additionally, our findings revealed variations in microbial residue accumulation across the microbial fertilizers, with Azotobacter chroococcum fertilizer being preferable to Bacillus mucilaginosus fertilizer due to its higher efficiency. In this scenario of nutrient addition, fungal residues may serve as the primary binding component or focal point for the production of new microaggregates, since the quantity of SOC provided by fungal residues increased while that supplied by bacterial residues decreased. Discussion: Our findings collectively suggested that the mechanisms behind the observed bacterial and fungal MRC (microbial residue carbon) responses to microbial fertilizer or organic fertilizer in bamboo forest soils are likely to be distinct. The application of microbial fertilizers for a limited duration led to a decline soil stable carbon pool, potentially influencing the regulation of soil nutrients in such hilly bamboo forests. [ABSTRACT FROM AUTHOR]

Aiming to address the multi-objective cooperative optimization problem of ship structure lightweight and crashed-resistance, this study proposed a concave reentrant honeycomb-based negative Poisson's ratio (NPR) sandwich structure to replace the stiffened plate. The feasibility of using the sandwich structure to improve ship crashworthiness is demonstrated through finite element analysis. An intelligent optimization method is established to address the issues of multiple parameters and complex effects associated with composite structures and optimize the crashworthiness of the sandwich structure. The effectiveness of the optimization method and the feasibility of the NPR sandwich structure in ship crashworthiness have been validated, providing a reference for the design of new multi-functional ship structures. [ABSTRACT FROM AUTHOR]

Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma. [ABSTRACT FROM AUTHOR]

Permian mafic dikes crop out widely within Beishan area in the southernmost Central Asian Orogenic Belt (CAOB). These mantle-derived products provide important clues for elucidating the genesis and geodynamic setting of Permian magmatism. The mafic dikes within the Beishan area display zircons U–Pb ages of 281 ± 4 Ma. Characterized by low SiO2 (44.88–47.73 wt.%) and high Mg# values (62.2–68.6), the type 1 dikes are relatively depleted in light rare earth elements (LREEs; (La/Yb)n = 0.72–1.43) but enriched in large ion lithophile elements (LILEs). They show high positive εNd(t) values (6.6–8.5) with a range of (87Sr/86Sr)i (0.703477–0.705789) ratios. In contrast, the type 2 dikes have higher SiO2 content (47.47–51.13 wt.%) and lower Mg# (40.9–63.0). They are enriched in LREEs ((La/Yb)n = 1.79–5.02) and LILEs, and have lower εNd(t) values (3.8–7.4) with a variable range of (87Sr/86Sr)i (0.702873–0.706949) ratios. Thus, the type 1 dikes resulted from lower degrees of fractional crystallization and contamination than the type 2 dikes. Considering the LILEs and Pb enrichments, high field strength elements depletions, and high Ba/Th (86–460) ratios, the mantle source was metasomatized by subduction-related fluids. These dikes should be derived from high degrees (>20%) of partial melting of a Sr–Nd isotope-depleted, phlogopite-bearing spinel lherzolite lithospheric mantle according to their high Rb/Sr (0.04–0.24), low Ba/Rb (0.9–3.3), low La/Sm, and constant Sm/Yb ratios in addition to Sr–Nd depletion. Combined with the coeval evidence of regional geology and novel tectonic discriminate diagrams, we suggest that the mafic dikes in Beishan area formed in arc-related setting rather than intracontinental setting during the Permian. The metasomatized lithospheric mantle by subduction-related fluids were heated by upwelling asthenosphere mantle triggered by the slab roll-back, resulting in the formation of the parental magma of the mafic dikes. [ABSTRACT FROM AUTHOR]

Introduction: The stress-strain relationship of clays characterized by strain hardening exhibits varying curves under different confining pressures and dry densities. Methods: Considering the viscoelastic properties of clays, a normalized viscoelastic model of strain-hardening clay was established based on fractional derivatives, and normalization factors were proposed. Results: The experimental results showed that the stress-strain relationship of the clay was strain hardening. It shows that Chengdu clay has better normalization conditions. Furthermore, the normalized analysis of this clay through the viscoelastic normalization model revealed that the straight line of normalized data displayed a goodness-of-fit of over 0.98. The obtained values were consistent with experimental results, suggesting the reasonability of the normalized strain-hardening parameters and elastic moduli. Discussion: In addition, the superiority of the developed model was verified by testing the strain-hardening clays in Wuhan, China and Bangkok, Thailand. After analyzing the strain-hardening parameters and normalization factors of our model, it was found that the slope of the normalized line can accurately reflect the strain-hardening ability of the clay. These findings demonstrated that the proposed normalization factor is preferred for a normalized viscoelastic model. It shows that the model proposed in this paper has clearer physical meaning and advancement. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of proprietary drugs targeting KRAS-mutant tumors has historically been a formidable challenge. This difficulty stems from the high affinity of RAS proteins for GTP and the lack of a hydrophobic "pocket" conducive to drug binding. However, the emergence of CRISPR technology, a groundbreaking gene-editing tool, has revolutionized tumor studies, particularly those focusing on KRAS mutations. This article offers a review of both fundamental and translational research leveraging the CRISPR system in the context of KRAS-mutant cancer. It encapsulates recent strides made in understanding KRAS biology's mechanistic nuances, shedding light on pivotal themes such as drug resistance, anti-tumor immune responses, epigenetic regulation, and the exploitation of synthetic lethality by mutant KRAS. In conclusion, the article touches upon the current limitations of employing CRISPR technology in KRAS-related research, while also suggesting avenues for future refinement and optimization in this dynamic field. Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS. [ABSTRACT FROM AUTHOR]

Land surface emissivity (LSE) represents an essential parameter for understanding land change and surface energy balance. While numerous algorithms have been proposed to retrieve LSE, they are seldom applied to remote sensing data with high spatial resolution. The SDGSAT-1 satellite provides an opportunity to retrieve LSE with high spatial resolution that can be regarded as references for validating LSE products generated from coarse-spatial-resolution satellite data. However, no study has yet explored LSE-retrieval based on SDGSAT-1. This research seeks to fill this gap through evaluating the radiometric calibration accuracy of SDGSAT-1, using five methods to retrieve pixellevel emissivity of Guangzhou, and comparing such results with emissivity generated from other satellites (e.g. Landsat 8, ECOSTRESS, and MODIS) that transited Guangzhou during the similar period. Our results indicated that SDGSAT-1 performed well in radiometric calibration. Heterogeneous vegetation and man-made surfaces registered significant emissivity differences in varying spatial resolutions, whereas relatively homogeneous water bodies registered smaller differences. Decreasing spatial resolution amplifies the emissivity differences of the same land cover among distinctive sensors. The five emissivity-retrieval methods performed exceptionally well based on SDGSAT-1, registering average absolute differences less than 0.026 as compared with Landsat 8; with decreasing spatial resolutions, the maximum difference between SDGSAT-1 and MODIS LSE product reached 0.124. [ABSTRACT FROM AUTHOR]

Background: The inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g., biosafety level 2 (BSL-2). However, in experimental animal research facilities, following exposure to viral vectors in a BSL-2 environment, rodents may not be reclassified to BSL-1 according to standard practice, preventing access to small animal micro-computed tomography (micro-CT) scanners that are typically housed in general access areas such as BSL-1 rooms. Therefore, our goal was to adapt the protocol so that the Cre-induced KP mouse model could be handled under BSL-1 conditions during the entire procedure. Results: The Kras-Lox-STOP-Lox-G12D/p53 flox/flox (KP)-based lung adenocarcinoma mouse model was activated by intratracheal instillation of either an adenoviral-based or a gutless, adeno-associated viral-based Cre delivery system. Tumor growth was monitored over time by micro-CT. We have successfully substituted the virus-based Cre delivery system with a commercially available, gutless, adeno-associated, Cre-expressing vector that allows the KP mouse model to be handled and imaged in a BSL-1 facility. By optimizing the anesthesia protocol and switching to a microscope-guided vector instillation procedure, productivity was increased and procedure-related complications were significantly reduced. In addition, repeated micro-CT analysis of individual animals allowed us to monitor tumor growth longitudinally, dramatically reducing the number of animals required per experiment. Finally, we documented the evolution of tumor volume for different doses, which revealed that individual tumor nodules induced by low-titer AAV-Cre transductions can be monitored over time by micro-CT. Conclusion: Modifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to observe the effect of the accordion technique (AT) during the distraction phase on chondrogenesis and bone regeneration in a rat femoral distraction osteogenesis (DO) model, and investigate its potential mechanism for reducing the total treatment time of DO. Methods: Fifty-four male Sprague-Dawley (SD) rats that were specific-pathogen- free (SPF) were subjected to DO surgery on the right femur. The distraction rate was 0.5mm/day for 10 days, following a latency period of 5 days. Rats were randomly divided into Control (no AT, n = 18), Group LA (low amplitude with AT, n = 18), and Group HA (high amplitude with AT, n = 18) according to different AT protocols in the distraction phase. Rats were respectively euthanized by anesthesia overdose at 2, 4 and 6 weeks of the consolidation phase, and the femurs were harvested. Digital radiography, micro-computed tomography (micro-CT), biomechanical tests, and histomorphological analysis were used to assess the quality of regenerated bone in the distraction area. Results: Digital radiographic, micro-CT, biomechanical tests, and histological analysis revealed an increase in early-stage callus formation (p < 0.05) and improved blood supply to the callus tissue in Group LA, as compared to both the Control and Group HA. The enhanced differentiation of fibrous and cartilaginous tissue into bone tissue was also observed in Group LA, leading to improved strength and stiffness (p < 0.05) of the regenerated bone at 6 weeks of the consolidation phase. The angiogenic (hypoxia-inducible factor--1α (HIF--1α) and vascular endothelial growth factor (VEGF), p < 0.05) and osteogenic (runt- related transcription factor 2 (RUNX2), osteocalcin (OCN) and osteopontin (OPN), p < 0.05) biomarkers were higher expressed in Group LA at 2 and 4 weeks of consolidation phase, whereas decreased at 6 weeks of consolidation phase. Conclusion: The application of ATwith lowamplitude during the distraction phase can enhance chondrogenesis and bone regeneration by activating the angiogenesis factor pathway and upregulating the expression of osteogenic-related biomarkers such as HIF-1α, VEGF, RUNX2, OCN, and OPN. [ABSTRACT FROM AUTHOR]

This paper presents a two-dimensional discrete vortex method that uses the vortex growing core model to simulate the unsteady force and the wake patterns of the pure pitching airfoil efficiently and accurately. To avoid the random fluctuation caused by the random walk method, a vortex growing core method is used to simulate the viscous diffusion motion. In addition, the vortices fall off randomly on the body surface. Referring to the experimental configurations of Mackowski and Williamson (2015), a good agreement is achieved through the comparisons between the present simulation results and the experimental results, including the mean force coefficients, oscillation amplitude and wake patterns. It shows that the twodimensional discrete vortex method can be used to predict the mechanical behavior and wake patterns on the pitching airfoil motion. [ABSTRACT FROM AUTHOR]

River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health. [ABSTRACT FROM AUTHOR]

The magnetoelectric effect is technologically appealing because of its ability to manipulate magnetism using an electric field rather than magnetic field or current, thus providing a promising solution for the development of energy‐efficient spintronics. Although 180° magnetization switching is vital to spintronic devices, the achievement of 180° magnetization switching via magnetoelectric coupling is still a fundamental challenge. Herein, voltage‐driven full resistance switching of a magnetic tunnel junction (MTJ) with dipole interaction on a ferroelectric substrate through switchable parallel/antiparallel magnetization alignment is demonstrated. Parallel magnetization alignment along the y direction is obtained under a bias magnetic field. By rotating the magnetic easy axis via strain‐mediated magnetoelectric coupling, the parallel magnetizations in the MTJ reorient to the x axis with opposite paths because of dipole interaction, thus resulting in antiparallel alignment. Moreover, this voltage switching of MTJs is nonvolatile owing to variations in dipole interaction and can be well understood via phase field simulations. The results provide an avenue to realize electrical switching of MTJs and are significant for exploring energy‐efficient spintronic devices. [ABSTRACT FROM AUTHOR]

Plant-based protein products, represented by "plant meat", are gaining more and more popularity as an alternative to animal proteins. In the present review, we aimed to update the current status of research and industrial growth of plant-based protein products, including plant-based meat, plant-based eggs, plant-based dairy products, and plant-based protein emulsion foods. Moreover, the common processing technology of plant-based protein products and its principles, as well as the emerging strategies, are given equal importance. The knowledge gap between the use of plant proteins and animal proteins is also described, such as poor functional properties, insufficient texture, low protein biomass, allergens, and off-flavors, etc. Furthermore, the nutritional and health benefits of plant-based protein products are highlighted. Lately, researchers are committed to exploring novel plant protein resources and high-quality proteins with enhanced properties through the latest scientific and technological interventions, including physical, chemical, enzyme, fermentation, germination, and protein interaction technology. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Marine Science titled "Prediction and (back) tracking of marine oil spill drift and diffusion." The editorial highlights a research topic focused on advancing the understanding of marine oil spill monitoring, specifically in the areas of prediction and tracking methodologies that consider drift and diffusion dynamics. The research topic includes five papers from various academic and industrial entities across eight countries. The papers cover a range of geological backgrounds and showcase cutting-edge research in the field. The editorial also suggests that further investigation is needed in the areas of deep learning methodologies for oil spill monitoring and oil spill backtracking. Overall, the research topic provides valuable insights and potential solutions for effective ocean environmental protection. [Extracted from the article]

Subcortical vascular mild cognitive impairment (svMCI) is associated with structural and functional changes in the cerebral cortex affecting major brain networks. While recent studies have shown that the intrinsic cerebral connectivity networks can bemapped onto the cerebellum, and the cortex and cerebellumare interconnected via the cortico-basal ganglia-cerebellar circuit, structural and functional disruptions in cerebellum in svMCI are rarely studied. In this study, we conducted voxel-based morphometry analysis to investigate graymatter atrophy pattern across cerebellar regions in 40 svMCI patients, and explored alterations in functional connectivity between the basal ganglia and cerebellum. The results showed that the amount of cerebellar atrophy within the default mode, salience, and frontoparietal networks correlated with their counterpart in the cerebral cortex. Moreover, key regions of the cerebellum, including the lobule VI, VIIb, VIII, and Crus I, which are reported to have a role in cognitive function, showed both anatomical atrophy and decreased functional connectivity with the striatum. These atrophy and connectivity patterns in the cerebellum also correlated with memory performances. These findings demonstrate that there are coupled changes in cerebral and cerebellar circuits, reflecting that degeneration patterns in svMCI are not limited to the cerebral cortex but similarly extend to the cerebellum as well, and suggest the cortico-basal ganglia-cerebellar circuit may play an important role in the pathology of svMCI. [ABSTRACT FROM AUTHOR]

Background: Corn peptides, a novel food prepared from corn gluten meal (CGM) by enzymatic hydrolysis or microbial fermentation, have attracted considerable interest owing to their various bioactive properties. However, the underlying mechanism of corn peptides attenuate non-alcoholic fatty liver disease (NAFLD) remains unclear. Objective: This study aimed to investigate the effect of corn peptides in NAFLD and to decipher the underlying mechanisms. Design:NAFLD was induced by a high-fat diet (HFD) for 10 weeks. Corn peptides were administered during the period. Human hepatocellular carcinomas (HepG2) cells induced by free fatty acids were used for this mechanism study. Results: Corn peptides alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, corn peptides blocked mitophagy suppression by HFD based on the increased LC3, ATG7 expressions, as well as decreased P62 levels. Corn peptides increased the expression of proteins involved in fatty acid β-oxidation, such as PPARα and PGC-1α. Corn peptides also improved the Ser/Thr kinase PINK1 (PINK1) and the E3 ubiquitin ligase Parkin (Parkin) translocation to mitochondria, which is confirmed by immunofluorescence. Furthermore, stable knockdown of PINK1 by PINK1 SiRNA in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Conclusion: Corn peptides improved cell injury and ameliorated mitochondrial dysfunction and lipid accumulation via PINK1/Parkin-mediated autophagy in NAFLD. Thus, corn peptides could be a promising nutritional molecule with natural functions for preventing NAFLD. [ABSTRACT FROM AUTHOR]

Simple Summary: Although cancer immunotherapy has become a "game changer" in treating LUSC patients, challenges still prevail due to the heterogeneous response and insufficient predictive biomarkers. Recently, NSD3, a neighbor gene of FGFR1, was identified as a key genetic driver of LUSC tumorigenesis. While previous studies have reported the relevance of NSD3 in innate antiviral immunity, the association of NSD3 with the TIME remains an open question requiring further investigation. We first show that NSD3 gene amplification is associated with an immune-desert phenotype and correlated with a worse immunotherapy outcome. Further molecular characterizations pinpoint that the high activity of UPR signaling might be a pivotal mediator for the non-inflamed TME phenotype of NSD3-amplified LUSC. Concordantly, the pharmaco-transcriptomic correlation analysis indicated that the intervention of UPR signaling could be a promising synthetic lethality target for NSD3-amplified LUSC. Our findings reveal a previously unappreciated immunological role for NSD3 in LUSC pathobiology and provide therapeutic rationales for this daunting disease. The histone H3 lysine 36 (H3K36) methyltransferase NSD3, a neighboring gene of FGFR1, has been identified as a critical genetic driver of lung squamous cell carcinoma (LUSC). However, the molecular characteristics, especially the immunological roles of NSD3 in driving carcinogenesis, are poorly understood. In this study, we systematically integrated multi-omics data (e.g., genome, transcriptome, proteome, and TMA array) to dissect the immunological profiles in NSD3-amplified LUSC. Next, pharmaco-transcriptomic correlation analysis was implemented to identify the molecular underpinnings and therapeutic vulnerabilities in LUSC. We revealed that NSD3-amplified LUSC presents a non-inflamed tumor immune microenvironment (TIME) state in multiple independent LUSC patient cohorts. Predictably, elevated NSD3 expression was correlated with a worse immunotherapy outcome. Further molecular characterizations revealed that the high activity of unfolded protein response (UPR) signaling might be a pivotal mediator for the non-immunogenic phenotype of NSD3-amplified LUSC. Concordantly, we showed that NSD3-amplified LUSCs exhibited a more sensitive phenotype to compounds targeting UPR branches than the wild-type group. In brief, our multi-level analyses point to a previously unappreciated immunological role for NSD3 and provide therapeutic rationales for NSD3-amplified squamous lung cancer. [ABSTRACT FROM AUTHOR]

Objective: Heart failure remains a global public health problem linked to rising morbidity and mortality. RNA-binding proteins (RBPs) are crucial regulators in post-transcriptionally determining gene expression. Our study aimed to comprehensively elucidate the diagnostic utility and biological roles of RBPs in heart failure. Methods: Genomic data of human failing and nonfailing left ventricular myocardium specimens were retrieved from the GEO datasets. Heart failure-specific RBPs were screened with differential expression analyses, and RBP-based subtypes were clustered with consensus clustering approach. GSEA was implemented for comparing KEGG pathways across subtypes. RBP-based subtype-related genes were screened with WGCNA. Afterwards, characteristic genes were selected through integrating LASSO and SVM-RFE approaches. A nomogram based on characteristic genes was established and verified through calibration curve, decision curve and clinical impact curve analyses. The abundance of immune cell types was estimated with CIBERSORT approach. Results: Heart failure-specific RBPs were determined, which were remarkably linked to RNA metabolism process. Three RBP-based subtypes (namely C1, C2, C3) were established, characterized by distinct pathway activities and PANoptosis gene levels. C2 subtype presented the highest abundance of immune cells, followed by C1 and C3. Afterwards, ten characteristic genes were selected, which enabled to reliably diagnose heart failure risk. The characteristic gene-based nomogram enabled to accurately predict risk of heart failure, with the excellent clinical utility. Additionally, characteristic genes correlated to immune cell infiltration and PANoptosis genes. Conclusion: Our findings comprehensively described the roles of RBPs in heart failure. Further research is required for verifying the effectiveness of RBP-based subtypes and characteristic genes in heart failure. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with limited treatment options. One of the standard treatments for MPM is chemotherapy, which consists of concurrent treatment with pemetrexed and cisplatin. Pemetrexed limits tumor growth by inhibiting critical metabolic enzymes involved in nucleotide synthesis. Cisplatin causes direct DNA damage, such as intra-strand and inter-strand cross-links, which are repaired by the nucleotide excision repair pathway, which depends on relatively high nucleotide levels. We hypothesized that prolonged pretreatment with pemetrexed might deplete nucleotide pools, thereby sensitizing cancer cells to subsequent cisplatin treatment. The MPM cell lines ACC-MESO-1 and NCI-H28 were treated for 72 h with pemetrexed. Three treatment schedules were evaluated by initiating 24 h of cisplatin treatment at 0 h (concomitant), 24 h, and 48 h relative to pemetrexed treatment, resulting in either concomitant administration or pemetrexed pretreatment for 24 h or 48 h, respectively. Multicolor flow cytometry was performed to detect γH2AX (phosphorylation of histone H2AX), a surrogate marker for the activation of the DNA damage response pathway. DAPI staining of DNA was used to analyze cell cycle distribution. Forward and side scatter intensity was used to distinguish subpopulations based on cellular size and granularity, respectively. Our study revealed that prolonged pemetrexed pretreatment for 48 h prior to cisplatin significantly reduced long-term cell growth. Specifically, pretreatment for 48 h with pemetrexed induced a cell cycle arrest, mainly in the G2/M phase, accumulation of persistent DNA damage, and induction of a senescence phenotype. The present study demonstrates that optimizing the treatment schedule by pretreatment with pemetrexed increases the efficacy of the pemetrexed-cisplatin combination therapy in MPM. We show that the observed benefits are associated with the persistence of treatment-induced DNA damage. Our study suggests that an adjustment of the treatment schedule could improve the efficacy of the standard chemotherapy regimen for MPM and might improve patient outcomes. [ABSTRACT FROM AUTHOR]

In the context of the publication of the National Action Plan for Scientific Literacy (2021-2035) and the 14th Five-Year Plan for the Development of the Modern Science and Technology Museum System (2021-2025), and based on a review of the history and characteristics of various science popularization venues, this paper analyses the mission of those venues in advocating scientific methods, disseminating scientific ideas and promoting the scientific spirit and the scientist spirit. It discusses the requirements for science popularization venues to strengthen scientific culture. Finally, the paper provides suggestions for fulfilling the guiding role of scientific culture through promoting the modern science and technology museum system, including enhancing strategic awareness, strengthening academic research and breaking disciplinary barriers. [ABSTRACT FROM AUTHOR]

Hypoxia spontaneously forms in the interior of glioma tissues and regulates the expression of various genes. However, the status of hypoxia-driven genes in glioma tissues is not completely known. In the current study, RNA-seq data of 695 glioma tissues in The Cancer Genome Atlas (TCGA) were set as a discovery cohort and were used to identify hypoxia-driven genes and construct a novel gene signature. The prognostic values of that signature were verified in data from the TCGA and the Chinese Glioma Genome Atlas (CGGA). The expression and diagnostic values of hypoxia-driven genes were analyzed using immunohistochemistry and receiver operator characteristic curves. Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay. A total of 169 hypoxia-driven genes were identified, which were associated with a poor outcome in glioma patients. Among them, 22 genes had a degree score =10 and 6 genes (WT1, HOXA2, HOXC6, MMP9, SHOX2 and MYOD1) were selected to construct a signature to classify glioma patients into low- or high-risk groups. That signature had a remarkable prognostic value for glioma patients in TCGA and CGGA. The expression of HOXC6, MMP9, SHOX2 and MYOD1 was associated with hypoxia degree in glioma tissues and in recurrent cases, had a remarkable diagnostic value and a significant relationship with disease free survival in glioma patients. Moreover, SHOX2 was highly expressed in glioma tissues with O-6-methylguanine-DNA methyltransferase (MGMT)- unmethylation and temozolomide (TMZ) resistant glioma cell lines, and associated with MGMT expression. Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia. [ABSTRACT FROM AUTHOR]

By the batch method, the effects of contact time, pH, ionic strength, initial concentration, temperature on the sorption of Re(VII) and Se(IV) were investigated. Our results illustrated that Re(VII) and Se(IV) sorption was well described by the pseudo-second-order kinetic model, as well as by Freundlich model. This suggests chemical reaction as a rate-controlling step on the surface with 0.51 and 2.24 mg/g maximum sorption capacity at pH 7.0. The pH has little effect on Re(VII) adsorption, While it significantly affects the Se(IV) sorption. The sorption capacity of Re(VII) and Se(IV) decreased with increasing NaCl concentration. And the adsorption processes of Re(VII) and Se(IV) were endothermic spontaneous processes. What's more, our results also show that the sorption of Re(VII) and Se(IV) in clay rock will not interfere with each other under various conditions. Additionally, the adsorption capacity of Se(IV) in clay is significantly increased under acidic conditions when organic acids in the solution, but not influenced under neutral and alkaline conditions. [ABSTRACT FROM AUTHOR]

Once considered a waste product of anaerobic cellular metabolism, lactate has been identified as a critical regulator of tumorigenesis, maintenance, and progression. The putative primary function of lactate dehydrogenase B (LDHB) is to catalyze the conversion of lactate to pyruvate; however, its role in regulating metabolism during tumorigenesis is largely unknown. To determine whether LDHB plays a pivotal role in tumorigenesis, we performed 2D and 3D in vitro experiments, utilized a conventional xenograft tumor model, and developed a novel genetically engineered mouse model (GEMM) of non-small cell lung cancer (NSCLC), in which we combined an LDHB deletion allele with an inducible model of lung adenocarcinoma driven by the concomitant loss of p53 (also known as Trp53) and expression of oncogenic KRAS (G12D) (KP). Here, we show that epithelial-like, tumor-initiating NSCLC cells feature oxidative phosphorylation (OXPHOS) phenotype that is regulated by LDHB-mediated lactate metabolism. We show that silencing of LDHB induces persistent mitochondrial DNA damage, decreases mitochondrial respiratory complex activity and OXPHOS, resulting in reduced levels of mitochondria-dependent metabolites, e.g., TCA intermediates, amino acids, and nucleotides. Inhibition of LDHB dramatically reduced the survival of tumor-initiating cells and sphere formation in vitro, which can be partially restored by nucleotide supplementation. In addition, LDHB silencing reduced tumor initiation and growth of xenograft tumors. Furthermore, we report for the first time that homozygous deletion of LDHB significantly reduced lung tumorigenesis upon the concomitant loss of Tp53 and expression of oncogenic KRAS without considerably affecting the animal’s health status, thereby identifying LDHB as a potential target for NSCLC therapy. In conclusion, our study shows for the first time that LDHB is essential for the maintenance of mitochondrial metabolism, especially nucleotide metabolism, demonstrating that LDHB is crucial for the survival and proliferation of NSCLC tumor-initiating cells and tumorigenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant pleural mesothelioma (MPM) is an extremely lethal cancer, notoriously known for its limited treatment options, lack of targeted therapies, and catastrophic survival rates. MPM tumors are highly heterogeneous and exhibit substantial variance in the genome landscape among individual patients, characterized by widespread loss-of-function mutations of tumor suppressor genes (TSGs) that are difficult to target. Therefore, there is an urgent and unmet need for novel therapeutic targets and strategies for personalized treatment. Patient-derived organoids (PDOs), the next generation tumor models that have significantly influenced the discovery of anticancer drugs and biomarkers of response to therapies in many other cancers, are emerging and promise to play a critical role in understanding the biology of MPM and, importantly, in identifying and developing precision oncology approaches tailored to specific subsets of MPM patients. MPM is an aggressive tumor originating from pleural mesothelial cells. A characteristic feature of the disease is the dominant prevalence of therapeutically intractable inactivating alterations in TSGs, making MPM one of the most difficult cancers to treat and the epitome of a cancer characterized by a significant lack of therapy options and an extremely poor prognosis (5-year survival rate of only 5% to 10%). Extensive interpatient heterogeneity poses another major challenge for targeted therapy of MPM, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for the discovery of new therapies and the development of personalized medicine. Organoids, an in vitro 'organ-like' 3D structure derived from patient tumor tissue that faithfully mimics the biology and complex architecture of cancer and largely overcomes the limitations of other existing models, are the next-generation tumor model. Although organoids have been successfully produced and used in many cancers, the development of MPM organoids is still in its infancy. Here, we provide an overview of recent advances in cancer organoids, focusing on the progress and challenges in MPM organoid development. We also elaborate the potential of MPM organoids for understanding MPM pathobiology, discovering new therapeutic targets, and developing personalized treatments for MPM patients. [ABSTRACT FROM AUTHOR]

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson’s disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG. [ABSTRACT FROM AUTHOR]

Hand motion sensing-based interaction, abbreviated as 'free-hand interaction', provides a natural and intuitive method for touch-less interaction on a large display. But due to inherent usability deficiencies of the unconventional size of the large display and the kinematic limitations of the user's arm joint movement, a large display-based free-hand interaction is suspected to have different performance across the whole areas of the large display. To verify this, a multi-directional target pointing and selection experiment was designed and conducted based on the ISO 9241-9 evaluation criteria. Results show that (1) free-hand interaction in display areas close to the center of the body had a higher accuracy than that in peripheral-body areas; (2) free-hand interaction was asymmetric at the left side and the right side of the body. More specifically, left-hand interaction in the left-sided display area was more efficient and accurate than in the right-sided display area. For the right-hand interaction, the result was converse; moreover, (3) the dominant hand generated a higher interaction accuracy than the non-dominant hand. Lessons and strategies are discussed for designing user-friendly natural user interfaces in large displays-based interactive applications. [ABSTRACT FROM AUTHOR]

The mechanism of the conversion of propane and carbon dioxide to propylene and formic acid on the M4--B24N28 (M = V, Cr, Ni, Cu) surface was studied based on density functional theory (DFT). Through the preliminary calculation of propane oxidation, it was found that Cu4--B24N28 has relatively good catalytic activity. After that, all possible paths for the oxidation reaction of propane and carbon dioxide on the surface of Cu4--B24N28 were calculated in detail. The calculation results showed that the optimal path is the dehydrogenation of the secondary carbon of propane combined with the carbon atoms of carbon dioxide to form a HCO2 intermediate, and then the secondary carbon continues to dehydrogenate to combine with the HCO2 intermediate to form a C3H6 intermediate and formic acid. After that the hydrogen atom of the primary carbon of the C3H6 intermediate is rearranged to the secondary carbon to produce propylene (CH3CH2CH3 + CO2 → CH3CHCH3 + OCHO → CH3CCH3 + HCOOH → CH2CHCH3 + HCOOH), the rate control step of the reaction process is the rearrangement of the hydrogen atom of the C3H6 intermediate, and then formic acid and propylene are desorbed with desorption energies of -0.23 eV and -0.50 eV respectively, and can be further recycled. In summary, Cu4--B24N28 can be used as an effective catalyst for the oxidation of propane by carbon dioxide, which can maintain the catalytic activity and take into account the catalytic stability without generating carbon deposits. [ABSTRACT FROM AUTHOR]

Quick charge/discharge polymer‐based composites filled with inorganic nanosheets have attracted extensive attention and provided a more efficient way to achieve high energy storage density (U) because of the alleviated agglomeration of fillers and the formation of conduction barriers. However, conductive paths have a chance to extend along out‐of‐plane directions by circumventing the micrometer‐sized nanosheets. Here, large‐sized (111)‐oriented BaTiO3 (BTO) films with outstanding epitaxiality and ferroelectricity are embedded in poly(vinylidene fluoride) (PVDF) using optimal transfer and hot‐pressing processes. The 2D–2D (2–2) type BTO/PVDF composites interlayered by 2‐layer BTO (about 0.2 µm thick of each layer) exhibit the highest U of 20.7 J cm‐3 at 690 MV m‐1, which is 222.6% that of pure PVDF. Phase‐field simulations reveal that high‐resistance PVDF films as outer layers can prevent the charges injection from electrodes and high‐dielectric BTO films as inner layers can effectively suppress the mobile charges across interfaces between layers, leading to a remarkable improvement of breakdown strength. This work puts forward a scalable approach to enhance the U of inorganic/organic composites for advanced energy storage materials and applications. [ABSTRACT FROM AUTHOR]

Reducing the switching energy of ferroelectric thin films remains an important goal in the pursuit of ultralow-power ferroelectric memory and logic devices. Here, we elucidate the fundamental role of lattice dynamics in ferroelectric switching by studying both freestanding bismuth ferrite (BiFeO3) membranes and films clamped to a substrate. We observe a distinct evolution of the ferroelectric domain pattern, from striped, 71° ferroelastic domains (spacing of ~100 nm) in clamped BiFeO3 films, to large (10's of micrometers) 180° domains in freestanding films. By removing the constraints imposed by mechanical clamping from the substrate, we can realize a ~40% reduction of the switching voltage and a consequent ~60% improvement in the switching speed. Our findings highlight the importance of a dynamic clamping process occurring during switching, which impacts strain, ferroelectric, and ferrodistortive order parameters and plays a critical role in setting the energetics and dynamics of ferroelectric switching. Reducing the switching energy of ferroelectric films remains an important goal. Here, the authors elucidate the fundamental role of lattice dynamics in ferroelectric switching on both freestanding BiFeO3 membranes and films clamped to a substrate. [ABSTRACT FROM AUTHOR]

Background: Oncogenic KRAS mutations are prevalent in human cancers, but effective treatment of KRAS-mutant malignancies remains a major challenge in the clinic. Increasing evidence suggests that aberrant metabolism plays a central role in KRAS-driven oncogenic transformation. The aim of this study is to identify selective metabolic dependency induced by mutant KRAS and to exploit it for the treatment of the disease. Method: We performed an integrated analysis of RNAi- and CRISPR-based functional genomic datasets (n = 5) to identify novel genes selectively required for KRAS-mutant cancer. We further screened a customized library of chemical inhibitors for candidates that are synthetic lethal with NOP56 depletion. Functional studies were carried out by genetic knockdown using siRNAs and shRNAs, knockout using CRISPR/Cas9, and/or pharmacological inhibition, followed by cell viability and apoptotic assays. Protein expression was determined by Western blot. Metabolic ROS was measured by flow cytometry-based quantification. Results: We demonstrated that nucleolar protein 5A (NOP56), a core component of small nucleolar ribonucleoprotein complexes (snoRNPs) with an essential role in ribosome biogenesis, confers a metabolic dependency by regulating ROS homeostasis in KRAS-mutant lung cancer cells and that NOP56 depletion causes synthetic lethal susceptibility to inhibition of mTOR. Mechanistically, cancer cells with reduced NOP56 are subjected to higher levels of ROS and rely on mTOR signaling to balance oxidative stress and survive. We also discovered that IRE1α-mediated unfolded protein response (UPR) regulates this process by activating mTOR through p38 MAPK. Consequently, co-targeting of NOP56 and mTOR profoundly enhances KRAS-mutant tumor cell death in vitro and in vivo. Conclusions: Our findings reveal a previously unrecognized mechanism in which NOP56 and mTOR cooperate to play a homeostatic role in the response to oxidative stress and suggest a new rationale for the treatment of KRAS-mutant cancers. [ABSTRACT FROM AUTHOR]

Youth-onset non-small cell lung cancer (NSCLC) is a heterogeneous disease. It has a unique clinicopathology and special genetic background. In this study, three key genes, CDC20, CCNB2, and BUB1, have been identified in youth-onset NSCLC tumor tissues based on the TCGA and GEO cohorts. Functional enrichment analysis reveals that the “oocyte meiosis,” “cell cycle,” and the “P53 signaling pathway” are significantly enriched. Additionally, four survival genes, including AKAP12, CRIM1, FEN1, and SLC7A11, that affect the prognosis of youth-onset NSCLC patients are identified in this study. Finally, we construct a risk model to predict the overall survival of youth-onset NSCLC patients, the AUC of the risk model in 1, 3, and 5 years of overall survival is 0.808, 0.844, and 0.728. This study aims to provide a novel idea to explore the pathogenic genes of youthonset NSCLC. [ABSTRACT FROM AUTHOR]

Micro-arc oxidation (MAO) coating was prepared on the surface of TC4 titanium alloy and sealed with (polytetrafluoroethylene [PTFE] + graphite) emulsion to obtain MAO/(PTFE + graphite) composite coating. The surface morphology and phase composition of the MAO coating were studied by scanning electron microscope (SEM) and X-ray diffractometer (XRD). The corrosion resistance of the coating was studied by the potentiodynamic polarization curve and the scanning Kelvin probe (SKP) micro-area voltage. The results show that the TiO2 ceramic oxide coating formed on the surface of the titanium alloy substrate has the characteristics of porous structure, which will become a channel for corrosive media to enter the coating and accelerate the corrosion of the MAO coating. However, the MAO/(PTFE + graphite) composite coating can prevent corrosive media from entering the coating and improve the corrosion resistance of the composite coating. The corrosion potential increased from 0.146 V to 0.241 V, the corrosion current density decreased from 4.31 x 10-7 A/cm² to 7.92 x 10-8 A/cm², and the self-corrosion current dropped to one fifth of the MAO coating. In addition, the charge transfer resistance has also increased from 5.305 x 104Ω⋅cm² to 2.493 x 105Ω⋅cm². [ABSTRACT FROM AUTHOR]

To refine microarc oxidation (MAO) coating surface micropores, and enhance the coating's toughness and oxidation resistance. In the process of MAO, negatively charged CeO2 particles are adsorbed and deposited into the coating under the action of electrophoresis, and a 6 g/L CeO2 doped MAO coating is prepared. Then, the Al2O3-SiO2 composite sol-gel seal coating was used to obtain the microarc oxidation-sol-gel composite coating (MAO-SG). The TC4 substrate, undoped MAO coating, CeO2 doped MAO coating, and MAO-SG composite coating were subjected to high-temperature oxidation at 650, 750, and 850°C, respectively. The results show that the composite coating exhibits excellent high-temperature oxidation resistance at three temperatures. Compared with the undoped MAO coating, the maximum oxidation weight gain per unit area of the MAO-SG coating was reduced by 13.44%, 23.87%, and 38.16%, and the average oxidation rate was reduced by 17.15%, 50.98%, and 69.37%, respectively. The sol-gel layer on the surface of the composite coating will decompose α-Al2O3 at high temperatures, and form a dense protective layer on the surface of the MAO coating and protect the MAO coating, which greatly improves the high-temperature oxidation resistance of the TC4 titanium alloy. [ABSTRACT FROM AUTHOR]

Polar vortex domains have recently become an emergent research field due to the abundant physical phenomena and potential applications in high-density memories. Here, we explore the mechanisms of creating polar vortex domains in the BiFeO3 (BFO) membranes subjected to different boundary conditions using phase-field simulations. A major difference is that the vortex in membrane can be stabilized even under short-circuit electrical boundary conditions compared to vortex in other systems, such as thin film or superlattice. We found that (a) the formation of polar vortex domains at the membrane interior under bending is mainly driven by the reduction of elastic energy under short-circuit boundary condition, and the vortex chirality (namely, clockwise and counterclockwise) could be identified by n-shape and u-shape bending; (b) in the unbent open-circuit BFO membrane case, exotic trapezoid-shaped vortex nanodomains form at the terminations of 109° domain walls (DWs) and partially charged 71° DWs, which is driven by the local depolarization field and the interplay among electrostatic, elastic, and gradient and Landau energies. We also examine Kittel's law by establishing the dependence of vortex periods on the membrane thickness. These results give further understanding of the effect of boundary conditions on the formation of polar vortex domains, guiding experimental designs of vortex-based high-density memories. [ABSTRACT FROM AUTHOR]

In order to achieve the double carbon goal of energy saving and carbon reduction in steel plant, the ladder self-sealing waste heat recovery technology was used to transform the waste heat power generation system of 280 sintering ring cooler in Lianyuan Iron and Steel Group Co., Ltd. The results show that the waste heat utilization efficiency of the reformed sintering ring cooler is significantly improved, and the dally average power generation per ton of ore and the maximum output of the waste heat power station have broken through a record high. CFD computational fluid dynamics software Fluent 6. 3 is used to simulate the gas flow field, temperature field, pressure distribution and blue gas flow distribution in the hood before and after the transformation. The results show that after the transformation, the cold air infiltration area of the blue gas flow field in "the waste heat recovery hood is significantly reduced, the temperature distribution is more uniform, the temperature drop gradient is belter, and the pressure distribution is more uniform than before the transformation. The actual measurement results of the temperature and medium pressure steam in the hood before and after the transformation show that the average temperature and average medium pressure steam output in the hood after the transformation are higher, and the pressure distribution of the flue gas in the hood is more uniform. The technical transformation of the waste heat recovery system of the sintering ring cooler by using the ladder self-sealing waste heat recovery technology can improve the waste heat recovery efficiency of the system and increase the power generation of the waste heat power station, which is conducive to the achievement of the double carbon goal of the steel plant. [ABSTRACT FROM AUTHOR]

The shape-dependent performance of metal co-catalysts in photocatalysis has been one of the research focal points in recent years. In this study, PtPd/C3N4 hybrid structures were constructed to reveal the effect of the shape of the PtPd bimetallic co-catalyst on the performance of photocatalytic hydrogen generation. PtPd nanocubes (NCs) and nanotetrahedrons (NTs) were sequentially deposited in situ on the surface of C3N4 nanosheets, establishing a strong contact interface to ensure the smooth transfer of photoinduced electrons. Ultraviolet–visible (UV–Vis) diffuse reflectance spectroscopy and photoelectrochemical experiments revealed that the PtPd NCs/C3N4 photocatalyst had comparable light absorption ability and equivalent carrier separation and transfer efficiency in comparison with the PtPd NTs/C3N4 photocatalyst, which excluded the influence of these factors on shape-dependent performance. The photocatalytic hydrogen generation results indicate that the hydrogen generation rate of the PtPd NCs/C3N4 photocatalyst is 1.33 times higher than that of the PtPd NTs/C3N4 photocatalyst, demonstrating that the cubic PtPd bimetallic co-catalyst is more conducive to hydrogen generation compared to the tetrahedral PtPd bimetallic co-catalyst. [ABSTRACT FROM AUTHOR]

KRAS oncoprotein is commonly mutated in human cancer, but effective therapies specifically targeting KRAS‐driven tumors remain elusive. Here, we show that combined treatment with fibroblast growth factor receptor 1 (FGFR1) and polo‐like kinase 1 (PLK1) inhibitors evoke synergistic cytotoxicity in KRAS‐mutant tumor models in vitro and in vivo. Pharmacological and genetic suppression of FGFR1 and PLK1 synergizes to enhance anti‐proliferative effects and cell death in KRAS‐mutant lung and pancreatic but not colon nor KRAS wild‐type cancer cells. Mechanistically, co‐targeting FGFR1 and PLK1 upregulates reactive oxygen species (ROS), leading to oxidative stress‐activated c‐Jun N‐terminal kinase (JNK)/p38 pathway and E2F1‐induced apoptosis. We further delineate that autophagy protects from PLK1/FGFR1 inhibitor cytotoxicity and that antagonizing the compensation mechanism by clinically approved chloroquine fully realizes the therapeutic potential of PLK1 and FGFR1 targeting therapy, producing potent and durable responses in KRAS‐mutant patient‐derived xenografts and a genetically engineered mouse model of Kras‐induced lung adenocarcinoma. These results suggest a previously unappreciated role for FGFR1 and PLK1 in the surveillance of metabolic stress and demonstrate a synergistic drug combination for treating KRAS‐mutant cancer. SYNOPSIS: Human cancers driven by oncogenic KRAS mutations are common and among the most difficult‐to‐treat tumors. This study reports a synergistic drug combination by targeting FGFR1 and PLK1 and identifies autophagy as a protective mechanism that limits the efficacy of FGFR1/PLK1 inhibitor therapy in KRAS‐mutant lung cancer, suggesting a novel strategy to treat the daunting disease. FGFR‐ and PLK1‐targeted agents synergize in inhibiting KRAS‐mutant lung and pancreatic cancer cells.FGFR/PLK1 inhibitor therapy targets a metabolic liability by abrogating ROS homeostasis in KRAS‐mutant cancer cells.Autophagy protects against FGFR/PLK1 inhibitor‐induced cytotoxicity.Combined inhibition of FGFR, PLK1, and autophagy shows potent anti‐tumor efficacy in mouse models of KRAS‐mutant lung cancer. [ABSTRACT FROM AUTHOR]

In this paper, carbon nanotubes (CNTs) reinforced Ti–12.8Mo–2.1Nb–2.7Al–0.2Si (TB8) matrix composites were synthesized by low-energy ball milling and cold pressing sintering. Based on theoretical calculation and thermodynamic simulation method to obtain phase transition points, CNTs/TB8 composites were subjected to a solid-solution and aging treatment. The effect of heat treatment and CNTs content on microstructure and mechanical properties of the composites was investigated. The results indicated that 0.5 wt% CNTs/TB8 composite formed α + β phase structure after different heat treatment processes, α phase dispersed in the β phase, grain refinement was distinct, and the microhardness of composite was significantly improved. It had the effect of solution strengthening and dispersion strengthening. The composites’ microhardness was the highest, reaching 615.3HV after 850 °C/3 h/AC and 550 °C/6 h/AC heat treatment. Under these conditions, with the CNTs content increasing, the microhardness of composite increased initially and then decreased. The microhardness of the composite containing 1.0 wt% CNTs reached 635.1HV, which was an increase of 21.9% compared to without executing heat treatment. In addition, the compression property of the titanium matrix composite at room temperature was excellent; the compressive strength and the fracture strain were 1263 MPa and 18.5%, respectively. [ABSTRACT FROM AUTHOR]

Background: The leucocyte esterase (LE) strip test often is used to diagnose periprosthetic joint infection (PJI). In accordance with the manufacturer's directions, the LE strip test result is read 3 minutes after exposing it to joint fluid, but this has not been supported by robust research. Moreover, we have noted that the results of the LE strip test might change over time, and our previous studies have found that centrifugation causes the results of the LE strip test to degrade. Still, there is no evidence-based recommendation as to when to read the LE strip test to maximize diagnostic accuracy, in general, and the best reading times for the LE strip test before and after centrifugation need to be determined separately, in particular.Questions/purposes: (1) What is the optimal timing for reading LE strip test results before centrifugation to diagnose PJI? (2) What is the optimal timing for reading LE strip test results after centrifugation to diagnose PJI?Methods: This study was a prospective diagnostic trial. In all, 120 patients who were scheduled for revision arthroplasty and had signs of infection underwent joint aspiration in the outpatient operating room between July 2018 and July 2019 and were enrolled in this single-center study. For inclusion, patients must have had a diagnosis of PJI or nonPJI, valid synovial fluid samples, and must not have received antibiotics within 2 weeks before arthrocentesis. As such, 36 patients were excluded; 84 patients were included for analysis, and all 84 patients agreed to participate. The 2018 International Consensus Meeting Criteria (ICM 2018) was used for the classification of 49 patients with PJI (score ≥ 6) and 35 without PJI (score ≤ 2). The classification was used as the standard against which the different timings for reading LE strips were compared. All patients without PJI were followed for more than 1 year, during which they did not report the occurrence of PJI. All patients were graded against the diagnostic criteria regardless of their LE strip test results. In 83 patients, one drop of synovial fluid (50 μL) was applied to LE strips before and after centrifugation, and in one patient (without PJI), the sample was not centrifuged because the sample volume was less than 1.5 mL. The results of the strip test were read on an automated colorimeter. Starting from 1 minute after centrifugation, these strips were automatically read once every minute, 15 times (over a period of 16 minutes), and the results were independently recorded by two observers. Results were rated as negative, ±, 1+, and 2+ upon the machine reading. Grade 2+ (dark purple) was used as the threshold for a positive result. An investigator who was blinded to the study performed the statistics. Optimal timing for reading the LE strip before and after centrifugation was determined by using receiver operative characteristic (ROC) analysis. The specificity, sensitivity, and positive predictive and negative predictive values were calculated for key timepoints.Results: Before centrifugation, the area under the curve was the highest when the results were read at 5 minutes (0.90 [95% CI 0.83 to 0.98]; sensitivity 0.88 [95% CI 0.75 to 0.95]; specificity 0.89 [95% CI 0.72 to 0.96]). After centrifugation, the area under the curve was the highest when the results were read at 10 minutes (0.92 [95% CI 0.86 to 0.98]; sensitivity 0.65 [95% CI 0.50 to 0.78]; specificity 0.97 [95% CI 0.83 to 1.00]).Conclusion: The LE strip test results are affected by time and centrifugation. For samples without centrifugation, we found that 5 minutes after application was the best time to read LE strips. We cannot deny the use of centrifuges because this is an effective way to solve the sample-mingling problem at present. We recommend 10 minutes postapplication as the most appropriate time to read LE strips after centrifugation. Multicenter and large-sample size studies are warranted to further verify our conclusion.Level Of Evidence: Level II, diagnostic study. [ABSTRACT FROM AUTHOR]