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[Objective] Tread defects are a primary manifestation of wheel failures in high-speed railway EMU (electrical multiple unites) trains, significantly impacting both EMU train operation safety and passenger ride comfort. Wheel tread defects are predominantly concentrated on front and rear cars, which may result from a combination of various factors, requiring predictive method that comprehensively integrate various influencing factors. [Method] Based on the wheel reprofiling maintenance data of EMU train operated by a railway bureau, the dataset sample consists of 10 features (including 4 nominal and 6 continuous features) and the data are preprocessed. By treating the imbalanced dataset through synthetic minority over-sampling technique (SMOTE), a standardized dataset is constructed. A DNN (deep neural network) model is established to combine the underlying features and form a high-level abstract representation of the features. The optimal learning performance of the model is achieved through network structure adjustment and hyperparameter optimization. The model is trained and tested to verify its prediction effect. [Result & Conclusion] The data-driven prediction method for wheel tread defects of front and rear cars demonstrates high-predictive accuracy and relatively excellent comprehensive performance, achieving a precision rate of 92.5%. Thus the probability of wheel tread damage of front and rear cars can be effectively predicted. [ABSTRACT FROM AUTHOR]

Pure electric vehicles (PEVs) lack engine noise; thus, the overall noise level within vehicle cabins are reduced. However, due to the absence of engine noise, previously overlooked noise sources are accentuated and detrimentally affect interior noise quality. Road noise is a predominant PEV noise source and significantly contributes to middle- and low-frequency interior noise levels. A novel approach combining data-driven methodologies and uncertainty analysis to predict and optimize vehicle road noise is proposed. To predict the frequency-domain characteristics of road noise, a refined attention mechanism based on the transformer model with a locality-sensitive hashing algorithm is introduced to enhance efficiency and ensure high accuracy. An interval vector optimization method using interval representations of parameter uncertainty is devised to strengthen the robustness and efficacy of the road noise optimization results. The proposed method is validated through a PEV road test, and the optimized noise conditions demonstrates an improvement exceeding 2 dB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Two-point contact is one of the fundamental problems of wheel-rail contact in switch area. The contact state and the distribution of forces are complex and essential points in wheel-rail relationship. Given the problem that the current dynamic wheel-rail contact state is challenging to detect, a theory to detect the two-point contact state of the wheel-rail in switch area using a discrete gauge column was presented and proved in the finite element model. This paper derived the relationship between strain gauge position and stress using a modified rail model. The patch scheme was determined using the rail waist bending moment difference method to achieve decoupling of the bridge circuit of the force measurement columns. The bridge circuit was calibrated by means of the modified theoretical calibration method, and the circuit test data was obtained for the two-point contact condition in the switch area. The study compared the results obtained from the wheel-rail column finite model and circuit test data for two-point contact conditions, demonstrated the method's ability to identify the two-point contact state and the wheel-rail force distribution characteristics in the switch area. The results show that the method can identify the two-point contact state in switch area and distribute characteristics of the wheel-rail force. And the wheel-rail contact point position can be deduced accurately according to the wheel-rail force. This test method provides a test verification scheme for wheel-rail two-point rolling contact theory and a new technology for the dynamic force testing of wheel-rail in switch area., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Autoimmune hepatitis (AIH) is an autoimmune disease accompanied by an autoimmune inflammatory response that often leads to severe liver damage. In addition, it may further lead to complications such as liver fibrosis, cirrhosis and liver failure. Dihydromyricetin (DHM) possesses various pharmacological properties, such as being anti-inflammatory, antioxidant, and antibacterial. In this experiment, we investigated the effect of DHM on autoimmune hepatitis mice based on the level of M1/M2 type macrophages., Methods: An autoimmune hepatitis mouse model was established by the administration of DHM followed by tail vein injection of Concanavalin A (Con A). Liver tissues were examined for pathological and morphological changes. Interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-4 (IL-4) levels in liver tissues were assessed. Serum hepatic function indexes were measured, including alanine aminotransferase (ALT), aspartate transaminase (AST), and lactatedehydrogenase (LDH). Oxidative stress indexes, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Nitric oxide (NO), were quantified. Additionally, tumor necrosis factor-α ( TNF-α ) and nuclear factor kappa-B ( NF-κB ) p65 mRNA and protein expression polarization were determined. The presence of M1/M2-type macrophages was also investigated., Results: Compared to the model group, mice in the DHM group exhibited a significant reduction in serum hepatic function indexes ( p < 0.05). Liver tissues from the DHM group showed a noteworthy decrease in MDA and NO levels, along with a significant increase in SOD and GSH-Px levels ( p < 0.05). Furthermore, in the liver tissues of mice from the DHM group, there was a notable reduction in the count of M1-type macrophages and a considerable elevation in the M2-type macrophages ( p < 0.05). IL-1β and IL-6 expression levels exhibited a significant decrease, whereas IL-10 and IL-4 levels displayed a significant increase ( p < 0.05). Additionally, both TNF-α and NF-κB p65 mRNA levels and protein expression experienced a noteworthy decrease ( p < 0.05)., Conclusion: DHM mitigates the inflammatory response in AIH mice by reducing oxidative stress and modulating macrophage polarization and the TNF-α/NF-κB pathway.

Effective pathogen inactivation is highly desired in public health but limited by existing methods each capable of assessing pathogen inactivation effectiveness (PIE) only in a specific condition. We therefore developed a novel method maxPIE designed to identify maximal PIEs across inactivation conditions by leveraging the power of massive array technologies. maxPIE implements a three-step algorithm to quickly identify maximal PIEs of inactivation treatments: (1) dilute pathogens into different initial titers each stored in an array well, (2) submit one sorted array to one treatment, (3) scan the treated array to find the maximum. maxPIE outperformed the conventional methods in (a) inactivating S. aureus using ultraviolet light of different wavelengths with different durations; (b) antibiotic treatment of S. aureus, E. coli, and multidrug-resistant E. coli; (c) inactivating S. aureus in plasma using ultraviolet light in different wavelengths with and without riboflavin. maxPIE was easy to understand and interpret and was robust in situations where conventional PIE methods would suffer. Hence, maxPIE can serve as an innovative and high throughput approach that can be widely used to enhance pathogen inactivation practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alloy-type materials are attractive for anodes in sodium-ion batteries (SIBs) owing to their high theoretical capacities and overall performance. However, the accumulation of stress/strain during repeated cycling results in electrode pulverization, leading to rapid capacity decay and eventual disintegration, thus hindering their practical applications. Herein, we report a 3D coral-like Sb-Cu alloy nanoarray with gradient distribution of both elements. The array features a Sb-rich bottom and a Cu-rich top with increasing Sb and decreasing Cu concentrations from top to bottom. The former is the active component that provides the high capacity, whereas the latter serves as an inert additive that acts against volume variation. The gradual transition in composition within the electrode introduces a ladder-type volume expansion effect, facilitating a smooth distribution and effective release of stress, thereby ensuring the wanted mechanical stability and structural integrity. The as-developed nanoarray affords a high reversible capacity (460 mAh g -1 at 0.5 C), stable cycling (89 % retention over 120 cycles at 1.0 C), and superior rate capability (354 mAh g -1 at 10 C). The concentration dual-gradient strategy paves a new pathway of designing alloy-type materials for SIBs., (© 2024 Wiley-VCH GmbH.)

Cardiovascular diseases (CVD) are the leading global threat to human health. The clinical application of vascular stents improved the survival rates and quality of life for patients with cardiovascular diseases. However, despite the benefits stents bring to patients, there are still notable complications such as thrombosis and in-stent restenosis (ISR). Surface modification techniques represent an effective strategy to enhance the clinical efficacy of vascular stents and reduce complications. This paper reviews the development strategies of vascular stents based on surface functional coating technologies aimed at addressing the limitations in clinical application, including the inhibition of intimal hyperplasia, promotion of re-endothelialization. These strategies have improved endothelial repair and inhibited vascular remodeling, thereby promoting vascular healing post-stent implantation. However, the pathological microenvironment of target vessels and the lipid plaques are key pathological factors in the development of atherosclerosis (AS) and impaired vascular repair after percutaneous coronary intervention (PCI). Therefore, restoring normal physiological environment and removing the plaques are also treatment focuses after PCI for promoting vascular repair. Unfortunately, research in this area is limited. This paper reviews the advancements in vascular stents based on surface engineering technologies over the past decade, providing guidance for the development of stents., Competing Interests: Prof. Zhilu Yang is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

The weak interlayer interaction and strong intralayer bonding in Van der Waals (vdW) layered materials give rise to ultralow friction at incommensurate contact interfaces, a phenomenon known as structural superlubricity. This phenomenon is complicated by the interplay between atomic degrees of freedom, twist angle, and normal force. In this Letter, we exploit naturally occurring cracks in vdW crystals and microfabrication techniques to qualitatively separate the contributions of edge, complete moiré tile, and incomplete moiré rim regions. It is observed that friction from the incomplete moiré rim region, scaling linearly with the rim area, plays a dominant role in determining the twist angle dependence of friction. Interestingly, despite lower friction contributions from complete moirés, friction from a complete moiré tile is independent of moiré size; consequently, friction from the moiré tile scales linearly with the total number of moirés. By integrating the contributions from edge, moiré tile, and incomplete moiré rim, a friction law for vdW heterojunctions is proposed. Finally, friction changes from positively to negatively correlating with normal force, contingent on the suppression of moiré ridge and the dissipation from edge atoms.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

In this paper, the electronic properties and transport characteristics of WSiGeN 4 /graphene heterostructures were explored by combining the quantum transport method with first-principle calculations. The band structures indicate that the heterostructures can form either p-type or n-type Schottky contacts, depending on the stacking mode. Due to the self-formed asymmetric Schottky contacts, we design an asymmetric van der Waals (vdW) metal-semiconductor-metal (MSM) structure, which exhibits a pronounced asymmetric current-voltage ( I - V ) curve. The corresponding physical mechanisms are attributed to carrier transport mechanisms, which are primarily governed by thermionic excitation at positive bias voltages and tunneling effects at negative bias voltages. Our study offers a viable strategy for integrating asymmetric Schottky barriers into MSM configurations, laying the groundwork for a wider range of applications in a range of Janus two-dimensional semiconductors.

Beta-cypermethrin (β-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of β-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17β-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of β-CYP and its specific isomers. Our results showed that β-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 μM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and β-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 μM 1R-trans-αS. Scratch assays revealed that β-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor β (ERβ), β-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of β-CYP, its isomers, and E2 for PDE3A than for ERα or ERβ. Consequently, β-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This survey aims to comprehensively understand occupational burnout among pre-hospital emergency medical personnel and explore associated risk factors., Methods: A cross-sectional online survey using a census method was conducted between 15 July, 2023, and ends on 14 August, 2023, in Chengdu, SiChuan province, China. The questionnaire included general demographic information, the Maslach Burnout Inventory-General Survey (MBI-GS) with 15 items, and the Fatigue Scale-14 (FS-14) with 14 items. Univariate analysis was conducted on all variables, followed by multivariate logistic regression models to examine the associations between occupational burnout and the risk factors., Results: A total of 2,299 participants,99.57% completed the survey effectively The participants were from 166 medical institutions in Chengdu, comprising 1,420 nurses (61.50%) and 889 clinical doctors (38.50%). A total of 33.36% participants experienced burnout, predominantly mild (30.27%), followed by moderate (2.78%) and severe (0.3%). Physicians, higher fatigue scores, age, work experience appeared to be related to burnout. Logistic regression models revealed that individuals aged over 50 were less prone to experience burnout compared to medical staff aged 18-30 (OR: 0.269, 95% CI: 0.115-0.627, p = 0.002). Physicians were more prone to experience burnout compared to nursing staff (OR: 0.690, 95% CI: 0.531-0.898, p = 0.006). Those with 0-5 years of experience were more prone to experience burnout compared to those with 6-10 years or over 15 years of experience (OR: 0.734, 95% CI: 0.547-0.986, p = 0.040; OR: 0.559, 95% CI: 0.339-0.924, p = 0.023). Additionally, for each 1-point increase in the fatigue score, the likelihood of burnout in medical staff increased by 1.367 times (OR: 1.367, 95% CI: 1.323-1.412, p < 0.0001)., Conclusion: Pre-hospital emergency medical personnel demonstrate a notable prevalence of mild job burnout. These results provide a groundwork for future focus on the various stages of job burnout within pre-hospital emergency staff, alerting hospital and departmental managers to promptly address the mental well-being of their personnel and intervene as needed., (© 2024. The Author(s).)

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15  PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Karstification plays a crucial role in forming magnificent scenery, and storing oil, natural gas, mineral resources, and water. Through the inspiration of karstification, a hierarchical layered double hydroxide (LDH) with funnel-like and cave-like structures (called Karst-LDH) is formed by the dissolution of acrylic acid/water solution. Meanwhile, the results of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) show that Karst-LDH has complicated and interconnected internal pipe networks. The actual maximum phosphate adsorption capacity of Karst-LDH reaches 126.38 mg g -1 due to the unique structures, protonation, ligand exchange, ion exchange, and hydrogen bonding, which is over ten times that of general LDH with a regular hexagonal structure. The results of isotherms and thermodynamics also indicate that Karst-LDH conforms to more heterogeneous and multilayer adsorption with a higher entropy-driven process. Karst-LDH exhibits good selectivity for chloride and nitrate ions. The change in the frontier orbital interaction between phosphate and different LDHs is a significant reason for quick macropore transmission, mesopore interception, and finally, phosphate storage in Karst-LDH. This work provides an efficient way for the design and fabrication of high adsorption performance materials with unique karst-type structures, which can be used for multiple fields potentially.

Background: In recent years, accelerated transcranial magnetic stimulation (aTMS) has been developed, which has a shortened treatment period. The aim of this study was to evaluate the efficacy and long-term maintenance effects of aTMS in patients with major depressive disorder (MDD)., Methods: We systematically searched online databases for aTMS studies in patients with MDD published before February 2023 and performed a meta-analysis on the extracted data., Results: Four randomized controlled trials (RCTs) and 10 before-and-after controlled studies were included. The findings showed that depression scores significantly decreased following the intervention (SMD = 1.80, 95% CI (1.31, 2.30), p < 0.00001). There was no significant difference in antidepressant effectiveness between aTMS and standard TMS (SMD = -0.67, 95% CI (-1.62, 0.27), p = 0.16). Depression scores at follow-up were lower than those directly after the intervention based on the depression rating scale (SMD = 0.22, 95% CI (0.06, 0.37), p = 0.006), suggesting a potential long-term maintenance effect of aTMS. Subgroup meta-analysis results indicated that different modes of aTMS may have diverse long-term effects. At the end of treatment with the accelerated repetitive transcranial magnetic stimulation (arTMS) mode, depressive symptoms may continue to improve (SMD = 0.29, 95% CI (0.10, 0.49), I 2  = 22%, p = 0.003), while the accelerated intermittent theta burst stimulation (aiTBS) mode only maintains posttreatment effects (SMD = 0.01, 95% CI (-0.45, 0.47), I 2  = 66%, p = 0.98)., Conclusions: Compared with standard TMS, aTMS can rapidly improve depressive symptoms, but there is no significant difference in efficacy. aTMS may also have long-term maintenance effects, but longer follow-up periods are needed to assess this possibility., Trial Registration: This article is original and not under simultaneous consideration for publication. The study was registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) (number: CRD42023406590)., (© 2024. The Author(s).)

Natural products and their derivatives are a precious treasure in the pursuit of potent anti-inflammatory drugs. In this work, we measured the toxicity of 78 LA derivatives at 20 μM using MTT, then we evaluated the NO release of compounds without obvious toxicity in LPS-induced RAW.264.7 by Griess reagent, we identified three compounds, namely compounds 6, 19, 70, which exhibited promising anti-inflammatory potential. These compounds exhibited IC 50 values of 10.34±2.05 μM, 18.18±4.80 μM and 15.66±0.88 μM. In addition, through ELISA kits, compounds 6, 19, 70 significantly reduce the production of inflammatory factors (TNF-α, IL-6, IL-1β). Real-time PCR and western blot analysis showed that compounds 6, 19, 70 inhibited the mRNA and protein expression of iNOS and COX-2. Notably, compound 6 exhibited the most potent inhibitory activity. In vitro, it inhibits LPS-induced phosphorylation of NF-κB p65, IκBα, ERK1/2, JNK, and p38 MAPKs in RAW264.7 cells. In vivo, compound 6 potently inhibits the secretion of inflammatory mediators and neutrophil activation in ALI mice. Our findings suggest that compound 6 may be a potential anti-inflammatory drug., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Due to the coupled contributions of adhesion and carrier to friction typically found in previous research, decoupling the electron-based dissipation is a long-standing challenge in tribology. In this study, by designing and integrating a graphene/ h -BN/graphene/ h -BN stacking device into an atomic force microscopy, the carrier density dependent frictional behavior of a single-asperity sliding on graphene is unambiguously revealed by applying an external back-gate voltage, while maintaining the adhesion unaffected. Our experiments reveal that friction on the graphene increases monotonically with the increase of carrier density. By adjusting the back-gate voltage, the carrier density of the top graphene layer can be tuned from -3.9 × 10 12 to 3.5 × 10 12 cm -2 , resulting in a ∼28% increase in friction. The mechanism is uncovered from the consistent dependence of the charge density redistribution and sliding barrier on the carrier density. These findings offer new perspectives on the fundamental understanding and regulation of friction at van der Waals interfaces.

Objective: To develop a Risk Assessment Tool for Cancer-related Venous Thrombosis in China., Methods: A modified two-round Delphi method was employed to establish consensus within a field to reach an agreement via a questionnaire or by interviewing a multidisciplinary panel of experts by collecting their feedback to inform the next round, exchanging their knowledge, experience, and opinions anonymously, and resolving uncertainties. Furthermore, The AHP (Analytic Hierarchy Process) was used to determine the final quality indicators' relative importance., Results: The expert's positive coefficient was 85.19% in the first round and 82.61% in the second round, with authoritative coefficients of 0.89 and 0.92 in the respective surveys. The P-value of Kendall's W test was all less than 0.001 for each round, and the W-value for concordance at the end of the two rounds was 0.115. The final Risk Assessment Tool for Cancer-related Venous Thrombosis consisted of three domains, ten subdomains, and 39 indicators, with patient factors weighing 0.1976, disease factors weighing 0.4905, and therapeutic factors weighing 0.3119., Conclusion: The tool is significantly valid and reliable with a strong authority and coordination degree, and it can be used to assess the risk of cancer-related VTE and initiate appropriate thrombophylactic interventions in China., (© 2024. The Author(s).)

Background: Metabolic reprogramming provides a new perspective for understanding cancer. The targeting of dysregulated metabolic pathways may help to reprogram the immune status of the tumor microenvironment (TME), thereby increasing the effectiveness of immune checkpoint therapy. Colorectal cancer (CRC), especially colon adenocarcinoma (COAD), is associated with poor patient survival. The aim of the present study was to identify novel pathways involved in the development and prognosis of COAD, and to explore whether these pathways could be used as targets to improve the efficacy of immunotherapy., Methods: Metabolism-related differentially expressed genes (MRDEGs) between tumor and normal tissues were identified using The Cancer Genome Atlas (TCGA) dataset, together with metabolism-related prognostic genes (MRPGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed separately for the MRDEGs and MRPGs. Gene Set Variation Analysis (GSVA) was also performed to explore the role of purine metabolism in COAD tumorigenesis. Consensus clustering of purine metabolism genes with the overall survival (OS) of patients and with anti-tumor immunity was also performed. Pearson correlation analysis was used to identify potential targets that correlated strongly with the expression of immune checkpoints., Results: A 6-gene signature that had independent prognostic significance for COAD was identified, together with a predictive model for risk stratification and prognosis. The most significantly enriched pathway amongst MRDEGs and MRPGs was purine metabolism. Differentially expressed purine metabolism genes could divide patients into two clusters with distinct prognosis and anti-tumor immunity. Further analysis suggested that purine metabolism was involved in anti-tumor immunity., Conclusions: This study confirmed the importance of metabolism-related pathways and in particular purine metabolism in the tumorigenesis, prognosis and anti-tumor immunity of COAD. We identified a 6-gene prognostic signature comprised of EPHX2 , GPX3 , PTGDS , NAT2 , ACOX1 and CPT2 . In addition, four potential immune-metabolic checkpoints ( GUCY1A1 , GUCY1B1 , PDE1A and PDE5A ) were identified, which could be used to improve the efficacy of immunotherapy in COAD., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Fluorescent materials have attracted widespread attention for information encryption owing to their stimuli-responsive color-shifting. However, the 2D encoding of fluorescent images poses a risk of information leakage. Herein, inspired by the mimic octopus capable of camouflage by changing colors and shapes, we develop a thermadapt shape-memory fluorescent film (TSFF) for integrating 2D/3D encoding in one system. The TSFF is based on anthracene group with reversible photo-cross-linking and poly (ethylene-co-vinyl acetate) network with thermadapt shape-memory properties. The reversible photo-cross-linking of anthracene is accompanied by repeatable fluorescence-shifting and enables rewritable 2D encoding. Meanwhile, the thermadapt shape-memory properties not only enables the reconfiguration of the permanent shape for creating and erasing 3D patterns, i.e., rewritable 3D information, but also facilitates recoverable shape programming for 3D encoding. This rewritable 2D/3D encoding strategy can enhance information security because only designated inspectors can decode the information by providing sequential heating for shape recovery and UV exposure. Overall, TSFF capable of rewritable 2D/3D encoding will inspire the design of smart materials for high-security information carriers., (© 2023. The Author(s).)

The application of most hydrogel bio-adhesives is greatly limited due to their high swelling, low underwater adhesion, and single function. Herein, a spatial multi-level physical-chemical and bio-inspired in-situ bonding strategy is proposed, to develop a multifunctional hydrogel bio-glue using polyglutamic acid (PGA), tyramine hydrochloride (TYR), and tannic acid (TA) as precursors and 4-(4,6-dimethoxytriazine-2-yl) -4-methylmorpholine hydrochloride(DMTMM) as condensation agent, which is used for tissue adhesion, hemostasis and repair. By introducing TYR and TA into the PGA chain, it is demonstrated that not only can the strong adhesion of bio-glue to the surface of various fresh tissues and wet materials be realized through the synergistic effect of spatial multi-level physical and chemical bonding, but also this glue can be endowed with the functions of anti-oxidation and hemostasis. The excellent performance of such bio-glue in the repair of the wound, liver, and cartilage is achieved, showing a great potential in clinical application for such bio-glue. This study will open up a brand-new avenue for the development of multifunctional hydrogel biological adhesive., (© 2023 Wiley-VCH GmbH.)

The [M 4 -Hal] - (M=the title compound; Hal=Cl, Br, and I) complexes were isolated in the form of salts of [Et 4 N] + cation and characterized by XRD, NMR, UV-Vis, DFT, QTAIM, EDD, and EDA. Their stoichiometry is caused by a cooperative interplay of σ-hole-driven chalcogen (ChB) and hydrogen (HB) bondings. In the crystal, [M 4 -Hal] - are connected by the π-hole-driven ChB; overall, each [Hal] - is six-coordinated. In the ChB, the electrostatic interaction dominates over orbital and dispersion interactions. In UV-Vis spectra of the M+[Hal] - solutions, ChB-typical and [Hal] - -dependent charge-transfer bands are present; they reflect orbital interactions and allow identification of the individual [Hal] - . However, the structural situation in the solutions is not entirely clear. Particularly, the UV-Vis spectra of the solutions are different from the solid-state spectra of the [Et 4 N] + [M 4 -Hal] - ; very tentatively, species in the solutions are assigned [M-Hal] - . It is supposed that the formation of the [M 4 -Hal] - proceeds during the crystallization of the [Et 4 N] + [M 4 -Hal] - . Overall, M can be considered as a chromogenic receptor and prototype sensor of [Hal] - . The findings are also useful for crystal engineering and supramolecular chemistry., (© 2023 Wiley-VCH GmbH.)

Background: Hepatitis C virus (HCV) infection is a global health threat to the public, and vaccines against it are not yet available. The HCV envelope glycoprotein E2 is a key target for anti-HCV vaccines. The majority of previous studies have focused on the hypervariable region and the glycosylation sites of the&#95;HCV structural protein. This study aims to investigate a conserved domain of HCV E2 glycoprotein and explore its potential to induce an immune response against HCV., Methods: HCV E2 conserved domain (encompassing amino acids 505-702) was prepared in Escherichia coli ( E. coli ). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HCV or healthy controls. Interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot assay was conducted to examine the HCV E2-specific immune response as reflected by IFN-γ-secreting cells/106 PBMCs., Results: HCV E2 conserved domain was highly conserved among 25 HCV subtypes, and its recombinant soluble production in E. coli was recognized by anti-HCV E2 monoclonal antibodies. This study characterized in vitro direct interaction between bacterially expressed HCV E2 conserved domain and human CD81 (hCD81). Furthermore, the recombinant HCV E2&#95;conserved domain markedly induced the production of IFN-γ by PBMCs from patients with HCV. Its stimulated specific immune response was significantly different from non-specific peptide controls or PBMCs isolated from healthy controls., Conclusions: HCV E2 conserved domain directly binds hCD81 and activates the production of IFN-γ in the PBMCs of patients with HCV. Therefore, the conserved domain of HCV E2 glycoprotein may be a new candidate for developing an HCV vaccine., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10  TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60  TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, often accompanied by poor prognosis and high incidence and mortality. p21 activated kinases (PAKs) have been used as therapeutic targets because of their central role in many oncogenic signaling networks. By exploring tumor databases, we found that PAK1 overexpression is associated with poor prognosis in colorectal cancer, and therefore, PAK1-targeted inhibition is a new potential therapeutic strategy for colorectal cancer. We identified that Balanol (compound 6, DB04098) can effectively target PAK1 by high-throughput virtual screening. In vitro, compound 6 exhibited favorable PAK1 inhibition with potent anti-proliferative and anti-migration activity in SW480 cells. Additionally, we also found that compound 6 induced apoptosis and cytoprotective autophagy in SW480 cells. Together, these results indicate that compound 6 is a potential novel PAK1 inhibitor, which would be utilized as a candidate compound for future CRC treatment., (© 2023 Wiley-VCH GmbH.)

Two-dimensional (2D) lamellar materials are normally capable of rendering super-low friction, wear protection, and adhesion reduction in nanoscale due to their ultralow shear strength between two basal plane surfaces. However, high friction at step edges prevents the 2D materials from achieving super-low friction in macroscale applications and eventually leads to failure of lubrication performance. Here, taking graphene as an example, the authors report that not all step edges are detrimental. The armchair (AC) step edges are found to have only a minor topographic effect on friction, while the zigzag (ZZ) edges cause friction two orders of magnitude larger than the basal plane. The AC step edge is less reactive and thus more durable. However, the ZZ structure prevails when step edges are produced mechanically, for example, through mechanical exfoliation or grinding of graphite. The authors found a way to make the high-friction ZZ edge superlubricious by reconstructing the (6,6) hexagon structure to the (5,7) azulene-like structure through thermal annealing in an inert gas environment. This will facilitate the realization of graphene-based superlubricity over a wide range of industrial applications in which avoiding the involvement of step edges is difficult., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Uninterrupted, efficient power supplies have posed a significant hurdle to the ubiquitous adoption of wearable devices, despite their potential for revolutionizing human‒machine interactions. This challenge is further compounded by the requirement of these devices to supply dependable energy for data-intensive sensing and transmission. Traditional thermoelectric solutions fail to deliver satisfactory performance under conditions of extremely low voltages. Here, we present a novel solution of a wearable thermoelectric generator integrated with an energy management system, which is capable of powering sensors and Bluetooth by harnessing body heat. Distinct from previous works, our innovation lies in its ability to consistently operate even with a minimal temperature difference (i.e., 4 K) between the human skin and the ambient environment, ensuring reliable data transmission within a time as short as 1.6 s. Furthermore, our system can recharge utilizing body heat under ultralow voltage conditions (30 mV). Our developed system provides a novel pathway for the continuous, reliable monitoring of self-contained wearable devices without depending on batteries., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Aerospace Information Research Institute, Chinese Academy of Sciences 2023.)

To solve the toxicity issues related to lead-based halide perovskite solar cells, the lead-free double halide perovskite Cs 2 AgBiBr 6 is proposed. However, reduced rate of charge transfer in double perovskites affects optoelectronic performance. We designed a series of pyridine-based small molecules with four different arms attached to the pyridine core as hole-selective materials by using interface engineering. We quantified how arm modulation affects the structure-property-device performance relationship. Electrical, structural, and spectroscopic investigations show that the N 3 , N 3 , N 6 , N 6 -tetrakis(4-methoxyphenyl)-9 H -carbazole-3,6-diamine arm's robust association with the pyridine core results in an efficient hole extraction for PyDAnCBZ due to higher spin density close to the pyridine core. The solar cells fabricated using Cs 2 AgBiBr 6 as a light harvester and PyDAnCBZ as the hole selective layer measured an unprecedented 2.9% power conversion efficiency. Our computed road map suggests achieving ∼5% efficiency through fine-tuning of Cs 2 AgBiBr 6 . Our findings reveal the principles for designing small molecules for electro-optical applications as well as a synergistic route to develop inorganic lead-free perovskite materials for solar applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: This study evaluated whether antibiotic treatment before chemoradiotherapy influenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC)., Methods: The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017 at West China Hospital of Sichuan University were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The influence of antibiotics on progression-free survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression., Results: Of 522 patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4 months, p < 0.001) and OS (20.4 vs. 25.3 months, p = 0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients who received chemoradiotherapy (HR 1.234; 95% CI 1.019-1.494; p = 0.031). Prognosis was also influenced by antibiotic type, length of treatment, and interval between discontinuation and chemoradiotherapy initiation. β‑lactamase inhibitors were found to be the most harmful (median OS for β‑lactamase inhibitors/fluoroquinolones/cephalosporins: 16.5/19.9/25.9 months, p = 0.045). Cutoff values for interval and duration calculated by the X‑tile procedure showed that intervals of 7-16 days or durations ≤ 6 days did not significantly affect OS relative to untreated patients (intervals: p = 0.9; duration: p = 0.93)., Conclusion: Antibiotic treatment for longer than 6 days, especially with β‑lactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16 days after antibiotic discontinuation may reduce these negative effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

Background: The aim of this study was to evaluate the reservoir, conduit, and contraction function of the left atrium and to evaluate the predictive value of left atrial strain (LAS) on exercise tolerance in hypertrophic cardiomyopathy (HCM) patients with an E/e' between 8 and 14 by two-dimensional speckle tracking using treadmill stress echocardiography., Methods: This was a retrospective study in which we analyzed a total of 70 patients with HCM between 2016 and 2017. According to the resting state E/e', patients were either assigned to an HCM-1 group (E/e' > 14) or an HCM-2 group (E/e' of 8 to 14). Thirty age-matched healthy controls were included in the normal group. Analysis involved the left atrial reservoir, conduit, contraction strain and reserve function., Results: The normal group had a higher left atrial reservoir and conduit strain than the HCM-2 group; the lowest values were in the HCM-1 group. The LAS reserve capacity of the HCM-1 and HCM-2 groups was lower than those of the normal group. The left atrial contraction strain reserve ( Δ LASct%) and global longitudinal strain reserve ( Δ GLS%) were lower in the HCM-2 and HCM-1 groups than in the normal group. We also found that the Δ LASct% and Δ GLS% in the HCM-2 group were higher than in the HCM-1 group. Furthermore, the metabolic equivalents (METS) in the HCM-2 group was greater than that in the HCM-1 group. Finally, the Rest-LASr indicated the highest differential diagnostic performance for METS < 6.0 (area under curve [AUC]: 0.759); the AUC of the composite model Rest-LASr+E/e'-rest was 0.8., Conclusions: Analysis showed that when the E/e' was between 8 and 14, the LAS and reserve capacity of HCM patients were significantly reduced. Our findings suggest that the routine assessment of LAS +E/e' can be a strategy with which to supplement current predictive models and facilitate clinical management strategies., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Ethnopharmacological Relevance: Ershiwuwei Zhenzhu Pill (EZP), a representative and classic formula in Tibetan medicine, is commonly used in the treatment of various cerebrovascular diseases, including ischemic stroke (IS). Nevertheless, their efficacy and potential mechanism in treating IS have yet to be investigated., Aim of the Study: This study aimed to investigate the potential mechanisms of EZP in the treatment of IS based on network pharmacology and experimental verification., Materials and Methods: The chemical profile of EZP was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The targets related to the compounds in EZP were predicted by the Swiss Target Prediction and Target Net platform, and targets of IS were collected from the Gene Cards and OMIM databases. Subsequently, a protein-protein interaction (PPI) network of targets was constructed and analyzed by the STRING database and Cytoscape software, version 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed, and an ingredient-target-pathway network was constructed. Ultimately, the middle cerebral artery occlusion (MCAO) model was established to evaluate the anti-IS effects of EZP by detecting the neurological deficit score, HE, Nissl and TCC staining, and inflammatory factors, and the expression of key protein targets was detected by western blotting., Results: A total of 129 components were identified in EZP. Network pharmacology revealed 3136 compound targets and 2826 disease-related targets, and 412 overlapping proteins were obtained as potential therapeutic targets. The PPI network results showed that 6 key targets (AKT1, SRC, VEGFA, TP53, TNF and EGFR) were core targets of EZP in the treatment of IS. Western blotting demonstrated that the expression levels of AKT1, VEGFA, TP53, SRC, TNF and EGFR in the brain tissue of MCAO rats were significantly changed after treatment with EZP compared to the model group., Conclusions: EZP ameliorated IS in MCAO rats. The underlying mechanism might be associated with inhibiting inflammation and apoptosis, promoting angiogenesis and protecting neurons by regulating multiple targets and pathways., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The synthesis of crystalline polymer with a well-defined orientated state and a two-dimensional crystalline size beyond a micrometer will be essential to achieve the highest physical feature of polymer material but remain challenging. Herein, we show the synthesis of the crystalline unipolymer monolayer with an unusual ultrahigh modulus that is higher than the ITO substrate and high conductance by simultaneous electrosynthesis and manipulation. We find that the polymer monolayer has fully extended in the vertical and unidirectional orientation, which is proposed to approach their theoretically highest density, modulus, and conductivity among all aggregation formations of the current polymer. The modulus and current density can reach 40 and 1000 times higher than their amorphous counterpart. It is also found that these monolayers exhibit the bias- and length-dependent multiple charge states and asymmetrically negative differential resistance (NDR) effect, indicating that this unique molecular tailoring and ordering design is promising for multilevel resistive memory devices. Our work demonstrates the creation of a crystalline polymer monolayer for approaching the physical limit of polymer electronic materials and also provides an opportunity to challenge the synthetically iterative limit of an isolated ultra-long polymer., (© 2022 Wiley-VCH GmbH.)

The present work investigated fundamental mediating mechanisms (i.e., flow experience, organizational identification, and trust), underlining the impact of authentic leadership on employee resilience during the turbulent COVID-19 pandemic. A total of 901 frontline employees working in a construction engineering company in China participated in this study. They were asked to respond to a battery of questionnaires comprising Trust Scale (affective-based, cognitive-based, and competence-based), Flow Proneness Questionnaire (FPQ), Organizational Identification Scale, Authentic Leadership Questionnaire, and Employee Resilience Scale. Results of structural equation modeling indicated that: (1) Authentic leadership positively predicted employee resilience in the COVID-19 pandemic, directly and indirectly. (2) As for the indirect relationship, two parallel mediation effects and one chain mediation were detected: employees' flow at work and organizational identification respectively and dependently mediated the relationship between authentic leadership and employee resilience; trust and organizational identification played as a chain mediation role within authentic leadership-employee resilience association. The study provides empirical evidence for organizations' resilience-building and leadership training programs. Findings also contribute to the literature by facilitating flow intervention, promoting organizational identification and trust to enhance the effect of authentic leadership in promoting positive psychological functioning of employee resilience. Limitations with respect to future research directions were also outlined., Competing Interests: Conflict of interestAll authors in this article declare that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9}  GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Background: Gliomas, especially high-grade gliomas, are highly malignant with a poor prognosis. Although existing treatments have improved the survival rate of patients with glioma, the recurrence and mortality rates are still not ideal. The molecular mechanisms involved in the occurrence and development of glioma are still poorly understood. We previously reported that thrombospondin-2 (TSP2) expression was increased in tumor specimens from rat models, promoting excitatory synapse formation. However, little is known about the effect of TSP2 on the biological characteristics of glioma., Methods: Glioma and cerebral cortex tissues were collected from 33 patients, and the expression of TSP2 in them was analyzed. Next, the proliferation and migration of TSP2 on glioma cells were analyzed in vitro. At last, a glioma transplantation model was constructed to explore the growth of TSP2 on glioma in vivo., Results: The expression of TSP2 in surgical glioma specimens was increased compared to that in the normal cortex. Interestingly, the TSP2 protein level was higher in high-grade glioma (HGG, World Health Organization (WHO) grades 3-4) than in low-grade glioma (LGG, WHO grades 1-2) tissues. Exogenous addition of the TSP2 protein at an appropriate concentration promoted the migration of glioma cells but did not significantly affect their proliferation. Surprisingly, overexpression of TSP2 promoted both the migration and proliferation of cultured glioma cells. Moreover, in vivo experimental data implied that overexpression of TSP2 in C6 cells promoted the malignant growth of gliomas, while knockout of TSP2 slowed glioma growth., Conclusions: TSP2 promotes the migration and proliferation of glioma cells, which may provide new ideas for blocking glioma progression., (© 2022. The Author(s).)

Solidification processing is essential to the manufacture of various metal products, including additive manufacturing. Solidification grain boundaries (SGBs) result from the solidification of the last liquid film between two abutting grains of different orientations. They can migrate, but unlike normal GB migration, SGB migration (SGBM) decouples SGBs from solidification microsegregation, further affecting material properties. Here, we first show the salient features of SGBM in magnesium-tin alloys solidified with cooling rates of 8-1690 °C/s. A theoretical model is then developed for SGBM in dilute binary alloys, focusing on the effect of solute type and content, and applied to 10 alloy systems with remarkable agreement. SGMB does not depend on cooling rate or time but relates to grain size. It tends to occur athermally. The findings of this study extend perspectives on solidification grain structure formation and control for improved performance (e.g. hot or liquation cracking during reheating, intergranular corrosion or fracture)., (© 2022. The Author(s).)