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Abstract The direct synthesis of light aromatics, especially para-xylene (p-X), from syngas/CO2 is drawing strong interest, but improving the space-time yield (STY) of p-X is a significant challenge. Here, a dynamic “dual-engine-driven” (DED) catalytic system is designed by combining two partners of ZnCr and FeMn (named “dual-engine”) with Z5@SiO2 capsule zeolite. The DED catalyst of 1.0%FeMn&[ZnCr&Z5@SiO2] shows an extremely higher p-X STY of 36.1 g p-x·kgcat -1·h-1, about eight times higher than that of [ZnCr&Z5]. DED manipulates ZnCr engine for methanol formation and drives FeMn engine for light olefins generation together, and then the formed methanol and light olefins are coordinately converted in situ into p-X-rich aromatics over Z5@SiO2. The DED model boosts the driving force for syngas/CO2 conversion, simultaneously concerting the cooperation of “dual-engine” for p-X generation, resulting in extremely high STY of p-X. This study achieves non-petroleum p-X production at industrial-relevant level and advances knowledge in designing innovative heterogeneous catalysts.

Abstract The artificial photocatalytic synthesis based on graphitic carbon nitride (g-C3N4) for H2O2 production is evolving rapidly. However, the simultaneous production of high-value products at electron and hole sites remains a great challenge. Here, we use transformable potassium iodide to obtain semi-crystalline g-C3N4 integrated with the I-/I3 - redox shuttle mediators for efficient generation of H2O2 and benzaldehyde. The system demonstrates a prominent catalytic efficiency, with a benzaldehyde yield of 0.78 mol g−1 h−1 and an H2O2 yield of 62.52 mmol g−1 h−1. Such a constructed system can achieve an impressive 96.25% catalytic selectivity for 2e- oxygen reduction, surpassing previously reported systems. The mechanism study reveals that the strong crystal electric field from iodized salt enhances photo-generated charge carrier separation. The I-/I3 - redox mediators significantly boost charge migration and continuous electron and proton supply for dual-channel catalytic synthesis. This groundbreaking work in photocatalytic co-production opens neoteric avenues for high-value synthesis.

Abstract To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan–Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P

Abstract Background The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. Methods This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell’s C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Results During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01–7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16–7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42–5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell’s C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P

Abstract We introduce University of Texas - GLObal Building heights for Urban Studies (UT-GLOBUS), a dataset providing building heights and urban canopy parameters (UCPs) for more than 1200 city or locales worldwide. UT-GLOBUS combines open-source spaceborne altimetry (ICESat-2 and GEDI) and coarse-resolution urban canopy elevation data with a machine-learning model to estimate building-level information. Validation using LiDAR data from six U.S. cities showed UT-GLOBUS-derived building heights had a root mean squared error (RMSE) of 9.1 meters. Validation of mean building heights within 1-km2 grid cells, including data from Hamburg and Sydney, resulted in an RMSE of 7.8 meters. Testing the UCPs in the urban Weather Research and Forecasting (WRF-Urban) model resulted in a significant improvement (55% in RMSE) in intra-urban air temperature representation compared to the existing table-based local climate zone approach in Houston, TX. Additionally, we demonstrated the dataset’s utility for simulating heat mitigation strategies and building energy consumption using WRF-Urban, with test cases in Chicago, IL, and Austin, TX. Street-scale mean radiant temperature simulations using the SOlar and LongWave Environmental Irradiance Geometry (SOLWEIG) model, incorporating UT-GLOBUS and LiDAR-derived building heights, confirmed the dataset’s effectiveness in modeling human thermal comfort in Baltimore, MD (daytime RMSE = 2.85°C). Thus, UT-GLOBUS can be used for modeling urban hazards with significant socioeconomic and biometeorological risks, enabling finer scale urban climate simulations and overcoming previous limitations due to the lack of building information.

Abstract Background The identification of spotted leaf 50 (spl50), a novel lesion mimic mutant (LMM) in rice, provides critical insights into the mechanisms underlying programmed cell death (PCD) and innate immunity in plants. Results Based on ethyl methane sulfonate (EMS)-induced mutagenesis, the spl50 mutant mimics hypersensitive responses in the absence of pathogen by displaying spontaneous necrotic lesions after the tillering phase. SPL50, an ARM repeat protein essential for controlling reactive oxygen species (ROS) metabolism and boosting resistance to blast disease, was identified by map-based cloning techniques. This work also demonstrates the detrimental effects of spl50 on photosynthetic efficiency and chloroplast development. The crucial significance of SPL50 in cellular signaling and stress response is shown by its localization to the cytoplasm and constitutive expression in various plant tissues. In light of growing concerns regarding global food security, this study highlights the pivotal role of SPL50 in regulating programmed cell death (PCD) and enhancing the immune response in plants, contributing to strategies for improving crop disease resistance. Conclusions The novel identification of the SPL50 gene in rice, encoding an ARM repeat protein, reveals its pivotal role in regulating PCD and innate immune responses independently of pathogen attack.

Abstract Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Abstract The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, through a critical examination of recent clinical trial data. Furthermore, we discuss the challenges posed by resistance mechanisms to these therapies and potential strategies to overcome them. We also explores the synergistic potential of combination therapies, integrating PD1/PD-L1 inhibitors with other immunotherapies, targeted therapies, and conventional modalities such as chemotherapy and radiotherapy. In addition, we examine emerging predictive biomarkers for response to PD1/PD-L1 blockade and biomarkers indicative of resistance, providing a foundation for personalized therapeutic approaches. Finally, we outline future research directions, highlighting the need for novel therapeutic strategies, deeper mechanistic insights, and the development of individualized treatment regimens. Our work summarizes the latest knowledge and progress in this field, aiming to provide a valuable reference for improving clinical efficacy and guiding future research on the application of PD1/PD-L1 inhibitors in ccRCC.

Abstract Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (−44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.

Abstract Spatial transcriptomics technologies permit the study of the spatial distribution of RNA at near-single-cell resolution genome-wide. However, the feasibility of studying spatial allele-specific expression (ASE) from these data remains uncharacterized. Here, we introduce spASE, a computational framework for detecting and estimating spatial ASE. To tackle the challenges presented by cell type mixtures and a low signal to noise ratio, we implement a hierarchical model involving additive mixtures of spatial smoothing splines. We apply our method to allele-resolved Visium and Slide-seq from the mouse cerebellum and hippocampus and report new insight into the landscape of spatial and cell type-specific ASE therein.

Objective: This study aimed to investigate the correlation between COVID-19 and the direct antiglobulin test (DAT) and establish an in-hospital mortality risk predictive model based on the DAT type, which can be used for the early prediction of inpatients with COVID-19. Methods: In this study, 502 patients admitted to our hospital who underwent DAT testing from January 29 to February 8, 2023, were included (252 DAT-positive and 250 DAT-negative). Among them, 241 cases of COVID-19 were screened(171 DAT-positive and 70 DAT-negative), clinical and laboratory indicators were compared between DAT-positive and DAT-negative groups. Univariate and multivariate logistic regression analysis, the Kaplan-Meier survival curve and receiver operating curves were used to explore the relation between the DAT type and in-hospital mortality of patients with COVID-19. Results: The proportion of confirmed COVID-19 cases was higher in the DAT-positive group than in the DAT-negative group (67.9 % vs. 28.0 %, P

Objective The objective of this study was to investigate the influence of yacon root extracts (YREs) on productive performance and health of laying hens. Methods Six hundred 30-week-old Xiaoshan Chicken layers were divided into 5 groups, control group, antibiotic positive control group, and 3 YREs treatment groups. In a 9-wk feeding experiment, at the end of wk 3, 6, and 9, twenty eggs were collected from each replicate to measure egg qualities. At the end of wk 9, three hen serum samples, and 5 hen cecal content samples were collected from each replicate. Results Compared to the control group, 0.8%, 1.6%, and 2.4% YREs treatments could increase hens’ daily feed intake, and YREs supplementation affected daily feed intake in linear manner. YREs did not change egg size, but 0.8% and 2.4% YREs changed egg shape by decreasing the egg shape index and sphericity, and 0.8% YREs tended to improve the eggshell breaking strength. Diet supplemented with 1.6% YREs might decrease yolk color grade but optimize the pH of thick egg white in fresh egg; moreover, 1.6% and 2.4% YREs might be helpful for eggs to inhibit water loss during storage, and YREs supplementation affected water loss rate in linear manner. 2.4% YREs could decrease the serum lactate dehydrogenases (LDH) level, and YREs supplemental levels linearly affected serum LDH content. Finally, YREs could enrich the diversity of intestinal microbiota of hens fed with 0.8% and be beneficial for the relative abundance of phylum Bacteroidota and Halobacterota; 2.4% YREs might increase the abundance of phylum Actinobacteriota and genus Bifidobacterium, while decrease genus Bacteroides; YREs supplemental levels affected the abundance of phylum Actinobacteriota, and genera Bifidobacterium and Bacteroides in linear manner. Conclusion Dietary supplementation with YREs could affect egg quality, protect the health of organs and exhibit prebiotic activity.

High-pressure waterjet-assisted tunnel boring machine (WTBM) is an efficient method for improving the tunneling performance of a tunnel boring machine (TBM) and reducing the wear of its disc cutters in hard rock with high geostresses. Confining pressure directly affects the efficiency of rock breaking and the configuration of the disc cutters. In this study, we evaluated the effect of confining pressure on WTBM rock breaking by developing a self-designed and manufactured experimental system, including confining pressure loading, TBM disc-cutter penetration, and high-pressure waterjet. The macro fracture, acoustic emission (AE), peak normal force drop, and specific energy (SE) were analyzed for four different confining pressures (10, 20, 30, and 35 MPa). The results showed that the cutting depth of the waterjet increased linearly as the waterjet pressure increased and decreased with the gradual increase in the nozzle moving speed. The expansion and development of cracks formed rock debris, and the size of the rock fragments decreased with an increase in confining pressure. When the waterjet pressure was 280 MPa, the nozzle moving velocity was 800 mm/min and the kerf space was 75 mm, which indicated that the confining pressure, which was 23.16 MPa, minimized the cutting SE under this condition. However, regardless of the confining pressure, the maximum normal force of WTBM was less than that of a TBM, whereas the SE of WTBM was less than that of complete TBM cutting mode (CTCM). The average force drop and average drop rate of SE were approximately 25%, and 80%, respectively. The results of this study can inspire the design and mechanism of a TBM assisted by a high-pressure waterjet.

A low-energy plasma electrolytic oxidation (LePEO) technique is developed to simultaneously improve energy efficiency and anti-corrosion. Ionic liquids (1‑butyl‑3-methylimidazole tetrafluoroborate (BmimBF4)) as sustainable corrosion inhibitors are chosen to investigate the corrosion inhibition behavior of ionic liquid (ILs) during the LePEO process for LA91 magnesium–lithium (Mg–Li) alloy. Results show that the ionic liquid BmimBF4 participates in the LePEO coating formation process, causing an increment in coating thickness and surface roughness. The low conductivity of the ionic liquid is responsible for the voltage and breakdown voltage increases during the LePEO with IL process (LePEO-IL). After adding BmimBF4, corrosion current density decreases from 1.159 × 10−4 A·cm−2 to 8.143 × 10−6 A·cm−2. The impedance modulus increases to 1.048 × 104 Ω·cm−2 and neutral salt spray remains intact for 24 h. The superior corrosion resistance of the LePEO coating assisted by ionic liquid could be mainly attributed to its compact and thick barrier layer and physical absorption of ionic liquid. The ionic liquid-assisted LePEO technique provides a promising approach to reducing energy consumption and improving film performance.

Abstract Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4+ T cell subsets remain unresolved. Here, we examine antigen-experienced CD4+ T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic TEM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with TCM/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4+ T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4+ T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.

Abstract High-sensitivity strain sensing elements with a wide strain range, fast response, high stability, and small sensing areas are desirable for constructing strain sensor arrays with high temporospatial resolution. However, current strain sensors rely on crack-based conductive materials having an inherent tradeoff between their sensing area and performance. Here, we present a molecular-level crack modulation strategy in which we use layer-by-layer assembly to introduce strong, dynamic, and reversible coordination bonds in an MXene and silver nanowire-matrixed conductive film. We use this approach to fabricate a crack-based stretchable strain sensor with a very small sensing area (0.25 mm2). It also exhibits an ultrawide working strain range (0.001–37%), high sensitivity (gauge factor ~500 at 0.001% and >150,000 at 35%), fast response time, low hysteresis, and excellent long-term stability. Based on this high-performance sensing element and facile assembly process, a stretchable strain sensor array with a device density of 100 sensors per cm2 is realized. We demonstrate the practical use of the high-density strain sensor array as a multichannel pulse sensing system for monitoring pulses in terms of their spatiotemporal resolution.

Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis-, trans-, and cluster signaling. When IL-6 binds to its membrane or soluble receptors, the co-receptor gp130 is activated to initiate downstream signaling and induce the expression of target genes. In the liver, IL-6 can perform its anti-inflammatory activities to promote hepatocyte reprogramming and liver regeneration. On the contrary, IL-6 also exerts the pro-inflammatory functions to induce liver aging, fibrosis, steatosis, and carcinogenesis. However, understanding the roles and underlying mechanisms of IL-6 in liver physiological and pathological processes is still an ongoing process. So far, therapeutic agents against IL‑6, IL‑6 receptor (IL‑6R), IL-6-sIL-6R complex, or IL-6 downstream signal transducers have been developed, and determined to be effective in the intervention of inflammatory diseases and cancers. In this review, we summarized and highlighted the understanding of the double-edged effects of IL-6 in liver homeostasis, aging, inflammation, and chronic diseases, for better shifting the “negative” functions of IL-6 to the “beneficial” actions, and further discussed the potential therapeutic effects of targeting IL-6 signaling in the clinics.

Abstract Artificial photosynthesis using carbon nitride (g-C3N4) holds a great promise for sustainable and cost-effective H2O2 production, but the high carrier recombination rate impedes its efficiency. To tackle this challenge, we propose an innovative method involving multispecies iodine mediators (I−/I3 −) intercalation through a pre-photo-oxidation process using potassium iodide (suspected deteriorated “KI”) within the g-C3N4 framework. Moreover, we introduce an external electric field by incorporating cationic methyl viologen ions to establish an auxiliary electron transfer channel. Such a unique design drastically improves the separation of photo-generated carriers, achieving an impressive H2O2 production rate of 46.40 mmol g−1 h−1 under visible light irradiation, surpassing the most visible-light H2O2-producing systems. Combining various advanced characterization techniques elucidates the inner photocatalytic mechanism, and the application potential of this photocatalytic system is validated with various simulation scenarios. This work presents a significative strategy for preparing and applying highly efficient g-C3N4-based catalysts in photochemical H2O2 production.

Abstract To counterbalance the abilities of global exploration and local exploitation of algorithm and enhance its comprehensive performance, a multi-objective particle swarm optimization with a competitive hybrid learning strategy (CHLMOPSO) is put forward. With regards to this, the paper first puts forward a derivative treatment strategy of personal best to promote the optimization ability of particles. Next, an adaptive flight parameter adjustment strategy is designed in accordance with the evolutionary state of particles to equilibrate the exploitation and exploration abilities of the algorithm. Additionally, a competitive hybrid learning strategy is presented. According to the outcomes of the competition, various particles decide on various updating strategies. Finally, an optimal angle distance strategy is proposed to maintain archive effectively. CHLMOPSO is compared with other algorithms through simulation experiments on 22 benchmark problems. The results demonstrate that CHLMOPSO has satisfactory performance.

Abstract Potentially fatal fungal sphenoid sinusitis (FSS) causes visual damage. However, few studies have reported on its visual impairment and prognosis. Five hundred and eleven FSS patients with ocular complications treated at Beijing Tongren Hospital were recruited and clinical features and visual outcomes were determined. Thirty-two of the 511 patients (6%) had visual impairment, with 13 and 19 patients having invasive and noninvasive FSS, respectively. Eighteen patients (56.25%) had diabetes and 2 patient (6.25%) had long-term systemic use of antibiotics (n = 1) and corticosteroids (n = 1). All patients had visual impairment, which was more severe in invasive FSS than in noninvasive FSS. Bony wall defects and sclerosis were observed in 19 patients (59.38%), and 11 patients (34.38%) had microcalcification in their sphenoid sinusitis on computed tomography (CT). After a 5-year follow-up, three patients (9.38%) died. Patients with noninvasive FSS had a higher improvement rate in visual acuity than their counterparts. In the multivariate analysis, sphenoid sinus wall sclerosis on CT was associated with better visual prognosis. FSS can cause vision loss with persistent headaches, particularly in those with diabetes. CT showed the sphenoid sinus wall sclerosis, indicating a better visual prognosis in FSS with visual impairment.

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G–) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G– bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.

Abstract Excited‐state intramolecular proton transfer (ESIPT) has attracted great attention in fluorescent sensors and luminescent materials due to its unique photobiological and photochemical features. However, the current structures are far from meeting the specific demands for ESIPT molecules in different scenarios; the try‐and‐error development method is labor‐intensive and costly. Therefore, it is imperative to devise novel approaches for the exploration of promising ESIPT fluorophores. This research proposes an artificial intelligence approach aiming at exploring ESIPT molecules efficiently. The first high‐quality ESIPT dataset and a multi‐level prediction system are constructed that realized accurate identification of ESIPT molecules from a large number of compounds under a stepwise distinguishing from conventional molecules to fluorescent molecules and then to ESIPT molecules. Furthermore, key structural features that contributed to ESIPT are revealed by using the SHapley Additive exPlanations (SHAP) method. Then three strategies are proposed to ensure the ESIPT process while keeping good safety, pharmacokinetic properties, and novel structures. With these strategies, >700 previously unreported ESIPT molecules are screened from a large pool of 570 000 compounds. The ESIPT process and biosafety of optimal molecules are successfully validated by quantitative calculation and experiment. This novel approach is expected to bring a new paradigm for exploring ideal ESIPT molecules.

Background: Endothelial dysfunction is a complication of diabetes mellitus (DM), characterized by impaired endothelial function in both microvessels and macrovessels, closely linked to atherosclerosis (AS). Endothelial dysfunction, characterized by impaired endothelial cell (EC) function, is a pivotal factor in AS and DM. Circular RNAs (circRNAs) are endogenous non-coding RNAs that can act as competing endogenous RNAs (ceRNAs) and regulate gene expression. However, the role of circRNAs in ECs dysfunction and AS under high glucose (HG) condition remains elusive. Methods: We performed high-throughput sequencing to identify differentially expressed (DE) circRNAs in human umbilical vein endothelial cells (HUVEC) exposed to HG, one risk factors of endothelial dysfunction and AS. We then validated eight candidate circRNAs by qRT-PCR and functional analysis, directing our attention to hsa_circ_0122319. Moreover, microarray analysis identified the differential expression profiles of miRNAs and mRNAs regulated by hsa_circ_0122319. Subsequently, the construction of the ceRNAs network employed bioinformatic analysis and Cytoscape software. Furthermore, the role of the PI3K-Akt signaling pathway in regulating ceRNAs was evaluated. Results: We detected 917 DE circRNAs in HG treated HUVEC. The parental genes of these circRNAs were enriched in cell cycle, cellular senescence and endocytosis related pathways. The differential expression of hsa_circ_0122319 was confirmed to be most obvious at the cellular level and in clinical samples by qPCR experiments. After overexpression of hsa_circ_0122319, 49 DE miRNAs and 459 DE mRNAs were identified using microarray analysis. Subsequently, a ceRNAs network was constructed, comprising hsa_circ_0122319, 8 miRNAs, and 41 mRNAs. Conclusion: In summary, our study delves into the role of circRNAs in endothelial dysfunction associated with DM and AS. Through high-throughput sequencing and validation, we identified hsa_circ_0122319 as a pivotal regulator of ECs function under HG conditions. It also showed that hsa_circ_0123319 has the potential to serve as a biomarker for DM and its vascular complications, and provides new evidence for future exploration of the intricate molecular mechanisms of endothelial dysfunction in the progression of DM and AS.

BackgroundHeterologous booster vaccines are more effective than homologous booster vaccines in combating the coronavirus disease 2019 (COVID-19) outbreak. However, our understanding of homologous and heterologous booster vaccines for COVID-19 remains limited.MethodsWe recruited 34 healthy participants from two cohorts who were primed with two-dose inactivated COVID-19 vaccine before, vaccinated with COVID-19 inactivated vaccine and adenovirus-vectored vaccine (intramuscular and aerosol inhalation of Ad5-nCoV) as a third booster dose. We assessed the immune responses of participants before and 14 days after vaccination, including levels of neutralizing antibodies, IgG, and cytokines, and quantified the transcriptional profile of peripheral blood mononuclear cells (PBMCs).ResultsThe Ad5-nCoV group showed a significantly higher neutralizing antibody geometric mean titer (GMT) compared to the ICV group after 14 days of heterologous boosting. The intramuscular Ad5-nCoV group had a GMT of 191.8 (95% CI 129.0, 285.1) compared to 38.1 (95% CI 23.1, 62.8) in the ICV1 group (p

Abstract The rheology of materials near fault zones controls the deformation of the fault, thus playing an important role in the rupture propagation of large earthquakes. Here, we model the postseismic deformation in the first 4 years following the 2019 Ridgecrest earthquake, and probe the laterally variable lower‐crustal viscosity and fault afterslip, using a combined model incorporating afterslip and viscoelastic relaxation. Modeling results reveal that laterally variable low‐viscosity zones (1017∼1018 Pa·s) beneath the Coso Volcanic Field are required to explain the observations well. These low‐viscosity materials may reduce the width of the brittle part of the fault, thus affecting the northwestward propagation of the 2019 Ridgecrest earthquake rupture and the spatial pattern of nearby seismicity. Numerical simulations reveal that the postseismic viscoelastic relaxation of the event will cause contractional strain in the upper‐crustal magma reservoirs, which may counteract the extensional strain caused by the coseismic rupture.

Cholangiocarcinoma (CCA) is a rare but highly invasive cancer, with its incidence rising in recent years. Currently, surgery remains the most definitive therapeutic option for CCA. However, similar to other malignancies, most CCA patients are not eligible for surgical intervention at the time of diagnosis. The chemotherapeutic regimen of gemcitabine combined with cisplatin is the standard treatment for advanced CCA, but its effectiveness is often hampered by therapeutic resistance. Recent research highlights the remarkable plasticity of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). TAMs play a crucial dual role in either promoting or suppressing tumor development, depending on the factors that polarize them toward pro-tumorigenic or anti-tumorigenic phenotypes, as well as their interactions with cancer cells and other stromal components. In this review, we critically examine recent studies on TAMs in CCA, detailing the expression patterns and prognostic significance of different TAM subtypes in CCA, the mechanisms by which TAMs influence CCA progression and immune evasion, and the potential for reprogramming TAMs to enhance anticancer therapies. This review aims to provide a framework for deeper future research.

Under the dual-carbon background, enterprises' ESG performance and sustainable development capability have become a topic of great concern to all sectors of society. The ESG industry in China is very young, and there isn't much research looking at how ESG performance relates to business risk for corporations. This paper empirically tests the impact of firms' ESG performance on their business risk. It discusses the mechanism from the viewpoints of financing constraints and agency costs, the moderating role of economic policy uncertainty, and the analysis of differences in corporate size. The results indicate that firms with strong ESG performance experience a significant reduction in business risk. These firms face lower financing constraints and agency costs, which contribute to the mitigation of business risk. Furthermore, economic policy uncertainty moderates the link between ESG performance and business risk. Additionally, the influence of ESG performance on business risk is more significant in larger-scale companies.

Abstract Background This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. Methods Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. Results Over the 30‐year follow‐up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all‐cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. Conclusion IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

Background: Hashimoto's thyroiditis (HT) is a thyroid autoimmune disease characterized by lymphocytic infiltration and thyroid destruction. Prunella vulgaris (PV) is a traditional Chinese herbal medicine with documented clinical efficacy in treating HT. We previously reported an immunoregulatory effect of PV in thyrocytes; however, the bioactive components of PV remained unclear. This study aimed to elucidate key components of PV for treating HT and their acting mechanisms. Methods: Network pharmacology was used to predict key PV components for HT. The predicted components were tested to determine whether they could exert an immunoregulatory effect of PV in human thyrocytes. Limited proteolysis-mass spectrometry (Lip-MS) was used to explore interacting proteins with PV components in human thyrocytes. Microscale thermophoresis binding assay was used to evaluate the affinity of PV components with the target protein. Results: Eleven PV components with 192 component targets and 3415 HT-related genes were gathered from public databases. With network pharmacology, a ‘component-target-disease’ network was established wherein four flavonoids including quercetin, luteolin, kaempferol, morin, and a phytosterol, β-sitosterol were predicted as key components in PV for HT. In stimulated primary human thyrocytes or Nthy-ori-31 cells, key components inhibited gene expressions of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon-β (IFN-β), cellular apoptosis, and activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3). Heat shock protein 90 alpha, class A, member 1 (HSP90AA1), was identified to interact with flavonoids in PV by Lip-MS. Morin had the highest affinity with HSP90AA1 (KD = 122.74 μM), followed by kaempferol (KD = 168.53 μM), luteolin (KD = 293.94 μM), and quercetin (KD = 356.86 μM). Conclusion: Quercetin, luteolin, kaempferol, morin, and β-sitosterol reproduced an anti-inflammatory and anti-apoptosis effect of PV in stimulated human thyrocytes, which potentially contributed to the treatment efficacy of PV in HT.

Background It is encountering the dilemma of lacking precise biomarkers to predict the response to neoadjuvant chemoimmunotherapy (NACI) and determine whether patients should use immune checkpoint inhibitors (ICIs) in early breast cancer (BC). We aimed to develop a gene signature to predict NACI response for BC patients and identify individuals suitable for adding ICIs.Patients and methods Two I-SPY2 cohorts and one West China Hospital cohort of patients treated with NACI were included. Machine learning algorithms were used to identify key genes. Principal component analysis was used to calculate the ImPredict (IP) score. The interaction effects between biomarkers and treatment regimens were examined based on the logistic regression analysis. The relationship between the IP score and immune microenvironment was investigated through immunohistochemistry (IHC) and multiplex IHC.Results The area under the curves of the IP score were 0.935, 0.865, and 0.841 in the discovery cohort, validation cohort 1, and in-house cohort. Marker-treatment interaction tests indicated that the benefits from immunotherapy significantly varied between patients with high and low IP scores (p for interaction

Background: Although associations between chronic obstructive pulmonary disease (COPD) or ischaemic heart disease (IHD) and lifestyle factors or air pollution factors (referred as LAFs below) are well-established, it is unclear the influences of LAFs on the trajectory of IHD and COPD multimorbidity (referred as ICM below). Therefore, this study investigated the influences of LAFs on the trajectory of ICM from healthy to IHD or COPD, to ICM, and to all-cause death. Methods: A cohort of 339,213 participants from the UK Biobank aged 37–73 who were free of IHD and COPD were included. A multi-state model was used to analyse the influences of high-risk factors including current smoking or quitting due to illness or physician's advice, current excessive alcohol drinking, physical inactivity, unhealthy body shape, and excessive air pollution with particulates matter with an aerodynamic diameter ≤2.5 μm (PM2.5) on ICM trajectory. Results: During a median follow-up of 13.74 years, 46,398 participants developed IHD or COPD (referred as IOC below), 3949 developed ICM, and 35,691 died from any cause. All five high-risk factors played crucial but different roles in these transitions. The hazard ratios (95 % confidence intervals) per one-factor increase were 1.29 (1.27–1.3), 1.38 (1.33–1.44), and 1.69 (1.56–1.84) for transitions from baseline to IOC, from IOC to ICM, and from baseline to ICM and 1.19 (1.17–1.21), 1.18 (1.15–1.21), and 1.12 (1.05–1.19) for mortality risk from baseline to all-cause death, from IOC to all-cause death, and from ICM to all-cause death, respectively. Conclusions: Our study revealed that LAFs have a stronger impact on morbidity outcomes than on morbidity outcomes. These findings provide evidence to develop strategies for managing the trajectory of ICM.

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear.Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%–30% range, significant large, low-velocity vortexes resulted in low TAWSS (40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2).Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%–50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%–30% DS near the stenoses and in the proximal LAD, while lesions with 30%–50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

The interaction between the immune system and the tumor matrix has a huge impact on the progression and treatment of cancer. This paper summarizes and discusses the crosstalk between T cells and cancer-associated fibroblasts (CAFs). CAFs can also produce inhibitors that counteract the function of T cells and promote tumor immune escape, while T cells can also engage in complex two-way interactions with CAFs through direct cell contact, the exchange of soluble factors such as cytokines, and the remodeling of the extracellular matrix. Precise targeted intervention can effectively reverse tumor-promoting crosstalk between T cells and CAFs, improve anti-tumor immune response, and provide a new perspective for cancer treatment. Therefore, it is important to deeply understand the mechanism of crosstalk between T cells and CAFs. This review aims to outline the underlying mechanisms of these interactions and discuss potential therapeutic strategies that may become fundamental tools in the treatment of cancer, especially hard-to-cure cancers.

Image denoising is a fundamental tool in the fields of image processing and computer vision. With the rapid development of multimedia and cloud computing, it has become popular for resource-constrained users to outsource the storage and denoising of massive images. However, it may cause privacy concerns and response delays. In this scenario, we propose an ef F icient priv A cy-prese R ving I mage de N oising sch E me (FARINE) for outsourcing digital images. By introducing a key conversion mechanism, FARINE allows removing noise from a given noisy image using a non-local mean way without leaking any information about the plaintext content. Due to its low computational latency/communication cost, edge computing is considered to improve the user experience. To achieve a dynamic user set efficiently, we design a fine-grained access control mechanism to support user authorization and revocation in multi-user scenarios. Extensive experiments over several benchmark data sets show that FARINE obtains comparable performance to plaintext image denoising.

This paper presents a numerical simulation study on the coupling of lasers and waterjets, focusing on the distribution of the spot power density. The analysis utilized a laser wavelength of 532 nm, chosen for its minimal energy attenuation in water. The key conditions for successful coupling were identified, including the necessity for the spot diameter of the laser beam to be smaller than the nozzle diameter of the waterjet fiber, the numerical aperture of the laser beam to be lower than that of the waterjet fiber, and the divergence angle of the laser to be smaller than the critical angle for total internal reflection. Using the ZEMAX simulation software, various coupling cases were explored, revealing that the radial displacement of the waterjet fiber relative to the laser axis has the most significant impact on the output power density, followed by angular deflection, whereas the axial displacement has the minimal effect. This study also investigates the combined effects of different influencing factors on the peak distribution of the output power density, uncovering distinct characteristics resulting from these deviations. Overall, the research findings provide theoretical insights for achieving effective coupling between fine waterjets and lasers as well as for the design of water-guided laser coupling devices.

The complex network approach is an effective method to analyze the global properties of complex biological systems, which can be used to explore the interactions between multiple compounds and protein targets of drug. Radix Pueraria has a long history of efficacy in different diseases, containing a variety of compounds that can produce multiple therapeutic effects via multiple targets. To explore the interrelationship between compounds of Radix Pueraria, protein targets, and pathways, the present investigation used the complex network approach to construct the compound-protein target-pathway network of Radix Pueraria. The analysis of the statistical and topological characteristics shows that the network has small-world and scale-free characteristics. The diameter of the network is 7, indicating that the information exchange between two nodes could quickly spread to the whole network. With the rank of degree value and integrated centrality as identification indicators, by taking the threshold of integrated centrality as 0.70, a total of nine key hub nodes containing three active compounds, two protein targets, and four biological pathways were identified: genistein, daidzein, puerarin, MAPK3, MAPK1, hsa01100, hsa05200, hsa05417, and hsa05207. The network analysis suggests these key hub nodes should play an important role in the pharmacological action of Radix Pueraria. The results of this study provide useful information and knowledge for further exploring the pharmacological mechanism of Radix Pueraria in the course of disease treatment.

ObjectiveTo propose a technique of gradual expansion of pedicle diameter to place screws on the thinner pedicle that is difficult to place screws in scoliosis orthopedic surgery, in order to place thicker pedicle screws in the premise of good safety to achieve good stability and orthopaedic effect.MethodsThe authors reviewed that 36 patients with Adolescent idiopathic scoliosis (AIS) (20 females, 16 males) in our department from June 2020 to March 2024 underwent posterior spinal correction and internal fixation were enrolled in the present study. 194 pedicles had narrower diameter ranging from 0 mm to 4.5 mm. After analysis, 155 pedicles (internal diameter: 2.5 mm–4.5 mm) were treated with gradually expanding pedicles technology. The angle between the inserted screws and the upper endplate of the vertebral body was measured 1 week after operation and 3 months after operation to evaluate the placement of the screws after pedicle expansion.ResultsAll operations were completed without dura mater rupture, nerve root injury, infection and poor incision healing. There was no screw breaking or screw pull-out in DR film at 3 months after operation compared with 1 week after operation. There was no significant difference in the angle between screw and upper endplate measured by the three observers at 3 months and 1 week after operation (Wilcoxon's signed rank test, p > 0.05). In the measurement at 1 week or 3 months after operation, there was no statistically significant difference among the three observers. There is a good consistency between the observers (Cronbach's alpha > 0.80).ConclusionIn AIS patients, the thinner pedicle with a diameter range of 2.5 mm to 4.5 mm can be safely inserted with relatively thicker pedicle screws after gradually expanding pedicle technology.

IntroductionWe aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between.MethodsUsing summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites.ResultsWe identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%.DiscussionOur study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

IntroductionPneumocystis jirovecii pneumonia (PJP) is a life-threatening infection in immunocompromised individuals. Immune checkpoint inhibitor (ICI) has brought significant survival benefit in lung cancer patients. Although the few studies showed there was high mortality in PJP patients with ICI use, these studies had no comparative control groups.MethodsA retrospective study was conducted to compare the mortality in PJP patients with lung cancer between those treated with ICI and a concurrent control group treated without ICI.ResultsA total number of 20 non-human immunodeficiency virus (HIV) patients with confirmed PJP and co-existing lung cancer were included in the current study, and classified into ICI group (n=9) and non-ICI group (n=11).There was a clear trend to a shorter onset of PJP in ICI group than non-ICI group (118.9 ± 60.9 vs 253.0 ± 185.1 days), although without statistical significance (p=0.053). Bronchoscopic alveolar lavage fluid were collected from all patients and used to identify Pneumocystis jirovecii. In both groups, metagenomics next-generation sequencing (mNGS) were the most used diagnostic techniques. Within 28 days after the onset of PJP, mortality was significantly higher in the ICI group than non-ICI group (33.3% vs 0, p=0.042)ConclusionLung cancer patients with ICI use had a higher mortality rate after PJP infection than patients without ICI use. Prospective studies with larger sample size and a multi-center design are warranted to further verify the present results.

Abstract Background Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. Methods Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. Results A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62–83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183–324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). Conclusions Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.

Purpose The goal of this study was to examine changes in testicular stiffness at various intervals after the induction of testicular torsion, as well as to assess the predictive value of testicular stiffness for testicular spermatogenesis after torsion. Methods Sixty healthy male rabbits were randomly assigned to one of three groups: complete testicular torsion, incomplete testicular torsion, or control. All rabbits underwent preoperative and postoperative scrotal ultrasonography, including shear wave elastography (SWE), at predetermined intervals. Changes in SWE values were analyzed and compared using repeated-measures analysis of variance. To assess the diagnostic performance of SWE in determining the degree of spermatogenic function impairment, the areas under the receiver operating characteristic curves (AUCs) were calculated. Results SWE measurements in both central and peripheral zones of the testicular parenchyma affected by torsion demonstrated significant negative correlations with spermatogenesis, with coefficients of r=-0.759 (P

The synergistic effect between heterogeneous structures has been proved to enhance the strength and plasticity of alloys, especially in the context of single-phase face-centered cubic (FCC) high-entropy alloys with low stacking fault energy. This study explores the synergistic effects of heterogeneous structures on the strength and plasticity of single-phase FCC FeCoCrNiMo0.2 high-entropy alloys. Through a combination of cryogenic rolling and annealing at 1000 °C for 0.5 h (RA-1000), the alloy demonstrates exceptional strength-ductility synergy and work-hardening ability. The heterogeneous structure comprises fine grains, nano-scale rich- (Cr, Mo) σ phase, and high-density annealing twins. The interaction of σ precipitation and FCC matrix induces heterogeneous deformation-induced strengthening (HDI), while annealing twins and stacking faults act as barriers to dislocation movement, enhancing strength and ductility through a dynamic Hall-Petch effect. Additionally, chemically ordered structures, ordered L12 phase, and type 63 topologically close-packed phases in RA-1000 alloys contribute to improved strain hardening via anti-phase boundaries. This work provides valuable insights for designing multi-scale heterogeneous structures to strengthen high-entropy alloys.

Li7La3Zr2O12 (LLZO) is considered as a promising solid-state electrolyte due to its high ionic conductivity, wide electrochemical window, and excellent electrochemical stability. However, its application in solid-state lithium metal batteries (SSLMBs) is impeded by the growth of lithium dendrites in LLZO due to some reasons such as its high electronic conductivity. In this study, lithium fluoride (LiF) was introduced into Ta-doped LLZO (LLZTO) to modify its grain boundaries to enhance the performance of SSLMBs. A nanoscale LiF layer was uniformly coated on the LLZTO grains, creating a three-dimensional continuous electron-blocking network at the grain boundaries. Benefiting from the electronic insulator LiF and the special structure of the modified LLZTO, the symmetric cells based on LLZO achieved a high critical current density (CCD) of 1.1 mA·cm−2 (in capacity-constant mode) and maintained stability over 2000 h at 0.3 mA·cm−2. Moreover, the full cells combined with a LiFePO4 (LFP) cathode, demonstrated excellent cycling performance, retaining 97.1% of capacity retention after 500 cycles at 0.5 C. Therefore, this work provides a facile and effective approach for preparing a modified electrolyte suitable for high-performance SSLMBs.

Abstract The aim to investigate the predictive efficacy of automatic breast volume scanner (ABVS), clinical and serological features alone or in combination at model level for predicting HER2 status. The model weighted combination method was developed to identify HER2 status compared with single data source model method and feature combination method. 271 patients with invasive breast cancer were included in the retrospective study, of which 174 patients in our center were randomized into the training and validation sets, and 97 patients in the external center were as the test set. Radiomics features extracted from the ABVS-based tumor, peritumoral 3 mm region, and peritumoral 5 mm region and clinical features were used to construct the four types of the optimal single data source models, Tumor, R3mm, R5mm, and Clinical model, respectively. Then, the model weighted combination and feature combination methods were performed to optimize the combination models. The proposed weighted combination models in predicting HER2 status achieved better performance both in validation set and test set. For the validation set, the single data source model, the feature combination model, and the weighted combination model achieved the highest area under the curve (AUC) of 0.803 (95% confidence interval [CI] 0.660–947), 0.739 (CI 0.556,0.921), and 0.826 (95% CI 0.689,0.962), respectively; with the sensitivity and specificity were 100%, 62.5%; 81.8%, 66.7%; 90.9%,75.0%; respectively. For the test set, the single data source model, the feature combination model, and the weighted combination model attained the best AUC of 0.695 (95% CI 0.583, 0.807), 0.668 (95% CI 0.555,0.782), and 0.700 (95% CI 0.590,0.811), respectively; with the sensitivity and specificity were 86.1%, 41.9%; 61.1%, 71.0%; 86.1%, 41.9%; respectively. The model weighted combination was a better method to construct a combination model. The optimized weighted combination models composed of ABVS-based intratumoral and peritumoral radiomics features and clinical features may be potential biomarkers for the noninvasive and preoperative prediction of HER2 status in breast cancer.