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ABSTRACT: Exploring the toxicity and metabolic mechanisms of aflatoxin B1 (AFB1) in ruminants can help to develop strategies to prevent or reduce the transfer of the toxin and its metabolites to milk and meat. This study aimed to explore the effects of 3 concentrations of dietary AFB1 (0, 50, and 500 μg/kg) on hepatic injury and metabolism in Saanen goats via histological examination, western blot analysis, as well as integrated multiomics techniques. Eighteen Saanen goats were assigned to 1 of 3 treatments and the AFB1 challenge lasted for 14 d. Results showed that the liver tissue was enlarged and the relative organ index of the liver was linearly increased with elevated AFB1 levels. The hepatocyte apoptosis rate was significantly increased after AFB1 exposure, and the western blotting results revealed that both the external apoptotic pathway and mitochondrial-mediated intrinsic apoptotic pathway might be involved in AFB1-induced hepatocyte apoptosis. We identified 251, 269, and 154 significant differentially expressed genes (DEG) and 340, 596, and 127 significant differential metabolites in comparisons between the control (CON; 0 μg/kg) and low-dose (LO; 50 μg/kg) groups, the CON and high-dose (HI; 500 μg/kg) groups, and the LO and HI groups, respectively. The DEG annotated were mainly involved in the cell part, cell, single-organism process, cellular process, binding, and other functional categories. The identified metabolites primarily belonged to glycerophospholipids, prenol lipids, carboxylic acids, and derivatives. Integrative analysis of transcriptomics and metabolomics revealed that glycerophospholipids metabolism and choline metabolism in cancer were the most affected pathways related to AFB1 exposure. The identified differential metabolites, DEG, and pathways might have played a crucial role in the hepatic injury induced by AFB1 in goats.

Papillary thyroid carcinoma (PTC) can exhibit lateral neck lymph node metastasis at an early stage. Lateral neck lymph node metastasis is a crucial factor affecting the prognosis of PTC and is an absolute indication for neck lymph node dissection surgery. Additionally, it is a relative contraindication of endoscopic surgery for most medical centers. Therefore, the preoperative identification of lateral neck lymph node metastasis is vital for surgical decision-making and prognosis assessment. Ultrasound, CT, cytology, and clinical features can provide some information on lateral neck lymph node metastasis, but their accuracy does not fully meet clinical needs. Deep learning is a primary method for medical image recognition or feature extraction. In recent years, deep learning-based ultrasound, CT, cytology, conventional clinical parameters, or multimodal models combining these data have been developed and are expected to achieve routine clinical application. With the establishment and sharing of large datasets, automated annotation, algorithm optimization, and resolution of data security issues, deep learning is expected to accurately predict lateral neck lymph node metastasis in PTC. Furthermore, it can be integrated into electronic medical record systems for automated real-time analysis and assist clinical decision-making.

Abstract Background The growth and health of young ruminants are regulated by their gut microbiome, which can have lifelong consequences. Compared with subjective grouping, phenotypic clustering might be a more comprehensive approach to revealing the relationship between calf growth state and core gut microbes. However, the identification of beneficial gut bacteria and its internal mechanisms of shaping host phenotype differentiation remains unclear. Results In this study, calves were divided into two clusters, cluster1 and cluster2, based on 29 phenotypic indicators using cluster analysis. Calves in cluster2 showed better growth performance, including higher body weight (BW), average daily gain (ADG), and dry matter intake (DMI), as well as better serum indicators with a high level of total superoxide dismutase (T-SOD), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) compared to those in cluster1. Multi-omics was used to detect microbial features among calves in different phenotypic clusters. Distinct differences were observed between the two clustered gut microbiomes, including microbial diversity and composition. The close relationships between growth performance, blood metabolites, and microbiome were also confirmed. In cluster2, Bifidobacterium members were the dominant contributors to microbial metabolic functions with a higher abundance. Furthermore, pathways involved in carbohydrate degradation, glycolysis, and biosynthesis of propionate and proteins were active, while methane production was inhibited. In addition, the diversity and richness of hindgut resistome in cluster2 were lower than those in cluster1. The isolation and culture of Bifidobacterium strain, as well as the mice experiment, indicated that B. longum 1109 from calf feces in cluster2 could promote the growth of young hosts, enhance their blood immunity and antioxidation, and improve the development of hindgut. Conclusions In summary, cluster analysis has proved to be a feasible and reliable approach for identifying phenotypic subgroups of calves, prompting further exploration of host-microbiome interactions. Bifidobacterium as a core microbe in the hindgut of calves may play a crucial probiotic role in host phenotypic differentiation. This study enhances our comprehension of how gut core microbe shapes the host phenotype and provides new insights into the manipulation of beneficial gut colonizers to improve the growth performance and productivity of young ruminants. Video Abstract

Abstract Background Functional constipation (FC) significantly impacts children’s health. This study investigates the prevalence and microbiota characteristics of FC in children aged 0–4 years in Zunyi area. Methods From October to December 2023, 2039 children aged 0–4 years in Zunyi were selected using stratified sampling and cross-sectional survey methods. A questionnaire based on Rome IV diagnostic criteria was used. Twenty-nine children with FC were randomly selected as the functional constipation group (FCG), and 26 healthy children, matched for age, sex, and area, were selected as the control group (CG). Results A total of 2051 questionnaires were collected, with 2039 valid responses. Among them, 151 children had FC, resulting in a prevalence rate of 7.4%. The prevalence rates in boys and girls were 6.6% and 8.5%, respectively, with no significant gender difference (P > 0.05). Alpha diversity analysis revealed higher richness and diversity of intestinal flora in the FCG compared to the CG. At the phylum level, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes were dominant in both groups. The FCG showed a higher relative abundance of Firmicutes, Actinobacteria, and Proteobacteria compared to the CG (P

Friction stir additive manufacturing (FSAM) is a novel solid-phase AM method which enables AM of Mg alloy components to achieve excellent mechanical properties. In this study, a high-strength laminated block of ZK61 Mg alloy was fabricated by the FSAM process. The microstructure evolution and mechanical properties were comprehensively studied. The microstructure in the additive zone of the Mg alloy component prepared by FSAM shows uniform and fine equiaxed grains with a size range of 2–6 μm. In the direction parallel to the traverse direction, a strong {0001} basal texture is formed. Microstructural studies were conducted respectively on the primary stirring zone (SZ), re-SZ, and reheating zone in the SZ. It is found that the degree of dynamic recrystallization in the secondary stirring region is more intense which can effectively refine the grains uniformly. The stratified tensile results show that the average ultimate tensile strength (UTS) of the uppermost additive zone can reach 320 MPa, exceeding the UTS of the base materials, which is 275 MPa. The UTS of the FSAM component in the horizontal direction can reach 265 MPa. Nevertheless, due to the high texture strength and increased anisotropy of the product, the average tensile strength in the building direction only reach 40% of that in the horizontal direction. The microhardness of the SZ is between 55 and 70 HV, slightly less than the hardness of the base metal. It reveals FSAM process is a promising method for AM of ZK61 Mg alloy.

The frequent occurrence of intense snowfall events and extreme temperature fluctuations in China significantly hampers the precise monitoring of snow-covered areas. The provision of near-real-time monitoring of fractional snow cover (FSC) in China is essential to bolster disaster management initiatives. The medium-resolution spectral imager (MERSI-II), aboard the FengYun-3D satellite, presents significant capabilities for effective snow monitoring. The aim of this article was to enhance the multiple endmember spectral mixture algorithm based on automatic extraction of endmembers for estimating FY-3D/MERSI-II FSC in China. The accuracy of these estimations was corroborated using 30-m FSC maps derived from Landsat-8/Operational Land Imager (OLI) images. This validation process resulted in RMSE and R2 values of 0.13 and 0.88, respectively, across 253 OLI-based FSC scenes. The article examined and analyzed the effects of diverse land cover types and complex terrain on the FSC estimates, focusing specifically on three major snow-covered areas in China. In comparison to areas with cultivated land and sparse vegetation, bare surfaces yielded the most accurate results, whereas forest regions showed the lowest accuracy. The comparative analysis revealed that the Tibetan Plateau and Northern Xinjiang achieved high accuracy in mapping snow cover. The maps of Northeast China were less precise, largely due to the prevalence of forests. Additionally, while the MERSI-II FSC is effective in monitoring snow cover on flat plains, its performance is less reliable in steep terrain. Moreover, the comparison between MERSI-II and moderate-resolution imaging spectroradiometer FSC indicated that MERSI-II has a marked advantage in areas with substantial snow cover.

Abstract Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are distinct histological subtypes of esophageal cancer. The tumor microenvironment of each subtype significantly influences the efficacy of immunotherapy. However, the characteristics of the tumor microenvironments of both subtypes, as well as their specific impacts on immunotherapy outcomes, still require further elucidation. Through the integration of gene expression profiles from ESCC and EAC obtained from The Cancer Genome Atlas database, alongside tumor tissues derived from Chinese patients, we identified TNFSF10, CXCL10, IL17RB, and CSF2 as pivotal immune molecules with significant prognostic implications. Elevated expression levels of TNFSF10 correlated with adverse outcomes in individuals diagnosed with ESCC. In contrast to patients from other geographical regions, CXCL10, IL17RB, and CSF2 exhibited distinct prognostic implications in Chinese patients with esophageal cancer. The Cox risk scores derived from the molecules TNFSF10 and CXCL10 for ESCC and IL17RB and CSF2 for EAC were used to assess their predictive capacity for immunotherapy efficacy. The results indicate that patients with lower Cox risk scores demonstrated an enhanced response to immunotherapeutic interventions. This study revealed significant disparities in the expression and functionality of immune-related molecules between ESCC and EAC and highlighted the potential of Cox risk scores derived from immune-related molecules to predict the efficacy of immunotherapy in patients. The findings underscore the clinical relevance of these biomarkers and emphasize the necessity for developing ethnic-specific biomarkers to guide personalized immunotherapy strategies between ESCC and EAC.

Abstract Helicene-shaped molecules are compelling chemical structures with unique twisted helical chirality and remarkable properties. Although progress occurs in the catalytic asymmetric synthesis of helicene (-like) molecules, the enantioselective synthesis of multiple helicenes, especially four or higher helicity, is still challenging and has yet to be achieved. Herein, we report an organocatalytic [4 + 2] cycloadditions to achieve double S-shaped quadruple helicene-like molecules with high enantioselectivity (up to 96% e.e.). The enantioselective synthesis of (P,P,P,P) and (M,M,M,M) configurational quadruple helical molecules can be achieved by modulating the structure of the catalyst. Density functional theory (DFT) calculations show that the reaction involves the formation of a duplex vinylidene ortho-quinone methide (VQM) intermediate and two successive cycloaddition reactions. Configurational stability studies elucidate the isomerization process between the isomers. In addition, the structural features and optical properties of the quadruple helicene-like molecules were investigated to explore their potential applications.

The sublevel top coal caving (SLTCC) mining technology is extensively employed in steeply inclined thick coal seams. Because of the typical characteristics of the short coal face in this mining method, a significant portion of the top coal is lost at the face end. For reducing the coal loss, the partially reverse drawing technique (PRDT) is proposed as a novel top coal drawing technique. Meanwhile, based on the Bergmark-Roos model (B-R model), a theoretical method for calculating the recovery ratio of top coal based on the top coal boundary equation and residual top coal amount is proposed. The mechanism of PRDT to reduce top coal loss at the face end is revealed by comparing with single-round sequential drawing technique (SSDT). Physical experiments and in-site observation data were used to verify the theoretical model. The results show that PRDT can effectively reduce the amount of residual coal near the roof by optimizing the shape characteristics of top coal boundary. Suggestions for improve recovery ratio in Wudong Coal Mine were given based on its face parameters.

The current work deals with the precipitation behaviors and mechanical properties of the high zinc content of the Mg-Zn-Cu system alloys using gravity casting. Differential scanning calorimetry (DSC) was conducted to describe the solidification process and precipitation behaviors. Thermodynamic calculations were carried out to determine the precipitation conditions using the Thermo-calc software. The microstructures were characterized by an optical microscope (OM), scanning electron microscope (SEM), electron probe micro analysis (EPMA), transmission electron microscopy (TEM), and confocal laser scanning microscope (CLSM). Tensile tests and micro-hardness tests were applied to investigate the mechanical properties. The results substantiated that the MgZnCu phase precipitates in Cu-containing alloys and that the precipitate content, as well as the precipitate temperature, increased with the Cu content from 0 to 3 wt.% according to the thermodynamic calculations and the DSC results. The measured micro-hardness of the alloy was 53.2, 57.9, 55.8, and 52.5 VHN, respectively. The ultimate tensile strength (UTS), yield strength (YS), and elongation (EL) revealed a λ-like trend of the alloys, and Mg-7Zn-1Cu alloy exhibits the optimum tensile properties with the UTS of 258.9 MPa, YS of 126.2 MPa, and the EL of 14.2%.

In this paper, the fixed-time time-varying formation of heterogeneous multi-agent systems (MASs) based on tracking error observer under denial-of-service (DoS) attacks is investigated. Firstly, the dynamic pinning strategy is used to reconstruct the communication channel for the system that suffers from DoS attacks to prevent the discontinuous transmission information of the communication network from affecting MASs formation. Then, considering that the leader state is not available to each follower under DoS attacks, a fixed-time distributed observer without velocity information is constructed to estimate the tracking error between followers and the leader. Finally, adaptive radial basis function neural network (RBFNN) is used to approximate the unknown ensemble disturbances in the system, and the fixed-time time-varying formation scheme is designed with the constructed observer. The effectiveness of the proposed control algorithm is demonstrated by the numerical simulation.

ABSTRACT: This study aimed to evaluate the effects of dietary supplementation with different types of Saccharomyces cerevisiae fermentation products (SCFP) on lactational performance, metabolism, acute phase protein response, and antioxidant capacity in dairy cows from −21 to 56 DIM. A total of 180 multiparous Holstein dairy cows were blocked by parity, expected calving date, pre-trial BCS, and previous 305-d mature-equivalent milk yield, and then randomly assigned to 1 of 3 dietary treatments: the basal control diet (CON; n = 60), the basal diet supplemented with 40 g/d of XPC (XPC; n = 60; Diamond V, Cedar Rapids, IA), and the basal diet supplemented with 19 g/d of NutriTek (NTK; n = 60, Diamond V). Blood (n = 15, 13, and 12 in the CON, XPC, and NTK groups, respectively) was sampled at −7 (± 3), +3, +7, +21, and +28 d, and milk (n = 19, 18, and 15 in the CON, XPC, and NTK groups, respectively) was sampled from 1 to 8 wk from a subset of cows from −21 to 56 d relative to calving. Data were analyzed using the MIXED procedure in SAS (SAS Institute Inc.). All data were subjected to repeated measures ANOVA. Dietary treatment (Trt), time, and their interaction (Trt × time) were considered as fixed effects and cow as the random effect. Cows fed XPC and NTK had greater ECM yield. Supplementing NTK increased milk fat content and yield and 3.5% FCM yield compared with CON. Milk urea nitrogen was lower in XPC cows than CON. We found that SCFP supplementation decreased plasma BHB, ceruloplasmin, haptoglobin (HPT), and IL-1β concentrations, and it increased plasma P concentrations. In addition, cows fed NTK showed lower creatinine (CR) and cortisol concentrations but increased plasma Ca and myeloperoxidase concentrations than CON cows. In addition, cows fed NTK and XPC both had reduced plasma concentrations of serum amyloid-A (SAA) at 3 DIM compared with CON cows. Furthermore, SCFP cows had greater concentrations of plasma glucose and Ca than CON cows at 7 DIM, and greater concentrations of plasma P at 21 DIM. Between the groups fed different types of SCFP, plasma concentrations of nonesterified fatty acids, malondialdehyde, CR, SAA, and HPT were lower in cows fed NTK compared with cows fed XPC at 7 DIM. Overall, our results indicate the potential benefits of supplementing SCFP in transition dairy cows by modulating immunity and liver metabolic function and supporting ECM yield. The results also suggest that NutriTek at 19 g/d appears to support the performance and health of dairy cows better compared with XPC at 40 g/d, based on improved metabolic and inflammatory status during the transition period.

The identification of paleontological fossil types and their distribution provides important information for geochronological, paleoenvironmental studies, and oil and gas exploration. However, traditional fossil identification methods are time-consuming, labor-intensive, and highly dependent on manual efforts, making it difficult to meet the current demand for rapid exploration and evaluation. Given the limited number of spore and pollen fossil images, the complex classification of taxa, and the specific taxonomy of family, genus, and species, this research focused on improving the automation for fossil image processing, image screening, object detection, and classification. By utilizing techniques such as deep learning for object detection and label smoothing, the efficiency of fossil screening and spore and pollen fossil classification was significantly enhanced. Taking the identification of the Cenozoic spore and pollen fossils from the Bohai Sea shallow area as a case study, a set of intelligent identification methods was developed using neural networks such as YOLOv5 and DenseNet, with an average identification accuracy of 94%, basically meeting the practical accuracy requirements for fossil identification in production. The system could assist in the manual identification of paleontological fossils. By effectively combining various deep learning techniques with specialized knowledge in paleontology, the generalization ability and recognition accuracy of the identification model were improved from both data and model perspectives. Its successful application demonstrates the feasibility of artificial intelligence in the traditional field of paleontological fossil identification, reducing time and labor costs while providing accurate results.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus. The paper focuses on reviewing the clinical applications of several novel ultrasound technologies, including the use of advanced hemodynamic parameters such as blood flow dispersion (Tur index) and wall shear stress (WSS). Carotid artery stenosis is closely associated with cardiovascular disease. Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent, with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity, the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.

Abstract Background Powdery mildew is a devastating fungal disease that poses a significant threat to wheat yield and quality worldwide. Identifying resistance genes is highly advantageous for the molecular breeding of resistant cultivars. GRAS proteins are important transcription factors that regulate plant development and stress responses. Nonetheless, their roles in wheat-pathogen interactions remain poorly understood. Results In this study, we used bioinformatics tools to identify and analyze wheat GRAS family genes responsive to biotic stresses and elucidated the function of TaeSCL6 within this family. A total of 179 GRAS genes in wheat were unevenly distributed on 7 chromosomes, and classified into 12 subfamilies based on phylogenetic relationship analysis. Gene duplication analysis revealed 13 pairs of tandem repeats and 142 pairs of segmental duplications, which may account for the rapid expansion of the wheat GRAS family. Expression pattern analysis revealed that 75% of the expressed TaeGRAS genes are responsive to biotic stresses. Few studies have focused on the roles of HAM subfamily genes. Consequently, we concentrated our analysis on the members of the HAM subfamily. Fourteen motifs were identified in the HAM family proteins from both Triticeae species and Arabidopsis, indicating that these motifs were highly conserved during evolution. Promoter analysis indicated that the promoters of HAM genes contain several cis-regulatory elements associated with hormone response, stress response, light response, and growth and development. Both qRT-PCR and RNA-seq data analyses demonstrated that TaeSCL6 responds to Blumeria graminis infection. Therefore, we investigated the role of TaeSCL6 in regulating wheat resistance via RNA interference and barley stripe mosaic virus induced gene silencing. Wheat plants with silenced TaeSCL6 exhibited increased susceptibility to powdery mildew. Conclusions In summary, this study not only validates the positive role of TaeSCL6 in wheat resistance to powdery mildew, but also provides candidate gene resources for future breeding of disease-resistance wheat cultivars.

Abstract The interaction between the gut-microbiota-derived metabolites and brain has long been recognized in both health and disease. The liver, as the primary metabolic organ for nutrients in animals or humans, plays an indispensable role in signal transduction. Therefore, in recent years, Researcher have proposed the Gut-Liver-Brain Axis (GLBA) as a supplement to the Gut-Brain Axis. The GLBA plays a crucial role in numerous physiological and pathological mechanisms through a complex interplay of signaling pathways. However, gaps remain in our knowledge regarding the developmental and functional influences of the GLBA communication pathway. The gut microbial metabolites serve as communication agents between these three distant organs, functioning prominently within the GLBA. In this review, we provide a comprehensive overview of the current understanding of the GLBA, focusing on signaling molecules role in animal and human health and disease. In this review paper elucidate its mechanisms of communication, explore its implications for immune, and energy metabolism in animal and human, and highlight future research directions. Understanding the intricate communication pathways of the GLBA holds promise for creating innovative treatment approaches for a wide range of immune and metabolic conditions.

Abstract Studies focusing on the kinematics of the ankle joint complex (AJC) have long been a key area of interest for biomechanists and orthopedic surgeons. However, it is not clear how additional weight-bearing walking affects the motion of the AJC compared to walking with a normal body weight (BW) or what adjustments the AJC would instinctively make to accommodate the additional load. To address this gap in knowledge, advanced dynamic biplane radiography combined with a model-based 2D-3D tracking technique was employed to elucidate the inherent kinematics of the AJC during the stance phase while walking with and without additional weight-bearing. It was found that walking with additional 50% body weight (BW + 50%) resulted in a greater dispersion of instantaneous axes of rotation in the talocrural and subtalar joints during the stance phase of gait. The talocrural joint is more plantarflexed and anteriorly translated during the early and late stance phases than during the midstance phases, which suggests that additional weight-bearing affects the stability of the AJC. Moreover, walking with BW + 50% showed that the center of rotation of the talocrural joint was positioned more superiorly and posteriorly during the foot flat to heel-off phase. This, accordingly, increases the ankle-foot gear ratio and the force of the dorsiflexors.

In this study, we investigated how the composition and population of rumen microbiota shifted in response to diurnal oscillations under 2 different diets (high grain vs. high forage). Five multiparous Holstein dairy cows with similar BW, DIM, and parity were enrolled in this study. The cows were fed high-grain (HG) diet for 21 d and then shifted to high-forage (HF) diet in the next 21 d (7-d washout and 14-d experimental period). During the experimental period, DMI and rumination activity were recorded, and rumen fluid was collected 8 times postfeeding every 6 h during the last 2 d of each dietary feeding period. The rumen microbial (bacterial, archaeal, and protozoal) population and composition were assessed using quantitative PCR and amplicon sequencing, respectively. The daily dynamic of measurements was assessed using the cosinor model. The associations between microbial taxa and rumen fermentation profiles were assessed using the linear mixed model, in which the cows were termed as random intercept effects. Daily rhythmicity was observed for DMI, rumination activity, and rumen fermentation profiles under both diets. Additionally, rumination time, rumen pH, and acetate/propionate ratio had a higher mesor (the average level of diurnal fluctuations) under HF diet than in HG diet. The amplitude (the distance between the peak and mesor) of DMI, rumen pH, ammonia nitrogen, and total volatile acid concentration were higher under the HG diet than in the HF diet. Although no significant diurnal oscillation was observed for the rumen microbial population, the relative abundance of 14 bacterial genera, 1 protozoal genus, and 2 archaeal species had significant diurnal oscillations under both HF and HG diets. Among them, the bacterial genera Ruminococcus and Colidextribacter had time at peak of rhythm within 0 to 12 h after feeding, which were also negatively associated with the rumen acetate/propionate ratio. The bacterial genus Rikenellaceae_RC9_gut_group had time at peak of rhythm within 12 to 24 h after feeding, which was also positively associated with the ruminal acetate/propionate ratio. Our study illustrated the daily dynamic on the rumen microbiota population and composition under different diets, and also identified the feeding-responsive rumen microbiota, highlighting that a more targeted approach is needed to manipulate rumen microbiota.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-β and PDGF-β inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

In this paper, the directional modification behavior of rare earth Ce on sulfide inclusions in steel is studied by thermodynamic calculation and experiment methods, and the mechanism of directional modification of rare earth Ce on sulfide inclusions in U71Mn heavy rail steel is proved. The results show that U71Mn heavy rail steel contained more large-sized inclusions and their distribution is more concentrated without the addition of rare earth Ce element. After the addition of rare earth Ce element, the average size of sulfur-containing inclusions in the steel decrease from 5.22 μm to 1.85 μm, and the number density of sulfur-containing inclusions in the steel increase from 83.65 mm−2 to 217.68 mm−2, indicating that the number of sulfur-containing inclusions in the steel increases after the addition of Ce element, and more small-sized sulfur-containing inclusions will form in the steel. The addition of rare earth Ce element can effectively reduce the existence of large-sized inclusions in the steel and modify large-sized inclusions into small-sized inclusions.

Abstract Giant trees are pivotal in forest ecosystems, yet our current understanding of their significance is constrained primarily by the limited knowledge of their precise locations and structural characteristics. Amidst escalating human‐induced disturbances globally, there is an urgent need to devise a practical approach to discover and measure giant trees accurately and efficiently. Here, we propose a novel light detection and ranging (lidar)‐based framework designed for the discovery and measurement of giant trees. Our framework integrates cutting‐edge lidar platforms, including spaceborne, Unmanned Aerial Vehicle (UAV), and backpack lidar, to create an end‐to‐end workflow. The algorithm involved in the proposed framework was compiled into a code package and made available as open source. The method successfully identified the tallest trees in China, including the tallest tree in Asia, a Cupressus austrotibetica with a height of 102.3 m, discovered in Yarlung Zangbo Grand Canyon in May 2023. This finding has not only established a new record but also demonstrated the efficacy of our proposed framework. Utilising lidar data, we performed meticulous measurements at both individual and stand levels, revealing the unique characteristics of this giant tree. The new framework for the discovery and measurement of giant trees, encompassing detailed procedures and codes, is expected to facilitate the discovery and measurement of giant trees with high efficiency, thus fostering advancements in giant tree ecology.

Abstract The catalyst is based on CeO2 cannot be widely used in SCR reaction because of its poor NH3 adsorption performance. In this study, Cu-doped CeTi catalyst was designed. The results show that the CeTiCu0.3 has a wide active temperature window of 200–450 °C in NH3-SCR reaction, and NO conversion is > 80%. This is mainly due to the fact that Cu doping provides more acidic sites on the surface of CeTi catalyst, especially the increase of Lewis acid sites is more obvious. NH3-TPD showed that CeTiCu0.3 had a large NH3 adsorption capacity and was mainly adsorbed at Lewis acid sites. In situ DRIFTs results show that NH3 first adsorbs on the Lewis acid site of catalyst in coordination state and reacts with gaseous NOx, while NOx adsorbed on catalyst surface has low reactivity. Therefore, the CeTiCu0.3 catalyst is mainly controlled by the Eley–Rideal mechanism. More Lewis acid sites, and abunda nt Cu2+/Cu+ and Ce4+/Ce3+ formed Cu2+, Ce3+ and surface reactive oxygen species are the main reasons for the excellent catalytic performance of CeTiCu.

Abstract Letermovir (LTV) prophylaxis is effective in reducing the incidence of clinically significant cytomegalovirus (CMV) infection (cs CMVi) after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Since our centre began administering LTV prophylaxis in June 2022, we have observed a certain increase in the incidence of Epstein–Barr virus (EBV) reactivation after haploidentical HSCT. We retrospectively analysed 230 consecutive patients who underwent haploidentical HSCT with rabbit anti-thymocyte globulin (ATG) from October 2022 to June 2023. The LTV group included 133 patients who received LTV prophylaxis, and the control group included 97 patients who did not receive LTV prophylaxis. At 1 year after HSCT, EBV reactivation was observed in 36 patients (27%) in the LTV group and 13 patients (13%) in the control group (p = 0.012). All patients with EBV reactivation had EBV-DNAemia, and one patient in each group developed EBV-associated posttransplantation lymphoproliferative disorder (PTLD). The proportion of patients with low EBV-DNA loads (> 5 × 102 to

Abstract Background The maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring. Results The microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly. Conclusions Our study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome. Video Abstract

Objectives: Clostridioides difficile ranks among the primary sources of healthcare-related infections and diarrhoea in numerous nations. We evaluated the drug susceptibility and resistance mechanisms of C. difficile isolates from a hospital in Chongqing, China, and identified resistance rates and resistance mechanisms that differed from previous findings. Methods: The toxin genes and drug resistance genes of clinical strains were detected using Polymerase Chain Reaction (PCR), and these strains were subjected to Multilocus Sequence Typing (MLST). The agar dilution technique was employed for assessing susceptibility of antibiotics. Clinical data collection was completed through a review of electronic medical records. Results: A total of 67 strains of toxin-producing C. difficile were detected. All C. difficile isolates demonstrated susceptibility to both metronidazole and vancomycin. However, resistance was observed in 8.95%, 16.42%, 56.72%, 56.72%, 31.34% and 5.97% of the isolates for tigecycline, tetracycline, clindamycin, erythromycin, moxifloxacin and rifampin, respectively. Among the strains with toxin genotypes A + B + CDT - and belonging to the ST3, six strains exhibited reduced susceptibility to tigecycline (MIC=0.5mg/L) and tetracycline (MIC=8mg/L). The tetA(P) and tetB(P) genes were present in these six strains, but were absent in tetracycline-resistant strains. Resistance genes (ermB, tetM, tetA(P) and tetB(P)) and mutations (in gyrA, gyrB, and rpoB) were identified in resistant strains. Conclusions: In contrast to prior studies, we found higher proportions of ST3 isolates with decreased tigecycline sensitivity, sharing similar resistance patterns and resistance genes. In the resistance process of tigecycline and tetracycline, the tetA(P) and tetB(P) genes may play a weak role.

Impact toughness, tensile properties, grains, and inclusions of industrial Al-killed steel Q355B were investigated by adding cerium (Ce) from 0, 0.0028%–0.0048%. The results revealed that: (1) With the increase of Ce additions, the size of inclusions decreased and the oxide inclusions significantly decreased while oxide-sulfide inclusions significantly increased; (2) Inclusions of sample without Ce were Al2O3 and Mn(Ca)S, inclusions of sample with adding 0.0028% Ce were CeAlO3, Mn(Ca)S, and Ce2O2S, and inclusions of sample with adding 0.0048% Ce were CeAlO3, Ce2S3, Ce2O2S, and Mn(Ca)S; (3) Grains of sample with Ce were refined. Microstructure with 0.0028% Ce addition displayed a more uniform ferrite and microstructure with 0.0048% Ce addition exhibited a more uniform pearlite, which was due to Ce2O2S as effective nucleating agent for α-Fe and MnS as effective nucleating agent for γ-Fe; (4) Impact toughness and yield strength of sample with 0.0028% Ce addition was highest in the three samples, because of the microstructure of refining and uniform ferrite grains and small Ce-based inclusions.

With the ongoing advancements and innovations of electronic device, the demand for low-melting-point solder is rising, especially for flexible printed electronics. The service environments of electronic device are complex and diverse, which have raised concerns regarding long-term service reliability in solder materials. In this work, a novel type of 30In33Sn25Bi4AgxZn low-melting-point alloy solder was proposed. The effects of Zn content on the corrosion resistance and electrochemical migration (ECM) resistance of the alloy system were investigated through electrochemical test and water drop test (WDT). The passivation film on the surface and the amorphous region of InSnBiAg8Zn alloys effectively inhibits the anodic dissolution of Zn atoms, improves the corrosion resistance of the alloy and delays the occurrence of electrochemical migration failure. The microscopic mechanism of ECM was revealed by conducting in-situ observations of the migration process of the alloy solder and analyzing the composition and morphology of the anode alloy and the migration products.

In this study, a novel localized selective remelting technique was proposed to treat the welding interface regions on the top and bottom surfaces of the AZ31 friction stir welded joint. Compared with the untreated joint, the treated joint achieved a favorable combination of strength (ultimate tensile strength of 238 MPa) and ductility (elongation of 13.3%). Digital image correlation (DIC) characterization revealed that the high strain-hardening ability primarily stemmed from the substantial mitigation of strain localization, which was caused by a comprehensive factor, including reduced SF value fluctuation between weld micro-zones, low residual dislocation density, and numerous extension twinning activation in the nugget zone.

Abstract Background New-onset atrial fibrillation (NOAF) is a common adverse outcome in acute ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI) and is associated with a worse prognosis. The platelet-to-albumin ratio (PAR) has been utilized to predict the severity and prognosis of cardiovascular diseases. This study aims to investigate the predictive value of PAR combined with the C2HEST score for NOAF in the elderly population with STEMI undergoing PCI. Methods 445 elderly STEMI patients without a history of atrial fibrillation (AF) who underwent PCI were consecutively enrolled in this study. Multivariate logistic regression analysis was used to identify independent risk factors for NOAF after PCI. Results 50 patients (11.2%) developed NOAF after PCI. Multivariate logistic regression analysis revealed that heart rate (HR), systemic immune-inflammation index (SII), uric acid (UA), PAR, and C2HEST score were independent risk factors for NOAF. The area under the curve (AUC) of the combined PAR and C2HEST score was 0.839, and Delong’s test indicated that the combined model had superior predictive value compared to individual markers (AUC of PAR: 0.738; AUC of C2HEST score: 0.752) (P

Abstract Hemolytic peptides are therapeutic peptides that damage red blood cells. However, therapeutic peptides used in medical treatment must exhibit low toxicity to red blood cells to achieve the desired therapeutic effect. Therefore, accurate prediction of the hemolytic activity of therapeutic peptides is essential for the development of peptide therapies. In this study, a multi-feature cross-fusion model, HemoFuse, for hemolytic peptide identification is proposed. The feature vectors of peptide sequences are transformed by word embedding technique and four hand-crafted feature extraction methods. We apply multi-head cross-attention mechanism to hemolytic peptide identification for the first time. It captures the interaction between word embedding features and hand-crafted features by calculating the attention of all positions in them, so that multiple features can be deeply fused. Moreover, we visualize the features obtained by this module to enhance its interpretability. On the comprehensive integrated dataset, HemoFuse achieves ideal results, with ACC, SP, SN, MCC, F1, AUC, and AP of 0.7575, 0.8814, 0.5793, 0.4909, 0.6620, 0.8387, and 0.7118, respectively. Compared with HemoDL proposed by Yang et al., it is 3.32%, 3.89%, 5.93%, 10.6%, 8.17%, 5.88%, and 2.72% higher. Other ablation experiments also prove that our model is reasonable and efficient. The codes and datasets are accessible at https://github.com/z11code/Hemo .

Highlights The constructions under internal and external driving forces were introduced and compared with each other. The physicochemical properties were analyzed for the assessment of crystalline quality and photoelectric characteristics. The photocatalytic applications, mechanisms, and developments of the core-shell semiconductor-graphene nanoarchitectures were illustrated in detail.

Dietary fat content can reduce the methane production of dairy cows; however, the relevance fatty acid (FA) composition has towards this inhibitory effect is debatable. Furthermore, in-depth studies elucidating the effects of unsaturated fatty acids (UFA) on rumen function and the mechanism of reducing methane (CH4) production are lacking. This study exposed 10 Holstein cows with the same parity, similar milk yield to two total mixed rations: low unsaturated FA (LUFA) and high unsaturated FA (HUFA) with similar fat content. The LUFA group mainly added fat powder (C16:0 > 90%), and the HUFA group mainly replaced fat powder with extruded flaxseed. The experiment lasted 26 d, the last 5 d of which, gas exchange in respiratory chambers was conducted to measure gas emissions. We found that an increase in the UFA in diet did not affect milk production (P > 0.05) and could align the profile of milk FAs more closely with modern human nutritional requirements. Furthermore, we found that increasing the UFA content in the diet lead to a decrease in the abundance of Methanobrevibacter in the rumen (|linear discriminant analysis [LDA] score| > 2 and P 2 and P

Objective The middle Miocene submarine fan in the Qiongdongnan Basin is an important target for natural gas exploration in the northern South China Sea. However, there has been no consensus on the source of submarine fan sediments for a long time. Provenance analysis will be important for the optimization of natural gas exploration in this area. Methods In this paper, the detrital zircon U-Pb age spectrum characteristics of drilling cores from the middle Miocene submarine fan in the Qiongdongnan Basin were analysed and compared with the U-Pb ages of zircons from potential provenance areas to determine the source of submarine fans in the study area. Results The results show that ① the U-Pb ages of detrital zircons from the N-1, N-2, N-3 and N-4 wells in the northern part of the basin are characterized by Yanshanian (160, 157, 133, 107, 102, 99 Ma), Indosinian (249, 241, 239 Ma) and Caledonian (466, 455 Ma) age peaks and have high similarity with the U-Pb age characteristics of detrital zircons from Hainan Island sediments but low similarity with the U-Pb age characteristics of detrital zircons from Red River and central Vietnam sediments. ② The detrital zircon U-Pb ages of three wells (S-1, S-2, and S-3) in the southern part of the basin show peak ages of Caledonian (435, 431, 425 Ma), Hercynian (396, 392 Ma), Indosinian (242, 238, 237 Ma), and Yanshanian (143 Ma). The S-2 well has a younger unimodal Himalayan (21 Ma) age peak. Conclusion The provenance of the middle Miocene in the northern part of the basin is Hainan Island. The influence of the provenance on the Red River and Central Vietnam is very limited. The provenance of the middle Miocene in the southern Qiongdongnan Basin was a double-source supply from the Red River and Hainan Island and was dominated by the former, with an obvious difference from west to east.

Background: Hyperbaric oxygen therapy (HBOT), which is widely used in clinical practice, is aimed at improving nerve function impairment after brain injury. Meanwhile, the effects of music therapy on brain function are unclear. This retrospective study was conducted to explore the application effect of HBOT combined with music therapy on patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Methods: For this retrospective study, 130 patients with aSAH after HBOT were selected from our hospital from June 2021 to June 2022. The patients were divided into the observation (n = 70) and control (n = 60) groups based on whether they received music therapy. Comparisons were made on general demographic data, blood flow rate in median cerebral artery (MCA), cerebral vasospasm (CVS), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) score, Self-Rating Depressive Scale (SDS), and Self-Rating Anxiety Scale (SAS) of patients. Results: Baseline data between the two groups showed no statistically significant difference (P > 0.05). After management, patients in the observation group presented significantly lower SAS and SDS scores (P < 0.05), lower blood flow rate in MCA, CVS and NIHSS scores (P < 0.05), and higher ADL scores than the control group (P < 0.05). Conclusions: The combination of HBOT and music therapy can considerably improve cerebral neurological deficits, slow down cerebral arterial blood flow, promote the recovery of postoperative cerebral function in aSAH patients, and improve anxiety and depression and the patients’ ADL.

In order to achieve structural health monitoring, a frequency-domain-based chipless radio-frequency identification sensor has been studied. The sensor is composed of an octagonal patch antenna and a Taconic CER-10 substrate, with overall dimensions of 24 × 24 × 1.27 mm3. Crack detection and strain detection simulations were conducted in the 3–6 and 6–12 GHz dual-frequency bands using HFSS. The results show that the sensor's resonant frequency decreases under tensile strain and increases under compressive strain. As the width, depth, and length of structural cracks increase, the sensor's resonant frequency shifts to lower frequencies. The designed structural health monitoring sensor can detect structural strain and damage with millimeter-level resolution through resonant frequency shifts. The sensor's maximum strain capacities under three different mechanical strains are −40% to 90%, −70% to 120%, and −40% to 90%, respectively. The sensor can detect changes in crack width, depth, and length without deformation, demonstrating a linear relationship between crack expansion and resonant frequency.

The antioxidant activity of natural products is closely related to their antiglycation effects. This study aimed to examine the antiglycation activity and elucidate the underlying mechanisms of two specific peptides, EDYGA (Glu-Asp-Tyr-Gly-Ala) and DLLCIC (Asp-Leu-Leu-Cys-Ile-Val), derived from protein hydrolysates of the Pelodiscus sinensis. Both EDYGA and DLLCIC were efficient in bovine serum albumin (BSA)/glucose model to inhibit BSA glycation, while DLLCIC showed higher antiglycation activity than EDYGA. Firstly, it was found that EDYGA and DLLCIC could inhibit the formation of NEG and AGEs. Moreover, EDYGA and DLLCIC were able to maintain the protein secondary structure and stabilize the band positions (amide I & II). Additionally, molecular simulations indicated that DLLCIC can spontaneously interact with the central site of BSA, specifically at Lys114 and Glu424 residues, through hydrogen bonds with an energy strength of −0.7 kcal/mol. Furthermore, CCK-8 and morphological experiments confirmed that EDYGA and DLLCIC improved cell survival against AGEs-induced cytotoxicity, with EC50 values of 17.64 μM for EDYGA and 15.08 μM for DLLCIC. These findings serve as a significant reference for the development of EDYGA and DLLCIC as effective antiglycation agents in the prevention of glycation-mediated diseases.

Conclusions: This study suggests that exacerbation of symptoms during air conditioning use can be considered a predictive factor for the severity of pediatric AR. Doctors and parents should pay special attention to these children to prevent more severe symptoms and improve the quality of life of these patients as early as possible.

ObjectiveThe purpose of this study was to explore the clinical characteristics, survival time and prognostic factors of patients undergoing craniotomy for brain metastases (BM) from lung adenocarcinoma (LUAD).MethodsA total of 208 patients with BM from LUAD who underwent craniotomy at the Zhengzhou University People’s Hospital, Henan province, China from March 2005 to October 2022 were included in this retrospective study. All patients were confirmed as BM of LUAD by histopathology. The clinical data included patient gender, age, occupation, family history of tumor, smoking history, alcohol drinking history, neurological symptoms, history of lung cancer treatment, tumor location, tumor number, tumor size, gene status, expression of S-100, CEA, Ki67, and PD-L1 by immunohistochemistry, KPS after craniotomy, whether tumor therapy was continued after craniotomy, and survival time. Univariate and multivariate Cox regression was used to analyze the prognostic factors of patients undergoing craniotomy for LUAD BM.ResultsA total of 208 patients met the inclusion and exclusion criteria, including 110 males (52.9%) and 98 females (47.1%), with an average age of 61.4 years. 203 patients (97.6%) had neurological symptoms. 84 patients (40.4%) had smoking history, 89 patients (42.8%) had alcohol drinking history, and 31 patients (14.9%) had the family history of tumor. Only 5 patients (2.4%) had received lung cancer treatment before craniotomy. The intracranial location of BM was mostly in the frontal lobe (54, 26.0%) and the metastatic sites were mostly single (117, 56.3%); the metastatic tumor size was mostly between 2-5 cm (141, 67.8%). Genetically, 43.3% patients (90 cases) had EGFR mutations, and immunohistochemical analysis showed that most patients were PD-L1 positive (160, 76.9%) and Ki67 > 30% (137, 65.9%). Most patients (145, 69.7%) had KPS score under 80 after craniotomy. Only 72 patients (34.7%) received continued tumor therapy after craniotomy. 190 patients (91.3%) were successfully followed up. The median survival time was 11.5 months, and the 3-year survival rate was 15.7%. Multivariate analysis revealed that smoking history, Ki67 percentage, KPS after craniotomy, and molecular targeted therapy after craniotomy were independent factors affecting the survival time of patients.ConclusionsAlthough survival remains poor, patients who had no-smoking history, Ki67 percentage ≤30%, KPS≥80 after craniotomy, and molecular targeted therapy after craniotomy can improve the prognosis and prolong the survival time.

Colorectal cancer (CRC) is widely recognized as the third most prevalent malignancy globally and the second leading cause of cancer-related mortality. Traditional treatment modalities for CRC, including surgery, chemotherapy, and radiotherapy, can be utilized either individually or in combination. However, these treatments frequently result in significant side effects due to their non-specificity and cytotoxicity affecting all cells. Moreover, a considerable number of patients face relapses following these treatments. Consequently, it is imperative to explore more efficacious treatment interventions for CRC patients. Immunotherapy, an emerging frontier in oncology, represents a novel therapeutic approach that leverages the body's immune system to target cancer cells. The principal advantage of immunotherapy is its capacity to selectively target cancer cells while minimizing damage to healthy cells. Its recent adoption as a neoadjuvant therapy presents significant potential to transform the treatment landscape for both primary resectable and metastatic CRC. This review endeavors to offer a comprehensive overview of current strategies in CRC immunotherapy, critically analyze existing literature, underscore anticipated outcomes from ongoing clinical trials, and deliberate on the challenges and impediments encountered within the field of immunotherapy.

IntroductionSalvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.MethodsThis study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.ResultsThe fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.DiscussionThis study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.

Background Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers.Methods In this prospective observational study, patients with mCRC receiving F&S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment.Results A total of 55 patients were included, of which 25 were in the RTC and 30 in the NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% vs 36.7%, p=0.002), median PFS (6.2 vs 2.7 months, p

Background: Cuproptosis is a unique form of cell death that is dependent on copper, which is fundamentally different from other recognized forms of cell death. However, the molecular and immune characteristics in cuproptosis-defined subgroups of cholangiocarcinoma (CCA) remain to be further illustrated. Methods: We conducted a comprehensive investigation into the genetic and transcriptional variation, prognostic significance, and expression profiles of 16 cuproptosis-related genes (CRGs). To construct a prognostic signature based on differentially expressed genes between molecular subtypes, we employed LASSO and multivariate Cox regression analyses. We then assessed the values of this signature in prognostic prediction, immune infiltration, and therapeutic responses in CCA. The robustness of the signature was further validated in the GEO and IMvigor210 cohorts. Additionally, qRT-PCR and Western blotting (WB) were utilized to confirm the expression of the signature genes across different cell lines. Results: A total of 16 CRGs were analyzed revealed differentially expressed, and two CRG-related clusters were identified, which displayed contrasting survival times.Then, a robust cuproptosis-related risk model was established and was an independent prognostic factor for CCA, which was further validated across two external cohorts. Low-risk patients had a better overall survival than high-risk patients. The comprehensive results showed that a low-risk score was correlated with metabolism-related pathways, high infiltration of CD8 T cells, B cells, and M1 macrophages, active immunity and less aggressive phenotypes, high chemotherapeutic sensitivity, and more benefit from immunotherapy. In contrast, a high-risk score was associated with cancer and metastasis-related pathways, high infiltration of M2 macrophages, high expression of immune checkpoint genes, suppressive immunity and more aggressive phenotypes, and less benefit from chemotherapeutic and immunotherapy. In addition, the critical CRGs were further validated through qRT-PCR and WB. Conclusions: We developed a novel risk model for CCA patients, which serves as a promising biomarker for distinguishing prognosis as well as molecular and immune characteristics.

Abstract The STING pathway plays a critical role in tumor immunosurveillance. However, the precise mechanisms by which STING regulates gamma delta (γδ) T cell function during tumor progression remain unclear. Herein, we find that tumor‐derived cyclic GMP‐AMP (cGAMP) activates a distinct STING pathway by inducing TBK1‐mediated phosphorylation of Eomes in γδ T cells during the early stage of tumor development is demonstrated. This activation leads to interferon‐gamma (IFN‐γ) production and consequent tumor surveillance. However, at advanced stages of tumor progression, the accumulation of immune‐suppressive cytokine transforming growth factor‐beta (TGF‐β) downregulates STING levels, compromising the function of γδ T cells. Notably, the synergism between TGF‐β inhibition and STING agonists effectively counteracts the immunosuppressive tumor microenvironment, thereby augmenting the antitumoral effects of γδ T cells. These findings present a novel mechanism involving STING‐mediated IFN‐γ production in γδ T cells and hold significant implications for the development of potent immunotherapeutic approaches against cancer.

Radiation damage is a critical concern for materials employed in radiation environments such as space, radiotherapy centers, and nuclear energy systems. Numerous models have been developed to estimate the primary radiation damage. The slightly modified Athermal Recombination-Corrected (mARC)-Displacement per Atom (DPA) model proposes a simple function to describe the atomic displacement near the Threshold Displacement Energy (TDE). The present work systematically investigates the global minimum TDE and the near-TDE mARC-DPA model against experimental electron irradiation damage data for 26 materials. The determined high-accuracy global minimum TDE values are generally consistent with previous studies. The corresponding theoretical calculations agree well with experimental measurements, implying the applicability of the mARC model. Renormalization of certain experimental data is required due to the potential issues related to experimental measurements, the value of resistivity change per Frenkel pair (ρFP), or average TDE (Ed). Nevertheless, while some experimental data are supposed to be adjusted, the analysis shows that the ratio of ρFP/Ed can be definitively determined if assuming the experimental data for the remainders.

Abstract Machine learning (ML) has made some significant contributions to stroke prevention, but the stability and accuracy of existing models for clinical applications are uncertain. This study develops and validates an interpretable ML model using metabolic and coagulation biomarkers to predict ischemic stroke in elderly hypertensive patients in Northwest China. The prediction model used 453 electronic medical records for the model building (80% as a training set and 20% as a test set) and 132 for external validation. The final seven key features (D‐dimer, cystatin C, homocysteine, hemoglobin A1c, prothrombin time, low‐density lipoprotein C, and triglyceride glucose‐body mass index) were selected by the advanced approach, elastic net, and classical wrapping approaches. The final model, eXtreme gradient boosting, was identified as having superior performance than the other 9 classifers (random forest, Gaussian process, multilayer perceptron, logistic regression, support vector machine, K‐nearest neighbor, decision tree, Gaussian naive bayes, and ensemble model), with area under the receiver‐operating characteristic curves of 0.97 and 0.94 for the test and external validation sets, respectively. The final model demonstrates excellent stability, accuracy, and clinical usefulness through various metrics and decision curve analysis. Additionally, an online human–machine interface application has been developed for clinical practice to help early identification and intervention for ischemic stroke in elderly hypertensive patients.

Signals from global navigation satellite systems (GNSSs) in urban areas suffer from serious multipath errors caused by building blockages and reflections. The use of deep neural networks offers great potential for predicting and eliminating complex multipath/non-line-of-sight (NLOS) errors. However, existing methods for predicting the original signals face two remaining challenges. The first challenge is an inability to effectively exploit irregular GNSS measurement data caused by an inconsistent number of visible satellites in different epochs. The second challenge is degradation in the generalization performance of the multipath/NLOS prediction model when using data collected from different locations and periods. To address these challenges, this paper proposes a novel graph transformer neural network (GTNN) for predicting satellite visibility that effectively learns environment representations from irregular GNSS measurements to both alleviate multipath interference and improve the generalization performance of the multipath prediction model. To learn from irregular GNSS measurements, a sky satellite graph is constructed as input to a graph neural network by using satellites captured in the same epoch, which can represent the spatial relationships between satellites and enable the model to learn satellite-related features sufficiently well. To improve the generalization ability of our multipath prediction model, a multihead attention mechanism is introduced to aggregate satellite node information by computing the correlation between satellites to extract the environment representation around the receiver. Based on the constructed sky satellite graph and the multihead attention mechanism, our novel GTNN for predicting satellite visibility can not only handle irregular GNSS measurements but can also learn an environment representation via graph attention. Comparative experiments were conducted on real-world GNSS measurement data in urban areas, demonstrating that the proposed method can achieve an accuracy exceeding 96% for satellite visibility prediction and obtain better generalization performance than existing multipath prediction methods. Moreover, the attention weights among satellites were visualized to demonstrate the environment representation learned by the GTNN from the sky satellite graph.

Background There is ample evidence to suggest that patients infected with SARS-CoV-2 Omicron variant may experience liver dysfunction. However, the impact of pre-infection liver function on postinfection mortality rates remains inadequately researched.Methods Data from 847 hemodialysis (HD) patients, diagnosed with Omicron across six HD centers between December 2022 and February 2023, were analyzed. Initial liver function assessments were conducted, following which patients were monitored for mortality outcomes. The stepwise multivariable Cox regression analysis and receiver operating characteristic (ROC) curves were utilized to identify the predictors of mortality.Results From the total, 98 patients (11.6%) succumbed, with a majority (80/98) within a month postinfection. The deceased patients were observed to be mostly older males with an increased prevalence of diabetes and tumors, signifying higher AST and C-reactive protein levels. These patients also exhibited lower hemoglobin, albumin, and prealbumin levels. An elevated AST [per 1 IU increment; HR 1.04 (95% CI 1–1.04), p = 0.026], AST/ALT ratio [per 1 increment; HR 1.52 (95% CI 1.27–2.36), p = 0.004], and reduced prealbumin [per 10 mg/L increment; HR 0.93 (95% CI 0.9–0.96), p

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1− T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1− T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.

This study investigates the phase evolution and enrichment mechanism of the cementitious materials in a blend of blast furnace (BF) and basic oxygen furnace (BOF) slags. Theoretical calculations reveal that there is an optimal modification temperature range of 1400–1550 °C, which is crucial for the transformation of the slag constituents. At lower temperatures (500–850 °C), the addition of BF slag reduces the proportion of calcium iron oxide (Ca2Fe2O5, C2F) and promotes the formation of merwinite (Ca3MgSi2O8, C3MS2). At higher temperatures (850–1450 °C), the addition of BF slag decreases the free CaO content, enhancing the stability of the modified slag. The presence of the dicalcium silicate and tricalcium phosphate complex (α-Ca2SiO4–Ca3(PO4)2, α-C2S-C3P), dicalcium ferrite (C2F), and magnesioferrite (MgFe2O4) in the modified slag facilitates the creation of dicalcium silicate (Ca2SiO4, C2S) and C3MS2 phases, which improve the stability of the slag and increase the amount of cementitious active materials, indirectly reducing crushing costs. Experimental results indicate that excessive BF slag content results in the over formation of gehlenite (Ca2Al2SiO7, C2AS) and C3MS2, potentially affecting the cementitious active material proportion. Insufficient BF slag does not fully utilize its CaO, SiO2, and Al2O3 for enhancing the BOF slag stability and increasing the cementitious material content. A BF slag content of approximately 30 % optimally consumes free CaO, promotes C2S formation, and enhances the stability of the modified slag. This research highlights the crucial role of the temperature and BF slag content in the phase evolution and cementitious potential of BF-modified BOF slags, providing guidelines for optimized utilization in construction materials.