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Objective: To evaluate the protective effect and possible mechanism of dandelion jujube juice on D-galactose-induced liver injury in Sprague Dawley (SD) rats. Methods: D-galactose was intraperitoneally injected into the rats at a dose of 500 mg/kg for six weeks to establish a chronic liver injury model. These rats treated with D-galactose were then randomly divided into model group and dandelion jujube juice group (treated with 10 mL/kg·d of dandelion jujube juice by intragastric administration for 28 d). The liver index was calculated, and the pathological changes in liver tissue were observed using HE staining and oil red O staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum, malondialdehyde (MDA) content and catalase (CAT) activity in liver tissue were determined by corresponding assay kit. Western blot analysis was used to detect the protein expression, including Kelch like epichlorohydrin associated protein 1 (Keap1), nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), BCL2 associated X (Bax), and B-cell lysoma-2 (Bcl-2) proteins in liver tissue. Results: Compared with the blank group, the liver index and liver lipid deposition area were increased in the model group. In addition, the model group showed a significant increase in the levels of serum ALT (P

Abstract The intestine, is responsible for food digestion, nutrient absorption, endocrine secretion, food residue excretion, and immune defense. These function performances are based on the intricate composition of intestinal epithelial cells, encompassing differentiated mature cells, rapidly proliferative cells, and intestinal stem cells. Although the characteristics of these cell types are well-documented, in-depth exploration of their representative markers and transcription factors is critical for comprehensive cell fate trajectory analysis. Here, we unveiled the feature genes in different cell types of the human and mouse gut through single-cell RNA sequencing analysis. Further, the locations of some specific transcription factors and membrane proteins were determined by immunofluorescence staining, and their role in regulating the proliferation and differentiation of intestinal epithelial cells were explored by CRISPR/Cas9 knockout. Therefore, this study not only reports new markers for various intestinal epithelial cell types but also elucidates the involvement of relevant genes in the determination of epithelial cell fate and maintenance of stem cell homeostasis, which facilitates the tracing and functional elucidation of intestinal epithelial cells.

Abstract Objectives Allergic rhinitis (AR) is a complex disorder with variable pathogenesis. Increasing evidence suggests that the LRRC8A is involved in maintaining cellular stability, regulating immune cell activation and function, and playing significant roles in inflammation. However, the involvement of LRRC8A in AR inflammation and its underlying mechanisms remain unclear. Methods LRRC8A expression in AR patients, confirmed by qRT-PCR and Western blotting, was analyzed to investigate its relationship with the clinical characteristics of AR patients. In vitro, IL-13 stimulated HNEpCs to establish a Th2 inflammation model, with subsequent LRRC8A knockout or overexpression. NOX1/NOX4 inhibitor (GKT137831) and chloride channel inhibitor (DCPIB) were utilized to investigate AR development mechanisms during LRRC8A overexpression. An OVA-induced AR model with nasal mucosa LRRC8A knockdown confirmed LRRC8A's regulatory role in AR inflammation. Results LRRC8A mRNA and protein levels were significantly elevated in AR patients, positively correlating with NADPH oxidase subunits and Th2 inflammatory markers. In vitro, IL-13 stimulation of HNEpCs resulted in upregulation of LRRC8A and increased expression of NOX1, NOX4, and p22phox, along with mitochondrial dysfunction and NF-κB pathway activation. The knockout of LRRC8A reversed these effects. In nasal mucosal epithelial cells, DCPIB and GKT137831 completely blocked mitochondrial dysfunction caused by the overexpression of LRRC8A, which led to up-regulation of NOX1, NOX4, and p22phox. In vivo, knocking down LRRC8A reduced eosinophil infiltration, downregulated the expression of NOX1, NOX4, p22phox IL-4, IL-5, and IL-13, and decreased NF-κB pathway activation. Conclusion LRRC8A drives the upregulation of NOX1, NOX4, and p22phox, leading to ROS overproduction and mitochondrial dysfunction. It also activates NF-κB, ultimately leading to nasal mucosal epithelial inflammation. LRRC8A may be a potential target for the treatment of AR.

Abstract Background Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.

Unraveling the mechanisms of community assembly in different ecosystems is a central ecological issue. Soil depth, which is the predominant characteristic of karst regions, possibly affects community assembly from the regional species pool into local communities. However, the influence of karst soil depth on plant community assembly mechanisms remains unclear. We investigated the community functional traits of karst shrublands by calculating community-weighted mean (CWM) traits for leaf dry matter content (LDMC), specific leaf area (SLA), leaf carbon content (LCC), leaf nitrogen content (LNC), leaf phosphorus content (LPC), and leaf potassium content (LKC). To explore the assembly pattern of karst shrublands, we assessed the extent of trait divergence or convergence using trait-based null model analyses. Additionally, we examined how community functional traits and assembly patterns changed with varying local soil depths. Karst shrublands were found to exhibit CWM trait combinations characterized by high LDMC and LCC, as well as low SLA, LNC, LPC, and LKC to adapting to harsh environments. Furthermore, the CWM of LDMC, LCC, LCC/LNC ratio, and LCC/LPC ratio significantly decreased, while SLA and LNC in karst shrublands significantly increased along soil depth gradients. This indicates that, as soil conditions improved, the karst shrubland community shifted from a conservative survival strategy to a resource-acquisition strategy. Overall, the convergence pattern prevailed in the karst shrubland communities for most leaf traits. As the karst soil depth increased, the traits of the shrubland communities shifted from a convergence pattern toward a neutral assembly. These results demonstrate for the first time that species were primarily assembled into karst shrubland communities through environmental filtering, while the importance of environmental filtering in the assembly process gradually weakened with increasing soil depth. Our study underlines the necessity of increasing soil quantity to allow more species from the regional species pool to enter local shrublands, thereby promoting karst community succession.

Inspired by the skin structure, an asymmetric wettability tri-layer nanofiber membrane (TNM) consisting of hydrophilic inner layer loaded with lidocaine hydrochloride (LID), hydrophobic middle layer with ciprofloxacin (CIP) and hydrophobic outer layer has been created. The hydrophobic outer layer endows the TNM with waterproof function and anti-adhesion from contaminants. The hydrophobic middle layer with CIP preserves long-term inhibition of bacteria growth and the hydrophilic inner layer with LID possesses optimal water-absorbing capacity and air permeability. The TNM dramatically elevates the water contact angles from 10° (inner layer) to 120° (outer layer), indicating an asymmetric wettability, which could directionally transport wound exudate within the materials and meanwhile maintain a comfortable and moist environment to promote wound healing. Furthermore, the sequential release of LID and CIP could relieve pain rapidly and achieve antibacterial effect in the long run, respectively. In addition, the TNM shows superior biocompatibility towards L929 ​cells. The in vivo results show the TNM could prevent infection, accelerate epithelial regeneration and significantly accelerate wound healing. This study indicates the developed TNM with asymmetrical wettability and synergetic drug release shows great potential as a wound dressing in clinical application.

Abstract Especially, the processing and utilization of biomass-based material is closely related to the vessel, e.g. the flow of vapour and additive. It is conventional that vessels in most plants can influence on water and nutrients transport between adjacent cells, which could just infer to be important in the wood-based panel industries. In this work, a complete characterization of vessels and pits is presented for three conventional biomasses in wood-based panel: poplar (Populus deltoides) (P), moso bamboo (Phyllostachys edulis) (B), and the fruit shell of oil camellia (Camellia Oleifera) (FS_OC). Every material is analyzed by combining several techniques including: light microscopy, scanning electron microscopy and surveying calculations from resin casting. The results show that among the three biomass materials, B has a significantly larger vessel width (164.8 ± 6.0 μm for B, 2.2 ± 6.2 μm for P, 10.0 ± 0.8 μm for FS_OC) and smaller inclination angle of the perforation plates (6.8° for B, 44.7° for P), which is more conductive to improving moisture transfer between the vessels. The vessel length of P varies widely from 676.8 μm to 1025.2 μm, which is related to its seasonal growth. By resin casting analysis, more differences in the morphology and distribution of pits in the vessel walls were observed between the three species. Such as, For B, there are numerous pits between vessel cells, while very few to none between vessel and parenchyma cells or fiber. In addition to pits, B and FS_OC also have spiral thickening structures on their vessel walls. The pit membrane is an elliptical shape in P, while slit-like shape in FS_OC and a combination of both elliptical and slit-like shape in bamboo. The unique microstructural characteristics of vessels is related to the individual plant growth traits, which is the basis for biomass-based material processing and utilization.

Soil moisture， as a key hydrological variable connecting the surface and atmospheric water and heat exchange， affects the land-air water and heat exchange and carbon cycle process.However， due to the difficulty in monitoring soil moisture in alpine mountain areas， there are some difficulties in related research.The study of time stability can reduce the difficulty of soil moisture acquisition by selecting representative points.In this study， the slope of Shangzhangfanggou grassland in Shiyang River basin of Qilian Mountain was selected to set up a high-density and high-time resolution soil moisture monitoring network to explore the temporal and spatial variation and temporal stability of soil moisture on the slope scale in alpine mountainous areas.The research results show that： （1） The surface soil moisture （10 cm， 15.90%） is significantly higher than that in the deep layer （50 cm， 11.78%）， and its temporal variability （CvT=19.46%） is also stronger than that in the deep layer （CvT=10.67%）， but its spatial variability （CvS=20.05%） is weaker than that in the deep layer （CvS=27.06%）.（2） The time stability Index of Temporal Stability （0.24） is stronger than that of the deep layer （0.34）， and the surface layer and the deep layer can represent the surface soil moisture of the slope through 3 or 5 soil moisture monitoring points respectively （R2> 0.90）.（3） Slope position and soil hydrological properties have obvious influence on time stability， and the time stability point is more likely to appear at the position with larger bulk density and smaller shape parameter n under the slope.The research results are helpful to better understand the temporal and spatial variation law， temporal stability characteristics and control function of soil moisture on slope in alpine mountain areas.

Abstract The contribution of the soil microbes to agroecosystem multifunctionality under global change remains poorly understood. Here, based on data from a field experiment involving elevated carbon dioxide (CO2) and warming in a rice-wheat agroecosystem, we found that soil microbes influence the impact of climate change on agroecosystem functions. The stability of food production during the rice season increased under elevated CO2 but decreased under warming, with no significant changes in the wheat season. The interactive influences of elevated CO2 and warming on agroecosystem multifunctionality were found to be minimal. The abundance of soil fungi and nematode was associated with agroecosystem stability during the rice and wheat seasons, respectively. Soil archaeal diversity and bacterial abundance were linked to agroecosystem multifunctionality in the rice and wheat seasons, respectively. Our work proves the positive effects of soil microbes on agroecosystem functions and highlights the implications of maintaining microbial diversity for agroecosystem health under climate change.

Abstract Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism.

Abstract Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Abstract Background Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression’s value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. Results From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p

Abstract Background Bone metastasis (BM) occurs when colon cancer cells disseminate from the primary tumor site to the skeletal system via the bloodstream or lymphatic system. The emergence of such bone metastases typically heralds a significantly poor prognosis for the patient. This study's primary aim is to develop a machine learning model to identify patients at elevated risk of bone metastasis among those with right-sided colon cancer undergoing complete mesocolonectomy (CME). Patients and methods The study cohort comprised 1,151 individuals diagnosed with right-sided colon cancer, with a subset of 73 patients presenting with bone metastases originating from the colon. We used univariate and multivariate regression analyses as well as four machine learning algorithms to screen variables for 38 characteristic variables such as patient demographic characteristics and surgical information. The study employed four distinct machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), to develop the predictive model. Additionally, the model was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), while Shapley additive explanation (SHAP) was utilized to visualize and analyze the model. Results The XGBoost algorithm performed the best performance among the four prediction models. In the training set, the XGBoost algorithm had an area under curve (AUC) value of 0.973 (0.953–0.994), an accuracy of 0.925 (0.913–0.936), a sensitivity of 0.921 (0.902–0.940), and a specificity of 0.908 (0.894–0.922). In the validation set, the XGBoost algorithm had an AUC value of 0.922 (0.833–0.995), an accuracy of 0.908 (0.889–0.926), a sensitivity of 0.924 (0.873–0.975), and a specificity of 0.883 (0.810–0.956). Furthermore, the AUC value of 0.83 for the external validation set suggests that the XGBoost prediction model possesses strong extrapolation capabilities. The results of SHAP analysis identified alkaline phosphatase (ALP) levels, tumor size, invasion depth, lymph node metastasis, lung metastasis, and postoperative neutrophil-to-lymphocyte ratio (NLR) levels as significant risk factors for BM from right-sided colon cancer subsequent to CME. Conclusion The prediction model for BM from right-sided colon cancer developed using the XGBoost machine learning algorithm in this study is both highly precise and clinically valuable.

Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Abstract Contemporary large-scale and systematic agricultural operations demand the collaborative efforts of multiple agricultural machines with distinct functionalities. However, the failure of a single agricultural machine during collaborative operations jeopardizes the entire undertaking. To address this challenge, this paper proposes a multi-machine collaborative dynamic job allocation method based on the improved ant colony algorithm. Initially, the improved ant colony algorithm is employed to determine the optimal solution for harvester scheduling. This solution is then fed into the data conversion algorithm to acquire the necessary unloading point information for transport vehicle scheduling. Subsequently, the improved ant colony algorithm is once again utilized to optimize the transport vehicle scheduling. In cases of agricultural machinery failure or changes in the operating environment, two distinct methods are employed based on the situation. The first involves double-layer rescheduling of both harvester and transport vehicles, while the second employs single-layer rescheduling exclusively for the transport vehicles, yielding the respective rescheduling results. The outcomes demonstrate that the proposed solution method effectively identifies the current optimal scheduling plan for both the harvester and transport vehicle in the event of malfunctions. Moreover, under the premise that the unproductive waiting time of the harvester is reduced to zero, and the number of transport vehicles is minimized, it achieves the minimization of operating time cost and transportation cost. This method exhibits significant potential for seamless integration into the practical application of unmanned farms, providing a foundation for addressing scheduling and management challenges in multi-agricultural machinery collaborative operations within complex farmland operating environments.

Abstract Vertical field effect transistor (VFET), in which the semiconductor is sandwiched between source/drain electrodes and the channel length is simply determined by the semiconductor thickness, has demonstrated promising potential for short channel devices. However, despite extensive efforts over the past decade, scalable methods to fabricate ultra-short channel VFETs remain challenging. Here, we demonstrate a layer-by-layer transfer process of large-scale indium gallium zinc oxide (IGZO) semiconductor arrays and metal electrodes, and realize large-scale VFETs with ultra-short channel length and high device performance. Within this process, the oxide semiconductor could be pre-deposited on a sacrificial wafer, and then physically released and sandwiched between metals, maintaining the intrinsic properties of ultra-scaled vertical channel. Based on this lamination process, we realize 2 inch-scale VFETs with channel length down to 4 nm, on-current over 800 A/cm2, and highest on-off ratio up to 2 × 105, which is over two orders of magnitude higher compared to control samples without laminating process. Our study not only represents the optimization of VFETs performance and scalability at the same time, but also offers a method of transfer large-scale oxide arrays, providing interesting implication for ultra-thin vertical devices.

Abstract Emergent superconductivity at the LaAlO3/KTaO3 interfaces exhibits a mysterious dependence on the KTaO3 crystallographic orientations. Here by soft X-ray angle-resolved photoemission spectroscopy, we directly resolve the electronic structure of the LaAlO3/KTaO3 interfacial superconductors and the non-superconducting counterpart. We find that the mobile electrons that contribute to the interfacial superconductivity show strong k ⊥ dispersion. Comparing the superconducting and non-superconducting interfaces, the quasi-three-dimensional electron gas with over 5.5 nm spatial distribution ubiquitously exists and shows similar orbital occupations. The signature of electron-phonon coupling is observed and intriguingly dependent on the interfacial orientations. Remarkably, the stronger electron-phonon coupling signature correlates with the higher superconducting transition temperature. Our observations help scrutinize the theories on the orientation-dependent superconductivity and offer a plausible and straightforward explanation. The interfacial orientation effect that can modify the electron-phonon coupling strength over several nanometers sheds light on the applications of oxide interfaces in general.

To explore the influence of slightly acidic electrolyzed water (SAEW) with different pH and available chlorine contents (ACC) on the germination of tartary buckwheat (Fagopyrum tataricum), the germination rate was taken as the index, and the germination process of tartary buckwheat sprouts with SAEW was optimized by single factor and response surface experiments. Moreover, to obtain good quality selenium-enriched tartary buckwheat sprouts, the effects of different Na2SeO3 concentrations on tartary buckwheat were studied on the basis of SAEW germination, with the total selenium content and germination rate as indexes. The optimum technological parameters were determined as follows: soaking time 2.3 h, pH6.5, germination temperature 21 ℃ and germination time 108 h. Under these conditions, the germination rate was 84.96%, which was close to the predicted value of the response surface group (85.36%), being 14.3% and 11.71% higher than those of distilled water and tap water groups, respectively. The optimal concentration of Na2SeO3 was 60 mg/L, under which the total selenium content of tartary buckwheat sprouts was 15.5 mg/L, and the germination rate was 85.63%, which were both higher than the predicted and actual values of response surface group. This study provided a theoretical and scientific basis for the development of SAEW and selenium-enriched treatment of tartary buckwheat sprouts.

Due to the lack of design guidance for high-performance Cr–V steel, it is challenging to identify the target steel within a vast design space. In this paper, a design loop combining property-oriented design criteria and machine learning prediction model is proposed. Based on the design criteria, the alloying values of the initial sample and the allowable variation range are given to narrow the search space. Then, the machine learning model is employed to predict properties across all design nodes within the design space. The results suggest that the samples within the design space, meeting the proposed design criteria, demonstrate higher hardness. However, wear resistance decreases rapidly as Cr increases and V/Cr decreases. The predicted optimal sample C2.1V3Cr4Mo2.5 is prepared and its properties are measured, showing that the absolute errors between the measured and predicted values are less than 5%. In addition, C2.1V3Cr4Mo2.5 is more cost-effective than Cr26 and V10. This design loop facilitates the rapid selection of the most promising steel for experimentation and provides a new avenue for the development of wear-resistant alloy steels.

The crucial role of heavy-tailed distributions in the analysis of financial and extreme value phenomena is widely acknowledged; however, there is a scarcity of probability distributions to accurately model such data. In the pursuit of analyzing financial data, researchers frequently seek out new and optimal statistical models. With a focus on this specific research domain, we present a groundbreaking model known as the new heavy-tailed exponentiated exponential distribution. The new model’s heavy-tailed behaviors are investigated through visual and mathematical methods. Estimation of the new model parameters is done through maximum likelihood estimators. Moreover, a Monte Carlo simulation study is undertaken to analyze the performance of estimators. In our study, we examine two specific data sets pertaining to the price quotations of Yamaha pianos in the United States to present the new distribution. The first set of data focuses on the prices of Yamaha upright pianos, while the second set highlights the prices of Yamaha Clavinova digital pianos. By conducting four evaluation tests, we evaluate the fitting performance of the NHTE-exponential distribution against the rival distributions.

Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells. The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma. With the increasing knowledge of host–pathogen interactions, especially bacterial strategies for survival and proliferation within host cells, host-directed therapy (HDT) has attracted increased interest and has emerged as a promising anti-infection method for treating intracellular infection. Herein, we applied a cell-based screening approach to a US Food and Drug Administration (FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium (S. Typhimurium). This screening allowed us to identify the antidiarrheal agent loperamide (LPD) as a potent inhibitor of S. Typhimurium intracellular proliferation. LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity. A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B (GPNMB) induced by LPD. In addition, LPD treatment effectively protected against S. Typhimurium infection in Galleria mellonella and mouse models. Thus, our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens. Moreover, LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

Abstract Previous research has established associations between amygdala functional connectivity abnormalities and major depressive disorder (MDD). However, inconsistencies persist due to limited sample sizes and poorly elucidated transcriptional patterns. In this study, we aimed to address these gaps by analyzing a multicenter magnetic resonance imaging (MRI) dataset consisting of 210 first-episode, drug-naïve MDD patients and 363 age- and sex-matched healthy controls (HC). Using Pearson correlation analysis, we established individualized amygdala functional connectivity patterns based on the Automated Anatomical Labeling (AAL) atlas. Subsequently, machine learning techniques were employed to evaluate the diagnostic utility of amygdala functional connectivity for identifying MDD at the individual level. Additionally, we investigated the spatial correlation between MDD-related amygdala functional connectivity alterations and gene expression through Pearson correlation analysis. Our findings revealed reduced functional connectivity between the amygdala and specific brain regions, such as frontal, orbital, and temporal regions, in MDD patients compared to HC. Importantly, amygdala functional connectivity exhibited robust discriminatory capability for characterizing MDD at the individual level. Furthermore, we observed spatial correlations between MDD-related amygdala functional connectivity alterations and genes enriched for metal ion transport and modulation of chemical synaptic transmission. These results underscore the significance of amygdala functional connectivity alterations in MDD and suggest potential neurobiological mechanisms and markers for these alterations.

Abstract The linear ubiquitin chain assembly complex (LUBAC) mediates the linear ubiquitination of various proteins and is involved in NF-κB signaling and immune regulation. However, the function and mechanism of linear ubiquitination in regulating oncogenic signaling and tumor growth have remained poorly understood. Herein, we identified Gli proteins, key transcription factors in the Hedgehog (Hh) signaling pathway, as novel substrates of LUBAC. Linear ubiquitination stabilizes Gli proteins, leading to the noncanonical activation of Hh signaling in CRC cells. Furthermore, LUBAC facilitates tumor growth in CRC cells. Additionally, elevated expression of LUBAC components in CRC tissues was observed, and higher expression levels of these components correlated with poor prognosis in CRC patients. Interestingly, inhibition of LUBAC using either a small molecule agonist or RNA silencing specifically suppressed cell growth in CRC cells but had no effect on normal intestinal cells. Taken together, aberrant expression of LUBAC components activates Hh signaling noncanonically by mediating linear ubiquitination, promoting tumor growth in CRC, demonstrating the novel function of linear ubiquitination in regulating the protein stability of its substrates and highlighting the potential of targeting LUBAC as a therapeutic strategy in CRC.

Abstract Dietary micronutrients are integral to the development and progression of constipation; however, the specific relationship between dietary copper intake and constipation has not been thoroughly investigated. This study aims to examine the correlation between dietary copper intake and constipation among U.S. adults, thereby offering novel insights and recommendations for the clinical management and prevention of constipation. Bowel health data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were analyzed. Subjects’ dietary information was collected through questionnaire records. Multivariate logistic regression analysis, subgroup analysis, and curve fitting analysis were used to assess the correlation between dietary copper intake and chronic constipation. After adjusting for all possible confounders, each unit increase in dietary copper intake (converted to natural logarithms) was associated with a 20% reduction in the prevalence of constipation (OR = 0.80; 95% CI 0.65–0.98; P = 0.037). The interaction P-values for all subgroups were greater than 0.05, indicating that the findings were stable and consistent across subgroups. The present study showed a significant negative association between dietary copper intake and chronic constipation in adults. This finding raises clinical and healthcare professionals’ awareness of the impact of dietary trace elements on intestinal health and has important implications for the development of personalized meal plans and rational supplementation of trace copper in patients with constipation.

Abstract Background Breast cancer has emerged as the foremost cause of female mortality worldwide, with triple negative breast cancer accounting for approximately 10–15% of all breast cancer cases. The triple negative breast cancer family has obvious familial heritability, but no potential pathogenic variation was found in BRCA1/2. Case presentation The patient was a 56-year-old woman of Han ethnicity. The clinical characteristics of this patient with breast cancer were summarized, peripheral blood of one normal female and two patients with breast cancer in this family was collected, DNA was extracted, and the potential pathogenic variation was analyzed by whole exome sequencing. The normal female and two patients with breast cancer in this family shared a maternal grandmother. The proband’s right breast mass was punctured, and the biopsy showed invasive carcinoma of the right breast, grade II–III, with necrosis. No mutation was found in BRCA1/2 gene test; immunohistochemical of surgical specimens showed triple negative breast cancer. Three mutation types and 17 gene mutation sites were detected through bioinformatics prediction analysis on the basis of co-segregation of genotype and phenotype within the family and whole exome sequencing results. Combined with the Cancer Genome Atlas database comprehensive analysis, the MT1E c.G107A (p.C36Y) mutation may be a potential pathogenic site. Conclusions Through whole exome sequencing, we identified a total of 17 potential pathogenic mutation loci, none of which have been reported thus far. Therefore, our work expanded the gene mutation spectrum of familial hereditary triple negative breast cancer, which can provide more basis for family genetic counseling.

Abstract Hierarchical compartmentalization responding to changes in intracellular and extracellular environments is ubiquitous in living eukaryotic cells but remains a formidable task in synthetic systems. Here we report a two-level compartmentalization approach based on a thermo-responsive aqueous two-phase system (TR-ATPS) comprising poly(N-isopropylacrylamide) (PNIPAM) and dextran (DEX). Liquid membraneless compartments enriched in PNIPAM are phase-separated from the continuous DEX solution via liquid-liquid phase separation at 25 °C and shrink dramatically with small second-level compartments generated at the interface, resembling the structure of colloidosome, by increasing the temperature to 35 °C. The TR-ATPS can store biomolecules, program the spatial distribution of enzymes, and accelerate the overall biochemical reaction efficiency by nearly 7-fold. The TR-ATPS inspires on-demand, stimulus-triggered spatiotemporal enrichment of biomolecules via two-level compartmentalization, creating opportunities in synthetic biology and biochemical engineering.

Abstract Intestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated m6A modification maintains intestinal homeostasis by impeding epithelial cell death. Mettl3 knockout induces both apoptosis and necroptosis in IECs. Targeting different modes of cell death with specific inhibitors unveils that RIPK1 kinase activity is critical for the cell death triggered by Mettl3 knockout. Mechanistically, this occurs via the m6A-mediated transcriptional regulation of Atf3, a transcription factor that directly binds to Cflar, the gene encoding the anti-cell death protein cFLIP. cFLIP inhibits RIPK1 activity, thereby suppressing downstream apoptotic and necroptotic signaling. Together, these findings delineate the essential role of the METTL3-ATF3-cFLIP axis in homeostatic regulation of the intestinal epithelium by blocking RIPK1 activity.

Abstract The rod-like viruses show anomalously rapid diffusion in bio-tissue networks originated from the rotation-facilitated transportation; however, the experimental investigation of the correlation of the rotational and translational dynamics is still in blank. Herein, typical rod-like and spherical gold nanoparticles (NPs) are dispersed in the classical Tetra-PEG gels, respectively, as model systems for light scattering studies. The contributions from translational and rotational diffusive dynamics, and network fluctuation dynamics can be well-resolved and the stretch exponent of rotational dynamics at 0.25 is proven to be the fingerprint for the coupled rotational and translational dynamics of nanorods. The rotation facilitated re-orientation finally leads to the fast transportation of nanorods. The discoveries are confirmed to be valid for rod-like biomacromolecule systems by studying the diffusive dynamics of Tobacco mosaic virus in gels. The work can be inspiring for the development of protocols to prevent infection of microorganism and regulate the transportation of nano-medicines.

Abstract Background Coral diseases are significant drivers of global coral reef degradation, with pathogens dominated by Vibrio coralliilyticus playing a prominent role in the development of coral diseases. Coral phenotype, symbiotic microbial communities, and host transcriptional regulation have been well-established as factors involved in determining coral disease resistance, but the underlying mechanisms remain incompletely understood. Methods This study employs high-throughput sequencing to analyse the symbiotic microbial and transcriptional response of the hosts in order to evaluate the disease resistance of Acropora valida and Turbinaria peltata exposed to Vibrio coralliilyticus. Results A. valida exhibited pronounced bleaching and tissue loss within 7 h of pathogen infection, whereas T. peltata showed no signs of disease throughout the experiment. Microbial diversity analyses revealed that T. peltata had a more flexible microbial community and a higher relative abundance of potential beneficial bacteria compared to A. valida. Although Vibrio inoculation resulted in a more significant decrease in the Symbiodiniaceae density of A. valida compared to that of T. peltata, it did not lead to recombination of the coral host and Symbiodiniaceae in either coral species. RNA-seq analysis revealed that the interspecific differences in the transcriptional regulation of hosts after Vibrio inoculation. Differentially expressed genes in A. valida were mainly enriched in the pathways associated with energy supply and immune response, such as G protein-coupled receptor signaling, toll-like receptor signaling, regulation of TOR signaling, while these genes in T. peltata were mainly involved in the pathway related to immune homeostasis and ion transport, such as JAK-STAT signaling pathway and regulation of ion transport. Conclusions Pathogenic challenges elicit different microbial and transcriptional shifts across coral species. This study offers novel insights into molecular mechanisms of coral resistance to disease.

In recent years, the emergence of novel biological threats has brought biosecurity issues to the forefront of societal concerns. The United Kingdom established the UK Biological Security Strategy in 2018, and after revisions, a new version was published in June 2023. The strategy presents the UK's new vision, mission, outcomes, and plans, and provides action plans from four perspectives: understanding, preventing, detecting, and responding to major biological threats to protect the UK's national interests and enhance biosecurity emergency preparedness and response capabilities. This article introduces the main contents and framework of the 2023 UK Biosecurity Strategy in detail, and reflects on its implications to provide a reference for the construction and development of China's biosecurity strategy.

Abstract Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.

Abstract The emitter-cavity strong coupling manifests crucial significance for exploiting quantum technology, especially in the scale of individual emitters. However, due to the small light-matter interaction cross-section, the single emitter-cavity strong coupling has been limited by its harsh requirement on the quality factor of the cavity and the local density of optical states. Herein, we present a strategy termed waveguide-assisted energy quantum transfer (WEQT) to improve the single emitter-cavity coupling strength by extending the interaction cross-section. Multiple ancillary emitters are optically linked by a waveguide, providing an indirect coupling channel to transfer the energy quantum between target emitter and cavity. An enhancement factor of coupling strength $$\widetilde{g}/g > 10$$ g ̃ / g > 10 can be easily achieved, which dramatically release the rigorous design of cavity. As an extension of concept, we further show that the ancillae can be used as controlling bits for a photon gate, opening up new degrees of freedom in quantum manipulation.

Abstract Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm−2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Abstract Background Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms. Methods iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP. Results Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI. Conclusion In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.

Abstract Removing texture while preserving the main structure of an image is a challenging task. To address this, this paper propose an image smoothing method based on global gradient sparsity and local relative gradient constraints optimization. To reduce the interference of complex texture details, adopting a multi-directional difference constrained global gradient sparsity decomposition method, which provides a guidance image with weaker texture detail gradients. Meanwhile, using the luminance channel as a reference, edge-aware operator is constructed based on local gradient constraints. This operator weakens the gradients of repetitive and similar texture details, enabling it to obtain more accurate structural information for guiding global optimization of the image. By projecting multi-directional differences onto the horizontal and vertical directions, a mapping from multi-directional differences to bi-directional gradients is achieved. Additionally, to ensure the consistency of measurement results, a multi-directional gradient normalization method is designed. Through experiments, we demonstrate that our method exhibits significant advantages in preserving image edges compared to current advanced smoothing methods.

Abstract To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P

Abstract In this study, a shaking table test was conducted on long-short composite anti-slide piles, the development process and dynamic response of cracks in a pile-supported slope were observed, and the failure mechanism of the slope was explored. The experiment showed that the failure of the pile-supported slope under an earthquake was a gradual process; cracks first occur at the top of the slope, where the support action of the piles was weak. As the input seismic action increased, cracks developed downwards along the slope. Owing to the support effect of the long-short anti-slide composite piles, the transmission path of the cracks changed, and the cracks developed along the top of the composite piles, ultimately leading to overtop failure. When cracks appeared on the slope or near final failure, the acceleration response law of the supported slope undergone a sudden change, which was an important indicator of slope instability. The distribution of dynamic soil stress on the pile body was greatly affected by the input peak ground acceleration, and the maximum bending moment of the long-short composite anti-slide piles was located near the weak interlayer.

Abstract Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas.

Abstract Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Abstract Intrinsic breast cancer molecular subtyping (IBCMS) provides significant prognostic information for patients with breast cancer and helps determine treatment. This study compared IBCMS methods on various gene-expression platforms in PALOMA-2 and PALLET trials. PALOMA-2 tumor samples were profiled using EdgeSeq and nanostring and subtyped with AIMS, PAM50, and research-use-only (ruo)Prosigna. PALLET tumor biopsies were profiled using mRNA sequencing and subtyped with AIMS and PAM50. In PALOMA-2 (n = 222), a 54% agreement was observed between results from AIMS and gold-standard ruoProsigna, with AIMS assigning 67% basal-like to HER2-enriched. In PALLET (n = 224), a 69% agreement was observed between results from PAM50 and AIMS. Different IBCMS methods may lead to different results and could misguide treatment selection; hence, a standardized clinical PAM50 assay and computational approach should be used. Trial number: NCT01740427

Abstract Background Research examining the healthy aging trajectory of retired older adults with multimorbidity is limited, leaving uncertainties regarding the optimal physical activity (PA) intensity and frequency necessary to sustain healthy aging during retirement. Methods Our study investigated the moderating effects of PA on the healthy aging trajectories of retired older adults living with multimorbidity in the United States (US). We utilized data from 1,238 retired individuals aged 50 to 102 who contributed 11,142 observations over 16 years from the Health and Retirement Study (HRS). We employed mixed effects modeling to assess the impact of various classes of multimorbidity on this group and examine how different PA, PA intensities, and PA frequencies influence the disability, physical, and cognitive functioning domains of healthy aging. Results The results reveal that while outcomes differed significantly, retired older adults in the US attained healthy aging at baseline. However, their ability to maintain healthy aging declined over time, with multimorbidity, especially musculoskeletal and neurological conditions, accelerating this decline. Fortunately, PA, especially light to moderate intensities, is associated with improving healthy aging and moderating the impact of multimorbidity on the disability and cognitive functioning domains of healthy aging. However, the specific moderating effects of PA depend on its frequency, intensity, and chronic conditions. Conclusions The significant variability in healthy aging attainment among retired older adults underlies the need to consider these differences when addressing healthy aging issues in the US. Accounting for these variations would aid in evaluating the potential impact of future interventions and contribute to achieving health equity. Fortunately, our dynamic findings facilitate this objective by identifying specific frequencies and intensities of PA tailored to different aspects of multimorbidity and healthy aging. This highlights PA, especially light-to-moderate intensity, as an essential, cost-effective, and amenable strategy for alleviating the impact of multimorbidity on healthy aging.

Abstract Background Cardiac myxomas are the most common type of primary cardiac tumors in adults, but they can have variable features that make them difficult to diagnose. We report two cases of atrial myxoma with calcification or ossification, which are rare pathological subgroups of myxoma. Case presentation A 47-year-old woman and a 35-year-old man presented to our hospital with different symptoms. Both patients had a history of chronic diseases. Transthoracic and transesophageal echocardiography revealed a mass in the left or right atrium, respectively, with strong echogenicity and echogenic shadows. The masses were suspected to be malignant tumors with calcification or ossification. Contrast transthoracic echocardiography(cTEE) showed low blood supply within the lesions. The patients underwent surgical resection of the atrial mass, and the pathology confirmed myxoma with partial ossification or massive calcification. Conclusion We report two rare cases of atrial myxoma with calcification or ossification and analyze their ultrasonographic features. Transthoracic echocardiography and cTEE can provide valuable information for the diagnosis and management of such mass. However, distinguishing calcification and ossification in myxoma from calcification in malignant tumors is challenging. More studies are needed to understand the pathogenesis and imaging characteristics of these myxoma variants.

Abstract Background Multicenter non-small cell lung cancer (NSCLC) patient data is information-rich. However, its direct integration becomes exceptionally challenging due to constraints involving different healthcare organizations and regulations. Traditional centralized machine learning methods require centralizing these sensitive medical data for training, posing risks of patient privacy leakage and data security issues. In this context, federated learning (FL) has attracted much attention as a distributed machine learning framework. It effectively addresses this contradiction by preserving data locally, conducting local model training, and aggregating model parameters. This approach enables the utilization of multicenter data with maximum benefit while ensuring privacy safeguards. Based on pre-radiotherapy planning target volume images of NSCLC patients, a multicenter treatment response prediction model is designed by FL for predicting the probability of remission of NSCLC patients. This approach ensures medical data privacy, high prediction accuracy and computing efficiency, offering valuable insights for clinical decision-making. Methods We retrospectively collected CT images from 245 NSCLC patients undergoing chemotherapy and radiotherapy (CRT) in four Chinese hospitals. In a simulation environment, we compared the performance of the centralized deep learning (DL) model with that of the FL model using data from two sites. Additionally, due to the unavailability of data from one hospital, we established a real-world FL model using data from three sites. Assessments were conducted using measures such as accuracy, receiver operating characteristic curve, and confusion matrices. Results The model’s prediction performance obtained using FL methods outperforms that of traditional centralized learning methods. In the comparative experiment, the DL model achieves an AUC of 0.718/0.695, while the FL model demonstrates an AUC of 0.725/0.689, with real-world FL model achieving an AUC of 0.698/0.672. Conclusions We demonstrate that the performance of a FL predictive model, developed by combining convolutional neural networks (CNNs) with data from multiple medical centers, is comparable to that of a traditional DL model obtained through centralized training. It can efficiently predict CRT treatment response in NSCLC patients while preserving privacy.

Abstract Background Pulmonary function is very important for the healthy development of children and adolescents. However, fewer studies have been conducted on pulmonary function trends in children and adolescents in remote areas. The aim of this study was to estimate the forced vital capacity (FVC) trend and its relationship with body mass index (BMI) among young people in Xinjiang during 1985–2014 using data from seven successive national surveys. Methods A total of 19,449 Xinjiang children and adolescents aged 7–18 years were extracted from the Chinese National Survey on Students’ Constitution and Health. Height, weight, and FVC were measured repeatedly in each survey. FVC comparisons between adjacent surveys by age and sex were conducted by nonparametric Kruskal-Wallis after Kolmogorov-Smirnov of normality. One-way ANOVA and least significant difference(LSD) method was used to compare differences in FVC levels of Xinjiang children and adolescents with different BMI. The relationship between BMI and FVC was investigated using a nonlinear regression model. Results The FVC levels of Xinjiang children and adolescents peaked in 2000, with overall FVC levels being 8.7% higher in 2000 than in 1985. Since then, a substantial decline occurred, contrasting to 2000, with FVC levels decreasing by 27% in 2014, which was still lower than that in 1985 by 20.73%. The proportion of overnutrition boys increased from 0.2% in 1985 to 22.1% in 2014, and girls from 0.5% in 1985 to 14.5% in 2014. An inverted U-shape association between FVC and BMI values was obtained for Xinjiang children and adolescents. Conclusions Targeted measures should be carried out in schools to control BMI levels to ensure good lung function in children and adolescents in Xinjiang. Future studies should pay more attention to other factors affecting FVC, such as dietary behaviour, physical activity, and racial differences among children and adolescents.

Abstract The widespread use of smartphones implies that intelligent systems must address the negative emotions experienced by a diverse user group when encountering usability difficulties. Therefore, exploring the relationship between users’ emotions and operational behaviors is crucial for further enhancing the accessibility of intelligent systems. Touch dynamics, as a method of dynamic touch data monitoring, has already provided many models for emotion recognition, which are beneficial in gaining insight into users’ accessibility needs for smartphones and exploring intelligent solutions to design issues. This paper validates this aspect through interviews and experimental studies. The study first conducted an open-ended interview, and then used a touch behavior experiment with emotional labels and a questionnaire to validate the association between accessibility design flaws in intelligent systems and user emotions. The interview results show that middle-aged and older smartphone users have difficulty activating accessibility tools independently. Consequently, this paper establishes a dataset for emotion classification based on touch gesture data, which is used to gain insight into implicit difficulties in the interaction process through negative emotions. From a touch experiment and questionnaire survey of 57 sample users, there is approximately a 78.57% match between the accessibility needs of intelligent systems and users’ negative emotions, with interaction fluency and interface cognition being the main reasons for this phenomenon. Therefore, touch dynamics, as a non-invasive method of emotion recognition, can use negative emotional feedback to gain insights into user needs that are difficult to detect by other methods. This has application value for enhancing users’ emotional experience and promoting a transformation in interaction design thinking.

Kylin-2 is an advanced neutronics lattice code, developed by Nuclear Power Institute of China. High-precision multigroup cross section library is need for KYLIN-2 to carry out simulation of current pressurized water reactor (PWR) and advanced reactor. In this paper a multigroup cross section library generation system named TPAMS was developed, the methods in TPAMS dealing with resonance data such as subgroup parameters, lambda factor, resonance integral were discussed. Moreover, the depletion chain simplification method was studied. TPAMS can produce multigroup library in binary and ASIIC formats, including detailed data contents for resonance, transport and depletion calculations. A multigroup cross section library has been generated for KYLIN-2 based on TPAMS system. The multigroup cross section library was verified through the analysis of various criticality and burnup benchmarks, the values of multiplication factor and isotope density were compared with the experiment data. Numerical results demonstrate the accuracy of the multigroup cross section library and the reliability of the multigroup cross section library generation system TPAMS.