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Abstract Background Antimicrobial resistance (AMR) is one of the most pressing global public health challenges; in particular, the rapid dissemination of carbapenem-resistant Enterobacterales (CRE) is emerging as a significant concern worldwide. Flies, serving as carriers of pathogens, pose a potential threat in the transmission of antibiotic-resistant bacteria (ARB) between animals and humans. The aim of this study was to evaluate and reveal the potential risk of AMR spread by flies. Methods A total of 450 flies were collected from four farms, four rural areas, and four urban areas in Dengfeng, Henan, China. To select CRE strains on the surface of flies, three flies sampled from the same geographical location were arbitrarily selected and placed into one tube of brain heart infusion broth (BHI), and the supernatant was screened using CHROMagar™ mSuperCARBA culture medium. Different colors and shapes of colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. Antimicrobial susceptibility testing for CRE strains was performed using broth microdilution. All CRE strains were whole-genome sequenced. Short-read sequencing was performed using MGISEQ-2000 and long-read sequencing was conducted using GridION. Results Totally, 150 BHI tubes were screened for CRE strains, and 33 strains were identified as CRE positive. In 24 mSuperCARBA plates, only one species of CRE strain was isolated from each plate. In three plates, two different species of CRE strains were identified in each plate. In one plate, three different species of CRE strains were simultaneously isolated. Carbapenem resistance genes were detected in 81.8% of CRE strains, and bla NDM−1 was predominant (66.7%). No significant correlations between carbapenem-resistant phenotypes and carbapenem resistance genes were observed. The complete genomes of all 33 strains were obtained. Genome analysis revealed that clonal transmission events may have occurred among different farms and rural areas. Phylogenetic analysis revealed that bla NDM−1 IncFII plasmids could break bacterial species barrier for cross-host transmission in diverse areas. Conclusions To understand and control the transmission of AMR from the perspective of One Health, it is imperative to enhance surveillance of ARB, antibiotic resistance genes, and antibiotic-resistant plasmids in flies.

Abstract Artificial oxide heterostructures have provided promising platforms for the exploration of emergent quantum phases with extraordinary properties. Here, we demonstrate an approach to stabilize a distinct oxygen octahedron rotation (OOR) characterized by $${a}^{-}{a}^{-}{c}^{+}$$ a − a − c + in the ultrathin LaNiO3 sublayers of the LaNiO3/CaTiO3 superlattices. Unlike the $${a}^{-}{a}^{-}{c}^{-}$$ a − a − c − OOR in the LaNiO3 bare film, the $${a}^{-}{a}^{-}{c}^{+}$$ a − a − c + OOR favors high conductivity, driving the LaNiO3 sublayer to a metallic state of ~100 K even when the layer thickness is as thin as 2 unit cells (u.c.). Simultaneously, strongly preferred occupation of $${d}_{{x}^{2}-{y}^{2}}$$ d x 2 − y 2 orbital is achieved in LaNiO3 sublayers. The largest change of occupancy is as high as 35%, observed in the 2 u.c.-thick LaNiO3 sublayers sandwiched between 4 u.c.-thick CaTiO3 sublayers. X-ray absorption spectra indicate that the $${a}^{-}{a}^{-}{c}^{+}$$ a − a − c + OOR pattern of LaNiO3 achieved in the LaNiO3/CaTiO3 heterostructures has significantly enhanced the Ni-3d/O-2p hybridization, stabilizing the metallic phase in ultrathin LaNiO3 sublayers. The present work demonstrates that modulating the mode of OOR through heteroepitaxial synthesis can modify the orbital-lattice correlations in correlated perovskite oxides, revealing hidden properties of the materials.

Abstract Assistive technologies (ATs) are essential for promoting social equity, particularly as the global population ages. This study addresses the persistent issue of high abandonment rates in mobility aids, specifically smart walkers (SWs), by developing a systematic design thinking methodology called Mobility Aid Design for the Elderly (MADE). The MADE approach integrates the Stanford Design Thinking Model (SDTM) with specific design methods tailored for SWs. It includes stages of empathy, define, ideate, prototype, and test, each providing actionable steps to ensure user-centered design. The methodology was applied in a case study involving 20 participants from urban settings, including elderly users and designers, using a combination of random, snowball, and purposive sampling. Interviews utilized the Evaluation Grid Method (EGM) and were analyzed using Quantification Theory Type I (QTT1) and TRIZ. The study found significant cognitive differences in preferences between elderly users and designers, particularly in esthetics and digital features. These findings were used to generate innovative design guidelines to reduce these cognitive gaps and improve user acceptance of SWs. The paper discusses the need for continuous innovation in assistive technology design to enhance social inclusion and reduce inequality. The study’s limitations, such as the use of images instead of physical products, and its urban focus, are acknowledged, suggesting areas for future research.

Abstract Background Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients’ blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation.

Abstract This paper presents an innovative adaptive strategy implemented in wireless power transmission (WPT) systems to overcome efficiency challenges due to coupling structure misalignment and load variability. A novel versatile transmitter, capable of alternating between single and dual voltage source states via two MOSFETs has been designed. Initially, the system operates in a single voltage source mode, mutual inductance and load characteristics are pinpointed using a particle swarm optimization algorithm. Subsequently, the system transitions to dual voltage source mode, where it fine‐tunes the auxiliary voltage source's amplitude and phase based on the determined mutual inductance and load values to realize zero phase angle for optimal impedance matching. The experimental results show that this method can obviously improve the output power of WPT system. This method stands out for its simplicity, adaptability and rapid response, suggesting its potential for practical use in dynamic charging applications.

Abstract Background The urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality. Methods This cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999–2018, with mortality follow-up through December 31, 2019. Normal UACR (

Abstract Against the backdrop of the deep integration of culture and technology, research and practice in digitization of intangible cultural heritage has continued to deepen. However, due to the lack of data and training, it is still very difficult to apply artificial intelligence to the field of cultural heritage protection. This article integrates image generation technology into the digital protection of Peking opera facial makeup, using a self-built Peking opera facial makeup dataset. Based on the StyleGAN2 network, we propose a style generative cooperative training network Co-StyleGAN2, which integrates the adaptive data augmentation (ADA) to alleviate the problem of discriminator overfitting and introduces the idea of cooperative training to stabilize the training process. We design a Peking opera facial makeup image transform conditional generation network TC-StyleGAN2 which is transferred from unconditional generation network. The weights of the unconditional pre-training model are fixed, and an adaptive filtering modulation module is added to modulate the category parameters to complete the conversion from unconditional to conditional StyleGAN2 to deal with the training difficulty of conditional GANs on limited data, which suffer from severe mode collapse. The experimental results show that the proposed training strategy is better than the comparison algorithms, and the image generation quality and diversity have been improved.

Abstract Background We investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians. Methods All participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan–Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk. Results A total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship (“L” type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166–1.598; P

The objective of this paper was to analyze the difference of composition between hybrid sorghum and conventional sorghum in southwest China, and to establish the method of variety identification. The basic physical and chemical components of 29 sorghum samples were determined, and the metabolite composition of 29 sorghum samples was determined by ultra high performance liquid chromatography coupled with Q Exactive HF-X mass spectrometry. The marker component screening and construction of variety identification model were carried out using stoichiometry, which included principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), cluster analysis and receiver operating characteristic (ROC) curve analysis. The model was based on the basic physicochemical composition and all metabolites. The results showed that the contents of amylopectin and tannin of the conventional varieties form southwest China were higher than that of hybrid varieties, while the contents of amylose and 1000-grain weight were lower. By analyzing the physicochemical properties, it was possible to identify certain samples. The OPLS-DA model was constructed with all 1048 compounds variables, and 46 of the differential metabolites that had a significant impact on the model identification were screened out. A novel OPLS-DA identification model was developed for sorghum varieties, achieving a 100% accuracy in identification. The conventional varieties from southwest China exhibited a relatively high concentration of phenolic compounds. Furthermore, after conducting receiver operating characteristic (ROC) curve analysis and assessing the relative standard deviation (RSD) of quality control sample (QC), 20 feature components that exhibited both high diagnostic accuracy and good reproducibility were identified. Among them, syringetin 3-glucoside and 6"-o-acetyldaidzein had higher expression abundance in conventional sorghum varieties, while D-glucarate, putsutrine, N-acetylputsutrine and L-glutamine had higher content in hybrid sorghum varieties. This study unveiled the disparity in metabolites between hybrid sorghum and conventional sorghum. The study successfully developed a scientifically rigorous and precise untargeted metabolomics approach using UHPLC-Q Exactive HF-X-MS. This method can be effectively utilized for the identification of sorghum varieties, offering a novel strategy for sorghum variety identification.

Abstract Background The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. Methods The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8+ T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC. Results MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8+ T cells in the tumor microenvironment. Conclusions Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8+ T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC.

Abstract Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its potential applications, the pharmacological properties of δOR, including the mechanisms of activation by small-molecule agonists and the complex signaling pathways it engages, as well as their relation to the potential side effects, remain poorly understood. In this study, we use cryo-electron microscopy (cryo-EM) to determine the structure of the δOR-Gi complex when bound to a small-molecule agonist (ADL5859). Moreover, we design a series of probes to examine the key receptor-ligand interaction site and identify a region involved in signaling bias. Using ADL06 as a chemical tool, we elucidate the relationship between the β-arrestin pathway of the δOR and its biological functions, such as analgesic tolerance and convulsion activities. Notably, we discover that the β-arrestin recruitment of δOR might be linked to reduced gastrointestinal motility. These insights enhance our understanding of δOR’s structure, signaling pathways, and biological functions, paving the way for the structure-based drug discovery.

Achieving diffraction-limited performance in fourth-generation synchrotron radiation sources demands monochromator crystals that can preserve the wavefront across an unprecedented extensive range. There is an urgent need for techniques of absolute crystal diffraction wavefront measurement. At the Beijing Synchrotron Radiation Facility (BSRF), a novel edge scan wavefront metrology technique has been developed. This technique employs a double-edge tracking method, making diffraction-limited level absolute crystal diffraction wavefront measurement a reality. The results demonstrate an equivalent diffraction surface slope error below 70 nrad (corresponding to a wavefront phase error of 4.57% λ) r.m.s. within a nearly 6 mm range for a flat crystal in the crystal surface coordinate. The double-edge structure contributes to exceptional measurement precision for slope error reproducibility, achieving levels below 15 nrad (phase error reproducibility < λ/100) even at a first-generation synchrotron radiation source. Currently, the measurement termed double-edge scan (DES) has already been regarded as a critical feedback mechanism in the fabrication of next-generation crystals.

Urban public safety management relies heavily on video surveillance systems, which provide crucial visual data for resolving a wide range of incidents and controlling unlawful activities. Traditional methods for target detection predominantly employ a two-stage approach, focusing on precision in identifying objects such as pedestrians and vehicles. These objects, typically sparse in large-scale, lower-quality surveillance footage, induce considerable redundant computation during the initial processing stage. This redundancy constrains real-time detection capabilities and escalates processing costs. Furthermore, transmitting raw images and videos laden with superfluous information to centralized back-end systems significantly burdens network communications and fails to capitalize on the computational resources available at diverse surveillance nodes. This study introduces DiffRank, a novel preprocessing method for fixed-angle video imagery in urban surveillance. The method strategically generates candidate regions during preprocessing, thereby reducing redundant object detection and improving the efficiency of the detection algorithm. Drawing upon change detection principles, a background feature learning approach utilizing shallow features has been developed. This approach prioritizes learning the characteristics of fixed-area backgrounds over direct background identification. As a result, alterations in ROI are efficiently discerned using computationally efficient shallow features, markedly accelerating the generation of proposed Regions of Interest (ROIs) and diminishing the computational demands for subsequent object detection and classification. Comparative analysis on various public and private datasets illustrates that DiffRank, while maintaining high accuracy, substantially outperforms existing baselines in terms of speed, particularly with larger image sizes (e.g., an improvement exceeding 300 % at 1920×1080 resolution). Moreover, the method demonstrates enhanced robustness compared to baseline methods, efficiently disregarding static targets like mannequins in display windows. The advancements in candidate area preprocessing enable a balanced approach between detection accuracy and overall detection speed, making the algorithm highly applicable for real-time on-site analysis in edge computing scenarios and cloud-edge collaborative computing environments.

This collection of 12 papers reflects the evolving research methods at different design and development stages of educational design research (EDR). With the theme of investigating human-cantered digital technologies serving inclusion, equity, and accessibility, the researchers conducted EDR to solve real-world problems and promote learning access. These research studies ranged from needs analysis, learner/user experience, prototype design and development, to implementation and evaluation. The empirical data or evidence at various testing phases of these studies extended the dimensions of EDR and informed intentional investment in digital technology and related research to build a more inclusion- and equity-driven learning environment.

Abstract In response to the covid-19 pandemic, the digital strategy of education has become a key pedagogical approach for higher engineering disciplines. In this complex environment, the outcome-oriented higher engineering discipline faces the challenge of educational equity in terms of curriculum design and learning outcome assessment for its online engineering practical courses. In order to solve this problem, this study develops a digital teaching assistant system to facilitate the reform of educational equity in higher engineering disciplines. The teaching and learning functions of the system aim to support the interaction between teachers and students in the teaching process and the visual display of learning outcomes, and its intelligent evaluation and analysis function is based on the multi-criterion group decision-making model of Quality Function Deployment (QFD) combined with t-test to realize the evaluation of course learning outcomes. The results show that the academic performance of this system is significantly better than that of other similar systems. The statistical results of the teacher-student satisfaction survey of the two systems show that the teacher-student interaction and multi-dimensional learning evaluation analysis report function provided by the system are the most highly recognized, and the system also has better educational equity in resource recommendation, interaction and collaboration, learning achievement display and learning achievement evaluation, etc. In addition, the system is more in line with the teaching characteristics of higher engineering disciplines, which can provide effective assistance for teachers of higher engineering disciplines to improve teaching plan and cultivate students’ disciplinary practicality, consequently creating favorable conditions for the establishment of teaching equity.

Abstract 53BP1 nucleates the anti-end resection machinery at DNA double-strand breaks, thereby countering BRCA1 activity. Loss of 53BP1 leads to DNA end processing and homologous recombination in BRCA1-deficient cells. Consequently, BRCA1-mutant tumors, typically sensitive to PARP inhibitors (PARPi), become resistant in the absence of 53BP1. Here, we demonstrate that the ‘leaky’ DNA end resection in the absence of 53BP1 results in increased micronuclei and cytoplasmic double-stranded DNA, leading to activation of the cGAS-STING pathway and pro-inflammatory signaling. This enhances CD8+ T cell infiltration, activates macrophages and natural killer cells, and impedes tumor growth. Loss of 53BP1 correlates with a response to immune checkpoint blockade (ICB) and improved overall survival. Immunohistochemical assessment of 53BP1 in two malignancies, high grade serous ovarian cancer and pancreatic ductal adenocarcinoma, which are refractory to ICBs, reveals that lower 53BP1 levels correlate with an increased adaptive and innate immune response. Finally, BRCA1-deficient tumors that develop resistance to PARPi due to the loss of 53BP1 are susceptible to ICB. Therefore, we conclude that 53BP1 is critical for tumor immunogenicity and underpins the response to ICB. Our results support including 53BP1 expression as an exploratory biomarker in ICB trials for malignancies typically refractory to immunotherapy.

Variable air volume air-conditioning system (VAV system) has multiple control loops that interfered with each other, which has serious impacts on its actual operation effect. To solve this problem, the index of global hydraulic stability, which takes the physical quantity of the pipe network pressure and the air flow rate as reference, is proposed based on Graph theory, and a pipe network model for the hydraulic calculation is built. Then, the simulation study based on the actual operation data is carried out in MATLAB. The distribution of the pressure and the air flow in the pipe network is obtained, and the action interferences among adjacent terminal boxes are analyzed based on global hydraulic stability under damper position regulation strategy (DP strategy) and fan frequency regulation strategy (FF strategy). Results indicate that the FF strategy can decrease the total change distance of the damper position compared with the DP strategy, and then the fluctuation of the pressure and the air flow can be reduced. The contribution of this study is to provide an evaluation index of global hydraulic stability, which can also be used in other air-conditioning systems with multiple terminals and multiple control loops.

Abstract Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.

Abstract DNA methylation plays an important role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine mostly occurring in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing successfully detect 5-methylcytosine DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present Rockfish, a deep learning algorithm that significantly improves read-level 5-methylcytosine detection by using Nanopore sequencing. Rockfish is compared with other methods based on Nanopore sequencing on R9.4.1 and R10.4.1 datasets. There is an increase in the single-base accuracy and the F1 measure of up to 5 percentage points on R.9.4.1 datasets, and up to 0.82 percentage points on R10.4.1 datasets. Moreover, Rockfish shows a high correlation with whole-genome bisulfite sequencing, requires lower read depth, and achieves higher confidence in biologically important regions such as CpG-rich promoters while being computationally efficient. Its superior performance in human and mouse samples highlights its versatility for studying 5-methylcytosine methylation across varied organisms and diseases. Finally, its adaptable architecture ensures compatibility with new versions of pores and chemistry as well as modification types.

Abstract Infrastructure networks are critical components of contemporary society, and numerous approaches have been suggested for the selection of strategies to protect these networks. However, for uncertain environments, research on attack and defense game models for infrastructure networks is limited. Therefore, after reviewing the existing approaches, a method based on interval-valued intuitionistic fuzzy set (IVIFS) theory is proposed for attack and defense games in critical infrastructure networks. First, we present the process of constructing the game model proposed in this paper, which mainly includes the formulation of the cost model, the strategies, and the method of generating IVIFS payoffs. Next, the Nash equilibria of the game are identified by a pair of nonlinear programming models based on IVIFS theory. Finally, experiments are conducted on a target scale-free network, and an investigation into the variation patterns of the Nash equilibria under different circumstances is also conducted. We provide explanations for these variation patterns by considering payoffs from the perspective of mathematical programming models. Furthermore, we find that compared to the existing attack and defense game model with crisp payoffs, the model proposed in this paper leads to superior Nash equilibria. Our work is a preliminary attempt to analyse attack and defense games for infrastructure networks based on IVIFS theory, providing a method for assessing payoffs in uncertain environments for the attacker and defender. This topic deserves further study.

Mine gas extraction has the dilemma of low extraction rate, short effective extraction cycle, and substandard gas pre-extraction concentration. In order to realize the precise pressure relief and permeability of high gas and low gas permeability coal seam, taking the working face of high gas and low gas permeability coal seam in Shunhe Coal Mine 2404 as the research object, based on the methods of rheological theory modeling, COMSOL numerical analysis and field experiment, a multi-field coupling model of gas transport of large-diameter borehole pressure relief coal seam was constructed, and the determination index of the effective extraction radius of large-diameter borehole gas was proposed - the residual gas pressure did not exceed 0.22 MPa. The mechanism of pressure relief and permeability enhancement, as well as the law of gas migration in large diameter coal seam drilling, are unveiled: the gas pressure within a single large diameter coal seam drilling exhibits an elliptical distribution with the center of the drilling circle serving as its symmetrical center. In other words, the gas pressure gradually increases from the center towards the outer edges of the drilling circle. Furthermore, with prolonged drainage time, there is a gradual expansion of the standard drainage area. The stress transfer around the borehole is characterized by the fact that with the increase of extraction time, the vertical stress of the peripheral points of a single large-diameter borehole shows a trend of first increasing and then decreasing, and the technology of high-gas and low-gas permeability coal seam large-diameter borehole pressure relief and enhanced penetration extraction is proposed. The simulation determined the effective extraction radius of the borehole, and the drilling hole with a hole spacing of 6.0 m and a diameter of 300 mm had the best pressure relief and penetration enhancement effect, and the average permeability within 3.0 m on both sides was 1.58×10−15 m2, which was much greater than the initial value of 1.15×10−17 m2. The field application demonstrates that gas extraction in a large diameter borehole is significantly superior to that in an ordinary borehole. In a 300 mm large diameter borehole, the maximum gas volume fraction reaches 47.2%, whereas it only amounts to 10.6% in a 75 mm original borehole. Furthermore, the extraction duration of high gas volume fraction increases by 40.2% in the large diameter borehole. This approach effectively addresses the challenge of controlling small diameter gas boreholes and provides an efficient method for precise pressure relief and permeability enhancement of high gas coal seams.

Abstract Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.

Objective The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Abstract Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.

Abstract Introduction Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. Methods A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. Results Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p

BackgroundThe sleep status of patients in the surgical intensive care unit (ICU) significantly impacts their recoveries. However, the effects of surgical procedures on sleep are rarely studied. ObjectiveThis study aimed to investigate quantitatively the impact of traditional open surgery (TOS) versus minimally invasive surgery (MIS) on patients’ first-night sleep status in a surgical ICU. MethodsPatients transferred to the ICU after surgery were prospectively screened. The sleep status on the night of surgery was assessed by the patient- and nurse-completed Richards-Campbell Sleep Questionnaire (RCSQ) and Huawei wearable sleep monitoring wristband. Surgical types and sleep parameters were analyzed. ResultsA total of 61 patients were enrolled. Compared to patients in the TOS group, patients in the MIS group had a higher nurse-RCSQ score (mean 60.9, SD 16.9 vs mean 51.2, SD 17.3; P=.03), self-RCSQ score (mean 58.6, SD 16.2 vs mean 49.5, SD 14.8; P=.03), and Huawei sleep score (mean 77.9, SD 4.5 vs mean 68.6, SD 11.1; P

ObjectivesTo investigate the epidemiological characteristics of Augmented Renal Clearance (ARC) in severe sepsis children with MRSA infection and find risk factors to establish a model predicting ARC onset in PICU.DesignRetrospective study, in which ARC was defined by estimated glomerular filtration rate (eGFR) measured by the modified Schwartz formula above 130 ml/min/1.73 m2. Univariable and multivariable logistic regression analyses were performed to find the predictor for ARC. Multi-strategy modeling was used to form an early prediction model for ARC, which was evaluated by the area under the ROC curve (AUC), accuracy (ACC) and other indicators.SettingOne China PICU.PatientsSevere sepsis children with MRSA infection admitted to PICU from May 2017 to June 2022 at Children's Hospital of Nanjing Medical University.InterventionsNone.Measurements and main results125 of 167 (74.9%) patients with severe sepsis with MRSA infection have occurred ARC during the hospitalization of PICU, of which 44% have an absolute decrease in vancomycin trough level (VTL), patients with ARC have a longer length of stay in both hospital and PICU, lower VTL and require longer anti-infective treatment. 20 different models were established for the early recognition of ARC. Among them, the best performer had an AUC of 0.746 and a high application prospect.ConclusionARC is a phenomenon significantly underestimated in pediatric patients with severe sepsis associated with MRSA infection, which can affect 74.9% of these patients and affects the process of anti-infection treatment and clinical outcomes. To achieve early prediction only by specific risk factors is unreliable, a model based on Multivariate Logistic Regression in this study was chosen to be used clinically.

BackgroundThis study aims to improve the solubility and the toxicity of Bufonis venenum, and finally enhance the therapeutic outcomes of hepatocellular carcinoma (HCC).MethodsThe cholesterol-free liposomes simultaneously encapsulate bufadienolides and indolealkylamines (Non-Cholesterol-Bufonis Venenum Extract-Liposome, Non-Chol-BVE-LP) was prepared by the thin-film evaporation technique. In vitro, the cytotoxicity, cell apoptosis study, cellular uptake and hemolysis studies were evaluated in HepG2 cells. In vivo, the biodistribution and anti-tumor activity studies were conducted in BALB/C mice with HepG2 cells.ResultsThe liposomes showed good size distribution, encapsulation efficiency drug loading capacity and slower drug release. Non-Chol-BVE-LP had higher cytotoxicity on HepG2 cells and induced more apoptosis on HepG2 Cells compared with BVE. In addition, the liposomes could accumulate in tumor by passive targeting, thus facilitating the anti-tumor effects. In vivo, Non-Chol-BVE-LP showed equivalent anti-tumor efficacy to the first-line anti-HCC drug sorafenib.ConclusionThe study provided new ideas for the development and clinical application of Bufonis venenum related formulation and offered new drug for the treatment of HCC.

Abstract Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic‐resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT‐Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences. ProT‐Diff generates thousands of AMPs with diverse lengths and structures within a few hours. After silico physicochemical screening, 45 peptides are selected for experimental validation. Forty‐four peptides showed antimicrobial activity against both gram‐positive or gram‐negative bacteria. Among broad‐spectrum peptides, AMP_2 exhibited potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. An in vivo assessment demonstrated its effectiveness against a drug‐resistant E. coli strain in acute peritonitis. This study not only introduces a viable and user‐friendly strategy for de novo generation of antimicrobial peptides, but also provides potential antimicrobial drug candidates with excellent activity. It is believed that this study will facilitate the development of other peptide‐based drug candidates in the future, as well as proteins with tailored characteristics.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

Based on poor efficacy and non-specific toxic side effects of conventional drug therapy for liver cancer, nano-based drug delivery system (NDDS) offers the advantage of drug targeting delivery. Subcellular targeting of nanomedicines on this basis enables more precise and effective termination of tumor cells. Mitochondria, as the crucial cell powerhouse, possesses distinctive physical and chemical properties in hepatoma cells different from that in hepatic cells, and controls apoptosis, tumor metastasis, and cellular drug resistance in hepatoma cells through metabolism and dynamics, which serves as a good choice for drug targeting delivery. Thus, mitochondria-targeting NDDS have become a recent research focus, showcasing the design of cationic nanoparticles, metal nanoparticles, mitochondrial peptide modification and so on. Although many studies have shown good results regarding anti-tumor efficacy, it is a long way to go before the successful translation of clinical application. Based on these, we summarized the specificity and importance of mitochondria in hepatoma cells, and reviewed the current mitochondria-targeting NDDS for liver cancer therapy, aiming to provide a better understanding for current development process, strengths and weaknesses of mitochondria-targeting NDDS as well as informing subsequent improvements and developments.

IntroductionPleural contact is present when the underlying pathology of the pleural tag (PT) involves the pleura. This study aimed to preoperatively predict PI by lung adenocarcinomas (ACCs) with PT, exploring CT imaging parameters indicative of PT consisting of pleura and tumor invasiveness.MethodsThis single-center, retrospective study included 84 consecutive patients diagnosed with solid ACCs with PT, who underwent resection at our hospital between May 2019 and July 2023. CT imaging parameters analyzed included: LPT (the length of PT), defined as the shortest distance from the tumor edge to the retracted pleura. Patients were divided into PI -ve group and PI +ve group according to PI status. Regression analyses were used to determine predictive factors for PI.ResultsThe study evaluated 84 patients (mean age, 62.0 ± 13.8 years; 45 females) pathologically diagnosed with ACCs with PT on CT. Multivariate regression analysis identified tumor size (OR 1.18, 95% CI 1.09-1.29, p = 0.000), LPT (OR 0.48, 95% CI 0.25-0.91, p = 0.03) and multiple PTs to multiple types of pleura (OR 3.58, 95% CI 1.13-11.20, p = 0.03) as independent predictors for PI. The combination of these CT features improved the predictive performance for preoperatively identifying PI, achieving high specificity and moderate accuracy. The sensitivity of predicting PI with only LPT < 3 mm was 96.9%.ConclusionThis study determined that LPT is effective for predetermining PI in ACCs with PT.

Attribution of forest disturbance types using satellite remote sensing is practicable and several methods have been developed to automate the procedure. However, limited by commonly used data and the methodology, achieving accurate and rapid attribution of forest disturbance types over broad spatial extents remains challenging. In this study, we developed a method for attributing forest disturbance types using Dynamic World class probability data (i.e., probabilities for Dynamic World land use land cover types). Specifically, we first obtained a high-quality probability time series by pre-processing the class probability data. Then, we segmented the entire time series into several subseries and classified them according to the hypothetical trajectories. Finally, we completed the attribution of forest disturbance types using the variables derived from the probability time series and the results of the subseries classification. We used the developed method to investigate the forest disturbance types in Myanmar from 2017 to 2023 and validated its effectiveness by conducting unbiased accuracy assessment. The overall accuracy of the type for the acquired map was approximately 93.3%, and the overall accuracy of the year was approximately 96.7%, proving that the method is feasible. This method is based on the Google Earth Engine, which allows users to attribute forest disturbance types in different areas rapidly by simple parameter adjustments. Even if available classes do not satisfy users’ needs, the method can facilitate more detailed attribution of disturbance types.

ObjectiveThe aim of this research was to examine the association between alcohol consumption and depressive symptoms in the Wa ethnic minority of China, a population where this relationship has been insufficiently explored.MethodsA cross-sectional analysis was conducted on a sample of 317 current drinkers from the Wa ethnic minority, a “direct fast-forward” group in Cangyuan County, between December 1, 2022, and February 28, 2023. Utilizing a multi-stage cluster sampling approach, participants were selected, each of whom exhibited an Alcohol Use Disorder Identification Test (AUDIT) score exceeding 0. Data were collected via face-to-face interviews employing a uniform questionnaire. Quantification of alcohol use was achieved through the application of the AUDIT, while the Patient Health Questionnaire (PHQ)-9 was employed to gauge depressive symptoms. The relationship between the severity of alcohol consumption and depressive symptoms was evaluated using a multivariable logistic regression model. Subsequently, potential non-linear associations were scrutinized through the application of a smoothing plot.ResultsThe study included 317 current drinkers (196 males [61.83%]; mean age 41.78 ± 12.91 years), of which 94 (29.65%) exhibited comorbid depressive symptoms. Multivariable logistic regression analysis, adjusting for confounders, revealed that higher AUDIT scores were significantly associated with an increased probability of depressive symptoms (OR = 1.09, 95% CI: 1.02–1.18, p = 0.008). The risk of depressive symptoms was notably greater in the group with alcohol dependent range in contrast the group at low-risk range (OR = 7.01, 95% CI: 1.66–29.62, p = 0.008). The smoothing plot indicated a J-shaped non-linear relationship with an inflection point at an AUDIT score of 15. To the left of this inflection point, no significant relationship was observed, whereas to the right, a positive correlation emerged (OR = 1.39, 95% CI: 1.11–1.74, p

BackgroundAlthough the application of brain-computer interface (BCI) technology in rehabilitation has been extensively studied, a systematic and comprehensive bibliometric analysis of this area remains lacking. Thus, this study aims to analyze the research progress of BCI technology in rehabilitation through bibliometric methods.MethodsThe study retrieved relevant publications on BCI technology in rehabilitation from the Web of Science Core Collection (WoSCC) between January 1, 2004, and June 30, 2024. The search was conducted using thematic queries, and the document types included “original articles” and “review articles.” Bibliometric analysis and knowledge mapping were performed using the Bibliometrix package in R software and CiteSpace software.ResultsDuring the study period, a total of 1,431 publications on BCI technology in rehabilitation were published by 4,932 authors from 1,281 institutions across 79 countries in 386 academic journals. The volume of research literature in this field has shown a steady upward trend. The United States of America (USA) and China are the primary contributors, with Eberhard Karls University of Tübingen being the most active research institution. The journal Frontiers in Neuroscience published the most articles, while the Journal of Neural Engineering was the most cited. Niels Birbaumer not only authored the most articles but also received the highest number of citations. The main research areas include neurology, sports medicine, and ophthalmology. The diverse applications of BCI technology in stroke and spinal cord injury rehabilitation, as well as the evaluation of BCI performance, are current research hotspots. Moreover, deep learning has demonstrated significant potential in BCI technology rehabilitation applications.ConclusionThis bibliometric study provides an overview of the research landscape and developmental trends of BCI technology in rehabilitation, offering valuable reference points for researchers in formulating future research strategies.

IntroductionTetrastigma hemsleyanum is a folk and rare medicinal plant, and specifically, it is distributed in the south, China. To investigate the cumulative properties of its medicinal components, we examined the effect of UV light on flavonoid content and related enzyme activity changes in T. hemsleyanum.MethodsThe leaves and tubers were treated with UV-A, UV-B and UV-C for 1 h, 1L/23D h, 3 h and 3L/21D h (D represents darkness treatment). High-performance liquid chromatography (HPLC) analysis showed that the content of many flavonoids decreased significantly during UV-A treatment, increased after UV-B and UV-C irradiation and accumulated again after darkness treatment.ResultsIn the root tubers of the UV-A group, naringin content in the 3L/21D h group (0.069 μg/g) was 16.30 times higher than that of 3 h group (0.0042 μg/g). The rutin content was elevated after UV irradiation but was not detected in the CK group. The test results of the enzyme-linked kit indicated that the activities of many enzymes were higher in the UV-A and UV-B irradiation groups than those in the CK group, but the results were reversed in the UV-C treatment. After darkness treatment, the activities of most enzymes were higher than those with UV irradiation alone; F3’5’H activity in the 3L/21D h group (97.25 U/L) was 1.24 times higher than that in the 3 h group (78.12 U/L) in the UV-A-treated group.DiscussionThe study results suggest that appropriate UV-B and UV-C irradiation, as well as darkness supplementation, had a promotive effect on flavonoids in the leaves and root tubers of T. hemsleyanum. Additionally, UV irradiation and darkness treatment enhanced the activity of most enzymes.

ObjectivesTo identify COVID-19 infectious disease models that accounted for social determinants of health (SDH).MethodsWe searched MEDLINE, EMBASE, Cochrane Library, medRxiv, and the Web of Science from December 2019 to August 2020. We included mathematical modelling studies focused on humans investigating COVID-19 impact and including at least one SDH. We abstracted study characteristics (e.g., country, model type, social determinants of health) and appraised study quality using best practices guidelines.Results83 studies were included. Most pertained to multiple countries (n = 15), the United States (n = 12), or China (n = 7). Most models were compartmental (n = 45) and agent-based (n = 7). Age was the most incorporated SDH (n = 74), followed by gender (n = 15), race/ethnicity (n = 7) and remote/rural location (n = 6). Most models reflected the dynamic nature of infectious disease spread (n = 51, 61%) but few reported on internal (n = 10, 12%) or external (n = 31, 37%) model validation.ConclusionFew models published early in the pandemic accounted for SDH other than age. Neglect of SDH in mathematical models of disease spread may result in foregone opportunities to understand differential impacts of the pandemic and to assess targeted interventions.Systematic Review Registration:[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020207706], PROSPERO, CRD42020207706.

IntroductionGenistin, as a kind of natural isoflavone glycoside, has good biological activity, and its weak absorption makes it closely related to intestinal flora. However, the role of the intestinal flora is still unclear and whether the metabolites produced by the intestinal flora are absorbed systemically is also variable.MethodsGenistin was fermented for 24 h based on fecal bacteria fermentation technology. The components were qualitatively and quantitatively analyzed by HPLC and UHPLC-Q-Exactive Orbitrap Mass spectrometry. The composition of intestinal flora in fermentation samples from fecal bacteria was detected by 16S rRNA sequencing. Five representative probiotics were cultured in vitro and fermented with genistin to determine similarities and differences in genistin metabolites by different bacteria at different times. Finally, the absorption results of metabolites by fermentation were verified by a Caco-2 cell monolayer.ResultsThe HPLC results of fecal fermentation showed that genistein levels increased from 0.0139 ± 0.0057 mg/mL to 0.0426 ± 0.0251 mg/mL and two new metabolites were produced. A total of 46 metabolites following fecal fermentation were identified, resulting from various biotransformation reaction products, such as decarbonylation, hydroxylation, and methylation. Simultaneously, the 16S rRNA results showed that the intestinal flora changed significantly before and after fermentation and that the intestinal microorganisms in the control (Con) group and the fermentation (Fer) group showed a significant separation trend. Five genera, Lactobacillus, Bifidobacterium, Parabacteroides, Sutterella, and Dorea, were considered the dominant flora for genistin fermentation. The qualitative results of fermentation of genistin by five probiotics at different times showed that there were significant differences in small molecule metabolites by fermentation of different bacteria. Meanwhile, most metabolites could be identified following fecal bacteria fermentation, which verified the importance of the dominant bacteria in the feces for the biotransformation of components. Finally, the absorption results of the metabolites based on the Caco-2 cell monolayer showed that 14 metabolites could be absorbed into the circulation in vivo through the mesentery.DiscussionThe small molecule metabolites of genistin by fermentation of fecal bacteria can be well absorbed systemically by the body. These studies provide a reference value for explaining the transformation and absorption of flavonoid glycosides in the intestine.

IntroductionThe prognostic value of 18F-FDG PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in diffuse large B-cell lymphoma (DLBCL) remains inadequately explored. This study aims to assess the correlation between these parameters and patient outcomes.MethodsA cohort of 156 DLBCL patients underwent 18F-FDG PET/CT imaging at baseline and after 3-4 cycles of R-CHOP or CHOP-like regimen. The third quartiles of liver uptake values were used as thresholds for calculating MTV and TLG. Patient outcomes were analyzed based on Ann Arbor staging and the 5-PS score. A nomogram was developed to predict overall survival (OS).ResultsPatients with low baseline TLG exhibited significantly better outcomes compared to those with high baseline TLG in both Ann Arbor stages I-II and III-IV (1-year PFS: 78.9% vs. 40%, p=0.016; OS: 94.7% vs. 40%, p=0.005 for stage I-II; 1-year PFS: 74.1% vs. 46.8%, p=0.014; OS: 85.4% vs. 71.8%, p=0.007 for stage III-IV). In interim PET/CT patients with a 5-PS score >3, the high ΔTLG group had superior prognosis (1-year PFS: 82.3% vs. 35.7%, p=0.003; OS: 88.2% vs. 85.7%, p=0.003). The nomogram achieved a C-index of 0.9 for OS prediction.DiscussionThe findings suggest that baseline TLG is a robust prognostic indicator for patients with DLBCL, particularly in early stages, while ΔTLG effectively distinguishes those with favorable outcomes in higher-risk groups. These metabolic parameters from 18F-FDG PET/CT could enhance treatment decision-making and patient management strategies.

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

IntroductionSelenium is an essential micronutrient the human body requires, which is closely linked to health. Rice, a primary staple food globally, is a major source of human selenium intake. To develop selenium-enriched rice varieties, it is imperative to understand the mechanisms behind selenium’s absorption and transport within rice, alongside identifying the key genes involved in selenium uptake, transport, and transformation within the plant.MethodsThis study conducted transcriptome sequencing on four types of rice materials (two with low-selenium and two with high-selenium contents) across roots, stems, leaves, and panicles to analyze the gene expression differences.Results and discussionDifferential gene expression was observed in the various tissues, identifying 5,815, 6,169, 7,609, and 10,223 distinct genes in roots, stems, leaves, and panicles, respectively. To delve into these differentially expressed genes and identify the hub genes linked to selenium contents, weighted gene co-expression network analysis (WGCNA) was performed. Ultimately, 10, 8, 7, and 6 hub genes in the roots, stems, leaves, and panicles, respectively, were identified. The identification of these hub genes substantially aids in advancing our understanding of the molecular mechanisms involved in selenium absorption and transport during the growth of rice.

Abstract Photonic crystals are a new class of optical microstructure materials characterized by a dielectric constant that varies periodically with space and features a photonic bandgap. Inspired by natural photonic crystals such as butterfly scales, a series of artificial photonic crystals are developed for use in integrated photonic platforms, biosensing, communication, and other fields. Among them, colloidal photonic crystals (CPCs) have gained widespread attention due to their excellent optical properties and advantages, such as ease of preparation and functionalization. This work reviews the classification and self‐assembly principles of CPCs, details some of the latest biomedical applications of large‐area, high‐quality CPCs prepared using advanced self‐assembly methods, summarizes the existing challenges in CPC construction and application, and anticipates future development directions and optimization strategy. With further advancements, CPCs are expected to play a more critical role in biosensors, drug delivery, cell research, and other fields, bringing significant benefits to biomedical research and clinical practice.

Contemporary research on the walking environment focuses closely on the construction logic and internal correlation. Walkability is one of the vital characteristics of the old town street space. To understand how to improve the old town street space effectively, the investigation of the correlation mechanism of street walkability is essential. This study utilizes structural equation model (SEM) to construct a street walkability measurement model composed of four unobserved factors. Then, take Old Southern Area in Nanjing as an example, integrate Depthmap, ArcGIS and Python to obtain multi-source data, and establish a database of observed factors on street space. Finally, the matrix of the observed factors is set by SEM to calculate the correlation of the unobserved factors. This paper provides a novel technical approach for the correlation study of spatial construction logic as well as a reference for strengthening the spatial quality of the contemporary built environment.

IntroductionThe incidence of hemiplegia caused by stroke is high. In particular, lower limb dysfunction affects the daily activities of patients, and lower limb robotic devices have been proposed to provide rehabilitation therapy to improve balance function in this patient population.ObjectiveTo assess the effectiveness of the LiteStepper® unilateral lower limb exoskeleton (ULLE) combined with conventional treatment for balance function training in patients with post-stroke hemiplegia.MethodsThis multicenter randomized controlled trial, conducted in the convalescent rehabilitation ward of four hospitals, involved 92 patients in their post-stroke phase. Participants were randomized into an experimental group (EG) or a conventional group (CG). The EG adopted the LiteStepper® ULLE combined with conventional treatment for 21 days. The CG underwent a standard daily rehabilitation routine for 21 days. The Berg Balance Scale (BBS), Functional Ambulation Category scale (FAC), 6-min walk test (6MWT), and Barthel Index (Barthel) were used for evaluations before and after 21 days of rehabilitative training.ResultsThe BBS scores in EG was significantly elevated compared to CG, exhibiting a profound statistical difference (P< 0.0001). Notably, these disparities persisted at both day 21 (P < 0.0001) and day 14 (P < 0.0047) post-intervention, underscoring the efficacy of the treatment in the EG. The EG demonstrated a markedly greater improvement in BBS scores from pre-rehabilitation to 21 days post-training, significantly outperforming the CG. Furthermore, at both day 14 and day 21, functional assessments including the FAC, 6MWT, and Barthel revealed improvements in both groups. However, the improvements in the EG were statistically significant compared to the CG at both time points: day 14 (FAC, P = 0.0377; 6MWT, P = 0.0494; Barthel, P = 0.0225) and day 21 (FAC, P = 0.0015; 6MWT, P = 0.0005; Barthel, P = 0.0004). These findings highlight the superiority of the intervention in the EG in enhancing functional outcomes. Regarding safety, the analysis revealed a solitary adverse event (AEs) related to the LiteStepper®ULLE device during the study period, affirming the combination therapy’s safety profile when administered alongside conventional balance training in post-stroke hemiplegic patients. This underscores the feasibility and potential of incorporating LiteStepper®ULLE into rehabilitation protocols for this patient population.Discussion and significanceThe LiteStepper® ULLE combined with conventional treatment is effective and safe for balance function training in patients with post-stroke hemiplegia.

Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH.

BackgroundPneumocystis jirovecii pneumonia (PJP) is an opportunistic infection caused by the yeast-like fungus P. jirovecii. As recommended by some guidelines, the first-line treatment for this infection is trimethoprim-sulfamethoxazole (TMP-SMX), and the second-line treatment includes drugs such as dapsone, pentamidine, primaquine, Atovaquone, clindamycin, and caspofungin. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene disorder in which treatment with oxidizing drugs, such as sulfonamides, dapsone, primaquine, can directly destroy hemoglobin present in red blood cells (RBCs), thereby inducing methemoglobin and hemolysis.Case presentationHere, we present the case of a lymphoma patient with previous G6PD deficiency who was admitted to ICU for the treatment of severe pneumonia combined with respiratory failure. PJP was detected by the next-generation sequencing of the bronchoalveolar lavage fluid. The patient was initially treated with the antifungal drug caspofungin; however, this treatment showed poor therapeutic effect. Based on the evaluation of G6PD enzyme activity and the patient’s previous history of G6PD deficiency, we finally treated the patient with low-dose TMP-SMX combined with caspofungin and provided rigorous medical care to the patient. Following this treatment, the patient’s clinical symptoms improved, lung computed tomography showed reduced pulmonary inflammation, and the fungal β-(1,3)-D-glucan test (G test) showed decreased levels of fungal D-glucan. After 57 days, the TMP-SMX treatment was discontinued. No symptoms related to G6PD deficiency, such as hemolysis, hematuria, and anemia, occurred during the treatment course.ConclusionThis is the first report mentioning the successful treatment of Pneumocystis jirovecii pneumonia with a double-drug regimen with low-dose TMP-SMX and caspofungin in a T-lymphoblastic leukemia/lymphoma patient with previous G6PD deficiency. Enzyme activity detection is the first step for anti-PJP treatment in patients with G6PD deficiency. Although patients with mild enzyme deficiency may not show any adverse reactions, we still recommend the regular monitoring of the levels of RBCs, hemoglobin, and hematocrit before and after the use of sulfonamides or sulfoxides and other oxidizing drugs in patients with G6PD deficiency. Among other things, early and correct diagnosis of Pneumocystis jirovecii pneumonia in hematological malignancies patients is very important. Relevant oncologists should be alert to the risk of Pneumocystis jirovecii pneumonia in these patients.

Objective: The main aim of this study was to evaluate the effect of oral probiotics on the human milk microbiota and determine whether that influenced infant microbiota development. Methods: A total of 27 pregnant women were recruited; 14 were assigned to the probiotic group, and the rest were assigned to the control group. Their infants were likewise assigned to the probiotic group or the control group. Pregnant women in the probiotic group received probiotic supplementation from 32 weeks of gestation until delivery. Human milk samples and infant fecal samples were collected at 6 months after delivery, and 16S rRNA sequencing was used to analyze the composition of the human milk and infant gut microbiota (NCT06241222). Results: In the control group, bacterial microbiota were detected in 8 out of 13 milk samples, whereas in the probiotic group, only 6 out of 14 milk samples contained bacterial microbiota. We examined the composition of the human milk and infant gut microbiota in both the control and probiotic groups. Spearman correlation analysis revealed that various genera in human milk were correlated with the infant gut microbiota. The Linear discriminant analysis effect size (LEfSe) showed that 6 bacteria in the human milk microbiota in the control group were significantly more abundant than those in the probiotic group. Nine bacteria were significantly more abundant in the human milk microbiota in the probiotic group than the control group. According to the LEfSe results, 11 bacteria in the infant gut microbiota in the control group were significantly more abundant than those in the probiotic group. Fourteen bacteria were significantly more abundant in the infant gut microbiota in the probiotic group than in the control group. Conclusion: The infant gut microbiota at 6 months has a complicated relationship with the maternal human milk microbiota. Oral probiotic supplementation can change the composition of the human milk microbiota and the infant gut microbiota.

Amid the escalating conflicts between urban demography, resource availability, and environmental constraints, there is an accelerating demand for emergency medical services prompted by a spectrum of factors including diseases, natural calamities, and unforeseen events. This growth is further accentuated by an imbalance in the allocation of emergency facilities, amplifying public anxiety and underscoring the urgent necessity for scientifically informed optimization of pre-hospital emergency facilities. To this end, the present study articulates specific optimization goals for facility deployment and introduces a nuanced set coverage optimization model that integrates spatiotemporal determinants of emergency service requirements. The model is fortified with a constellation of constraints, including spatial constraint, temporal constraint, and coverage constraint. For spatial constraints, we use the Monte Carlo simulation to predict the spatial distribution of emergency demands. Temporal constraints involve determining the actual travel time matrix from predicted demand points to candidate sites. Coverage constraints specify the effective demand coverage rate. This study uses Nanjing as a case example, utilizing multisource big data, including ambulance GPS logs from June 2016 to May 2017, Amap traffic congestion indicators, and survey data on existing emergency facilities in Nanjing City. By preprocessing and analyzing the existing data, this study thoroughly investigates the spatiotemporal distribution of emergency demands and the impact of traffic congestion on emergency service effectiveness. Consequently, the model incorporates constraints that ensure, under the specified planning and actual traffic conditions, 95 % of the simulated emergency demands can be met within an 8-minute on-route time. Locations for pre-hospital emergency stations are optimized using a genetic algorithm, achieving the best solution at the 120th iteration. Verification confirms 134 optimal sites; after excluding 52 existing sites, 82 potential sites are identified. The new layout plan has reduced Nanjing’s average emergency response time from 18.6 min to 12 min. Additionally, under peak and average traffic conditions, emergency demand coverage rates improved from 76.92 % and 83.18 % at 15 min to 95.61 % and 98.10 % at 12 min, respectively. These results demonstrate that the new layout significantly enhances practical application effectiveness. The approach presented in this paper addresses the previously overlooked randomness of emergency incidents and traffic conditions, offering innovative strategies for improving the efficiency and effectiveness of emergency station planning and site selection models.