Search

Abstract The Patient-Derived Organoids (PDOs) has demonstrated significant potential in personalized medicine. However, the initial establishment of lung cancer organoids (LCOs), and timely therapeutic recommendations face several challenges. Particularly, the current culture systems have not yet achieved the capability to long-term cultivation of all lung tumor sample sources, including malignant pleural effusion (MPE), which poses significant barriers to the rapid clinical translation of PDOs. Here, we established a LCOs biobank derived from various tumor cell origins and investigated the impact of supplementing culture media with MPE supernatant on organoid formation, culture duration, and drug sensitivity. Our findings indicate that MPE can enhance the successful rate of LCOs by extending the passage number and promoting the initial formation of difficult-to-culture samples, such as those derived from MPE or cell lines that were previously unsuccessful in Airway Organoid (AO) medium. MPE also facilitates the rapid proliferation of LCOs, reducing the culture duration by over 50%. Additionally, LCOs exhibit increased chemoresistance in the presence of MPE, which modifies stem cell distribution and reshapes the internal structure of the organoids. Overall, this study highlights the significance of MPE in facilitating the establishment and maintenance of LCOs, and its potential for translational applications in lung cancer research and personalized.

Abstract 5-Methylcytosine (m5C) is closely associated with cancer. However, the role of m5C in breast cancer(BC)remains unclear. This study combined single-cell RNA sequencing (scRNA-Seq) and transcriptomics datasets to screen m5C regulators associated with BC progression and analyze their clinical values. Firstly, This study elucidates the mechanisms of the m5C landscape and the specific roles of m5C regulators in BC patients. we found that the dysregulation of m5C regulators with m5Cscore play the essential role of the carcinogenesis and progression in epithelial cells and myeloid cells of BC at single cell level. External validation was conducted using an independent scRNA-Seq datasets. Then, three distinct m5C modification patterns were identified by transcriptomics datasets. Based on the m5C differentially expressed regulators, the m5Cscore was constructed, and used to divide patients with BC into high and low m5Cscore groups. Patients with a high m5Cscore had more abundant immune cell infiltration, stronger antitumor immunity, and better prognoses. Finally, Quantitative real-time (PCR) and immunohistochemistry were used for the in vitro experimental validation, which had extensive prognostic value. In this study, we aimed to assess the expression of m5C regulators involved in BC and investigate their correlation with the tumor microenvironment, clinicopathological characteristics, and prognosis of BC. The m5C regulators could be used to effectively assess the cell specific regulation prognosis of patients with BC and develop more effective immunotherapy strategies.

Abstract Photon‐counting detector‐based computed tomography (PCD‐CT) is an advanced realization of spectral CT, the multi‐energy projection data is captured from the same object, hence, CT images can provide additional spectral resolution, making it possible to perform material decomposition. However, multiple projections may have a low signal‐to‐noise ratio (SNR), such that CT images suffer from noise. To handle this problem, a spectral CT image reconstruction method based on anisotropic sparse transformation (AST) is proposed. To increase the quality of reconstruction, AST through an anisotropic guided filter (AGF) and L0 quasi norm is proposed. Then, as a new regularization, AST is introduced into an iterative reconstruction process, generating an AST‐based method. Moreover, to utilize the correlation among projection data, the average image serves as the guidance image of AGF, it varies with the iterative index, resulting in a technique of dynamic average image (DAI). The AST‐based model involves L0 quasi norm minimization, hence an effective strategy is employed to solve the corresponding problem. A series of experiments were performed. The experiment showed that, compared to other listed methods, the result of the AST‐based method can achieve better visualization and higher quantitative indexes, hence it has application potential in the medical imaging field.

Abstract Background We developed a framework for segmenting and modeling lenticulostriate arteries (LSAs) on 7-T time-of-flight magnetic resonance angiography and tested its performance on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients and controls. Methods We prospectively included 29 CADASIL patients and 21 controls. The framework includes a small-patch convolutional neural network (SP-CNN) for fine segmentation, a random forest for modeling LSAs, and a screening model for removing wrong branches. The segmentation performance of our SP-CNN was compared to competitive networks. External validation with different resolution was performed on ten patients with aneurysms. Dice similarity coefficient (DSC) and Hausdorff distance (HD) between each network and manual segmentation were calculated. The modeling results of the centerlines, diameters, and lengths of LSAs were compared against manual labeling by four neurologists. Results The SP-CNN achieved higher DSC (92.741 ± 2.789, mean ± standard deviation) and lower HD (0.610 ± 0.141 mm) in the segmentation of LSAs. It also outperformed competitive networks in the external validation (DSC 82.6 ± 5.5, HD 0.829 ± 0.143 mm). The framework versus manual difference was lower than the manual inter-observer difference for the vessel length of primary branches (median -0.040 mm, interquartile range -0.209 to 0.059 mm) and secondary branches (0.202 mm, 0.016–0.537 mm), as well as for the offset of centerlines of primary branches (0.071 mm, 0.065–0.078 mm) and secondary branches (0.072, 0.064–0.080 mm), with p

Abstracts This study constructs a indicators system of urban ecological resilience based on “resistance-adaptation-recovery”, and measures the level of cities within the Yangtze River Economic Belt and the Yellow River Basin from 2006 to 2021. Utilizing the Dagum Gini coefficient, traditional and spatial kernel density methods, and geographical detector, the study comprehensively analyzes the spatiotemporal evolution and causes of urban ecological resilience in these regions across multiple dimensions. Furthermore, it explores different paths for enhancing resilience of the two regions. The results indicate: (1) The urban ecological resilience level of the Yangtze River Economic Belt is significantly lower than that of the Yellow River Basin, yet it exhibits a faster growth rate. Both regions show a distribution characterized by “higher in the east, lower in the west”. (2) The overall internal differences between the two regions show a downward trend. The Yangtze River Economic Belt exhibited more pronounced spatial imbalances compared to the Yellow River Basin; however, since 2011, this trend has reversed. (3) The overall resilience in both regions is improving, and the absolute gap is gradually narrowing, showing a significant trend towards polarization in terms of evolutionary features. Cities with lower resilience levels demonstrate increased upward mobility, while cities with higher levels exhibit low mobility or even a decline. (4) Differences in restoration and adaptative capabilities are the principal intrinsic factors affecting the resilience differences between the two regions, whereas variations in economic development and capital efficiency serve as important extrinsic factors determining their spatiotemporal evolution differences. (5) Increasing investment in green technologies, promoting industrial low-carbon transformations, encouraging social green investments, and strengthening green technological innovations are crucial strategies for enhancing urban ecological resilience in both regions. Meanwhile, optimizing open channels significantly improves the urban ecological resilience in the Yellow River Basin.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

Abstract As a newly defined type of programmed cell death, ferroptosis is considered a potent weapon against tumors due to its distinct mechanism from other types of programmed cell death. Ferroptosis is triggered by the uncontrolled accumulation of hydroperoxyl polyunsaturated fatty acid-containing phospholipids, also called lipid peroxidation. The lipid peroxidation, generated through enzymatic and non-enzymatic mechanisms, drives changes in cell morphology and the destruction of membrane integrity. Here, we dissect the mechanisms of ferroptosis induced enzymatically or non-enzymatically, summarize the major metabolism pathways in modulating lipid peroxidation, and provide insights into the relationship between ferroptosis and tumor suppression. In this review, we discuss the recent advances of ferroptosis in tumor microenvironments and the prospect of potential therapeutic application.

Abstract Background Multiple models intravoxel incoherent motion (IVIM) based 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance(18F-FDG PET/MR) could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored. Objective To compare the value of 18F-FDG PET/MR metabolic parameters and diffusion parameters in the prognostic assessment of patients with NSCLC. Meterial and methods Chest PET and IVIM scans were performed on 61 NSCLC patients using PET/MR. The maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), diffusion coefficient (D), perfusion fraction (f), pseudo diffusion coefficient (D*) and apparent diffusion coefficient (ADC) were calculated. The impact of SUVmax, MTV, TLG, D, f, D*and ADC on survival was measured in terms of the hazard ratio (HR) effect size. Overall survival time (OS) and progression-free survival time (PFS) were evaluated with the Kaplan–Meier and Cox proportional hazard models. Log-rank test was used to analyze the differences in parameters between groups. Results 61 NSCLC patients had an overall median OS of 18 months (14.75, 22.85) and a median PFS of 17 months (12.00, 21.75). Univariate analysis showed that pathological subtype, TNM stage, surgery, SUVmax, MTV, TLG, D, D* and ADC were both influential factors for OS and PFS in NSCLC patients. Multifactorial analysis showed that MTV, D* and ADC were independent predicting factors for OS and PFS in NSCLC patients. Conclusion MTV, D* and ADC are independent predicting factors affecting OS and PFS in NSCLC patients. 18F-FDG PET/MR-derived metabolic parameters and diffusion parameters have clinical value for prognostic assessment of NSCLC patients.

Objectives: The guidelines recommend fractional flow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative flow ratio (QFR) is a novel coronary angiography (CAG)-based fractional flow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. Methods: This observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis ≥50%) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR ≤0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis ≥50% (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. Results: After propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 ± 0.7 vs 1.6 ± 0.5 [P

Abstract Accurate identification of animals and the verification of their parentage can be used to pedigree populations and support selective breeding. The International Society for Animal Genetics recommended 16 cattle STRs for individual identification and parentage testing in cattle, but no multiplex STR typing system contains these 16 STRs. Here, we develop an efficient 17-plex multiplex typing system for cattle that contains the 16 ISAG recommend STRs and a sex-determining marker. Compared to the Bovine Parenting Typing Kit (containing 11 of the 16 ISAG recommend STRs), our new typing system not only increases the number of molecular markers, but also simplifies the PCR operation and shortens the time for the typing procedure (from 4.5 h to 1 h 37 min). Profile can be generated from a single PCR reaction using as little as 1 ng of DNA. The combined probabilities of paternity exclusion CPEduo and CPEtrio were 0.999804697 and 0.999999260, respectively. These results indicate that our 17-plex typing system is a fast, sensitive and species-specific method for the identification of individuals and their parentage for cattle. The application of this system will improve the efficiency of the identification of cattle individuals and their paternity, supporting population genetic research and the selective breeding of cattle.

Abstract Background Podocyte injury causes proteinuria and accelerates glomerular sclerosis during diabetic kidney disease (DKD). Disruptor of telomeric silencing 1-like (DOT1L), an evolutionarily conserved histone methyltransferase, has been reported in preventing kidney fibrosis in chronic kidney disease models. However, whether DOT1L exerts beneficial effects in diabetes induced podocyte injury and the underlying molecular mechanisms need further exploration. Methods The expression of DOT1L was confirmed by Western blotting in MPC-5 cells and cortex of kidney from db/db mice, as well as immunofluorescence staining in human renal biopsy samples. The effect of DOT1L on podocyte injury was obtained using MPC-5 cells and db/db mice. The potential target genes regulated by DOT1L was measured by RNA-sequencing. Then, a series of molecular biological experiments was performed to investigate the regulation of PLCL1 by DOT1L in MCP-5 cells and db/db mice. Lipid accumulation was assessed by UPLC-MS/MS analysis and Oil Red O staining. Results DOT1L expression was significantly declined in high glucose (HG)-treated MPC-5 cells, podocyte regions of kidney tissues from db/db mice and human renal biopsy samples. Subsequent investigations revealed that upregulation of DOT1L ameliorated HG-induced cell apoptosis in MPC-5 cells as well as primary podocytes. Furthermore, podocyte-specific DOT1L overexpression inhibited diabetic podocyte injury in db/db mice. Mechanistically, we revealed that DOT1L upregulated phospholipase C-like 1 (PLCL1) expression by mediating H3K79me2 at its promoter and PLCL1 silencing suppressed the protective role of DOT1L on podocyte injury. Moreover, DOT1L improved diabetes induced abnormal fatty acid metabolism in podocytes and PLCL1 knockdown reversed its protective effects. Conclusions Taken together, our results indicate that DOT1L protects podocyte injury via PLCL1-mediated fatty acid metabolism and provides new insights into the therapeutic target of DKD.

Abstract Background Disorders of consciousness (DoC) are a group of conditions that affect the level of awareness and communication in patients. While neuroimaging techniques can provide useful information about the brain structure and function in these patients, most existing methods rely on a single modality for analysis and rarely account for brain injury. To address these limitations, we propose a novel method that integrates two neuroimaging modalities, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), to enhance the classification of subjects into different states of consciousness. Method and results The main contributions of our work are threefold: first, after constructing a dual-model individual graph using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we introduce a brain injury mask mechanism that consolidates damaged brain regions into a single graph node, enhancing the modeling of brain injuries and reducing deformation effects. Second, to address over-smoothing, we construct a dual-level graph that dynamically construct a population-level graph with node features from individual graphs, to promote the clustering of similar subjects while distinguishing dissimilar ones. Finally, we employ a subgraph exploration model with task-fMRI data to validate the interpretability of our model, confirming that the selected brain regions are task-relevant in cognition. Our experimental results on data from 89 healthy participants and 204 patients with DoC from Huashan Hospital, Fudan University, demonstrate that our method achieves high accuracy in classifying patients into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), or normal conscious state, outperforming current state-of-the-art methods. The explainability results of our method identified a subset of brain regions that are important for consciousness, such as the default mode network, the salience network, the dorsal attention network, and the visual network. Our method also revealed the relationship between brain networks and language processing in consciousness, and showed that language-related subgraphs can distinguish MCS from UWS patients. Conclusion We proposed a novel graph learning method for classifying DoC based on fMRI and DTI data, introducing a brain injury mask mechanism to effectively handle damaged brains. The classification results demonstrate the effectiveness of our method in distinguishing subjects across different states of consciousness, while the explainability results identify key brain regions relevant to this classification. Our study provides new evidence for the role of brain networks and language processing in consciousness, with potential implications for improving the diagnosis and prognosis of patients with DoC.

Abstract Understanding the relationship between various socioeconomic factors and urban forest structure is essential for directing resources to ensure equitable distribution of green space. Through a case study of a desert city, i.e., Phoenix, AZ, this study provides a novel application of Multiscale Geographically Weighted Regression (MGWR) in which we explore the spatially variable relationships between a wide array of socioeconomic indicators and urban forest attributes. Through the computation of various scales of influence for different explanatory variables, MGWR enhances our analysis’s precision and stresses the association between socioeconomic status and urban forest structure at local and regional scales. Our results indicate that although there has been a pattern of green inequality where minority and low-income communities have less access to urban forests, education levels were mostly insignificant based on the MGWR results. In some instances, higher incomes are negatively correlated with tree canopy coverage. Additionally, the stem density model outperformed the canopy coverage model in terms of prediction accuracy. This research adds a new dimension to urban forestry literature and emphasizes the value of customized urban planning strategies and the environmental justice implications of urban forestry, particularly in arid environments.

Abstract This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30–50 Gy in 5–10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p

Li metal batteries (LMBs) with LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes could release a specific energy of >500 Wh kg−1 by increasing the charge voltage. However, high-nickel cathodes working at high voltages accelerate degradations in bulk and at interfaces, thus significantly degrading the cycling lifespan and decreasing the specific capacity. Here, we rationally design an all-fluorinated electrolyte with addictive tri(2,2,2-trifluoroethyl) borate (TFEB), based on 3, 3, 3-fluoroethylmethylcarbonate (FEMC) and fluoroethylene carbonate (FEC), which enables stable cycling of high nickel cathode (LiNi0.8Co0.1Mn0.1O2, NMC811) under a cut-off voltage of 4.7 V in Li metal batteries. The electrolyte not only shows the fire-extinguishing properties, but also inhibits the transition metal dissolution, the gas production, side reactions on the cathode side. Therefore, the NMC811||Li cell demonstrates excellent performance by using limited Li and high-loading cathode, delivering a specific capacity >220 mA h g−1, an average Coulombic efficiency >99.6% and capacity retention >99.7% over 100 cycles.

Abstract Background Anaplastic lymphoma kinase (ALK) test in advanced non‐small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real‐world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. Methods In this real‐world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)‐VENTANA‐D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. Results The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC‐VENTANA‐D5F3 revealed an intra‐hospital consistency rate of 98.2% (879/895) and an inter‐hospital consistency rate of 99.2% (646/651). IHC‐VENTANA‐D5F3 was used in 53.6%, real‐time polymerase chain reaction (RT‐PCR) in 25.4%, next‐generation sequencing (NGS) in 18.3%, and fluorescence in‐situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC‐VENTANA‐D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT‐PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). Conclusions This study highlights the real‐world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC‐VENTANA‐D5F3 with high consistency and distinct clinicopathological features in ALK‐positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision‐making in NSCLC.

Abstract Background The existing predictive models for metabolic-associated fatty liver disease (MAFLD) possess certain limitations that render them unsuitable for extensive population-wide screening. This study is founded upon population health examination data and employs a comparison of eight distinct machine learning (ML) algorithms to construct the optimal screening model for identifying high-risk individuals with MAFLD in China. Methods We collected physical examination data from 5,171,392 adults residing in the northwestern region of China, during the year 2021. Feature selection was conducted through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Additionally, class balancing parameters were incorporated into the models, accompanied by hyperparameter tuning, to effectively address the challenges posed by imbalanced datasets. This study encompassed the development of both tree-based ML models (including Classification and Regression Trees, Random Forest, Adaptive Boosting, Light Gradient Boosting Machine, Extreme Gradient Boosting, and Categorical Boosting) and alternative ML models (specifically, k-Nearest Neighbors and Artificial Neural Network) for the purpose of identifying individuals with MAFLD. Furthermore, we visualized the importance scores of each feature on the selected model. Results The average age (standard deviation) of the 5,171,392 participants was 51.12 (15.00) years, with 52.47% of the participants being females. MAFLD was diagnosed by specialized physicians. 20 variables were finally included for analyses after LASSO regression model. Following ten rounds of cross-validation and parameter optimization for each algorithm, the CatBoost algorithm exhibited the best performance, achieving an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.862. The ranking of feature importance indicates that age, BMI, triglyceride, fasting plasma glucose, waist circumference, occupation, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, ethnicity and cardiovascular diseases are the top 13 crucial factors for MAFLD screening. Conclusion This study utilized a large-scale, multi-ethnic physical examination data from the northwestern region of China to establish a more accurate and effective MAFLD risk screening model, offering a new perspective for the prediction and prevention of MAFLD.

Abstract Background Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short‐term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH. Methods Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo. Results Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses. Conclusion Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.

Background Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Permeability plays a pivotal role in water resources management, oil and gas exploration and production, as well as geological hazard assessment. Previous studies primarily explores the influencing factors of permeability through indirect methods, and lacks direct means to describe the relationship between porous media and permeability, and the relationship between permeability and the internal pore structure of porous media is still unclear. This study developed an experimental system featuring controllable pore space properties to investigate the relationship between permeability in porous media and factors including porosity, the horizontal and vertical distribution of pores, the regularity of particle arrangements, and the aspect ratio of elliptical pores. The experimental results demonstrate a positive correlation between permeability and porosity in porous media. Circular porous media generally adhere to the Kozeny-Carman equation, while variations in particle circularities and arrangements lead to pronounced permeability anisotropy. Due to the transverse arrangement of porous media leading to the fluid with a long flow path, permeability in horizontally arranged pores aligned with the flow direction is significantly higher than that in vertically arranged pores. Irregularly arranged porous media exhibit higher permeability compared to regularly arranged porous media, because 1) the irregular arrangement of the particles can lead to some large pores in the porous media that can provide large channels to facilitate the penetration of the fluid; 2) the irregular arrangement increases the flow path within the porous medium, leading to more fluid paths in the porous medium. Porous media with an aspect ratio of 1 for the long and short axes exhibits the highest permeability. The findings of this study provide essential insights into the evolution of penetration rates in porous media and their relationship with pore space properties.

Abstract Rockeries have a complex and significant role in classical Chinese garden designs. They present distinct artistic characteristics and spatial hierarchies and are crucial to garden heritage conservation. Craftsmanship in rockery construction is a significant part of China’s intangible cultural heritage. Rockeries are primarily composed of naturally occurring rocks chosen for their uniqueness and complex shapes and textures. These rocks present challenges as nonstandard elements within the traditional Chinese garden context, as it is not easy to depict them using conventional blueprints and models. This complicates the design, adjustment, display, and construction of rockeries, which lacks tangible bases for reference. Consequently, the preservation and restoration of garden rockeries is difficult, and the perpetuation and dissemination of rockery construction skills face numerous challenges. This study introduces a method that combines laser scanning and photographic measurements to digitize precisely nonstandard elements of rockery stones. This approach presents an innovative design and construction workflow for rockeries by refining design processes, showcasing real effects, and resolving assembly issues. The results demonstrate that the combination of three-dimensional laser scanning and close-range photogrammetry can accurately replicate the complex forms and textures of these nonstandard elements. The stone coding and digital management system devised based on the logic of construction effectively satisfies the design and building requirements of rockeries. Correspondingly, the proposed digital construction workflow enhances the accuracy of rockery design, presentation, and evaluation, thereby contributing to the protection and restoration of rockery heritage sites and the transmission of rockery construction techniques.

Abstract To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P

Based on meteorological data collected over nearly 60 years (1960–2017) from four national meteorological stations along the margins of the Badain Jaran Desert, this study analyzed the spatiotemporal variations in evaporation from water surfaces and identified the dominant controlling factors. Methods used included linear trend analysis, linear tendency estimation, the departure method, the rank correlation coefficient-based method, and Multiple Linear Regression (MLR). Results indicate notable spatiotemporal differences in evaporation distribution and evolution. Spatially, average annual evaporation exhibited a pronounced altitude effect, decreasing at a rate of about 8.23 mm/m from east to west with increasing altitude. Temporally, annual evaporation showed significant upward trends after 1996 at the northeastern (Guaizi Lake) and western (Dingxin) margins, with rates of 132 mm/10a and 105 mm/10a, respectively. Conversely, along the northwestern (Ejina Banner) and southern (Alxa Right Banner) margins of the desert, an evaporation paradox was observed, with annual evaporation trending downward at rates of 162 mm/10a and 187 mm/10a, respectively, especially after 1987. The dominant factors controlling evaporation varied spatially: Average annual temperature and relative humidity influended the western margin (Dingxin), average annual temperature was the key factor for the northeastern margin (Guaizi Lake), and average wind speed was crucial for the northern (Ejina Banner) and southern (Alxa Right Banner) margins.

The development of skeletal muscle is a crucial factor in determining the meat yield and economic benefits of broiler production. Recent research has shown that mulberry leaves and their extracts can be used to significantly improve the growth performance of livestock and poultry. The present study aims to elucidate the mechanisms involved in the regulation of skeletal muscle development in broiler offspring by dietary mulberry-leaf flavonoids (MLF) supplementation from the perspective of maternal effect theory. A total of 270 Qiling broiler breeder hens were randomly assigned to 3 treatments with different doses of MLF (0, 30, 60 mg/kg) for 8 weeks before collecting their fertilized eggs. The chicken offspring at 13 and 19 d of embryonic stage, and from 1 to 28 d old after hatching were included in this study. The results showed that maternal supplementation increased the breast muscle weight and body weight of the offspring at the embryo and chick stages (P

At present, there is an increasing demand for real-time communication and data transmission between the air and the sea. Therefore, it is important to study robust and reliable air-sea cross-domain communication technologies. However, due to the different characteristics of the two media and the impact of harsh environments, air-sea cross-domain communication channels are complex and varied, making it difficult to smoothly pass through the air-water interface. In order to better understand the development of air-sea cross-domain communication technologies, the current research on air-sea cross-domain communication was comprehensively summarized, and its working environment and development of communication technologies were explained. The technologies were divided into two categories: air-sea cross-domain link-level direct communication and air-sea cross-domain relay communication. Then, the research status, difficulties, and proposed solutions were summarized. Finally, future research directions were discussed. The research can help to promote the development of air-sea cross-domain communication technologies.

Photocatalytic assisted uranium extraction technology is a rapidly developed technology for uranium extraction from wastewater and seawater in recent years, which can significantly improve the extraction capacity and extraction rate of uranium. However, the activity of most photocatalysts in air atmosphere is inhibited, which hinders the practical application of this technology. Based on this, this paper discusses the latest progress of photocatalytic assisted uranium extraction technology in air atmosphere, focusing on the analysis of different mechanisms and product characteristics of photocatalytic assisted uranium extraction in air atmosphere, especially the photoreaction and chemical reaction mechanism in the absence of catalyst. There are mainly two mechanisms for the photocatalysis assist uranium extraction. The first one is based on the photocatalytic reduction of U(Ⅵ) to U(Ⅳ). Under illumination, electrons and holes pairs are generated on photocatalysts, and the electrons could reduce the soluble \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} to insoluble uranium oxide(UO2). However, under air atmosphere, at the presence of oxygen, the newly formed UO2 could be oxidated back to \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} and dissolved into solution, resulting in the decrease of uranium extraction performance. Therefore, this mechanism is usually applied under inert atmosphere. Although with proper design of photocatalyst, the oxygen could be covert to \begin{document}${ · {\mathrm{O}}_2^- } $\end{document} to further reduce \begin{document}${\mathrm{UO}}_2^{2+} $\end{document}, the performance is still not comparable with that under inert atmosphere. The other recently developed photocatalysis assisted extraction mechanism is based on the convert of soluble \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} to uranium peroxide((UO2)O2•xH2O), which can work well under air atmosphere. Under light illumination, hydrogen peroxide(H2O2) can be first produced with the assist of efficient photocatalysts or the photoactivity of \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} itself. Then H2O can react with to \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} form insoluble uranium peroxide. As uranium peroxide is stable under air and oxygen may contribute to the formation of H2O2, this mechanism can obtain excellent performance under air. Researchers have developed composite materials such as carbon nitride, carbon dots, graphene aerogels, and metal-organic frameworks(MOFs), which exhibit superior uranium removal performance under aerobic conditions. Besides, research on uranium extraction via photocatalysis under air is still in its infancy, and the specific reaction mechanisms may vary under different environments, necessitating further investigation. Based on the mechanism of uranium extraction via the photo-assisted transformation to uranium peroxides, the design of catalysts and uranium extraction materials will be greatly broadened. Combined with the discussion of the reaction mechanism of uranium extraction under light conditions and the design of catalyst materials, we hope to provide inspiration for researchers to develop highly efficient uranium extraction catalyst and mechanism research under air atmosphere.

Uranium is the main fuel of nuclear power, and the removal of uranium from uranium-containing wastewater is important for environmental protection and resource recovery. Photo-induced uranyl ion removing is an economical and efficient method to remove U(Ⅵ) from uranium-containing wastewater. Many materials have been used for photo-induced reduction of U(Ⅵ). However, the practical application of most materials is still limited by many factors, such as the complexity of its synthesis process, the harsh conditions required, and the poor selectivity and reusability in the photocatalytic process. More importantly, most materials can only be photocatalyzed under the protection of an inert atmosphere. In the presence of oxygen, the photocatalytic product uranium dioxide(UO2) is unstable and easily oxidized resulting in reduced removal effect, so it becomes particularly vital to find an effective catalyst. Carbon dots(CDs) are a new type of carbon-based materials with excellent fluorescence performance, good water solubility and biocompatibility. However, due to the small size and hydrophilicity of the CDs, it is difficult to separate from water. It needs to be combined with other solid materials when applied. The application of CDs to the photocatalytic removal of uranyl ions in water has rarely been studied. Silica(SiO2) is an ideal loader due to its excellent mechanical strength and irradiation stability, as well as its large specific surface area and easy modification. In this paper, a blue carbon dot was prepared by solvothermal method and CDs/SiO2 composites were synthesized by sol-gel method. The morphology of the composite was characterized by scanning electron microscopy(SEM) and transmission electron microscopy(TEM) technologies, and their application in photocatalytic removal of uranium were studied. Under visible light irradiation, CDs/SiO2-b can remove more than 95% of uranium in 100 min. Experiments have found that the photo-precipitation rate of silica to uranium after the introduction of carbon dots is about 5.8 times of that of the pure silica, and uranium can be transformed into solid product of (UO2)O2•2H2O under air atmosphere, with a removal capacity of more than 800 mg/g. The morphology and structure of the photocatalytic products were characterized by SEM and XPS technology, and the solid products were easy to separate and remove. In order to evaluate the practical application of CDs/SiO2 light-induced reduction of uranium under visible light irradiation, pH and other influencing factors were systematically studied. Moreover, the removal efficiency of uranium is higher 85% after 5 cycles of recycling, showing excellent recycling performance. CDs/SiO2 composites are simple to prepare and can efficiently remove uranyl ions in water through photoinduction, which provides a new method and material for photoinduced removal of uranium.

Abstract Purpose Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. Methods A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. Results The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P

Abstract Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.

Abstract Background Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. Methods A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. Results H. pylori can colonize the host’s stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. Conclusions H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process. Graphical abstract

Abstract Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.

Abstract Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

Abstract Background The traumatic spinal cord injury (SCI) can cause immediate multi-faceted function loss or paralysis. Microglia, as one of tissue resident macrophages, has been reported to play a critical role in regulating inflammation response during SCI processes. And transplantation with M2 microglia into SCI mice promotes recovery of motor function. However, the M2 microglia can be easily re-educated and changed their phenotype due to the stimuli of tissue microenvironment. This study aimed to find a way to maintain the function of M2 microglia, which could exert an anti-inflammatory and pro-repair role, and further promote the repair of spinal cord injury. Methods To establish a standard murine spinal cord clip compression model using Dumont tying forceps. Using FACS, to sort microglia from C57BL/6 mice or CX3CR1GFP mice, and further culture them in vitro with different macrophage polarized medium. Also, to isolate primary microglia using density gradient centrifugation with the neonatal mice. To transfect miR-145a-5p into M2 microglia by Lipofectamine2000, and inject miR-145a-5p modified M2 microglia into the lesion sites of spinal cord for cell transplanted therapy. To evaluate the recovery of motor function in SCI mice through behavior analysis, immunofluorescence or histochemistry staining, Western blot and qRT-PCR detection. Application of reporter assay and molecular biology experiments to reveal the mechanism of miR-145a-5p modified M2 microglia therapy on SCI mice. Results With in vitro experiments, we found that miR-145a-5p was highly expressed in M2 microglia, and miR-145a-5p overexpression could suppress M1 while promote M2 microglia polarization. And then delivery of miR-145a-5p overexpressed M2 microglia into the injured spinal cord area significantly accelerated locomotive recovery as well as prevented glia scar formation and neuron damage in mice, which was even better than M2 microglia transplantation. Further mechanisms showed that overexpressed miR-145a-5p in microglia inhibited the inflammatory response and maintained M2 macrophage phenotype by targeting TLR4/NF-κB signaling. Conclusions These findings indicate that transplantation of miR-145a-5p modified M2 microglia has more therapeutic potential for SCI than M2 microglia transplantation from epigenetic perspective. Graphical Abstract

Abstract Background Obesity is known as a risk factor for cardiovascular disease (CVD). However, there is an absence of preoperative cardiac risk assessment in bariatric surgery candidates and the incidence of CVD among these high-risk patients is still unknown. Methods A consecutive series of bariatric surgery candidates at two Chinese tertiary hospitals received coronary CT angiography or coronary angiography from 2017 to 2023. Patients were categorized as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) based on the presence or absence of MetS. CVD was diagnosed based on the maximum intraluminal stenosis > 1% in any of the segments of the major epicardial coronary arteries. Obstructive CVD was defined as coronary stenosis ≥ 50%. Binary multivariable logistic regression was performed to analyze the association between CVD and metabolic status. The number of principal MetS components was categorized into zero (without glycemic, lipid, and BP components), one (with one of the components), two (with any two components), and three (with all components) to explore their association with CVD. Results A total of 1446 patients were included in the study. The incidence of CVD and obstructive CVD were 31.7% and 9.6%. Compared with MHO patients, MUO patients had a significantly higher incidence of mild (13.7% vs. 6.1%, P

Abstract The beveling process is an important process in the manufacturing of resonators, which has a significant impact on the frequency stability of resonators. Without understanding the frequency characteristics of the resonator after beveling, it is impossible to accurately design the beveled resonators. Thus, in order to investigate the vibration characteristics of AT-cut beveled resonators, we investigated the high-frequency vibration in this work by using the subregional geometric fitting method (SGFM) based on Mindlin’s plate theory. Quartz crystal plates with nonuniform thicknesses are partitioned into three regions and each region is fitted by using the polynomial functions based on the measured geometric morphology data. The governing equations are obtained based on Mindlin’s two-dimensional theory and the coupled vibrations are further solved using the partial differential equation module of COMSOL. In the numerical calculation, we compare the results obtained by the SGFM with those obtained by the global fitting method and the measured data. The accuracy and effectiveness of the SGFM are also verified. It is found that the frequencies obtained by the SGFM are slightly higher than the frequencies obtained by the global fitting method, and the results of SGFM are closer to the measured results. Meanwhile, as the beveling time increases, the frequency increases and the energy trapping effect becomes more significant. The proposed method can significantly improve the computational efficiency of thickness-shear vibration while ensuring accuracy. It is expected to provide a new geometric fitting method for the analysis of beveled crystal resonators.

Abstract Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

Deep coalbed methane (DCBM), an unconventional gas reservoir, has undergone significant advancements in recent years, sparking a growing interest in assessing pore pressure dynamics within these reservoirs. While some production data analysis techniques have been adapted from conventional oil and gas wells, there remains a gap in the understanding of pore pressure generation and evolution, particularly in wells subjected to large-scale hydraulic fracturing. To address this gap, a novel technique called excess pore pressure analysis (EPPA) has been introduced to the coal seam gas industry for the first time to our knowledge, which employs dual-phase flow principles based on consolidation theory. This technique focuses on the generation and dissipation for excess pore-water pressure (EPWP) and excess pore-gas pressure (EPGP) in stimulated deep coal reservoirs. Equations have been developed respectively and numerical solutions have been provided using the finite element method (FEM). Application of this model to a representative field example reveals that excess pore pressure arises from rapid loading, with overburden weight transferred under undrained condition due to intense hydraulic fracturing, which significantly redistributes the weight-bearing role from the solid coal structure to the injected fluid and liberated gas within artificial pores over a brief timespan. Furthermore, field application indicates that the dissipation of EPWP and EPGP can be actually considered as the process of well production, where methane and water are extracted from deep coalbed methane wells, leading to consolidation for the artificial reservoirs. Moreover, history matching results demonstrate that the excess-pressure model established in this study provides a better explanation for the declining trends observed in both gas and water production curves, compared to conventional practices in coalbed methane reservoir engineering and petroleum engineering. This research not only enhances the understanding of DCBM reservoir behavior but also offers insights applicable to production analysis in other unconventional resources reliant on hydraulic fracturing.

Increasing research has focused on semantic communication, the goal of which is to convey accurately the meaning instead of transmitting symbols from the sender to the receiver. In this paper, we design a novel encoding and decoding semantic communication framework, which adopts the semantic information and the contextual correlations between items to optimize the performance of a communication system over various channels. On the sender side, the average semantic loss caused by the wrong detection is defined, and a semantic source encoding strategy is developed to minimize the average semantic loss. To further improve communication reliability, a decoding strategy that utilizes the semantic and the context information to recover messages is proposed in the receiver. Extensive simulation results validate the superior performance of our strategies over state-of-the-art semantic coding and decoding policies on different communication channels.

Abstract Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants’ trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people’s trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.

Abstract Background Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology. Methods On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers. Results As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences. Conclusions Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.

Abstract Background Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. Methods The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. Results This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49–3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03–2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28–3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17–3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24–4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01–3.49) were associated with increased odds of infertility, respectively. Conclusion There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Non-isocyanate polyurethane (NIPU) adhesives represent a cutting-edge advancement in adhesive technology, poised to significantly diminish the dependency on isocyanate-based PU within the industry. In the context of the increasing scarcity of petroleum-based resources and the growing imperative for sustainable environmental practices, the pursuit of a comprehensively sustainable, bio-derived non-isocyanate polyurethane (NIPU) adhesive has swiftly become a pivotal area of interest within the scientific research community. In this study, the cashew phenol cyclic carbonate (CPCC) was synthesized through the addition polymerization process involving cashew phenol glycidyl ether (602A) with carbon dioxide (CO2), followed by a curing step utilizing a diamine extracted from biomass-derived oil to produce bio-based NIPU at ambient temperature. The synthesized NIPU adhesive demonstrated remarkable thermal stability and exceptional adhesion to a variety of substrate materials. Notably, the adhesive showcased superior bonding efficacy at ultra-low temperatures, with steel bonding strength reaching up to 7.78 MPa at −37 °C. This study presents an efficient and accelerated synthesis approach for the preparation of bio-based NIPU, offering a significant contribution to the field. Moreover, it provides a valuable reference for future advancements in NIPU adhesive technology, particularly for the applications requiring robust bonding at low-temperature environments.

ABSTRACT Abdominal aortic aneurysm (AAA) is a large-vessel disease with high mortality, characterized by complex pathogenic mechanisms. Current therapeutic approaches remain insufficient to halt its progression. Fungi are important members of the gut microbiota. However, their characteristic alterations and roles in AAA remain unclear. This study investigated the role of gut fungal communities in the development of AAA through metagenomic sequencing of fecal samples from 31 healthy individuals and 33 AAA patients. We observed significant dysbiosis in the gut mycobiomes of AAA patients compared to healthy individuals, characterized by an increase in pathogenic fungi like Candida species and a decrease in beneficial yeasts such as Saccharomyces cerevisiae. The changes in fungal populations correlated strongly with clinical indicators of AAA, highlighting their potential for diagnosing and predicting AAA progression. Furthermore, our animal experiments demonstrated that Saccharomyces cerevisiae significantly ameliorated pathological alterations in AAA mice, suggesting a protective role for specific yeast strains against AAA development. These findings underscore the significant impact of gut mycobiomes on AAA and suggest that modulating these fungal communities could offer a novel therapeutic approach. Our research advances the understanding of the influence of gut microbiome on vascular diseases and suggests potential non-surgical approaches for managing AAA. By elucidating the diagnostic and therapeutic potential of gut fungi in AAA, this study provided important clues for future clinical strategies and therapeutic developments in the field of vascular medicine.IMPORTANCEOur research highlights the crucial role of gut fungi in abdominal aortic aneurysm (AAA) development. By analyzing fecal samples from AAA patients and healthy controls, we discovered significant dysbiosis in gut fungal communities, characterized by an increase in harmful Candida species and a decrease in beneficial yeasts like Saccharomyces cerevisiae. This dysbiosis was correlated with the severity of AAA. Importantly, in animal experiments, supplementing with Saccharomyces cerevisiae significantly slowed AAA progression. These findings suggest that modulating gut fungi may offer a novel, non-surgical approach to the diagnosis and treatment of AAA, potentially reducing the need for invasive procedures.

Herein, an integrated electro‐optically tunable narrow‐linewidth III–V laser with an output power of 738.8 μW and an intrinsic linewidth of 45.55 kHz at the C band is demonstrated. The laser cavity is constructed using a fiber Bragg grating (FBG) and a tunable Sagnac loop reflector (TSLR) fabricated on thin‐film lithium niobate. The combination of the FBG and the electro‐optically tunable TSLR offers the advantages of single spatial mode, single frequency, narrow linewidth, and wide wavelength tunability for the electrically pumped hybrid integrated laser, which features a frequency tuning range of 20 GHz and a tuning efficiency of 0.8 GHz V−1.

Microplastics (MPs, ＜5mm in size) have rapidly spread across aquatic ecosystems, which urgently needs systematic assessment for their ecological risk. Fish species have frequently been selected as indicator organisms in evaluating MPs contaminants. However, it has been questioned that which organs of fishes should be examined due to tissue-specific results. In this study, we investigated the accumulation and depuration process of MPs in the main organs of zebrafish under different MPs concentrations as well as the presence and absence of food resources. Our results recorded consistently higher MPs accumulation in fish guts among different MPs concentrations, implying fish guts as stable organs representing organisms’ MPs contaminants. Meanwhile, MPs accumulated in fish guts increased significantly with increasing exposure concentrations, highlighting fish guts as sensitive organs in reflecting MPs contamination in aquatic environments. In addition, MPs accumulated in fish guts under non-feeding conditions followed a logistic “S” curve while fluctuated under feeding conditions, suggesting increased ecological MPs risk with the absence of food resources. The depuration rate in fish guts was significantly higher in the feeding group than in the non-feeding group, implying better expelling ability of MPs with the presence of food resources. Our study proposes fish guts as the optimal indicator organs in assessing the ecological risk of MPs contaminants in both fish bodies and aquatic environments, and highlights the importance of sustaining sufficient food resources in aquatic environments to reduce the MPs triggered adverse effects on fish species.

Background: Aberrant functional connectivity is a hallmark of schizophrenia. The precise nature and mechanism of dysconnectivity in schizophrenia remains unclear, but evidence suggests that dysconnectivity is different in wake versus sleep. Microstate analysis uses electroencephalography (EEG) to investigate large-scale patterns of coordinated brain activity by clustering EEG data into a small set of recurring spatial patterns, or microstates. We hypothesized that this technique would allow us to probe connectivity between brain networks at a fine temporal resolution and uncover previously unknown sleep-specific dysconnectivity. Methods: We studied microstates during sleep in patients with schizophrenia by analyzing high-density EEG sleep data from 114 patients with schizophrenia and 79 control participants. We used a polarity-insensitive k-means analysis to extract a set of 6 microstate topographies. Results: These 6 states included 4 widely reported canonical microstates. In patients and control participants, falling asleep was characterized by a shift from microstates A, B, and C to microstates D, E, and F. Microstate F was decreased in patients during wake, and microstate E was decreased in patients during sleep. The complexity of microstate transitions was greater in patients than control participants during wake, but this reversed during sleep. Conclusions: Our findings reveal behavioral state–dependent patterns of cortical dysconnectivity in schizophrenia. Furthermore, these findings are largely unrelated to previous sleep-related EEG markers of schizophrenia such as decreased sleep spindles. Therefore, these findings are driven by previously undescribed sleep-related pathology in schizophrenia.