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Abstract Accurately understanding the critical elements influencing college students’ professional commitment is both an urgent practical requirement and a critical theoretical proposition in today’s intensely competitive job market. In order to provide new light on career development in the context of higher education, this study intends to investigate the complex interactions among college students between perceived organizational justice, academic stress, and professional commitment. Using descriptive statistics, correlation analysis, regression analysis, and structural equation modeling, we carried out a thorough investigation of H University’s full-time undergraduate students in Central China in order to thoroughly examine our hypothesis. The results show that students’ professional commitment is much lower when they view organizational justice to be lacking, and that there is a partial mediating role for academic stress in this relationship. Interestingly, organizational justice has a positive correlation with professional commitment and a negative correlation with academic stress. These findings provide educators and policymakers with insightful information, indicating that, in an increasingly competitive labor market, professional commitment is largely dependent on students’ ability to manage their academic stress and develop a sense of organizational justice. This study adds a new understanding of career development in higher education settings by merging professional commitment research with organizational justice theory. It also has significant implications for educational practices and career support measures.

Abstract Background Total knee replacement (TKA) is a frequent modality performed in patients with knee osteoarthritis (OA). The aim of this study was to perform a meta-analysis and systematic review to evaluate the efficacy after TKA by gait analysis in patients with OA. Methods PubMed, EMBASE, the Cochrane library, and Web of Science were searched for relevant studies from inception to July 2024. STATA SE 14.0 software was used for statistical analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline. Results A total of 2525 reports were identified with 24 studies meeting pre-designed inclusion criteria. Several gait parameters were investigated. In patients with knee OA after TKA, there existed an increase in the Max knee flexion (WMD, 3.12; 95% CI, 0.93 to 5.32; I2 = 73.9%, P

Abstract Stereotactic radiation therapy (SBRT) has emerged as a promising treatment modality for locally advanced pancreatic cancer. The aim of this study is to assess the dosimetric efficacy of online adaptive radiotherapy (ART) in comparison to image-guided radiation therapy (IGRT) for pancreatic cancer. We conducted a retrospective analysis involving 8 patients diagnosed with locally advanced pancreatic cancer. The gross tumor volume (GTV) delineates the visible extent of the tumor on imaging, while the planning tumor volume (PTV) was generated by expanding 5 mm from the GTV and ensuring a 3 mm distance from the small intestine, duodenum, and stomach simultaneously. Treatment planning was executed using the United Imaging Healthcare Treatment Planning System workstation. The control group underwent evaluation based on daily validated fan-beam CT (FBCT) scans, assessing both the dose delivered to actual organs at risk (OARs) and the target volume. Radiotherapy plans were developed utilizing simulation CT, and conventional radiotherapy with daily image-guided radiation therapy (IGRT) was administered using FBCT-Linac. Conversely, patients in the study group received daily validated FBCT-guided adaptive radiotherapy plans, with a focus on mean dose assessment of both the target volume and OARs. Subsequently, we compared the average outcomes of each treatment fraction between IGRT and online adaptive radiotherapy (ART). Comparison between ART and IGRT treatment plans revealed significant differences in various dosimetric parameters: For PTV: V98%: ART (96.28%) vs IGRT (89.73%), p = 0.000, V95%: ART (96.28%) vs IGRT (89.73%), p = 0.031, V90%: ART (98.58%) vs IGRT (93.65%), p = 0.000, Dmean: ART (4912.91) vs IGRT (4804.11), p = 0.000. For GTV: V100%: ART (97.96%) vs IGRT (94.85%), p = 0.314, V98%: ART (100.00%) vs IGRT (96.83%), p = 0.000, V90%: ART (100.00%) vs IGRT (97.75%), p = 0.000, Dmean: ART (4972.17) vs IGRT (4907.23), p = 0.000. For the duodenum: D0.5cc: ART (2883.92) vs IGRT (3359.35), p = 0.000, D1cc: ART (2726.32) vs IGRT (3128.66), p = 0.001, D5cc: ART (2051.96) vs IGRT (2273.93), p = 0.015, D10cc: ART (1650.73) vs IGRT (1731.74), p = 0.211. For the small bowel: D0.5cc: ART (3022.3) vs IGRT (3142.64), p = 0.037. D5cc: ART (2151.09) vs IGRT (2389.15), p = 0.043, D10cc: ART (1775.20) vs IGRT (1942.00), p = 0.079. For the stomach: D0.5cc: ART (3353.92) vs IGRT (4117.85), p = 0.000, D5cc: ART (2860.20) vs IGRT (3235.41), p = 0.000, D10cc: ART (2553.72) vs IGRT (2836.73), p = 0.000. For the Dmean of the left kidney and right kidney: Left kidney: ART (248.28) vs IGRT (239.65), p = 0.100. Right kidney: ART (314.55) vs IGRT (307.17), p = 0.345. These results suggest significant improvements in PTV coverage and sparing of OARs with ART compared to IGRT, indicating the potential of ART in optimizing treatment outcomes for pancreatic cancer patients. Compared to conventional IGRT-guided SBRT programs, ART-based SBRT for pancreatic cancer not only enhances the dose distribution to the target volume but also mitigates the radiation exposure to critical organs-at-risk (OARs) such as the duodenum, small intestine, and stomach. This approach may offer a more favorable safety profile while concurrently enhancing treatment efficacy.

Abstract This paper investigates the impact of big data on deep learning models to help solve the full waveform inversion (FWI) problem. While it is well known that big data can boost the performance of deep learning models in many tasks, its effectiveness has not been validated for FWI. To address this gap, we present an empirical study that investigates how deep learning models in FWI behave when trained on openfwi, a collection of large-scale, multi-structural, synthetic datasets published recently. In particular, we train and evaluate the FWI models on a combination of 10 2D subsets in openfwi that contain 470 K pairs of seismic data and velocity maps in total. Our experiments demonstrate that training on the combined dataset yields an average improvement of 13.03% in MAE, 7.19% in MSE and 1.87% in SSIM compared to each split dataset, and an average improvement of 28.60%, 21.55% and 8.22% in the leave-one-out generalization test. We further demonstrate that model capacity needs to scale in accordance with data size for optimal improvement, where our largest model yields an average improvement of 20.06%, 13.39% and 0.72% compared to the smallest one.

The digital image correlation (DIC) technology was used to investigate the evolution law of the coal surface strain field under different loading rates and to analyze the influence of loading rate on the evolution of the deformation field, deformation localization, and surface deformation energy density. The experimental results indicate that the higher the loading rate is, the more complete the final failure mode of the coal body, and the failure mode of the coal body also transitions from shear failure to tensile failure; the loading rates of different magnitudes also affect the localization time of coal deformation. The higher the loading rate is, the greater the proportion of the initiation time of coal deformation localization to the overall failure time. The higher the loading rate is, the more obvious the growth trend of deformation energy density before deformation localization, and the more energy accumulates in the surface deformation localization area; the qreater the stress at the start time of deformation localization.

Abstract The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis. Graphical Abstract

Abstract Cystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein–ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens.

Abstract Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

Abstract Allergic diseases, characterized by a broad spectrum of clinical manifestations and symptoms, encompass a significant category of IgE-mediated atopic disorders, including asthma, allergic rhinitis, atopic dermatitis, and food allergies. These complex conditions arise from the intricate interplay between genetic and environmental factors and are known to contribute to socioeconomic burdens globally. Recent advancements in the study of allergic diseases have illuminated the crucial role of DNA methylation (DNAm) in their pathogenesis. This review explores the factors influencing DNAm in allergic diseases and delves into their mechanisms, offering valuable perspectives for clinicians. Understanding these epigenetic modifications aims to lay the groundwork for improved early prevention strategies. Moreover, our analysis of DNAm mechanisms in these conditions seeks to enhance diagnostic and therapeutic approaches, paving the way for more effective management of allergic diseases in the future.

Abstract Background Mycoplasma pneumoniae pneumonia is a common respiratory infection among children. However, the occurrence of thromboembolism with plastic bronchitis in association with Mycoplasma pneumoniae pneumonia is extremely rare. This case series presents five cases of children with Mycoplasma pneumoniae pneumonia who developed thromboembolism and plastic bronchitis. The clinical presentation, diagnostic approach, and management strategies are discussed. Methods A retrospective analysis was conducted on medical records from a pediatric hospital. Patient demographics, clinical features, laboratory findings, imaging results, treatment modalities, and outcomes were collected. Results The patients in our case series presented with varying degrees of respiratory distress, cough, and fever. Imaging studies revealed evidence of thromboembolism based on pulmonary artery occlusion. Bronchial casts were observed by bronchoscopy. Laboratory tests demonstrated elevated D-dimer levels and fibrinogen degradation products. All patients received a combination of low molecular weight heparin anticoagulation and supportive care. Conclusion Thromboembolism with plastic bronchitis associated with Mycoplasma pneumoniae pneumonia is a rare but potentially serious complication in children. Prompt recognition and management are crucial for improving patient outcomes. This case series highlights the diverse clinical presentations, diagnostic challenges, and treatment strategies for this unique clinical entity. Further research is needed to better understand the pathogenesis and optimal management of this condition.

Abstract Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.

Abstract Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising l-arabinose and d-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. l-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Background Tumor-infiltrating regulatory T cells (TI-Tregs) are well-adapted to thrive in the challenging tumor microenvironment (TME) by undergoing metabolic reprogramming, notably shifting from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) for energy production. The extracellular matrix is an important component of the TME, contributing to the regulation of both tumor and immune cell metabolism patterns by activating mechanosensors such as YAP. Whether YAP plays a part in regulating TI-Treg mitochondrial function and the underlying mechanisms are yet to be elucidated.Methods To gain insights into the effect of matrix stiffness on YAP activation in Tregs, alterations in stiffness were performed both in vitro and in vivo. YAP conditional knockout mice were used to determine the role of YAP in TI-Tregs. RNA-seq, quantitative PCR, flow cytometry, lentivirus infection and mitochondrial function assay were employed to uncover the mechanism of YAP modulating mitochondrial function in TI-Tregs. A YAP inhibitor and a low leucine diet were applied to tumor-bearing mice to seek the potential antitumor strategy.Results In this study, we found that YAP, as a mechanotransducer, was activated by matrix stiffness in TI-Tregs. A deficiency in YAP significantly hindered the immunosuppressive capability of TI-Tregs by disrupting mitochondrial function. Mechanically, YAP enhanced mitochondrial OXPHOS by upregulating the transcription of Lars2 (Leucyl-tRNA synthetase 2, mitochondrial), which was essential for mitochondrial protein translation in TI-Tregs. Since Lars2 relied much on its substrate amino acid, leucine, the combination of a low leucine diet and YAP inhibitor synergistically induced mitochondrial dysfunction in TI-Tregs, ultimately restraining tumor growth.Conclusions This finding uncovered a new understanding of how YAP shapes mitochondrial function in TI-Tregs in response to mechanical signals within the TME, making the combined strategy of traditional medicine and diet adjustment a promising approach for tumor therapy.

Theanine (N-ethyl-γ-glutamine), as a unique non-protein amino acid, plays vital roles in abiotic stress resistance, while its roles in biotic stress resistance are still unclear. Gray mold caused by Botrytis cinerea is a major disease in strawberries. Effects of theanine on the development of gray mold, cell-wall and phenylpropanoid metabolisms in strawberries were investigated in this study. Results showed that 5 mmol L−1 theanine treatment reduced disease incidence and severity of gray mold in strawberries with antifungal activity in vitro. Meanwhile, theanine treatment enhanced the accumulation of phenolic compounds and lignin, especially ellagic acid, cyanidin, and quercetin, which was associated with increased phenylpropanoid pathway related enzyme activities. Moreover, theanine induced callose deposition and suppressed cell- wall disassembling enzymes, accompanied by higher levels of water insoluble pectin, hemicellulose and cellulose. Therefore, theanine treatment could alleviate decay of B. cinerea-inoculated strawberries by regulating phenylpropanoid and cell-wall metabolisms, maintaining higher levels of phenolic compounds and cell-wall components, thereby contributing to disease resistance and cell-wall structure integrity.

Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.

A low-temperature-tolerant simultaneous nitrification-denitrification bacterial strain of Acinetobacter kyonggiensis (AKD4) was identified. It showed high efficiency in total nitrogen (TN) removal (92.45% at 10°C and 87.51% at 30°C), indicating its excellent low-temperature tolerance. Transcriptomic analysis revealed possible metabolic mechanisms under low-temperature stress. Genes involved in cell growth, including ATP synthase (atpADGH), amino acid (glyA, dctA, and ilvE), and TCA cycle metabolism (gltA, fumC, and mdh) were remarkably upregulated from 1.05–3.44-fold at 10°C, suggesting that their actions enhance survivability at low temperatures. The expression levels of genes associated with nitrogen assimilation (glnAE, gltBD, and gdhA), nitrogen metabolism regulation (ntrC, glnB, and glnD), and denitrification processes (napA) were increased from 1.01–4.38-fold at 10°C, which might have contributed to the bacterium’s highly efficient nitrogen removal performance at low temperatures. Overall, this study offers valuable insights into transcriptome, and enhances the comprehension of the low-temperature-tolerant mechanism of simultaneous nitrification and denitrification processes.

Abstract This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2–2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 μm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 μm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.

Background: Revealing out the hot zone and feature of early gastric cancers (EGCs) and dysplasia frequently developed is important for endoscopic screening and surveillance. This study aimed to investigate the distribution and location characteristics of EGCs and dysplasia. Methods: A total of 503 pathological diagnosed EGCs and dysplasia from 445 patients were reviewed retrospectively. The distribution of EGCs and dysplasia in stomach was mapped, and its associated clinicopathological findings were analyzed. Results: EGCs and dysplasia were predominately in the lesser curvature transversely, and vertical distributed frequently in lower third (51.7%) of stomach. In addition, lesions in upper third is associated with older age (p ​= ​0.014), male sex (p ​= ​0.002), smaller size (p < 0.001) and more differentiated EGCs, but fewer low-grade dysplasia and undifferentiated EGCs (p < 0.001). Moreover, most (461/503, 91.7%) lesions were found in endoscopy diagnosed atrophic mucosa, and are predominately differentiated EGCs and dysplasia (384/461, 83.3%). For the lesions in endoscopy diagnosed non-atrophic mucosa, more than half (23/42, 54.8%) are undifferentiated EGCs, which predominantly in middle (52.2%) and lower third (39.1%) of stomach. Whereas, differentiated EGCs accounts for 23.8% (10/42), and mainly (90%) located in the upper third of the stomach. Conclusions: The distribution of dysplasia, differentiated and undifferentiated EGCs was associated to location and atrophic mucosa. Those location characteristics are useful for endoscopic screening and surveillance.

The forming technology of surface micropattern structure was widely used in practical manufacturing as a means to texture the surface of materials and to promote advanced and functional materials. The main methods of surface micropattern forming include hot embossing, chemical etching, electrical discharge machining(EDM), photolithography and 3D printing depending on the application areas of materials. The different surface micropattern structure forming techniques and the basic principles of preparing surface texturise functional materials were reviewed, and their practical applications in photovoltaics, electronic information, intelligent manufacturing, ultra-precision manufacturing and other fields were listed. The characteristics and scope of application of different surface micropattern structure forming technologies are summarized, and the key problems faced in realizing the surface texturisation and functionalization of materials are put forward, which provides certain reference for the micromachining technology of surface micropattern structures.

Abstract The integration of electrochromic devices and energy storage systems in wearable electronics is highly desirable yet challenging, because self‐powered electrochromic devices often require an open system design for continuous replenishment of the strong oxidants to enable the coloring/bleaching processes. A self‐powered electrochromic device has been developed with a close configuration by integrating a Zn/MnO2 ionic battery into the Prussian blue (PB)‐based electrochromic system. Zn and MnO2 electrodes, as dual shared electrodes, the former one can reduce the PB electrode to the Prussian white (PW) electrode and serves as the anode in the battery; the latter electrode can oxidize the PW electrode to its initial state and acts as the cathode in the battery. The bleaching/coloring processes are driven by the gradient potential between Zn/PB and PW/MnO2 electrodes. The as‐prepared Zn||PB||MnO2 system demonstrates superior electrochromic performance, including excellent optical contrast (80.6%), fast self‐bleaching/coloring speed (2.0/3.2 s for bleaching/coloring), and long‐term self‐powered electrochromic cycles. An air‐working Zn||PB||MnO2 device is also developed with a 70.3% optical contrast, fast switching speed (2.2/4.8 s for bleaching/coloring), and over 80 self‐bleaching/coloring cycles. Furthermore, the closed nature enables the fabrication of various flexible electrochromic devices, exhibiting great potentials for the next‐generation wearable electrochromic devices.

IntroductionAcute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear.MethodsWe utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis. The signature was validated across three independent datasets including a total of 1,215 AML patients. ssGSEA and ESTIMATE algorithms were employed to dissect the tumor immune microenvironment. Ex vivo drug screening and in vitro experimental validation were performed to identify potential therapeutic approaches for the high-risk patients. In vitro knockdown and functional experiments were employed to investigate the role of SLC25A51, a mitochondrial NAD+ transporter gene implicated in the signature.ResultsAn 8-gene NAD metabolism signature (NADM8) was generated and demonstrated a robust prognostic value in more than 1,800 patients with AML. High NADM8 score could efficiently discriminate AML patients with adverse clinical characteristics and genetic lesions and serve as an independent factor predicting a poor prognosis. Immune microenvironment analysis revealed significant enrichment of distinct tumor-infiltrating immune cells and activation of immune checkpoints in patients with high NADM8 scores, acting as a potential biomarker for immune response evaluation in AML. Furthermore, ex vivo drug screening and in vitro experimental validation in a panel of 9 AML cell lines demonstrated that the patients with high NADM8 scores were more sensitive to the PI3K inhibitor, GDC-0914. Finally, functional experiments also substantiated the critical pathogenic role of the SLC25A51 in AML, which could be a promising therapeutic target.ConclusionOur study demonstrated that NAD metabolism-related signature can facilitate risk stratification and prognosis prediction in AML and guide therapeutic decisions including both immunotherapy and targeted therapies.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan–Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Abstract Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity

Abstract Background Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored. Methods We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells. Results We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking. Conclusion Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.

Rail surface cracks are widespread damage that can lead to uneven surfaces of railheads and affect traveling safety. Non-destructive testing is needed to inspect rails regularly to ensure the normal operation of railroads. This paper proposes a laser ultrasonic testing method combining variational mode decomposition and diffractive Rayleigh wave time-of-flight to detect tiny cracks on the rail surface quantitatively. The finite element method was combined with experiments to simulate and experimentally investigate cracks of different sizes numerically. In the numerical simulation, the location of the crack was determined by B-scan. Afterward, the interaction between various types of ultrasound and cracks was comparatively analyzed, and the crack size was quantitatively characterized using useful information from the ultrasound signals. The results show that the time-of-flight method can detect arbitrary cracks with low error. Therefore, the experimentally acquired ultrasound signals used the time difference between the diffracted Rayleigh wave and other ultrasound waves to detect the crack information quantitatively. The variational mode decomposition method was used to separate the ultrasonic signals and extract the best surface wave modes to improve the signal-to-noise ratio. The results show that the combination of variational mode decomposition and time-of-flight method can effectively detect the size of cracks.

Background: The accumulation of diverse molecular and cytogenetic variations contributes to the heterogeneity of acute myeloid leukemia (AML), a cluster of hematologic malignancies that necessitates enhanced risk evaluation for prognostic prediction and therapeutic guidance. The ubiquitin–proteasome system plays a crucial role in AML; however, the specific contributions of 49 core proteasome family members (PSMs) in this context remain largely unexplored. Methods: The expression and survival significance of 49 PSMs in AML were evaluated using the data from BeatAML2.0, TCGA, and the GEO database, mainly through the K-M plots, differential genes enrichment analysis, and candidate compounds screening via R language and statistical software. Results: we employed LASSO and Cox regression analyses and developed a model comprising three PSMs (PSMB8, PSMG1, and PSMG4) aimed at predicting OS in adult AML patients, utilizing expression profiles from the BeatAML2.0 training datasets. Patients with higher risk scores were predominantly found in the AML–M2 subtype, exhibited poorer ELN stratification, showed no complete remission following induction therapies, and had a higher mortality status. Consistently, significantly worse OS was observed in high-risk patients across both the training and three validation datasets, underscoring the robust predictive capability of the three-PSMs model for AML outcomes. This model elucidated the distinct genetic abnormalities landscape between high- and low-risk groups and enhanced the ELN risk stratification system. Ultimately, the three-PSMs risk score captured AML-specific gene expression signatures, providing a molecular basis for selecting potential therapeutic agents. Conclusions: In summary, these findings manifested the significant potential of the PSM model for predicting AML survival and informed treatment strategies.

Summary: Zeolite-encaged metal nanoparticles (NPs) catalysts are emerging as a new frontier owing to their superior ability to stabilize the structure and catalytic performance in the thermal and environmental catalytic reaction. However, the pore size below 2 nm of the conventional zeolites usually limits the accessibility of metal active sites. Herein, Co-Cu NPs of about 2.5–3.5 nm were uniformly encapsulated in the intracrystalline mesoporous Silicalite-1 (S-1) through alkali-treatment ligand-assisted strategy. The obtained sample (termed CoxCu1-x@HS-1) exhibited efficient activity and stability in the ammonia borane hydrolysis with the highest TOF value of 21.46 molH2·molMe−1·min−1. UV–vis DRS spectra indicated that intracrystalline mesopores have greatly improved the openness and accessibility of the active sites, thus improving their catalytic performance. The introduction of Cu regulates the electronic properties of Co, further increasing hydrogen production activity. This research creates new prospects to design other high-performance hierarchical porous zeolite-confined metal/metal oxide catalysts.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types of AD: familial and sporadic. Familial AD is linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). On the other hand, sporadic AD is the more common form of the disease and has genetic, epigenetic, and environmental components that influence disease onset and progression. Investigating the epigenetic mechanisms associated with AD is essential for increasing understanding of pathology and identifying biomarkers for diagnosis and treatment. Chemical covalent modifications on DNA and RNA can epigenetically regulate gene expression at transcriptional and post-transcriptional levels and play protective or pathological roles in AD and other neurodegenerative diseases.

BackgroundCreatinine-to-cystatin C ratio (CCR) and body composition (BC) parameters have emerged as significant prognostic factors in cancer patients. However, the potential effects of CCR in gastric cancer (GC) remains to be elucidated. This multi-center retrospective study explored the predictive and prognostic value of CCR and BC-parameters in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy.MethodsOne hundred and thirteen GC patients undergoing PD-1 inhibitors-based combination therapy were enrolled at three academic medical centers from January 2021 to July 2023. A deep-learning platform based on U-Net was developed to automatically segment skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI). Patients were divided into two groups based on the median of CCR or the upper tertile of BC-parameters. Logistic and Cox regression analysis were used to determine the effect of CCR and BC-parameters in predicting response rates and survival rates.ResultsThe CCR was positively correlated with SMI (r=0.43; P0.05). Multivariable logistic analysis identified that both low CCR (OR=0.423, P=0.066 for ORR; OR=0.026, P=0.005 for DCR) and low SATI (OR=0.270, P=0.020 for ORR; OR=0.149, P=0.056 for DCR) were independently associated with worse objective response rate (ORR) and disease control rate (DCR). Patients with low CCR or low SATI had significantly lower 8-month progression-free survival (PFS) rate and 16-month overall survival (OS) rate than those with high CCR (PFS rate, 37.6% vs. 55.1%, P=0.011; OS rate, 19.4% vs. 44.9%, P=0.002) or those with high SATI (PFS rate, 37.2% vs. 53.8%, P=0.035; OS rate, 8.0% vs. 36.0%, P

IntroductionSorghum plant color is the leaf sheath/leaf color and is associated with seed color, tannin and phenol content, head blight disease incidence, and phytoalexin production.ResultsIn this study, we evaluated plant color of the sorghum mini core collection by scoring leaf sheath/leaf color at maturity as tan, red, or purple across three testing environments and performed genome-wide association mapping (GWAS) with 6,094,317 SNPs markers.Results and DiscussionEight loci, one each on chromosomes 1, 2, 4, and 6 and two on chromosomes 5 and 9, were mapped. All loci contained one to three candidate genes. In qPC5-1, Sobic.005G165632 and Sobic.005G165700 were located in the same linkage disequilibrium (LD) block. In qPC6, Sobic.006G149650 and Sobic.006G149700 were located in the different LD block. The single peak in qPC6 covered one gene, Sobic.006G149700, which was a senescence regulator. We found a loose correlation between the degree of linkage and tissue/organ expression of the underlying genes possibly related to the plant color phenotype. Allele analysis indicated that none of the linked SNPs can differentiate between red and purple accessions whereas all linked SNPs can differentiate tan from red/purple accessions. The candidate genes and SNP markers may facilitate the elucidation of plant color development as well as molecular plant breeding.

This study investigates the utilization of polyethylene fiber (PEF) and microsilica for the production of high-strength and high-toughness geopolymer concrete (HSHTGC). The influence of the PEF factor or microsilica content on fracture parameters and strength is evaluated, while acoustic emission (AE) response and crack morphologies are employed to validate the fracture performance results. By combing PEF with microsilica, this study successfully prepared HSHTGC with compressive strength exceeding 90 MPa, significant multi-cracking characteristics, as well as high toughness and ductility. The optimal microsilica content and fiber volume fraction are determined to be 32 wt% and 1.5 vol%, respectively. It is observed that when the fiber factor exceeds 800, there is a decline in compressive strength, initiation, and unstable fracture toughness, however, the fracture energy and ductility index consistently increase monotonically. These findings indicate that fiber toughening has a more pronounced effect than fiber strengthening. Moreover, microsilica plays a crucial role in filling voids and improving bonding between fibers and matrix under both tensile and compressive loads throughout the entire process. HSHTGCs with high fiber factors and increased microsilica contents exhibit a multi-cracking mode along with elevated RA values but reduced AF values during failure process, which correspondingly reflect their enhanced toughness.

To explore the predictive value of thyroid function in severe aplastic anemia (SAA) patients treated with immunosuppressive therapy (IST), 149 SAA patients in our center were enrolled between February 2015 and June 2020 in this study. We assessed the thyroid function of 134 patients without primary thyroid diseases, and discovered that 89 patients were accompanied by abnormal thyroid hormone, especially low triiodothyronine (T3). Patients with higher pretreatment-free T3 (FT3) levels (>5 pmol/L) demonstrated superior response rates at 3 and 6 months after IST compared to those with lower FT3 levels (54.5% vs 35.4%, P = .020; 67.3% vs 46.9%, P = .020). Multivariate analysis indicated that shorter disease duration (≤56 days) and response at 6 months were independent favorable factors of overall survival (relative risk [RR] = 2.66, 95% confidence interval [CI] = 1.03–6.90, P = .040; RR = 30.10, 95% CI = 4.02–225.66, P = .001). The 6-year failure-free survival (FFS) was 53.8% (95% CI = 40.9%–65.1%). Multivariate analysis revealed that patients with a response at 6 months, shorter duration (≤56 days) and receiving rabbit antithymocyte globulin (ATG) had better FFS outcomes than those without a response at 6 months, with a longer duration and receiving porcine ATG (RR = 22.6, 95% CI = 7.9–64.9, P < .001; RR = 2.4, 95% CI = 1.3–4.5, P = .006; RR = 2.5, 95% CI = 1.1–5.8, P = .030). In conclusion, FT3 levels reflect the severity of SAA, and patients with higher FT3 levels (>5 pmol/L) had superior response rates than those with lower ones.

Summary: Splenectomy often accompanies distal pancreatectomy for pancreatic cancer. However, debates persist on splenic function loss impact. Prior studies in mice revealed splenectomy promotes pancreatic cancer growth by altering CD4/Foxp3 and CD8/Foxp3 ratios. The effect on other immune cells remains unclear. Clinical observations indicate splenectomy induces immunosuppression, heightening recurrence and metastasis risk. Here, we established an orthotopic pancreatic cancer model with splenectomy and observed a significant increase in tumor burden. Flow cytometry revealed elevated MDSCs, CD8+PD-1high+ T cells, and reduced CD4+ T cells, CD8+ T cells, and natural killer cells in tumors. Bulk sequencing identified increased MicroRNA (miRNA) hsa-7b-5p post-splenectomy, correlating with staging and immunosuppression. Similar results were obtained in vivo by constructing a KPC-miRNA hsa-7b-5p-sh cell line. These findings suggest that splenectomy enhances the expression of miRNA hsa-7b-5p, inhibits the tumor immune microenvironment, and promotes pancreatic cancer growth.

Abstract Background Previous studies have verified the dysfunction of mesenchymal stem cells (MSCs) for immunoregulation in acquired aplastic anemia (AA) patients. Exosomes derived from MSCs can partially substitute MSCs acting as immune regulator. Dysfunction of exosomes (Exos) derived from AA-MSC (AA-Exos) may play a key role in immunologic dissonance. Method In this study, CD3 + T cells were collected and cocultured with AA-Exos and exosomes derived from HD-MSC (HD-Exos). The proliferation, differentiation and activation of CD3 + T cells were detected to compare the immunosuppressive effects between AA-Exos and HD-Exos. An immune-mediated murine model of AA was structured to compare the therapeutic effect of AA-Exos and HD-Exos. Furthermore, total RNA including miRNA from exosomes we purified and total RNA of CD3 + T cells were extracted for RNA-seq in order to construct the miRNA–mRNA network for interactions and functional analysis. Results AA-Exos had impaired inhibition effects on CD3 + T cells in terms of cell proliferation, activation and differentiation compared with exosomes from HD-Exos. HD-Exos showed a more effective rescue of AA mice compared to AA-Exos. Importantly, we found some differentially expressed miRNA involved in immune response, such as miR-199, miR-128 and miR-486. The Gene Ontology analysis of differentially expressed genes (DEGs) revealed involvement of various cellular processes, such as lymphocyte chemotaxis, lymphocyte migration and response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes analysis illustrated upregulation of critical pathways associated with T cell function after coculturing with AA-Exos compared with HD-Exos, such as graft-versus-host disease, Th17 cell differentiation and JAK-STAT signaling pathway. A miRNA–mRNA network was established to visualize the interaction between them. Conclusion In summary, AA-Exos had impaired immunosuppressive effect on T cells, less ability to rescue AA mice and differently expressed miRNA profile, which might partly account for the pathogenesis of AA as well as provide a new target of AA treatment.

Abstract Composite hydrogels with excellent properties can open new opportunities to terminate the need for auto/allografts in bone augmentations. However, their clinical application has been limited by their insufficient mechanical strength and lack of osteoinductivity. Here we report a new strategy to design an injectable bioactive double network hydrogel reinforced by inorganic calcium/magnesium phosphate cement (CMPC) hydrates to meet the mechanical performance requirements for bone regeneration. The engineered CMPC hydration endows the composite hydrogel with an appropriate gelation time and temperature for injection, which shows no harm in the defect site. CMPC hydrates could also provide a lower swelling ratio and higher biodegradation rate fitting the in vivo bone regeneration needs. In vitro and in vivo experiments prove that the ions released from inorganic particles endow biocompatibility, cell migration, adhesion, differentiation, and significantly higher bone regeneration capacity. Taken together, the simple addition of CMPC particles imparts in‐demand features that bring us closer to the clinical utilization of hydrogel‐based materials for bone regeneration.

Abstract The purpose of this study was to explore the role of coixendide (Coix) combine with temozolomide (TMZ) in the treatment of Glioblastoma (GBM) and explore its possible mechanism. CCK-8 was used to determine the inhibitory rate of Coix group, TMZ group and drug combination group on GBM cells, and the combination index (CI) was calculated to determine whether they had synergistic effect. Then RNA was extracted from each group, transcriptome sequencing was performed, and differentially expressed genes (DEGs) were identified. The possible mechanism was analyzed by GO enrichment analysis and KEGG enrichment analysis. The CI of Coix and TMZ indicating a synergistic effect when TMZ concentration is 0.1 mg/ml and Coix concentration is 2 mg/ml. Transcriptome sequencing analysis showed that interferon (IFN) related genes were down-regulated by Coix and up-regulated by TMZ and combined drugs, however, the up-regulation induced by combined drugs was less than that of TMZ. Besides IFN related genes, cholesterol metabolism pathway were also been regulated. Coix and TMZ have synergistic effects in the treatment of GBM at certain doses. RNA-Seq results suggested that the abnormal on genetic materials caused by DNA damage induced by TMZ treatment can be sensed by IFN related genes and activates antiviral IFN signaling, causing the activation of repairing mechanism and drug resistance. Coix inhibits IFN related genes, thereby inhibits drug resistance of TMZ. In addition, the activation of ferroptosis and the regulation of DEGs in cholesterol metabolism pathway were also contributed to the synergistic effects of Coix and TMZ.

This work provides a facile route to synthesize the homogeneous hierarchical nanosheets of nickel phyllosilicate (HN-NiPS), which are imparted into epoxy resin (EP) to yield the composites. Various measurements are adopted to examine the structure and compositions of HN-NiPS and the structure-property relationships of EP composites. Results show that HN-NiPS is composed of multi-scaled nanosheets, of which the tiny nanopetals of nickel phyllosilicate grow in situ perpendicularly to a relatively large metal-organic-framework-derived plane. Adequate HN-NiPS disperses well in the EP matrix, not only moderately elevating the tensile strength and elastic modulus, but also improving the tribological properties significantly under starved lubrication. The lowest wear rate of 1.94 × 10−5 mm3/Nm is achieved with 3% HN-NiPS and ca. 72.1% lower than pure EP. The introduced HN-NiPS suppresses the weight loss rate and changes the reaction order insignificantly based on Carrasco whereas activation energies decline gradually with increased filler content. This study contributes robust, thermal stable and wear-resistant polymeric composites strengthened involving the homogeneous hierarchical nanosheets.

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

This study unveils a machine learning (ML)-assisted framework designed to optimize the stacking sequence and orientation of carbon fiber-reinforced polymer (CFRP)/metal composite laminates, aiming to enhance their mechanical properties under quasi-static loading conditions. This work pioneers the expansion of initial datasets for ML analysis in the field by uniquely integrating the experimental results with finite element simulations. Nine ML models, including XGBoost and gradient boosting, were assessed for their precision in predicting tensile and bending strengths. The findings reveal that the XGBoost and gradient boosting models excel in tensile strength prediction due to their low error rates and high interpretability. In contrast, the decision trees, K-nearest neighbors (KNN), and random forest models show the highest accuracy in bending strength predictions. Tree-based models demonstrated exceptional performance across various metrics, notably for CFRP/DP590 laminates. Additionally, this study investigates the impact of layup sequences on mechanical properties, employing an innovative combination of ML, numerical, and experimental approaches. The novelty of this study lies in the first-time application of these ML models to the performance optimization of CFRP/metal composites and in providing a novel perspective through the comprehensive integration of experimental, numerical, and ML methods for composite material design and performance prediction.

Abstract Metal halide perovskites are promising for next-generation flexible photodetectors owing to their low-temperature solution processability, mechanical flexibility, and excellent photoelectric properties. However, the defects and notorious ion migration in polycrystalline metal halide perovskites often lead to high and unstable dark current, thus deteriorating their detection limit and long-term operations. Here, we propose an electrical field modulation strategy to significantly reduce the dark current of metal halide perovskites-based flexible photodetector more than 1000 times (from ~5 nA to ~5 pA). Meanwhile, ion migration in metal halide perovskites is effectively suppressed, and the metal halide perovskites-based flexible photodetector shows a long-term continuous operational stability (~8000 s) with low signal drift (~4.2 × 10−4 pA per second) and ultralow dark current drift (~1.3 × 10−5 pA per second). Benefitting from the electrical modulation strategy, a high signal-to-noise ratio wearable photoplethysmography sensor and an active-matrix photodetector array for weak light imaging are successfully demonstrated. This work offers a universal strategy to improve the performance of metal halide perovskites for wearable flexible photodetector and image sensor applications.

Abstract Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Epithelial–mesenchymal transition (EMT)-related proteins (Slug, vimentin, and N-cadherin) are downregulated by Protein Z silencing, which significantly prohibits cellular proliferation and EMT activity (decrease of cellular migration and invasion) in non-small-cell lung cancer cells.

Abstract. Background:. Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. Methods:. In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand–receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. Results:. 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3, SASH1, SEPTIN7, and NUB1, which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand–receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. Conclusion:. Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell–cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.

Background and purpose: Recent evidence suggests that N6, 2'-O- dimethyladenosine (m6Am) modifying enzyme phosphorylated C-terminal domain-interacting factor 1 (PCIF1) may be an important biomarker/therapeutic target in gastric cancer. However, the relationship between this novel PCIF1 molecular mechanism and gastric cancer progression remains to be further explored. In this study, we analyzed the regulatory role of PCIF1 on gastric cancer proliferation, migration and invasion and the mechanism of its regulatory target gene ACOT8 in gastric cancer progression. Methods: PCIF1 expression in gastric cancer and non-gastric cancer tissues of gastric cancer patients was analyzed using Gene Expression Profile Interaction Analysis (GEPIA), and the correlation of PCIF1 expression with overall survival in gastric cancer patients was analyzed. We collected all gastric cancer tissues and matched para-cancerous tissues from 89 primary gastric cancer patients treated in Department of Gastroenterology of Changsha First Hospital from 2019 to 2021. PCIF1 expression was analyzed by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. In in vitro experiments, SNU5 cells were divided into PCIF1 knockdown (sh-PCIF1) group and corresponding control (sh-NC) group, and AGS cells were divided into vehicle as normal control (NC) group and PCIF1 overexpression (PCIF1) group. The effect of PCIF1 on gastric cancer cell proliferation, invasion and migration was investigated using cell counting kit-8 (CCK-8), EdU and transwell assays. Furthermore, ACOT8 expression was knocked down in PCIF1-overexpressing AGS cells, and rescue experiments were performed. A subcutaneous xenograft model was used to determine the biological effects of PCIF1 in gastric cancer in vivo. Results: PCIF1 expression was abnormally high in gastric cancer tissues and cell lines, with significant correlation between PCIF1 expression and the prognosis of gastric cancer patients. Compared with the sh-NC group, the cell viability, EdU positive cells, migration and invasion cell numbers in the sh-PCIF1 group were significantly decreased (P

Understanding the active sites is essential for advanced catalyst design. Here, the authors report a bifunctional mechanism for the methanol electrooxidation reaction using NiMn hydroxide with NiIII and oxygen active sites which work in a cooperative manner to promote either spontaneous or non-spontaneous methanol oxidation.

Many of the most sensitive X-ray detectors are based on toxic elements such as lead, limiting their safe applications. Here, the authors report the realization of sensitive X-ray detectors based on solution-grown thick BiI/BiI3/BiI van der Waals heterostructures, showing a detection limit down to 34 nGy s−1 and high stability.

Fresh-cut potatoes (Solanum tuberosum L.) are susceptible to browning and microbial contamination during storage. In this study, the effects of trans-2-hexenal (E2H), ascorbic acid (VC), dimethyl dicarbonate (DMDC), and the combined treatment of E2H, VC, and DMDC on quality deterioration in fresh-cut potatoes were investigated. The response surface methodology (RSM) demonstrated that E2H, VC, and DMDC concentrations of 0.010%, 0.65%, and 240 mg/L, respectively, were the optimum conditions for fresh-cut potato preservation. Further analysis showed that the combined treatment of E2H, VC, and DMDC was the most effective method of reducing quality deterioration in potatoes compared to the control and individual treatments. Furthermore, the combined treatment of E2H, VC, and DMDC could decrease the accumulation of reactive oxygen species (ROS) via improving antioxidant enzyme activities. Meanwhile, energy-metabolism-related enzyme activities and glutamate decarboxylase (GAD) activity were enhanced, while γ-aminobutyric acid transaminase (GABA-T) activity was reduced via the combined treatment of E2H, VC, and DMDC, which contributed to maintaining high energy levels and GABA content in potatoes. These findings suggested that the combined treatment of E2H, VC, and DMDC could protect membrane integrity through enhancing antioxidant capacity, energy levels, and GABA content to maintain quality in fresh-cut potatoes.

With the rise of social media and the internet, the rapid dissemination of information has increased the likelihood of reputation infringement. This study utilizes judicial big data and AI to analyze intrinsic connections in reputation infringement cases, aiding judges in delivering consistent rulings. The challenge lies in balancing freedom of speech with the right to reputation and addressing the ambiguity and subjectivity in infringement cases. This research constructs a structured reputation infringement case dataset from Chinese Judgments Online. It introduces a Fractional Fuzzy Neural System (FFNS) to tackle the vagueness in reputation infringement acts and judicial language, enhancing prediction accuracy for case outcomes. The FFNS, integrating fractional calculus, fuzzy logic, and neural networks, excels in adaptability and nonlinear modeling. It uses fractional order fuzzy membership functions to depict the extent and severity of reputation infringement accurately, combining these outputs with neural networks for predictive analysis. The result is a more precise adjudication tool, demonstrating significant potential for judicial application.

For vibration isolation systems, vibration suppression and platform positioning are both important. Since absolute velocity feedback causes difficulty in achieving positioning while suppressing vibration, an H∞ control strategy based on sensor fusion feedback is proposed in this paper. The signals of inertial and displacement sensors are fused through a pair of complementary filters. Thus, active control based on the fusion signal could concurrently achieve vibration and position control since it is a displacement signal. In addition, the obtained fusion signals have a lower noise level. In this way, simultaneous positioning and vibration suppression can be established using the sensor fusion strategy. On this basis, in order to obtain an optimal H∞ controller, system damping can be maximized by using the performance weight function to attenuate noise; the system bandwidth is determined by the uncertainty weight function, which can avoid the effect of high-frequency modes of the system. The effectiveness of the proposed strategy is verified by comparing it with the conventional absolute velocity feedback strategy on a 3-DOF isolator.