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Abstract Colon cancer is a prevalent malignancy, substantially it prevented most effectively from killing patients through early endoscopic detection. With the rapid development of artificial intelligence technology, the early diagnosis rate of colonic polyps achieves greater clinical efficacy for colon cancer by applying target detection algorithms to colonoscopy images. This paper presents two outcomes achieved through the application of the improved YOLOv5s algorithm with annotated microscopy images of clinical cases and publicly available polyp image data: (1) enhancement of the C3(Cross Stage Partial Networks) module with multiple layers to C3SE(Cross Stage Partial Networks with Squeeze-and-Excitation) via the attention mechanism SE (squeeze-and-excitation) and (2) fusion of higher-level features utilizing BiFPN (the weighted bi-directional feature pyramid network). Experimental comparisons are performed based on a new image dataset of colonic polyps among more than 6 target detection algorithms to validate the better detection capability. The tests indicate that the YOLOv5s + BiFPN and YOLOv5s-1st-2nd-C3SE models exhibit enhancements of detection capability compared to the YOLOv5 algorithm according to the main indicators of the mAP, accuracy, and recall. The YOLOv5s + SEBiFPN model demonstrate a substantial improvement over the YOLOv5s algorithm, and establishing a benchmark technology for advancing computer-assisted diagnostic systems is feasible.

Abstract In this paper, we utilize the continuation theorem due to Mawhin to investigate the solvability for a class of Caputo fractional system integral boundary value problems at resonance. To broaden the applicability of the main results, we employ the Moore–Penrose pseudoinverse matrix to construct projectors.

Abstract Soil conditioner has good performance in improving soil environment and solving soil barrier problems. The purpose of this study was to analyze the effects of different types of soil conditioners on the distribution of soil aggregates and the yield of corn, and to find out the suitable soil conditioners for improving the barren soil in the Yellow River irrigation area. The treatments include no soil conditioner (CK), cow dung organic fertilizer soil conditioner with different organic matter contents (Om-20%, Om-30%, Om-40%, Om-45%), humic acid soil conditioner (Hu-20%) and amino acid soil conditioner (Am-25%). The result indicated that different types of soil conditioners promoted the formation of aggregates with particle size > 0.25 mm, improved the stability of aggregates, and increased the content of organic carbon and total nitrogen in macroaggregates. Compared with CK, the contents of organic carbon and total nitrogen of various soil conditioners in macroaggregates increased by 20.08-48.89% and 8.36-42.86%, respectively. The organic carbon content of macroaggregates under Am-25% treatment was significantly increased by 7.15% compared with Hu-20% treatment. The contents of available phosphorus, available potassium, organic carbon and total nitrogen under Am-25% treatment was increased by 6.37-45.86%, 6.29-22.39%, 3.49-12.05% and 2.64-19.74% than that of cow dung organic fertilizer soil conditioner treatments, respectively. Correlation analysis and structural equation model analysis showed that macroaggregates with particle size greater than 0.25 mm were positively correlated with corn hay yield. Aggregate stability and chemical properties accounted for 71% of corn hay yield changes, and organic carbon mainly affected corn hay yield through soil C/N ratio. Therefore, the application of soil conditioner, especially amino acid soil conditioner, to the barren soil in the Yellow River irrigation area can improve the physical and chemical properties of soil, promote the formation of macroaggregates, improve the stability of aggregates, and promote the high and stable yield of corn.

Abstract Background Tendomodulin (TNMD) is pivotal in various malignancies, including colorectal cancer (CRC). However, its comprehensive impact across cancers, particularly its immunomodulatory function in CRC, remains underexplored. This study explored the role of TNMD in CRC by focusing on its immunomodulatory functions through comprehensive molecular and clinical analyses. Methods Multiple bioinformatics databases and analytical tools were utilized for the TNMD in pan-cancer analysis. To validate the role of TNMD in CRC, we performed experiments, including immunofluorescence (IF), immunohistochemistry (IHC), real-time quantitative reverse transcription PCR (qPCR), western blotting, and cell migration assays. Results TNMD expression and gene mutation vary across cancers and offer high diagnostic value. Survival analysis found that TNMD is associated with prognosis in multiple cancers. Notably, in patients with high microsatellite instability (MSI-H) CRC, TNMD expression correlated positively with various immune cells, particularly natural killer (NK) cells, whereas it was inversely correlated with regulatory T cells (Tregs). Crucially, in patients with microsatellite stability (MSS) CRC, high TNMD expression was associated with better immunotherapy outcomes, indicating its potential as a biomarker for patient stratification and tailored treatment approaches. Furthermore, single-cell sequencing data revealed stronger interactions between TNMD-positive tumor cells and fibroblasts or macrophages in the tumor microenvironment. Finally, TNMD was overexpressed in CRC tumor tissues and cell lines, thereby promoting invasion and metastasis. Conclusions Our findings reveal a critical immunomodulatory role of TNMD in CRC, particularly in influencing tumor–immune interactions. Beyond its potential diagnostic and prognostic biomarker, TNMD promotes CRC metastasis and invasion, thus emerging as a promising therapeutic target. These findings highlight TNMD’s significance in CRC and potentially other malignancies.

Abstract Objectives The classification of malignant breast nodules into four categories according to the Breast Imaging Reporting and Data System (BI-RADS) presents significant variability, posing challenges in clinical diagnosis. This study investigates whether a nomogram prediction model incorporating automated breast ultrasound system (ABUS) can improve the accuracy of differentiating benign and malignant BI-RADS 4 breast nodules. Methods Data were collected for a total of 257 nodules with breast nodules corresponding to BI-RADS 4 who underwent ABUS examination and for whom pathology results were obtained from January 2019 to August 2022. The participants were divided into a benign group (188 cases) and a malignant group (69 cases) using a retrospective study method. Ultrasound imaging features were recorded. Logistic regression analysis was used to screen the clinical and ultrasound characteristics. Using the results of these analyses, a nomogram prediction model was established accordingly. Results Age, distance between nodule and nipple, calcification and C-plane convergence sign were independent risk factors that enabled differentiation between benign and malignant breast nodules (all P

Abstract Alterations in intestinal microbiota have been identified as a key risk factor in rheumatoid arthritis (RA). This study presents a multidimensional gut microbiota profile from a large cohort of RA patients, stratified by disease stage and treatment regimens, and compared to healthy controls. Our dataset comprises gut microbiota profiles from 2,238 individuals, including 1,034 RA patients (Ascia Pacific RA cohort, APRAC) and 1,204 healthy controls. This dataset is enriched with detailed clinical metadata, including patient profiles, treatment histories, and environmental factors, providing a comprehensive “disease exposome” for RA. By integrating 16S rRNA gene sequencing with demographic, clinical, and environmental data, we offer a valuable resource to explore the complex relationships between gut microbiota and RA progression. This large-scale dataset is expected to be a foundation for collaborative research, advancing our understanding of the microbiome’s systemic effects in RA and other autoimmune diseases and potentially guiding new therapeutic approaches.

Abstract Objectives Respiratory syncytial virus (RSV) is a leading cause of hospitalization for lower respiratory tract infections amongst infants under 1 year, posing a significant global health challenge. The incidence of RSV exhibits marked seasonality and is influenced by various meteorological factors, which vary across regions and climates. This study aimed to analyze seasonal trends in RSV-related hospitalization in Tianjin, a region with a semi-arid and semi-humid monsoon climate, and to explore the relationship between these trends and meteorological factors. This research intends to inform RSV prevention strategies, optimize public health policies and medical resource allocation while also promoting vaccine and therapeutic drug development. Methods This study analyzed data from a cohort of 6222 children hospitalized with RSV-related infections. Meteorological data were collected from the Tianjin Binhai International Airport meteorological station, encompassing temperature (℃), air pressure (mmHg), wind speed (m/s), humidity (%), and precipitation (mm). We employed seasonal ARIMA and GAM models to investigate the association between meteorological factors and RSV-related hospitalizations. Results The SARIMA (1,0,0) (0,1,2)12 model effectively predicted RSV-related hospital admissions. Spearman correlation and GAM analysis revealed a significant negative association between the monthly average temperature and RSV hospitalizations. Conclusions Our findings indicated that meteorological factors influence RSV infection-related hospital admissions, with higher monthly average temperatures associated with fewer hospitalizations. The predictive capabilities of the SARIMA model bolster the formulation of targeted RSV prevention strategies, enhancing public health policy and medical resource allocation. Furthermore, continued research into vaccines and therapeutic drugs remains indispensable for augmenting public health outcomes.

To develop plant-based protein 3D-printed food suitable for patients with swallowing difficulties, this study explored the use of a composite polysaccharide comprising flaxseed gum and konjac glucomannan at a mass ratio of 2:3. The composite polysaccharide was combined with pea protein isolate (PPI) under shearing treatment to investigate the effects of different concentrations (0.5%, 0.7%, 0.9%, 1.1%, and 1.3%) on the particle size, rheological properties, and 3D printing performance of emulsion gels. Additionally, the emulsion gels were evaluated using the International Dysphagia Diet Standardization Initiative (IDDSI) framework. The results indicated that the composite polysaccharide exhibited varying effects on the improvement of emulsion gels depending on its concentration. Particle size analysis revealed a decreasing trend in the particle size of PPI emulsion gel with increasing polysaccharide concentration. Rheological properties showed that the addition of polysaccharides endowed the gels with viscoelastic properties, as evidenced by G' > G'' for all samples. At a concentration of 1.1%, the emulsion gel exhibited the smallest particle size, the highest G' and G'' values, and optimal viscoelasticity. Furthermore, the printed structures displayed the most distinct textures, stable frameworks, and superior printing adaptability. The IDDSI evaluation indicated that emulsion gels containing 1.1% and 1.3% polysaccharides could be classified as Level Ⅳ transitional foods. In conclusion, the composite polysaccharide at a concentration of 1.1% significantly enhanced the 3D printing performance of PPI-based emulsion gels, providing a theoretical basis for developing plant-based 3D printing inks.

The pursuit of optimal neural network architectures is foundational to the progression of Neural Architecture Search (NAS). However, the existing NAS methods suffer from the following problem using traditional search strategies, i.e., when facing a large and complex search space, it is difficult to mine more effective architectures within a reasonable time, resulting in inferior search results. This research introduces the Generative Pre-trained Transformer NAS (GPT-NAS), an innovative approach designed to overcome the limitations which are inherent in traditional NAS strategies. This approach improves search efficiency and obtains better architectures by integrating GPT model into the search process. Specifically, we design a reconstruction strategy that utilizes the trained GPT to reorganize the architectures obtained from the search. In addition, to equip the GPT model with the design capabilities of neural architecture, we propose the use of the GPT model for training on a neural architecture dataset. For each architecture, the structural information of its previous layers is utilized to predict the next layer of structure, iteratively traversing the entire architecture. In this way, the GPT model can efficiently learn the key features required for neural architectures. Extensive experimental validation shows that our GPT-NAS approach beats both manually constructed neural architectures and automatically generated architectures by NAS. In addition, we validate the superiority of introducing the GPT model in several ways, and find that the accuracy of the neural architecture on the image dataset obtained from the search after introducing the GPT model is improved by up to about 9%.

With offshore becoming the main battlefield of wind power generation, modular multilevel converter-based high-voltage DC (MMC-HVDC) transmission technology has become an ideal solution for offshore wind power integration and received rapid development. However, wideband oscillation events have seriously threatened stable operation of power systems. By far, existing oscillation mitigation methods are usually designed for specific oscillation cases and are not capable of mitigating wideband oscillations. In order to mitigate various oscillations adaptively, this article proposes an adaptive wideband oscillation mitigation control for MMC-HVDC system connected to offshore wind farms. Analytical wideband impedance models of the wind farm side MMC (WFMMC) and offshore wind farm composed of permanent-magnetic synchronous generator-based wind turbine generators (PMSG-WTGs) are derived, respectively, which are verified by measured impedances from time-domain simulations. Then, a wideband oscillation mechanism is revealed by impedance-frequency characteristics. On this basis, an adaptive wide band oscillation mitigation control is proposed, and its working principle as well as implementation process are elaborated. Case studies of a sub-/super-synchronous oscillation (SSO) event and a high-frequency oscillation (HFO) event of an offshore wind farm with MMC-HVDC system are carried out to verify effectiveness of the proposed adaptive wideband oscillation mitigation control.

Abstract To investigate the incidence rate, risk factors, and clinical implications of postoperative pulmonary complications (PPCs) in patients undergoing colorectal cancer surgery (CRC). The study extracted data from the National Inpatient Sample (NIS) between 2010 and 2019. Patients’ data were analyzed to identify predictors of PPCs, and the association between possible factors and PPCs were also assessed. A total of 169,067 CRC surgery patients were included and 15,494 (9.16%) were diagnosed with PPCs in the study. Our study found that age, gender, number of comorbidities, type and location of hospital, and certain preoperative comorbidities, such as fluid and electrolyte disorders (odd ratio [OR] 2.53), coagulopathy (OR 2.16), congestive heart failure (OR 1.91), and chronic pulmonary disease (OR 1.57) were the risk factors of PPCs. In addition, postoperative complications, such as continuous mechanical ventilation (OR 8.18), sepsis (OR 4.46), deep vein thrombosis (OR 4.17) and shock (OR 4.07) were the most important risk factors of PPCs. PPCs prolonged the length of hospital stay (14 days vs. 6 days) and led to a higher mortality rate (13.04% vs. 1.20%). Optimizing perioperative care practices are essential steps to reduce the incidence rate of PPCs in CRC patients.

Abstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are the main cause of early host-induced tissue injury. This paper intends to investigate the possible mechanisms of neutrophil involvement in acute rejection in renal transplantation. Methods Samples were analyzed for their relationship with immune cells using CIBERSORT. WGCNA was used to identify modules with high relevance to neutrophils and hub genes in the modules were extracted. The effect on neutrophil function after blocking formyl peptide receptor 1 (FPR1) was tested in vitro experiments. The effects of blocking FPR1 on neutrophil function as well as acute rejection were tested in vivo after constructing a mouse kidney transplant model. Results The proportion of neutrophils was higher in the AR group than in the non-rejection group, and FPR1 was identified as an important gene in the regulation of acute rejection in kidney transplantation by neutrophils. At the cellular level, blocking FPR1 inhibited the activation of the ERK1/2 pathway, decreased ferrous ion content, affected the expression of iron metabolism-related proteins, and suppressed the formation of NETs. In the acute rejection model of renal transplantation, blockade of FPR1 decreased graft neutrophil infiltration and NETs content. Meanwhile, blocking FPR1 attenuated graft injury during acute rejection. Conclusion This study found that FPR1 might be an important molecule involved in neutrophils during acute rejection of kidney transplantation, explored the relationship between kidney transplantation and neutrophils, and provided potential treatment methods for clinical practice.

Abstract Purpose Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis. Methods ICD was induced by short exposure to lethal dose of chemotherapeutic drug doxorubicin (Dox), which initiated an irreversible ICD program in tumor cells. We immunized mice with ICD dying tumor cells in prevention, therapy in lung metastasis models, and Gprc5a-knockout (ko) model of lung tumorigenesis. T cells and macrophages isolated from lymph nodes or tumor tissues were analyzed by flow cytometry. Cytokines were analyzed by ELISA or Q-PCR analysis. Results Immunization with these live but ICD dying tumor cells induced potent tumor-specific anti-tumor T cell immunity, which not only protected host from challenge by these tumor cells in prevention and therapy in mouse model of lung metastasis, but also prevented tumors development in Gprc5a-ko mouse model of lung tumorigenesis. The lymphocytes from lymph nodes and tumor tissues exhibited greatly enhanced activities of Th1 cells and M1 macrophages. Conclusion Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy.

Abstract Multiple myeloma (MM) is the second most common hematological malignancy. Previous studies have validated the prognostic significance of the platelet-to-lymphocyte ratio (PLR) in patients with certain solid tumors. However, the relationship between the PLR and prognosis in myeloma patients has not been clearly demonstrated. In our study, we included 122 newly diagnosed MM patients who were treated with bortezomib-based chemotherapy. These patients were divided into low-PLR and high-PLR groups based on their initial PLR values. We compared the clinical characteristics between the two groups and utilized restricted cubic splines (RCSs) in the regression model to estimate the nonlinear relationship between the initial PLR and overall survival (OS) in MM patients. The results showed that patients in the low-PLR group had significantly worse OS (P = 0.00031) and progression-free survival (PFS) (P

Abstract Background Foreign body inhalation is rare in older children, often leading to underdiagnosis and delayed treatment. Most cases involve a single foreign body, but instances of multiple foreign bodies are exceedingly uncommon. This report presents a case of an elder child who inhaled two pen caps, emphasizing the need for clinical vigilance and thorough medical history collection. Case presentation A twelve-year-old boy was admitted with a persistent cough lasting over two months, accompanied by sputum with a peculiar odor. Previous treatments with oral Cefdinir (0.1 g, three times daily) and inhaled Budesonide Suspension had not improved his condition. Physical examination revealed decreased breath sounds on the right side without signs of respiratory distress or wheezing. Imaging studies, including chest X-ray and CT scan, along with bronchoscopy, confirmed the presence of two foreign bodies in the right bronchus. The patient was started on anti-infective therapy to address any underlying infection before proceeding with removal. A combination of flexible bronchoscopy and rigid bronchoscopy, supplemented by a cryotherapy instrument, successfully extracted the pen caps. Post-procedure assessments indicated that the patient’s body temperature returned to normal, cough symptoms resolved, and lung ventilation significantly improved. Conclusion This case highlights the critical need for clinicians to remain vigilant regarding bronchial foreign bodies in older children. The rare occurrence of multiple foreign bodies, particularly resulting from active inhalation, necessitates a comprehensive medical history during patient evaluation. Early recognition and intervention can lead to significant improvements in patient outcomes, underscoring the importance of thorough clinical assessment in similar cases.

Time-series InSAR is an advanced technology for real-time monitoring and precise analysis of object deformation. However, large-span steel truss structure bridges have complex bridge structures and deformation forms, which make it difficult for the traditional persistent scatterer interferometry (PSI) method to realize the precise detection of their deformation, resulting in a series of limitations. In order to solve these problems, an improved PSI method is proposed in this article, which is first to carry out preliminary elevation measurement by a small temporal baseline, use the preliminary elevation results to PS-arcs construction based on 3-D spatial network, and utilize the optimal model coherence coefficient adaptive selection based on constant false alarm rate to carry out the parameter estimation so as to realize the accurate monitoring of deformation of large-span steel truss structure bridges. In this article, 24 ascending CSK stripmaps are used to monitor the deformation of Dongting Lake Bridge of the Menghua Railway, and the monitoring results show that the method not only realizes the accurate detection of deformation of large-span steel truss structure bridges but also improves the accuracy and robustness of parameter estimation. The results show that the proposed method improves the accuracy of deformation parameter estimation by comparing with the deformation parameters solved by the traditional method, and the method reduces the average residual phase standard deviation by 10%, which provides the experience and reference for the deformation monitoring of similar bridges.

This is an article in the field of mineral materials. In order to make high-value utilization and harmless treatment of bulk industrial solid waste, CaO-MgO-Al2O3-SiO2-Cr2O3 system glass-ceramics were prepared by melting method with Baotou Steel blast furnace slag, low-carbon chromium iron alloy slag and quartz sand as the raw materials. The optimum ratio of raw materials was explored by means of differential thermal analysis (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results showed that when the mass ratio of blast furnace slag, low-carbon chromium iron alloy slag and quartz sand was 60∶40∶31, the crystalline phases of glass-ceramics were diopside and omphacite. At this time, the performance of glass-ceramics was the best, the flexural strength reached 126.25 MPa, the crystallinity reached 89.19%, and the microstructure was ideal. The glass-ceramics prepared under the optimal raw material ratio met the requirements for national class A decoration materials, i.e. IRa≤1.0 and Iγ≤1.3, and the leaching concentration of heavy metal chromium in the glass-ceramics met the national standard, indicating that it is feasible to prepare glass-ceramics with blast furnace slag and low-carbon chromium iron alloy slag.

Drilling motors are widely used in unconventional oil and gas exploration. Due to the increased non-productive time and drilling costs brought about by accidental damage to drilling motors, predictive maintenance for drilling motors is necessary to optimize asset utilization. However, service companies face significant challenges in achieving predictive maintenance: operational data acquisition, automated statistics analysis, and drilling state recognition. This paper presents a miniature vibration recorder, an automatic statistical analysis method, and a layered recognition algorithm to resolve these challenges and improve tool maintenance efficiency. The designed recorder can be installed in the catch of a conventional mud motor to record drilling dynamics over a drilling motor's entire operation cycle. Time-series data from the recorder can be used to automatically generate operation statistics, mitigating the costs incurred by manual data analysis. The layered recognition algorithm then enables the automatic identification of drilling operation states, i.e., surface, downhole non-drilling, downhole sliding, and downhole rotation. The solutions were validated by deploying the recorder in drilling field runs and analyzing recorded data using the associated design software, yielding a functional data collection, automatic data statistical analysis, and operation state recognition accuracy of 95%. Through achieving improved data collection and analysis, the recorder and software introduced in this work can notify motor owners of the detailed operation history of their tools and enable informed preventive maintenance.

Abstract This article used network pharmacology, molecular docking, GEO analysis, and Gene Set Enrichment Analysis to obtain 38 main chemical components and 66 corresponding targets involved in Alzheimer's disease (AD) treatment in "Cistanche deserticola‐Polygala". Through further Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis, we obtained AD signalling pathways, calcium signalling pathways, and other signalling pathways related to the treatment of AD with “Cistanche deserticola‐Polygala”. Molecular docking showed that most of the core chemical components had good binding ability with the core targets. This article aims to reveal the mechanism of “Cistanche deserticola‐Polygala” in treating AD and provide a basis for the treatment of AD with “Cistanche deserticola‐Polygala”.

Abstract Background Smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). This study aimed to investigate the effects of smoking on the pancreatic microbiome and metabolome in resectable and unresectable male PDAC patients. Methods The pancreatic tissue samples were collected from resectable PDACs via surgery and unresectable PDACs via endoscopic ultrasound fine needle aspiration (EUS-FNA). Surgical samples obtained from 10 smoking and 6 non-smoking PDACs were measured by 16S ribosomal RNA (16S rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC/MS). Fine needle aspiration (FNA) samples obtained from 20 smoking and 14 non-smoking PDACs were measured by 16S rRNA gene sequencing. Results From resectable to unresectable patients, the dominant genus in the pancreas changed from Achromobacter to Delftia. Smoking further altered the abundance of specific bacteria, mainly manifested as an increase of Slackia in surgical tumor tissue of the smoking group, and an enrichment of Aggregatibacter and Peptococcus in FNA samples of the smoking group. In tumor tissue, smoking caused an enrichment of the cancer-promoting cAMP signaling pathway and L-lactic acid. In paracancerous tissue, smoking also induced a detrimental disturbance in the pancreatic microbiome and metabolome, including an enrichment of Veillonella, Novosphingobium, Deinococcus, and 3-hydroxybutanoic acid, and a reduction of linoleic acid. Besides, the cancer-promoting L-lactic acid was negatively correlated with Faecalibacterium in tumor tissue based on the correlation analysis. Conclusion There were differences in the pancreatic microbiome of PDAC patients at different stages, and smoking can further disrupt the pancreatic microbiome and metabolism in PDAC.

Abstract For any unitary conformal field theory in two dimensions with the central charge c, we prove that, if there is a nontrivial primary operator whose conformal dimension ∆ vanishes in some limit on the conformal manifold, the Zamolodchikov distance t to the limit is infinite, the approach to this limit is exponential ∆ = exp(−αt + O(1)), and the decay rate obeys the universal bounds c −1/2 ≤ α ≤ 1. In the limit, we also find that an infinite tower of primary operators emerges without a gap above the vacuum and that the conformal field theory becomes locally a tensor product of a sigma-model in the large radius limit and a compact theory. As a corollary, we establish a part of the Distance Conjecture about gravitational theories in three-dimensional anti-de Sitter space. In particular, our bounds on α indicate that the emergence of exponentially light states is inevitable as the moduli field corresponding to t rolls beyond the Planck scale along the steepest path and that this phenomenon can begin already at the curvature scale of the bulk geometry. We also comment on implications of our bounds for gravity in asymptotically flat spacetime by taking the flat space limit and compare with the Sharpened Distance Conjecture.

Abstract Background Dorper sheep are celebrated for their fast maturation and superior meat quality, with some shedding their wool each spring. Wool shedding occurs naturally due to the hair follicle (HF) cycle, but its regulatory mechanisms remain unclear and need further investigation. Results In this study, shedding and non-shedding sheep were selected from the same Dorper flock. Skin samples were collected in September of the first year and January and March of the following years. RNA sequencing was performed on these samples. Principal component analysis (PCA) was used to assess the results. A total of 2536 differentially expressed genes (DEGs) were identified. Using a clustering heatmap and fuzzy clustering analysis three distinct gene expression patterns were identified: A pattern (high expression in anagen), T1 pattern, and T2 pattern (high expression in telogen). For each pattern, differentially expressed genes (DEGs) were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Combining this with pathway expression analysis, six A-pattern and fourteen T-pattern pathways linked to telogen-anagen transition in the HF cycle were identified. Networks of key pathways were then constructed. Additionally, key genes were identified in the telogen-anagen transition, including one A-pattern gene and seven T-pattern (T1, 1; T2, 6) genes, using the Maximal Clique Centrality (MCC) tool in Cytoscape. Predicted transcription factors (TFs) involved in key pathways, such as LEF and STAT5B, were identified. Finally, RNA-seq results were confirmed by RT-qPCR. Conclusion This study highlights critical genes and pathways in the telogen-anagen transition, and transcriptome sequencing along with bioinformatics analysis provides new insights into the regulatory mechanisms of the HF cycle and development.

Abstract Background Upland rice varieties exhibit significant genetic diversity and broad environmental adaptability, making them ideal candidates for identifying consistently expressed stress-responsive genes. F-box proteins typically function as part of the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes to precisely regulate gene expression and protein level, playing essential roles in the modulation of abiotic stress responses. Therefore, utilizing upland rice varieties for screening stress-responsive F-box genes is a highly advantageous approach. Results Through mRNA-seq analysis in the Brazilian upland rice (cv. IAPAR9), the research identified 29 drought-responsive F-box genes. Gene distribution and duplication analysis revealed these genes are distributed on 11 of the 12 chromosomes and 10 collinear gene pairs were identified on different chromosomes. 13 cis-elements or binding sites were identified in the promoters of the 29 drought-responsive F-box genes by analysis. Protein domain, stability and subcellular localization analysis results suggest that these F-box proteins possess F-box domain and several other domains, and they are mostly unstable proteins with subcellular localization in cytoplasm, nucleus, chloroplasts, mitochondria and endoplasmic reticulum. Most of drought-responsive F-box genes exhibited expression in various tissues such as root, stem, leaf, leaf sheath and panicle except for OsFBO10 and OsFBX283. These genes exhibited various responses to abiotic stresses such as osmotic, cold, heat, and salt stresses, along with ABA treatment. Importantly, a frame-shift mutation in OsFBX148 was created in the ZH11 variety, leading to altered ABA signal transduction and ROS accumulation. The study further elucidated the interaction of OsFBX148 with SKP1 family proteins OSK4/7/17 to form the SCF complex, dependent on the F-box domain. Conclusions The research identified and analyzed 29 drought-responsive F-box genes in upland rice and provides valuable insights into the role of OsFBX148 in ABA and ROS responses. It establishes a basis for future exploration of F-box genes in improving resistance to abiotic stresses, especially drought.

Abstract Major Depressive Disorder (MDD) is a common mental disorder characterized by cognitive impairment, and its pathophysiology remains to be explored. In this study, we aimed to explore the efficacy of brain network topological properties (TPs) in identifying MDD patients, revealing variational brain regions with efficient TPs. Functional connectivity (FC) networks were constructed from resting-state functional magnetic resonance imaging (rs-fMRI). Small-worldness did not exhibit significant variations in MDD patients. Subsequently, two-sample t-tests were employed to screen FC and reconstruct the network. The discriminative ability of TPs between MDD patients and healthy controls was analyzed using receiver operating characteristic (ROC), ROC analysis showed the small-worldness of binary reconstructed FC network (p

Abstract Liver fibrosis is a common progressive liver disease that can cause liver dysfunction and lead to serious complications. Zi Qi decoction (ZQ) is a traditional formulation that exerts pharmacological effects on the treatment of liver fibrosis. However, precise intervention mechanisms remain unclear. The aim of this study was to synergistically harness proteomics and metabolomics techniques to elucidate the specific target of ZQ and its potential mechanism of action. A carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was established. Subsequently, the protective effect of ZQ on liver fibrosis mice was evaluated according to histopathological examination and biochemical indicators. Quantitative proteomics based on data independent acquisition (DIA) and non-targeted metabolomic analyses revealed the pharmacodynamic mechanism of ZQ. In addition, various cellular and molecular assays were used to detect changes in glycolysis levels in LSECs and mouse liver fibrosis models. The study results showed that ZQ significantly alleviated CCl4-induced liver injury and fibrosis in mice. DIA-based quantitative proteomics and non-targeted metabolomics analyses indicated that ZQ treatment downregulated glycolysis-related proteins such as PKM2, PFKP, and HK2, while regulating glycolysis-related metabolites and pathways. In addition, ZQ down-regulated glycolytic activity in mice with liver fibrosis and in LSECs, and inhibited CXCL1 secretion and neutrophil recruitment. ZQ inhibited LSEC glycolysis and mitigated neutrophil infiltration, thereby playing a therapeutic role in liver fibrosis.

To study the new method of aflatoxin removal by Lactobacillus plantarum materials, and provide a new idea for the efficient biological removal of aflatoxin B1, this study used the polydopamine-based atom transfer radical polymerization (p-ATRP) and cell-catalyzed copper-free atom transfer radical polymerization (c-ATRP) to modify the surface modification of living cells of Lactobacillus plantarum, and guided the self-assembly polymerization reaction within the ATRP system to form polymer materials, characterized the modified Lactobacillus plantarum and compared its adsorption and desorption capabilities towards aflatoxin B1 before and after modification. Results showed that, the unmodified Lactobacillus plantarum had a smooth cell surface, while the Lactobacillus plantarum modified by p-ATRP had a very rough cell surface, and the Lactobacillus plantarum modified by c-ATRP had wrinkles on the cell surface. The Zeta point of unmodified Lactobacillus plantarum was -8.43 mV, while the points of Lactobacillus plantarum after PD and PNIPAAm modification were 1.791 and 13.767 mV, respectively. The adsorption rate of Lactobacillus plantarum for aflatoxin B1 at concentrations ranging from 0.1~100 μg/mL was 75.3%. Furthermore, the adsorption capacity of p-ATRP and c-ATRP modified Lactobacillus plantarum exhibited an increase of 7.8% and 6.4%, respectively, compared with unmodified Lactobacillus plantarum. Additionally, at the same concentration of aflatoxin B1, the desorption rate of Lactobacillus plantarum was 6.1%, while the desorption capabilities of p-ATRP and c-ATRP modified Lactobacillus plantarum were enhanced by 14.4% and 42%, respectively. Overall, the modified Lactobacillus plantarum demonstrated a significant enhancement in both adsorption and desorption abilities towards aflatoxin.

Abstract Background Studies have reported that ciprofol has the advantage of reducing injection pain compared to propofol during gastroscopy, colonoscopy, and fiberoptic bronchoscopy. The effect of ciprofol on the injection pain in painless hysteroscopy needs to further explore. Methods A double-blind randomized controlled trial (RCT) was designed, and patients were recruited from the First Central Hospital of Baoding from March 2024 to June 2024. The eligible participants were allocated into ciprofol group (ciprofol combined with alfentanil) and propofol group (propofol combined with alfentanil) at 1:1 ratio. The primary outcome was injection pain. The secondary outcomes included sedation success rate, anesthesia success rate, adverse events, patient satisfaction, and comparison of vital signs before and after administration. Results A total of 217 participants were included for analysis, with 109 participants in the ciprofol group and 108 participants in the propofol group. The injection pain rate of ciprofol group (18.35%) was significantly lower than the propofol group (40.74%). Both the ciprofol group and propofol group had 100% of the sedation success rate. The anesthesia success rate between the two groups was comparable (P > 0.05). The rate of adverse events was lower (27.52% vs. 45.37%) and patient satisfaction was higher (9.84 ± 0.45 vs. 9.65 ± 0.85) in the ciprofol group than the propofol group. In addition, values of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in propofol group were significantly lower than those in ciprofol group at the time of cervical dilation and consciousness recovery. Conclusions Ciprofol exhibits comparable efficacy to that of propofol, and is associated with less injection pain rate, fewer adverse events, higher patient satisfaction, and more stable hemodynamics when used for general anesthesia during the painless hysteroscopy. Clinical trial number NCT06413862.

Abstract Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

Abstract The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Here we introduce SNAP-MS, a Stationary-phase-dissolvable Native Affinity Purification and Mass Spectrometric characterization strategy. It allows for highly efficient purification and characterization from inputs at the pico-mole level. SNAP-MS replaces traditional elution with matrix dissolving during the recovery of captured targets, enabling the use of high-affinity bait-target pairs and eliminates interstitial voids. The purified intact protein complexes are compatible with native MS, which provides structural information including stoichiometry, topology, and distribution of proteoforms, size variants and interaction states. An algorithm utilizes the bait as a charge remover and mass corrector significantly enhances the accuracy of analyzing heterogeneously glycosylated complexes. With a sample-to-data time as brief as 2 hours, SNAP-MS demonstrates considerable versatility in characterizing native complexes from biological samples, including blood samples.

Abstract Background Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. Methods The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. Results We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid β-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. Conclusion Our findings indicate that the Igκ/ETFA axis deregulates fatty acid β-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC.

Abstract Coal and gas outbursts, along with rock bursts, are common dynamic disasters in coal mining, threatening the safety and green production of coal mines. The distribution of coal seam stress is an external factor contributing to coal mine power disasters. The drainage of confined water in coal seam roof is the primary factor of coal seam stress changes. Using theoretical analysis and numerical simulations, the influence of roof confined water on coal seam stress by looking at the law of stress and stress conservation transfer in the drainage layer is investigated. Our results show that: (1) after drainage, there is an increase in the local stress within the coal seam, with a stress concentration factor of 1.35. The influence range of theoretically calculated stress is consistent with the measured results. (2) the maximum value of drainage boundary stress correlated positively with the angle of the water-rich abnormal area, with a linear fitting of R2 = 0.98. These findings hold significant theoretical and practical implications for preventing and controlling dynamic disasters during the mining of water-rich coal seams.

Abstract Background Asthma poses a significant global health challenge, characterized by high rates of morbidity and mortality. Despite available treatments, many severe asthma patients remain poorly managed, highlighting the need for novel therapeutic strategies. This study aims to identify potential drug targets for asthma by examining the influence of circulating plasma proteins on asthma risk. Methods This study employs summary-data-based Mendelian randomization (MR) and two-sample MR methods to investigate the association between 2940 plasma proteins from the UK Biobank study and asthma. The analysis includes discovery (FinnGen cohort) and replication (GERA cohort) phases, with Bayesian colocalization used to validate the relationships between proteins and asthma. Furthermore, protein–protein interaction and druggability assessments were conducted on high-evidence strength protein biomarkers, and candidate drug prediction and molecular docking were performed for proteins without targeted drugs. Given the complexity of asthma pathogenesis, the study also explores the relationships between plasma proteins and asthma-related endpoints (e.g., obesity-related asthma, infection-related asthma, childhood asthma) to identify potential therapeutic targets for different subtypes. Results In the discovery cohort, 75 plasma proteins were associated with asthma, including IL1RAP, IL1RL1, IL6, CXCL5, and CXCL8. Additionally, 6 proteins (IL4R, LTB, CASP8, MAX, PCDH12, and SCLY) were validated through co-localization analysis and validation cohort. The assessment of drug targetability revealed potential drug targets for IL4R, CASP8, and SCLY, while candidate drugs were predicted for LTB and MAX proteins. MAX exhibited strong binding affinity with multiple small molecules indicating a highly stable interaction and significant druggability potential. Analysis of the 75 proteins with 9 asthma-related endpoints highlighted promising targets such as DOK2, ITGAM, CA1, BTN2A1, and GZMB. Conclusion These findings elucidate the link between asthma, its related endpoints, and plasma proteins, advancing our understanding of molecular pathogenesis and treatment strategies. The discovery of potential therapeutic targets offers new insights into asthma drug target research.

BackgroundThe prevalence of overactive bladder (OAB) is increasing in the elderly population and there is growing evidence that malnutrition affects the urinary system. Despite this, research on the relationship between nutritional factors and OAB remains limited.MethodsWe included 17,161 elderly individuals from the National Health and Nutrition Examination Survey conducted between 2005 and 2018. Overactive Bladder Symptom Scores (OABSS) were utilized to assess symptoms of OAB. A multifactorial logistic regression analysis was employed to evaluate the independent association between the Geriatric Nutritional Risk Index (GNRI) and the prevalence of OAB. Restricted cubic spline plots examined the potential non-linear relationship between GNRI and OAB. Influencing factors were assessed through subgroup analyses, while the predictive utility of GNRI was assessed with receiver operating characteristic (ROC) curves. The influence of inflammatory response and cognitive function on the interaction between GNRI and OAB was also examined by mediation analysis.ResultsGNRI in the OAB group was significantly lower than that in the non-OAB group. Multifactorial logistic regression analysis revealed that GNRI significantly predicts OAB (p

Objectives The aim of this study was to develop and internally validate a hepatocellular carcinoma (HCC) risk prediction model incorporating repeated-measures data (longitudinal model), and compare with baseline predictions. Methods A total of 1097 participants with chronic hepatitis C after direct-acting antivirals (DAA) treatment were included in this prospective cohort study. The framework of joint models for longitudinal and survival data was used to construct the longitudinal prediction model. For comparison, a baseline model incorporating the same predictors was constructed through the multivariate Cox regression models. Model performance was evaluated using dynamic discrimination index (DDI), areas under the receiver-operating characteristics curves (AUROC), and Brier scores. Results Over a median follow-up of 7.25 years, 60 patients (5.5%) developed HCC. Key risk factors identified were aspartate aminotransferase (AST), cholinesterase, gamma-glutamyl transferase (GGT), albumin, hemoglobin (Hb), platelet count, alpha-fetoprotein (AFP), antigen-125 (CA-125), and carcinoembryonic antigen (CEA). The final joint model, with GGT and CEA removed, showed superior average predictive performance (DDI = .871) compared to models with all predictors included. Validation showed high predictive accuracy for HCC, with AUROCs above .9 for 1-, 3-, 4-, and 5-year predictions. In comparison, the baseline Cox model only achieved mediocre AUROCs of .7 (.75, .67, .69, and .67, respectively). Conclusion Compared to static models, our dynamic prediction model can predict the risk of HCC in patients after DAA treatment more accurately, providing better information to distinguish high-risk populations.

Immunometabolism is an emerging field that explores the intricate interplay between immune cells and metabolism. Regulatory T cells (Tregs), which maintain immune homeostasis in immunometabolism, play crucial regulatory roles. The activation, differentiation, and function of Tregs are influenced by various metabolic pathways, such as the Mammalian targets of rapamycin (mTOR) pathway and glycolysis. Correspondingly, activated Tregs can reciprocally impact these metabolic pathways. Tregs also possess robust adaptive capabilities, thus enabling them to adapt to various microenvironments, including the tumor microenvironment (TME). The complex mechanisms of Tregs in metabolic diseases are intriguing, particularly in conditions like MASLD, where Tregs are significantly upregulated and contribute to fibrosis, while in diabetes, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), they show downregulation and reduced anti-inflammatory capacity. These phenomena suggest that the differentiation and function of Tregs are influenced by the metabolic environment, and imbalances in either can lead to the development of metabolic diseases. Thus, moderate differentiation and inhibitory capacity of Tregs are critical for maintaining immune system balance. Given the unique immunoregulatory abilities of Tregs, the development of targeted therapeutic drugs may position them as novel targets in immunotherapy. This could contribute to restoring immune system balance, resolving metabolic dysregulation, and fostering innovation and progress in immunotherapy.

Conclusion: MGQD alleviated UC by suppressing inflammation and oxidative stress via the modulation of NF-κB and Nrf2/HO-1 pathways, suggesting that MGQD may be a candidate therapy for UC.

Background: The influence of air pollution on osteoarthritis (OA) remains underexplored. Methods: We conducted a prospective cohort study in the UK Biobank, estimating exposure levels of particulate matter (PM2.5, PM10, PM2.5–10), nitrogen oxides (NO2, NOx), and air pollutants exposure score (APES). Cox models assessed associations between air pollution exposure and OA incidence, joint replacement, and survival. Additionally, using genome-wide association statistics, we examined the potential causal associations between air pollution-related DNA methylation (DNAm) and OA risk. Gene-environment interaction analyses were conducted to explore the potential modification effect of DNA methylation-related genetic variants on the impact of air pollution on OA risk. Results: Individual exposure to each air pollutant was associated with an increased risk of developing OA, but not with progression from OA to joint replacement. For APES, the hazard ratio for incident OA was 1.09 (95 % CI = 1.04–1.13), and the hazard ratio of progression from OA to death was 1.16 (95 % CI = 1.00–1.35) in the highest quartile group compared to the lowest quartile group. Moreover, genetically predicted methylation at the PM2.5-related CpG site cg04027612 near the GDF5 gene was associated with a lower risk of OA. A potential epigenetic modification effect of cg04027612 near GDF5 on OA risk was observed. Conclusion: Long-term exposure to air pollution was associated with an increased risk of OA in the population and poorer survival outcomes for OA patients, with epigenetic changes in GDF5 potentially playing a role in the underlying mechanisms.

PurposeThis study aims to investigate the specific effects of glucocorticoids (GC) on the efficacy of immune checkpoint inhibitors (ICIs), and whether this effect is influenced by the timing and dosage of GC administration. Changes in the neutrophil percentage and the helper/suppressor T lymphocyte ratio [NEUT %/(CD4+/CD8+)] during GC administration were monitored.MethodsThe clinical results of 130 patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs were analyzed and compared with those of patients who did not use GC. Cox proportional hazards regression model and Logistic regression analysis were used to analyze the factors affecting ORR and PFS, and t test was used to analyze the changes of NEUT %/(CD4 +/CD8 +) during GC use.ResultsMultivariate Logistic analysis showed that GC use was associated with a higher ORR in 130 patients treated with ICIs [HR = 3.07,95% CI (1.31-7.21), P = 0.010]. Univariate Cox analysis showed that GC use was not significantly correlated with PFS [HR = 0.926,95% CI (0.603-1.420), P = 0.710]. Patients who used GC during the baseline period of ICIs treatment had a higher ORR than those who used GC at the early stage of ICIs treatment (65.4% vs 30.8%, p = 0.024). Multivariate Cox analysis showed that GC use had longer PFS [HR = 0.37,95% CI (0.17-0.78), p = 0.009]. The timing of GC use was different, and there was a difference in NEUT %/(CD4 +/CD8 +) levels before and after treatment. There was no significant difference in ORR and PFS between GC duration and dose.ConclusionThe use of GC helps to enhance the efficacy of immunotherapy. In particular, GC use during the baseline period leads to higher ORR and PFS, regardless of the dose or duration of GC use. The levels of NEUT %/(CD4+/CD8+) varied depending on the timing of GC administration.

BackgroundLung cancer has become the malignant tumor with the highest morbidity and mortality in the world. This study aims to analyze the burden of lung cancer and risk factors associated with lung cancer in the BRICS from 1990-2021 and to project the burden of lung cancer in the BRICS from 2021-2035.MethodsThe Global Burden of Disease (GBD) 2021 database was searched to collect the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and risk factors of lung cancer in the BRICS. Trends in lung cancer burden from 1990-2021 were analyzed using Joinpoint 4.9.1.0, and Bayesian age-period-cohort (BAPC) analyses were performed using R4.4.1 to project the disease burden of lung cancer from 2021-2035.ResultsAAPC(average annual percentage change) and EAPC(estimated average percentage change) of ASIR(age-standardized incidence), ASPR(age-standardized prevalence), ASMR(age-standardized mortality), and ASDR(age-standardized disability-adjusted life year) for lung cancer in Brazil, Russia, and Ethiopia 1990-2021 were less than 0. Egypt’s AAPC and EAPC for ASIR, ASPR, ASMR, and ASDR were all greater than 0 for 1990-2021, and China’s ASIR, ASPR, ASMR, and ASDR were all at the top of the BRICS in 2021. According to BAPC projection Brazil, Iran, Russia, and South Africa will have a decreasing trend in ASIR, ASPR, ASMR, and ASDR from 2021-2035. Egypt will have an increasing trend in ASIR, ASPR, ASMR, and ASDR from 2021-2035. With the exception of Ethiopia, the top tier level 1 and level 2 risk factors in the rest of the BRICS were behavioral factors and smoking factors, respectively.ConclusionThe BRICS still have a heavy burden of lung cancer, and there are significant differences in the burden of lung cancer among the BRICS. At the same time, many BRICS lung cancer prevention and control measures are worth learning from other developing countries.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of B-cell non-Hodgkin’s lymphoma (NHL), up to 30%–40% of patients will relapse and 10%–15% of patients have primary refractory disease, so exploring new treatment options is necessary. Ferroptosis is a non-apoptotic cell death mode discovered in recent years. Its occurrence pathway plays an essential impact on the therapeutic effect of tumors. Numerous studies have shown that modulating critical factors in the ferroptosis pathway can influence the growth of tumor cells in hematological malignancies including DLBCL. This review highlights recent advances in ferroptosis-related genes (FRGs), including STAT3, Nrf2, and ZEB1, and focuses on the clinical potential of ferroptosis inducers such as IKE, α-KG, DMF, and APR-246, which are currently being explored in clinical studies for their therapeutic effects in DLBCL. Correlational studies provide a novel idea for the research and treatment of ferroptosis in DLBCL and other hematological malignancies and lay a solid foundation for future studies.

Abstract Hepatocellular carcinoma (HCC) is characterized by frequent intrahepatic and distant metastases, resulting in a poor prognosis for patients. Epithelial–mesenchymal transition (EMT) plays a pivotal role in this process. However, the expression of NOP2/Sun RNA methyltransferase 5 (NSUN5) in HCC and its role in mediating EMT remain poorly understood. In this study, clinicopathological analyses are conducted across multiple independent HCC cohorts and induced tumor formation in Nsun5‐knockout mice. The findings reveal an upregulation of NSUN5 expression in tumor tissues; conversely, the absence of Nsun5 hinders the malignant progression of HCC, indicating that NSUN5 may serve as a significant oncogene in HCC. Furthermore, elevated levels of NSUN5 enhance EMT processes within HCC cells. NSUN5‐knockout cells exhibit reduced invasion and migration capabilities under both in vivo and in vitro conditions, while overexpression of NSUN5 yields opposing effects. Mechanistically, high levels of NSUN5 promote the enrichment of trimethylated histone H3 at lysine 4 (H3K4me3) at the promoter region of SMAD3 through recruitment of the WDR5, thereby facilitating HCC metastasis via SMAD3‐mediated EMT pathways. Collectively, this study identifies NSUN5 as a novel driver of metastasis in HCC and provides a theoretical foundation for potential therapeutic strategies against this malignancy.

Abstract Multidimensional power devices can achieve performance beyond conventional limits by deploying charge‐balanced p‐n junctions. A key obstacle to developing such devices in many wide‐bandgap (WBG) and ultra‐wide bandgap (UWBG) semiconductors is the difficulty of native p‐type doping. Here the WBG nickel oxide (NiO) as an alternative p‐type material is investigated. The acceptor concentration (NA) in NiO is modulated by oxygen partial pressure during magnetron sputtering and characterized using a p‐n+ heterojunction diode fabricated on gallium oxide (Ga2O3) substrate. Capacitance and breakdown measurements reveal a tunable NA from

Chimeric Antigen Receptor (CAR) T cell therapy has gained success in adoptive cell therapy for hematological malignancies. Although most CAR cell therapies in clinical trials or markets remain autologous, their acceptance has been limited due to issues like lengthy manufacturing, poor cell quality, and demanding cost. Consequently, “Off-the-shelf”, universal CAR (UCAR) cell therapy has emerged. Current concerns with UCAR therapies revolve around side effects such as graft versus host disease (GVHD) and host versus graft response (HVGR). Preclinical research on UCAR cell therapies aims to enhance efficacy and minimize these side effects. Common approaches involve gene editing techniques to knock out T cell receptor (TCR), human leukocyte antigen (HLA), and CD52 expression to mitigate GVHD and HVGR risks. However, these methods carry drawbacks including potential genotoxicity of the edited cells. Most recently, novel editing techniques, such as epigenetic editing and RNA writer systems, have been developed to reduce the risk of GVHD and HVGR, allowing for multiplex editing at different sites. Additionally, incorporating more cell types into UCAR cell therapies, like T-cell subtypes (DNT, γδT, virus-specific T cells) and NK cells, can efficiently target tumors without triggering side effects. In addition, the limited efficacy of T cells and NK cells against solid tumors is being addressed through CAR-Macrophages. In summary, CAR cell therapy has evolved to accommodate multiple cell types while expanding applications to various diseases, including hematologic malignancies and solid tumors, which holds tremendous growth potential and is promised to improve the lives of more patients in the future.

Abstract Linear frequency modulation (LFM) signal is a common radar signal in modern electronic warfare, and smeared spectrum (SMSP) can generate multiple false targets, causing jamming to radar detection. The authors propose a chirplet‐based masking algorithm that can solve the problem of SMSP jamming suppression and address a more complex problem: the separation of jamming signal and multiple LFM signals from intercepted mixed signal. First, the authors obtain matched chirp rates of the source signals through the changing tendency of the Rényi entropy. Then, the ridge of each source signal is extracted from the high‐resolution chirplet transform result using an image processing‐based algorithm. Finally, the jamming and LFM signals are accurately reconstructed through the time‐frequency mask to achieve separation. Even in the extreme case where multiple source signals with close chirp rates are overlapped, the proposed slope‐matching ridge extraction method and iterative update reconstruction method can still achieve commendable signal separation effects. Extensive experimental results demonstrate that the proposed algorithm performs well under extreme conditions of low signal‐to‐noise ratio, high jamming‐to‐signal ratio, and high sea state.

The Road of Tang Poetry in Eastern Zhejiang is a cultural route where nature and culture harmoniously intertwine. Mountain-type scenic areas play a vital role in providing core cultural ecosystem services (CES). To investigate the significance and distribution of landscape resources along the Poetry Road, a preliminary study was conducted in the densely concentrated areas of Shaoxing, Taizhou, and Ningbo. From these regions, six representative mountain-type scenic areas were selected for the research: Kuaiji Mountain, Qinwang Mountain, Wanwei Mountain, Tianmu Mountain, Tiantai Mountain, and Xuedou Mountain. Based on their designation status, these areas were categorized into national and non-national scenic areas. The research employed a combination of online and offline questionnaires, as well as semi-structured interviews. An importance-performance analysis (IPA) was introduced, and SPSS software was utilized to conduct U-tests on the statistical results. This analysis aimed to compare the differences in importance and performance of CES among the various mountain-type scenic areas. Furthermore, an overall evaluation of CES for the mountain-type scenic area was carried out using an optimization demand zoning approach, involving categories such as “Keeping up the good job”, “Concentrate here”, “Possible overkill”, and “Low priority”. Additionally, a comparative analysis was conducted between the two types of mountain-type scenic areas, considering aspects like aesthetic value, leisure tourism, cultural diversity, and nature education. The findings indicate that the overall importance of the core CES provided by mountain-type scenic areas significantly exceeds the performance score, implying that public expectations for these sites surpass the actual experience. Notably, the distinction between the two types of mountain-type scenic areas, national and non-national, lies primarily in their performance. Among the evaluation subcomponents, respondents’ perceptions are notably influenced by natural resource advantages, architectural style, recreation offerings, site iconicity, and historical heritage and preservation. The abundance of cultural activities emerges as a crucial factor contributing to the substantial performance disparity between the two types of scenic areas, underscoring the significant impact of cultural heritage on the development imbalance in mountain-type region. Furthermore, cultural heritage plays a pivotal role in promoting the establishment and enhancing the competitiveness and identity of mountain-type scenic areas. Consequently, prioritizing the protection and utilization of non-national mountain-type scenic areas cultural heritage can effectively elevate the level of CES supply and meet the demand in mountain-type scenic areas. The IPA has promoted the CES performance of mountain-type scenic areas to be closer to its importance, thereby fostering a more balanced CES of the Road of Tang Poetry in Eastern Zhejiang.

Abstract We study the operator algebra of extended conformal defects in more than two spacetime dimensions. Such algebra structure encodes the combined effect of multiple impurities on physical observables at long distances as well as the interactions among the impurities. These features are formalized by a fusion product which we define for a pair of defects, after isolating divergences that capture the effective potential between the defects, which generalizes the usual Casimir energy. We discuss general properties of the corresponding fusion algebra and contrast with the more familiar cases that involve topological defects. We also describe the relation to a different defect setup in the shape of a wedge. We provide explicit examples to illustrate these properties using line defects and interfaces in the Wilson-Fisher CFT and the Gross-Neveu(-Yukawa) CFT and determine the defect fusion data thereof.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features. Methods Transcriptomic datasets from three independent iCCA cohorts (iCCA cohorts 1–3, n = 382) and formalin-fixed and paraffin-embedded tissues from iCCA cohort 4 (n = 31) were used. An unbiased global screening strategy was established, including the transcriptome analysis with the activated malignancy/stemness (MS) signature in iCCA cohorts 1–3 and the mass spectrometry analysis of the sorted stemness reporter-positive iCCA cells. A group of cellular assays and subcutaneous tumor xenograft assay were performed to investigate functional roles of the candidate. Immunohistochemistry was performed in iCCA cohort 4 to examine the expression and localization of the candidate. Molecular and biochemical assays were used to evaluate the membrane localization and functional protein domains of the candidate. Cell sorting was performed and the corresponding cellular molecular assays were utilized to examine cancer stem cell features of the sorted cells. Results The unbiased global screening identified RRM2 as the top candidate, with a significantly higher level in iCCA patients with the MS signature activation and in iCCA cells positive for the stemness reporter. Consistently, silencing RRM2 significantly suppressed iCCA malignancy phenotypes both in vitro and in vivo. Moreover, immunohistochemistry in tumor tissues of iCCA patients revealed an unreported cell membrane localization of RRM2, in contrast to its usual cytoplasmic localization. RRM2 cell membrane localization was then confirmed in iCCA cells via immunofluorescence with or without cell membrane permeabilization, cell fractionation assay and cell surface biotinylation assay. Meanwhile, an unclassical signal peptide and a transmembrane domain of RRM2 were revealed experimentally. They were essential for RRM2 trafficking to cell membrane via the conventional endoplasmic reticulum (ER)–Golgi secretory pathway. Furthermore, the membrane RRM2-positive iCCA cells were successfully sorted. These cells possessed significant cancer stem cell malignant features including cell differentiation ability, self-renewal ability, tumor initiation ability, and stemness/malignancy gene signatures. Patients with membrane RRM2-positive iCCA cells had poor prognosis. Conclusions RRM2 had an alternative cell membrane localization. The membrane RRM2-positive iCCA cells represented a malignant subpopulation with cancer stem cell features.

Abstract Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Metal–organic frameworks (MOFs) are highly promising porous materials known for their exceptional porosity, extensive surface area, and customizable pore structures, making them an ideal solution for hydrogen storage. However, most MOFs research remains confined to the laboratory, lacking practical applications. To address this, the author proposes a shift towards practical applications, the creation of a comprehensive MOFs database, alignment of synthesis with practical considerations, and diversification of MOFs applications. These steps are crucial for harnessing the full potential of MOFs in real-world energy challenges.