Search

Abstract Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including CEACAM5 and CD24. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.

Abstract The Sc2.0 global consortium to design and construct a synthetic genome based on the Saccharomyces cerevisiae genome commenced in 2006, comprising 16 synthetic chromosomes and a new-to-nature tRNA neochromosome. In this paper we describe assembly and debugging of the 902,994-bp synthetic Saccharomyces cerevisiae chromosome synXVI of the Sc2.0 project. Application of the CRISPR D-BUGS protocol identified defective loci, which were modified to improve sporulation and recover wild-type like growth when grown on glycerol as a sole carbon source when grown at 37˚C. LoxPsym sites inserted downstream of dubious open reading frames impacted the 5’ UTR of genes required for optimal growth and were identified as a systematic cause of defective growth. Based on lessons learned from analysis of Sc2.0 defects and synXVI, an in-silico redesign of the synXVI chromosome was performed, which can be used as a blueprint for future synthetic yeast genome designs. The in-silico redesign of synXVI includes reduced PCR tag frequency, modified chunk and megachunk termini, and adjustments to allocation of loxPsym sites and TAA stop codons to dubious ORFs. This redesign provides a roadmap into applications of Sc2.0 strategies in non-yeast organisms.

Abstract Human papillomaviruses, particularly high-risk human papillomaviruses, have been universally considered to be associated with the oncogenesis and progression of various cancers. The genome of human papillomaviruses is circular, double-stranded DNA that encodes early and late proteins. Each of the proteins is of crucial significance in infecting the epithelium of host cells persistently and supporting viral genome integrating into host cells. Notably, E6 and E7 proteins, classified as oncoproteins, trigger the incidence of cancers by fostering cell proliferation, hindering apoptosis, evading immune surveillance, promoting cell invasion, and disrupting the balance of cellular metabolism. Therefore, targeting human papillomaviruses and decoding molecular mechanisms by which human papillomaviruses drive carcinogenesis are of great necessity to better treat human papillomaviruses-related cancers. Human papillomaviruses have been applied clinically to different facets of human papillomavirus-related cancers, including prevention, screening, diagnosis, treatment, and prognosis. Several types of prophylactic vaccines have been publicly utilized worldwide and have greatly decreased the occurrence of human papillomavirus-related cancers, which have benefited numerous people. Although various therapeutic vaccines have been developed and tested clinically, none of them have been officially approved to date. Enhancing the efficacy of vaccines and searching for innovative technologies targeting human papillomaviruses remain critical challenges that warrant continuous research and attention in the future.

Abstract Background Recent advancements in contemporary therapeutic approaches have increased the survival rates of lung cancer patients; however, the long-term benefits remain constrained, underscoring the pressing need for novel biomarkers. Surfactant-associated 3 (SFTA3), a long non-coding RNA predominantly expressed in normal lung epithelial cells, plays a crucial role in lung development. Nevertheless, its function in lung adenocarcinoma (LUAD) remains inadequately understood. Methods Single-cell RNA sequencing data were utilized to identify novel cancer cell-intrinsic gene signatures associated with the progression of LUAD, and their roles in LUAD were comprehensively analyzed. Serum samples were collected to quantify the expression levels of SFTA3 in LUAD patients. Furthermore, a series of biological experiments, including cell viability assays, scratch wound healing assays, and colony formation assays, were conducted to demonstrate the tumor-suppressive effects of SFTA3. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SFTA3 in lung cancer cells. Results We constructed a prognostic model comprising eight genes: ALDOA, ATP5MD, SERPINH1, SFTA3, SLK, U2SURP, SCGB1A1, and SCGB1A3. The model effectively stratified patients into high- and low-risk categories, revealing that low-risk patients experienced superior clinical outcomes, exhibited an immunologically hot tumor microenvironment (TME), and had a greater probability of responding to immunotherapy. In contrast, the high-risk group exhibited a cold TME and may benefit more from chemotherapy. Furthermore, our study revealed that a progressive decrease in SFTA3 expression in cancer cells was correlated with tumor advancement. Notably, the serum levels of SFTA3 significantly decreased in patients with LUAD, suggesting its potential utility in liquid biopsy for LUAD diagnosis. Additionally, the knockdown of SFTA3 enhances the proliferation and migration of lung cancer cells, whereas its overexpression inhibits these phenotypes. The epithelial-mesenchymal transition pathway was significantly enriched following SFTA3 silencing, suggesting that SFTA3 may impact tumor progression by modulating this process. We also identified key transcription factors and epigenetic mechanisms implicated in the downregulation of SFTA3 in LUAD. Conclusion We developed a robust prognostic model and identified SFTA3 as a novel biomarker with potential applications in the diagnosis, prognosis, and personalized treatment of LUAD. Additionally, our findings offer new insights into the mechanisms underlying LUAD tumorigenesis and immune evasion.

Blue light induced eye damage (BLED) belongs to modern diseases. It is an ophthalmic disease caused by prolonged exposure to electronic devices or screens containing a large amount of high-energy short waves (blue light). Specific symptoms include dryness and discomfort in the eyes, blurred vision, headache, insomnia, and in severe cases, it may also cause various eye diseases such as cataracts and glaucoma. At present, the development of health products and drugs for eye blue light injury faces many difficulties. Therefore, further exploration and research are needed on the pathogenesis, pathophysiology, and pharmacological mechanisms of blue light injury. Natural medicine ingredients and preparations have unique advantages in targeting eye blue light injury fatigue products due to their multi-component synergistic effects, overall regulation, and mild and safe characteristics. Starting from the disease-related mechanisms and pathophysiological characteristics of eye blue light injury, this article elucidates the pharmacological mechanisms of various drugs for treating eye blue light injury. At the same time, it reviews the research on in vitro cultured cell and animal model conditions for blue light injury eyes, in order to provide reference for subsequent blue light injury modeling experiments. And explore future research directions to provide new ideas and methods for the prevention and treatment of BLED.

Chlorophyll density (ChD) can reflect the photosynthetic capacity of the winter wheat population, therefore achieving real-time non-destructive monitoring of ChD in winter wheat is of great significance for evaluating the growth status of winter wheat. Derivative preprocessing has a wide range of applications in the hyperspectral monitoring of winter wheat chlorophyll. In order to research the role of fractional-order derivative (FOD) in the hyperspectral monitoring model of ChD, this study based on an irrigation experiment of winter wheat to obtain ChD and canopy hyperspectral reflectance. The original spectral reflectance curves were preprocessed using 3 FOD methods: Grünwald-Letnikov (GL), Riemann-Liouville (RL), and Caputo. Hyperspectral monitoring models for winter wheat ChD were constructed using 8 machine learning algorithms, including partial least squares regression, support vector regression, multi-layer perceptron regression, random forest regression, extra-trees regression (ETsR), decision tree regression, K-nearest neighbors regression, and gaussian process regression, based on the full spectrum band and the band selected by competitive adaptive reweighted sampling (CARS). The main results were as follows: For the 3 types of FOD, GL-FOD was suitable for analyzing the change process of the original spectral curve towards the integer-order derivative spectral curve. RL-FOD was suitable for constructing the hyperspectral monitoring model of winter wheat ChD. Caputo-FOD was not suitable for hyperspectral research due to its insensitivity to changes in order. The 3 FOD calculation methods could all improve the correlation between the original spectral curve and Log(ChD) to varying degrees, but only the GL method and RL method could observe the change process of correlation with order changes, and the shorter the wavelength, the smaller the order, and the higher the correlation. The bands screened by CARS were distributed throughout the entire spectral range, but there was a relatively concentrated distribution in the visible light region. Among all models, CARS was used to screen bands based on the 0.3-order RL-FOD spectrum, and the model constructed using ETsR reached the best accuracy and stability. Its R2c, RMSEc, R2v, RMSEv, and RPD were 1.0000, 0.0000, 0.8667, 0.1732, and 2.6660, respectively. In conclusion, based on the winter wheat ChD data set and the corresponding canopy hyperspectral data set, combined with 3 FOD calculation methods, 1 band screening method, and 8 modeling algorithms, this study constructed hyperspectral monitoring models for winter wheat ChD. The results showed that based on the 0.3-order RL-FOD, combined with the CARS screening band, ETsR modeling has the highest accuracy, and hyperspectral estimation of winter wheat ChD can be realized. The results of this study can provide some reference for the rapid and nondestructive estimation of ChD in winter wheat.

Narcolepsy is a sleep-wake disorder with an onset commonly seen in individuals aged 10–30 years. Due to various reasons, the diagnosis of narcolepsy often experiences a delay of at least ten years. Diagnosing narcolepsy in children is particularly challenging due to atypical symptoms, leading to frequent misdiagnosis or missed diagnoses. We report a case of narcolepsy in a four-year-old girl to provide insights into the early diagnosis and treatment of narcolepsy in children. As a chronic condition, narcolepsy can lead to decreased quality of life, including psychological issues such as depression and anxiety. Furthermore, there are few randomized controlled trials involving pediatric narcolepsy patients. To provide a comprehensive treatment approach for pediatric narcolepsy, we review the current progress in the treatment of narcolepsy in children.

The acceleration of urbanization and development of marine resources has led to the imbalance of land structure, which threatens the sustainable development of the human living environment. Exploring the spatial distribution patterns of land-sea and its spatio-temporal evolution characteristics is an important initiative to resolve conflicts and optimise the spatial structure of land-sea use. Taking the Liaoning Coastal Economic Belt as an example, this paper constructs a system to measure the value of Production-Living-Ecological Functions (PLEF) of the coastal zone and realizes the identification of Production-Living-Ecological Spaces (PLES) and the division of their combination patterns. At the same time, it analyses the spatio-temporal evolution of PLES using land use transfer matrix, center of gravity transfer and standard deviation ellipse models and explores the interaction mechanism of PLES from the perspective of land-sea coordination. The results show that: (1) The production and living spaces on land are concentrated near the coastline, and the ecological space is mainly distributed in the mountainous forest area. The sea is dominated by the production space, and the living and ecological spaces occupy a relatively small proportion. (2) While the land has significant multifunctionality, the sea has a single PLEF, with the production function dominating and accounting for more than 90%. (3) In the period 2005–2010, the frequency of mutual transformation of the different PLES was the highest. The increase is mainly in the living space on land and the production space at sea. (4) From 2005 to 2010, the patterns of land and sea PLES changed significantly, and from 2010 to 2020, they were relatively stable. This study analyses the spatial structure of land-sea from the perspective of spatial multifunctionality and proposes optimization schemes based on land-sea interactions, which can provide decision support for the identification and optimization of coastal zone space and sustainable development.

Abstract Background Activin A, a noteworthy member of the TGF‐β superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8+ T cells. Methods This study established a mouse subcutaneous transplantation model of hepatoma to explore whether activin A has a regulatory effect of CD8+ T cells. And reveal the biological characteristics of ActRIIA high CD8+ T cells. Results We discovered that CD8+ T cells express ActRIIA, ActRIIB, and Smad2,3,4. Unlike high‐dose activin A, low‐dose activin A increased the content of CD8+ T cells while also suppressing tumor growth. In addition, low‐dose activin A promoted expression of perforin, granzyme B, CD69, CD11c, CD49b, Ki67 and ActRIIA in CD8+ T cells. And the results indicated that high‐dose activin A promotes the expression of PPM1A in T cells, while low‐dose activin A has no effect on these cells. The tumor contained more ActRIIA high CD8+ T cells compared to the peripheral blood and spleen. ActRIIA high CD8+ T cells highly express cytotoxic molecules and cytokines. And ActRIIA high CD8+ T cells not only expressed high levels of activation/co‐stimulatory markers CD69, CD278, and CD28, but also high levels of inhibitory markers CD366 and KLRG1. Different chemokine receptors displayed varying levels of expression in ActRIIA high CD8+ T cells. Additionally, these cells have a high proliferative potential. Finally, overexpression of Mettl3 inhibited the expression of ActRIIA in CD8+ T cells. Conclusions This study demonstrated that low‐dose activin A enhanced the anti‐tumor effect of CD8+ T cells, and ActRIIA high CD8+ T cells actively contribute to tumor immunity.

This work attempts to provide a new interpretation for the hot corona in active galactic nuclei (AGNs). A thin parabolic magnetic reconnection layer, anchored at the innermost disk and extending along the boundary of the magnetic tower for a few tens of gravitational radii, serves as a hard-X-ray source above the disk. Within this reconnection layer, the tearing instability leads to the formation of a chain of plasmoids, which contain relativistic electrons that generate X-ray radiation through inverse-Compton (IC) scattering of soft photons emitted by the accretion disk. Based on previous theoretical works and numerical simulations, we develop a heuristic framework to parameterize the geometry and magnetization of the reconnection layer, as well as to compute both the power of the IC-scattering radiation and the height of the reconnection layer. Our model allows for a quantitative investigation of the relation between the height of the corona and the X-ray radiation luminosity, which can be directly compared against the observed relation from X-ray reverberation mapping of individual AGNs. The theoretical results are in good agreement with the observations of IRAS 13224-3809, indicating the validation of our model.

Accurately predicting the remaining useful life (RUL) of critical mechanical components is a central challenge in reliability engineering. Stochastic processes, which are capable of modeling uncertainties, are widely used in RUL prediction. However, conventional stochastic process models face two major limitations: (1) the reliance on strict assumptions during model formulation, restricting their applicability to a narrow range of degradation processes, and (2) the inability to account for potential variations in the degradation mechanism during modeling and prediction. To address these issues, we propose a novel mechanism-equivalence-based Tweedie exponential dispersion process (ME-based TEDP) for adaptive degradation modeling and RUL prediction of mechanical components. The proposed model enhances the original Tweedie exponential dispersion process (TEDP) by incorporating degradation mechanism equivalence, effectively capturing the correlation between model parameters. Furthermore, it improves prediction accuracy and interpretability by employing a dynamic testing–modeling–predicting strategy. Application of the ME-based TEDP model to high-speed rail bogie systems demonstrates its effectiveness and superiority over existing approaches. This study advances the theory of degradation modeling and significantly improves the precision of RUL predictions.

Cryptococcal pneumonia is a severe fungal infection of the respiratory system, predominantly caused by Cryptococcus neoformans. Its incidence is increasing, driven by evolving pathogen dynamics and heightened susceptibility among patient populations. This investigation aimed to assess the combined therapeutic efficacy of Fluconazole and Amphotericin B for cryptococcal pneumonia and to explore the roles of miR-15b and TGF-β1 in modulating treatment response. Twenty-eight patients diagnosed with cryptococcal pneumonia were randomly allocated to receive either Amphotericin B monotherapy (control group) or a combination of Amphotericin B and Fluconazole (observation group) over a 14-day period. Key respiratory function indices—forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratios—were measured pre- and post-treatment, alongside levels of procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), miR-15b, and TGF-β1. Results demonstrated marked improvements in pulmonary function within the observation group, with significantly higher FEV1, FVC, and FEV1/FVC values than those in the control group (P < 0.05). Additionally, the observation group exhibited greater reductions in PCT and sTREM-1, coupled with notable elevations in miR-15b and TGF-β1 levels. The combination therapy achieved a total response rate of 92.86%, significantly surpassing the control's 57.14% efficacy (P < 0.05). These findings indicate that Fluconazole combined with Amphotericin B not only enhances clinical efficacy by mitigating inflammation but also supports lung function recovery with a favourable safety profile, highlighting its utility in managing cryptococcal pneumonia effectively. [ABSTRACT FROM AUTHOR]

Today, in the modern world, allergic diseases, also described as atopic allergies, are classified as a type of multifactorial disorder due to the complex interplay between genetics, environment, and socioeconomic factors that influence the disease's manifestation, severity, and one's predisposition to allergic diseases. It is undeniable that many reported studies have pointed out that the mast cell is one of the leading key players involved in triggering an allergic reaction. To improve our understanding of the molecular and cellular mechanisms underlying allergy, various mast cell lines have been employed in vitro to study the pathogenesis of allergic diseases for the past decades. However, there is no consensus on many fundamental aspects associated with their use, such as the effects of culture media composition and the type of inducer used for cell degranulation. As the standardization of research protocols and disease models is crucial, we present the outcome of a systematic review of scientific articles using three major immortalized in vitro mast cell lines (HMC-1, LAD2, and RBL-2H3) to study allergy. This systematic review described the cell source, culture conditions, inducers used for degranulation, and mediators released for examination. We hope that the present systematic review may help to standardize the use of immortalized in vitro mast cell lines in allergy research and serve as a user's guide to understand the fundamental aspects of allergy as well to develop an effective allergy therapy in the future for the betterment of human good health and wellbeing. [ABSTRACT FROM AUTHOR]

Somatic cell nuclear transfer (SCNT) has been successfully employed across various mammalian species, yet cloned animals consistently exhibit low pregnancy rates, primarily due to placental abnormalities such as hyperplasia and hypertrophy. This study investigated the involvement of the Hippo signaling pathway in aberrant placental development in SCNT-induced bovine pregnancies. SCNT-derived cattle exhibited placental hypertrophy, including enlarged abdominal circumference and altered placental cotyledon morphology. RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas. Coexpression of YAP1 and CCND1 was observed in cloned blastocysts, placental tissues, and bovine placental mesenchymal stem cells (bPMSCs). Manipulation of YAP1 expression demonstrated the capacity to regulate bPMSC proliferation. Experimental assays confirmed the direct binding of YAP1 to CCND1, which subsequently promoted CCND1 expression in bPMSCs. Furthermore, inhibition of CDK6, a downstream target of CCND1, attenuated SCNT bPMSC proliferation. This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression, facilitating cell cycle progression. These findings offer potential avenues for enhancing cloning efficiency, with implications for evolutionary biology and the conservation of valuable germplasm resources. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM), both a longstanding medical practice in Asia and an increasingly utilized supplement or alternative medicine in Western countries, has become a focal point within the life sciences in recent years. TCM formulations represent a cornerstone of treatment, with their chemical composition serving as the fundamental basis for their pharmacological effects. However, the intricate nature of chemical composition, low abundance of various constituents, and presence of numerous isomeric compounds, alongside interactions among different medicinal substances, render the effective separation and identification of the components in TCM herbs challenging by using traditional analytical methods. In this study, an analytical method of ultra-high-performance liquid chromatography-quadrupole/Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) was developed for identifying the chemical components in the traditional Chinese medicine formula of Jiuwei decoction. The sample pretreatment method involved ultrasonic/microwave-assisted extraction, ensuring comprehensive extraction of the active components in Jiuwei decoction. Parameters of this extraction included a microwave power at 300 W, ultrasonic power at 340 W, temperature at 45 ℃, and an extraction duration of 30 min. Subsequent to extraction, chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 column (150 mm×2.1 mm, 1.7 µm) at 30 ℃, with an injection volume of 2 μL per run. The mobile phase consisted of water with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.3 mL/min. Before entering the quadrupole/Orbitrap high-resolution mass spectrometer for detection, samples underwent ionization under both positive and negative ion modes. Data acquisition was then conducted in full MS scan/data-dependent MS/MS scan (Full MS/dd-MS2) acquisition mode. Following data collection, chromatographic peak alignment and extraction were performed using the Xcalibur 4.1 software. Accurate mass information of precursor ions and fragment ions was meticulously compared with various databases, including the Orbitrap Traditional Chinese Medicine Library (OTCML), as well as other online databases such as TCMSP, ChemSpider, PubChem, PubMed, and Web of Science, in addition to a self-curated database for identification purposes. A total of 144 compounds are successfully identified, encompassing 24 flavonoids, 30 alkaloids, 12 terpenes, 23 phenylpropanoids, 26 phenols, 10 amino acids, 7 organic acids, 5 steroids, and 7 other types of compounds. Among these compounds, alkaloids such as sinomenine, phellodendrine, magnoflorine, isocorydine, and corydinematrine exhibit notably high contents and mass spectrometric responses, whereas flavonoids and saponins display comparatively lower MS responses. The herbal sources of these compounds were identified, and the fragmentation patterns of representative compounds were thoroughly analyzed. This study provides a precise identification of the chemical constituents in Jiuwei decoction, thus furnishing a robust scientific foundation for further exploration into its pharmacological effects and mechanisms of action. Moreover, this study serves as an invaluable reference for the analysis of the chemical composition of TCM formulations. Nonetheless, it is crucial to acknowledge the inherent limitations and scopes of various analytical methods and instruments. Therefore, in the pursuit of analyzing active components in TCMs, it is advisable to delve deeper into separation and identification through the utilization of diverse techniques such as nuclear magnetic resonance spectroscopy, ultraviolet/infrared spectroscopy, and capillary electrophoresis-mass spectrometry.

Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.

BackgroundThe application of nanomedicine in inflammatory bowel disease (IBD) has gained significant attention in the recent years. As the field rapidly evolves, analyzing research trends and identifying research hotpots are essential for guiding future advancements, and a comprehensive bibliometric can provide valuable insights.MethodsThe current research focused on publications from 2001 to 2024, and was sourced from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were employed to visualize authors, institutions, countries, co-cited references, and keywords, thereby mapping the intellectual structure and identifying emerging trends in the field.ResultsThe analysis covered 1,518 literature across 447 journals, authored by 9,334 researchers from 5,459 institutions and 287 countries/regions. The global publication numbers exhibited an upward trend, particularly in the last decade, with China leading as the top publishing country and the Chinese Academy of Sciences emerging as the foremost institution. Dr. Xiao Bo is the prominent figure in advanced drug delivery systems. This interdisciplinary field, which spans materials science, pharmacy, and medicine, has seen influential publications mainly concentrated on targeted nanoparticles treatment for IBD. Keyword analysis revealed that current research hotspots include drug delivery, immune cell regulation, antioxidant damage, intestinal microbiota homeostasis, and nanovesicles.ConclusionThis study offers a comprehensive overview of global research landscape, emphasizing the rapid growth and increasing complexity of this field. It identifies key research hotspots and trends, including efforts to enhance the precision, efficacy, and safety of nanomedicine applications. Emerging directions are highlighted as crucial for further progress in this evolving area.

Precast systems are increasingly favored in modern construction to meet the growing demands for faster project delivery, cost control, and enhanced quality assurance. Yet, the feasibility of connections between precast elements remains a crucial factor affecting the overall structural performance of these systems. Considering the versatility and dimensional consistency of structural steel sections, this study introduces an emulative column-to-column hybrid connection achieved by using welding-spliced steel tubes, with a view to improving assembly efficiency and on-site quality control. Reversed cyclic loading tests were conducted on five near full-scale column specimens to assess the seismic performance of the proposed connection. Results indicated that this connection method could provide seismic performance comparable to that of the traditional cast-in-place counterpart. Nevertheless, the anchorage of the column longitudinal rebars played a critical role, as inadequate anchorages led to significant reductions in the columns’ lateral capacity. For this reason, increasing the tube thickness was shown to be insufficient as a substitute for proper anchorage detailing. Moreover, it was found that the incorporation of the welded steel tubes shifted the plastic hinge region upward, resulting in a more extended damage zone—a consequence of the localized stiffening effect. Finally, existing equations and methods are employed to evaluate the lateral strength, load-displacement response, and plastic hinge length of the tested specimens.

Objectives: Recent research indicates that the plasma lipidome composition may undergo alterations following hemorrhagic stroke. Nevertheless, the causal inference between plasma lipidome and hemorrhagic stroke remains elusive., Materials and Methods: Exposure data were achieved from a recent Genome-wide Association Study (GWAS) study of 179 lipid species involving 7,174 individuals, while the outcome data were obtained from the FinnGen consortium (R10), including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-traumatic intracranial hemorrhage (nITH). Two-sample bidirectional Mendelian randomization (MR) analyses were used to assess the causal inference between liposome and hemorrhagic stroke, and inverse variance weighted served as the main method. Genetic correlations between liposome and hemorrhagic stroke were assessed using Linkage disequilibrium score regression (LDSC)., Results: After the false discovery rate (FDR) correction, Phosphatidylcholine (O-18:2&#95;20:4) was identified as a substantial risk factor for ICH (OR,1.199; 95% CI, 1.073-1.341; P FDR  = 0.073). Alternatively, Phosphatidylinositol (16:0&#95;18:1) was a relevant protective factor (OR, 0.773; 95% CI, 0.666-0.896; P FDR  = 0.069). Furthermore, the Sterol ester (27:1/20:3) (OR, 1.138; 95% CI, 1.024-1.264; P FDR  = 0.086) was identified as the prominent risk factor for SAH. Finally, Sterol ester (27:1/20:4) (OR, 1.073; 95% CI, 1.026-1.121; P FDR  = 0.030) and Phosphatidylinositol (16:0&#95;18:1) levels (OR, 0.794; 95% CI, 0.709-0.889; P FDR =0.007) was identified as risk and protective factors for nITH, respectively., Conclusions: The causal relationship between plasma lipidome and hemorrhagic stroke is evident. Studying the plasma lipidome offers promising preventive strategies and potential therapeutic approaches for hemorrhagic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Hemorrhagic stroke (HS) mainly includes intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), both of which seriously affect the patient's prognosis. Cerebrospinal fluid (CSF) metabolites and HS showed a link in observational studies. However, the causal association between them is not clear. We aimed to establish the optimal causality of CSF metabolites with HS. Mendelian randomization (MR) was employed to identify associations between CSF metabolites and different sources of HS. Univariable MR and false discovery rates (FDR) were used to identify initial causal associations. Linkage disequilibrium score regression determined genetic correlations. Multiple sensitive analyses ensured the reliability of the results. Multivariable MR and MR Bayesian Model Averaging were used to identify the optimal causal associations. The combined effects of metabolites and HS were assessed by meta-analyses. Pathway analyses were performed to identify potential pathways of action. Reverse MR was also conducted to identify reverse causal associations. Finally, Corresponding blood metabolites were used to explore the multiple roles of metabolites. We identified 20 CSF metabolites and six metabolic pathways associated with ICH; 15 CSF metabolites and three metabolic pathways associated with SAH. Nineteen and seven metabolites were causally associated with deep and lobar ICH, respectively. CSF levels of mannose (OR 0.63; 95% CI 0.45-0.88; P combined  = 0.0059) and N-acetyltaurine (OR 0.68; 95% CI 0.47-0.98; P combined  = 0.0395) may serve as the optimal exposures for ICH and SAH, respectively. Additionally, CSF ascorbic acid 3-sulfate levels significantly decrease the risk of deep ICH (OR 0.79; 95% CI 0.66-0.94; p = 0.0065; P FDR  = 0.091). Supplemental analysis of blood metabolites suggested multiple roles for CSF and blood N-formylanthranilic acid and hippurate. There are significant causal associations between CSF metabolites and HS, which provides a further rationale for the prevention and monitoring of ICH and SAH., (© 2025 International Society for Neurochemistry.)