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The objective of this study was to investigate the effects of dietary lysine restriction on the global gene expression profile of skeletal muscle in growing pigs. Twelve crossbred (Yorkshire × Landrace) barrows (initial BW 22.6 ± 2.04 kg) were randomly assigned to two dietary treatments (LDD: a lysine-deficient diet; LAD: a lysine-adequate diet) according to a completely randomized experiment design (n = 6). After feeding for 8 weeks, skeletal muscle was sampled from the longissimus dorsi of individual pigs. The muscle total RNA was isolated and cDNA libraries were prepared for RNA sequencing (RNA-Seq) analysis. The RNA-Seq data obtained was then analyzed using the CLC Genomics Workbench to identify differentially expressed genes (DEGs). A total of 80 genes (padj ≤ 0.05) were differentially expressed in the longissimus dorsi muscle of the pigs fed LDD vs. LAD, of which 46 genes were downregulated and 34 genes were upregulated. Gene Ontology (GO) analysis of the DEGs (padj ≤ 0.05) for functional annotation identified those GO terms that are mostly associated with the molecular functions of structural molecules and metabolic enzymes (e.g., oxidoreductase and endopeptidase), biological process of acute-phase response, and amino acid metabolism including synthesis and degradation in the extracellular matrix region. Collectively, the results of this study have provided some novel insight regarding the molecular mechanisms of muscle growth that are associated with dietary lysine supply.

This research is concerned with individuals’ symbolic interactions with the Charging Bull statue. We chose this statue because it is an extremely popular tourist attraction and the most visited nonhuman statue in New York City. However, there is no research devoted to understanding how visitors interact with the statue. To fill this gap in the literature, we examine people’s interactions as a unique way of communicating with the Charging Bull statue in New York City through a photo analysis approach. Using the general framework of symbolic interactionism, the paper investigates poses, gestures, and more generally interactions of individuals near or with the statue to gain insights into the impact of the Charging Bull beyond a mere visual representation. The findings reveal various forms of interaction, including souvenir photography, active participation, unexpected interactions, and public-made symbolism. This study of these interactions contributes to the literature on collective memory and the study of statues. Additionally, this research highlights the inventiveness of the dynamic relationship between individuals and statues as symbols in the urban environment.

ObjectivesThe SF-12 version 2 is a survey instrument for collecting data on subjective health. The US-based scoring method is the recommended standard for measuring subjective health with data collected with this instrument. The inadequacy of the US-based scoring method of the SF-12 version 2 instrument for non-US populations is widely documented. However, few studies systematically assessed relative performance of alternative scoring methods against the US-based method, our main objective in this paper. Through this investigation, we also intend to shed light on Filipina migrant workers’ subjective health in Hong Kong, our case study.MethodsThis study investigates the feasibility of eight such scoring methods—six latent-variable models, the raw score index, and the US-based method—for analyzing an SF-12 version 2 instrument via a range of bootstrapped samples of varying sizes and an empirical study of the original 2017 Hong Kong Domestic Workers survey data with a set of covariates associated with Filipina migrant domestic workers’ subjective mental and physical health in Hong Kong.FindingsOur analyses favor the latent-variable factor model with the normal distribution and the identity link for analyzing the SF-12 version 2 type of data. Our empirical study of the survey data provides evidence for the beneficial effects of education, social support, and positive working conditions on migrant domestic workers’ subjective physical health and especially subjective mental health, with these two types of health analyzed jointly on the same measurement scale.ConclusionFor studying non-US populations with the SF-12 version 2 instrument, we recommend using the latent confirmatory factor analysis model that assumes a normal distribution and an identity link function for analyzing the MCS and PCS dimensions simultaneously.

This study investigated the impact of an increased arginine (ARG) level in a boar diet on semen production, sperm quality, and seminal plasma proteome. Adult Nebraska Index Line boars were assigned to two groups, one receiving a control diet with 0.77% arginine (n = 4) and the other a high-arginine diet with 1.77% arginine (n = 5). Semen was collected twice a week over the whole experiment, including one week before, six weeks during, and six weeks after the supplementation. Parameters such as semen volume and concentration were assessed immediately after collection, alongside sperm motility and morphology. Centrifugation of raw semen samples yielded seminal plasma for a gel-based proteome analysis. The seminal plasma proteins were extracted, quantified, and separated via 2D gel electrophoresis, allowing protein identification through mass spectrometry. Data analysis involved two-way ANOVA for comparisons (p < 0.05). Results showed that arginine supplementation improved semen volume and total sperm counts, with averages of 21 ± 3 doses in the control group versus 24 ± 2 in the ARG group (p = 0.05). Although sperm motility and morphology remained unaffected (p > 0.05), dietary arginine upregulated ten proteins and downregulated two. In summary, increased dietary arginine did not significantly alter key parameters of semen output or sperm quality but significantly impacted seminal plasma proteome, warranting further research on sperm viability.

Oxidative stress impairs pigs’ health and production performance. This study examined the effects of level and source of methionine (Met) supplementation against the diquat-induced oxidative stress in pigs. Forty growing barrows were randomly assigned to four groups. Groups 1 and 2 received a basal diet that was adequate in energy and nutrients (Diet 1), Group 3 received a DL-Met-supplemented diet, and Group 4 received an MHA-Ca-supplemented diet. After 3 weeks of feeding (Phase 1), pigs were injected with 10 mL saline (Group 1) or 10 mg/kg-BW diquat in 10 mL saline (Groups 2, 3, and 4), and then continually fed for one week (Phase 2). During or at the end of Phase 1, there were no differences in nearly all of the growth performance and redox parameters among the four groups. During or at the end of Phase 2, however, the ADFI and ADG were lower (p < 0.01) in Group 2 than in Group 1 while the serum malondialdehyde content was higher (p < 0.05) in Group 2 than in Group 1. The serum glutathione peroxidase (GPX) activity and liver superoxide dismutase (SOD) activity were lower (p < 0.05) in Group 2 than in Group 1. The serum GPX activity, the serum total antioxidant capacity, and the liver GPX activity were higher (p < 0.05) in Group 3 than in Group 2. There were nearly no differences in these redox parameters between Groups 3 and 4. In conclusion, MHA-Ca and DL-Met, when used at an equivalent bioefficacy level, had similar effects on the pigs’ growth performance and antioxidative status. Therefore, increased Met supplementation can improve pigs’ antioxidative status.

State-of-the-art point cloud classification methods mostly process raw point clouds, using a single point as the basic unit and calculating point cloud features by searching local neighbors via the k-neighborhood method. Such methods tend to be computationally inefficient and have difficulty obtaining accurate feature descriptions due to inappropriate neighborhood selection. In this paper, we propose a robust and effective point cloud classification approach that integrates point cloud supervoxels and their locally convex connected patches into a random forest classifier. We apply a centroid cloud extracted from supervoxels into the proposed classifier, which effectively improves the point cloud feature calculation accuracy and reduces the computational cost. Considering the different types of point cloud feature descriptions, we divide features into three categories (point-based, eigen-based, and grid-based) and accordingly design three distinct feature calculation strategies to improve feature reliability. The proposed method achieves state-of-the-art performance, with average F1-scores of 89.16%, respectively. The successful classification of point clouds with great variation in elevation also demonstrates the reliability of the proposed method in challenging scenes to some extents.

Atherosclerosis (AS) is a chronic inflammatory disease, and pyroptosis-a recently discovered pro-inflammatory programmed cell death process-can exacerbate these inflammatory responses. Vascular endothelial cell pyroptosis contributes to AS progression. Cathepsin B (CTSB) is a crucial member of the cysteine protease family found in lysosomes. However, its exact role in vascular endothelial cell pyroptosis remains unclear. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, inhibits pyroptosis and alleviates AS independent of its hypoglycemic effect. This study utilized oxidized low-density lipoprotein (ox-LDL) to induce pyroptosis in human umbilical vein endothelial cells (HUVECs) and investigated the effect of this process. The study revealed that ox-LDL induced HUVEC pyroptosis in a concentration-dependent manner, resulting in Na + and Ca 2+ overload, lysosomal damage, and increased CTSB release into the cytosol. Lentiviral vectors were used to overexpress or silence CTSB; subsequent analysis revealed that CTSB promotes NLRP3-mediated pyroptosis through nuclear factor κB (NF-κB) activation. Finally, we found that DAPA attenuated HUVEC pyroptosis by inhibiting the NF-κB/NLRP3 pathway and decreasing the expression of CTSB. This effect may be attributed to its ability to alleviate lysosomal damage caused by Na + -Ca 2+ overload, thereby reducing CTSB release into the cytosol., 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.)

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a crucial signaling adaptor involved in multiple cellular events. However, its role in regulating osteoclastogenesis and energy metabolism remains unclear. Here, we report that TRAF1 promotes osteoclastogenesis and oxidative phosphorylation (OXPHOS). Employing RNA sequencing, we found that TRAF1 is markedly upregulated during osteoclastogenesis and is positively associated with osteoporosis. TRAF1 knockout inhibits osteoclastogenesis and increases bone mass in both normal and ovariectomized adult mice without affecting bone mass in childhood. Furthermore, TRAF1 promotes osteoclast OXPHOS by increasing the phosphorylation level of AKT. Mechanistically, TRAF1 functions to inhibit TRAF2-induced ubiquitination of Gβl, a known activator of AKT, and further upregulates AKT phosphorylation. Rescue experiments revealed that the inhibitory effects of TRAF1 knockout on osteoclastogenesis, OXPHOS, and bone mass are dependent on AKT. Collectively, our findings uncover a previously unrecognized function of TRAF1 in regulating osteoclastogenesis and energy metabolism, and establish a novel TRAF1-AKT-OXPHOS axis in osteoclasts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: In China, motor vehicles and non-motorized vehicles (bicycles or e-bikes) are the most common modes of transportation. However, individuals with epilepsy may face significant challenges and barriers when using these modes of transportation. This study aims to assess the current status and challenges faced by people with epilepsy in terms of transportation., Methods: From September 2022 to September 2023, a cohort of patients with a previous diagnosis of epilepsy was invited to complete a self-administered questionnaire during their visit to Huashan Hospital, Fudan University. The questionnaire focused on understanding the transportation habits of Chinese patients with epilepsy, their perceptions regarding travel, and their specific transportation needs., Results: A total of 243 patients participated in the study. Of those, 86 (35.3 %) patients used motor vehicles as one of their main modes of transportation and 133 (54.7 %) patients used non-motorized vehicles as one of their primary modes of transportation. Additionally, 117 (48.1 %) patients reported being aware of laws pertaining to transportation for individuals with epilepsy, primarily through the Internet and consultations with their healthcare providers. Patients with fewer seizures per year were more likely to travel primarily use motor vehicles (RR = 1.364, 95 % CI:1.139-1.633, p < 0.001), and those who were aware of the epilepsy-related transportation laws were less likely to use motor vehicles (RR = 0.644, 95 % CI:0.462-0.898, p = 0.010)., Conclusion: In China, both motor vehicles and non-motorized vehicles are commonly used by individuals with epilepsy. However, people with epilepsy still do not have enough knowledge about the relevant laws, so the advocacy of medical professionals may make an important contribution to improve the legal knowledge of patients and promote traffic safety. Furthermore, the social issue of individuals with epilepsy driving non-motorized vehicles warrants further investigation, encompassing medical, legal, infrastructure, and public policy perspectives to ensure the safety and mobility of patients., 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 Elsevier Inc. All rights reserved.)

The redox imbalance induced by excessive reactive oxygen species (ROS) contributes to senescent phenotypes of chondrocytes in osteoarthritis (OA). However, there is limited evidence regarding the involvement of NADPH oxidase-4 (NOX4)/NFE2-related factor 2 (Nrf2) redox imbalance in OA. Isoquercetin (IQ), a quercetin derivative, exhibits promising antioxidative and anti-aging properties. Here, we found that IQ promoted redox homeostasis by inhibiting NOX4 and activating Nrf2-mediated antioxidant responses, thereby ameliorating OA. Specifically, IQ significantly suppressed the expression of senescence-associated secretory phenotypes (SASPs) in senescent chondrocytes. RNA sequencing analysis revealed that cellular senescence and oxidative stress were involved in the mechanism of IQ's effect on senescent chondrocytes. IQ effectively reversed redox imbalance, as evidenced by reduced levels of ROS and endogenous oxidants, and increased mitochondrial membrane potential and, elevated levels of endogenous antioxidants. Mechanistically, the elevated expression of NOX4 observed in patients with severe OA confirms its role in OA pathogenesis. Molecular docking and NOX4 knockdown experiments suggested that IQ may interact with NOX4 and inhibit its expression. This study identifies a potential therapeutic target and provides a promising candidate for OA treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in this work., (Copyright © 2025. Published by Elsevier B.V.)

MicroRNA (miRNA) is involved in the genesis in viand development of colorectal cancer. The in vivo imaging of miRNA at the tumor sites is essential for understanding its role in colorectal cancer pathology and therapeutic target identification. However, achieving accurate imaging of miRNA at the tumor sites is hindered by the low abundance of miRNAs in tumor cells and nonspecific signal leakage in normal tissues. Here, we report a multivariate-gated catalytic hairpin assembly (CHA) nanosensor for the specific amplified imaging of microRNA-21 (miR-21) in human colorectal cancer tissues to reveal the underlying miR-21-associated molecular mechanism. The endogenous glutathione and exogenous near-infrared multivariate-gated design in combination with CHA probes improves the signal strength of target miR-21 and reduces the background interference. The nanosensor enables specific amplified imaging of miR-21 in vivo, and the signal-to-background ratios are 1.6-fold compared with traditional CHA methods. With the assistance of the designed nanosensor, we achieve the preliminary identification of tumor tissues and normal tissues from human clinical surgical resection samples. The overexpressed miR-21 is found to suppress the core mismatch repair recognition protein human mutS homologue 2 involved in DNA damage recognition and repair to inhibit the therapeutic efficacy of colorectal cancer. The strategy of probe design, which combines multivariate-gated activation methods with a signal amplification system, is applicable for accurate miRNA imaging and disease-relevant molecular mechanism research.

Objectives: Genetics significantly impact systemic lupus erythematosus (SLE) risk, disease manifestations, and damage. Our aim was to identify genetic risk loci for disease activity burden over time., Methods: We included participants from a tertiary care Lupus Clinic. Participants met ACR and/or SLICC classification criteria for SLE, were genotyped on one of three arrays, and had > =3 measures of disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) to derive adjusted mean SLEDAI-2K and glucocorticoid scores (AMSG). We completed a genome-wide association study (GWAS) of AMSG, adjusted for sex and 5 PCs, and stratified by array, then meta-analyzed GWAS (P < 5x10-8). Meta-GWAS results were used in colocalization analyses with expression quantitative trait loci in multiple tissues. In a subset of patients, we examined the association between the top SNP for AMSG and interferon-stimulated gene expression., Results: The cohort included 538 individuals with SLE (88% female), with a median age at diagnosis of 30.7 years (IQR = 23.3, 41.7 years). Most patients (75%) had a first clinic visit within 1 year of SLE diagnosis and were followed for a mean of 4.5 years (SD = 0.95). The median AMSG was 5.5 (Q25, Q75 = 3.2,8.8). Meta-GWAS identified a genome-wide significant SNP for AMSG (rs4561613) on chromosome 2, intronic to AGAP1 (Beta = 0.34, SE = 0.06, p = 4.16x1 0 -9). Colocalization analysis did not identify a significant difference in gene expression for the top SNP. Interferon gene scores were significantly associated with AMSG (Beta = 0.02, SE = 8.70x10-3, p = 0.006)., Conclusion: We identified a genome-wide significant locus intronic to AGAP1 for SLE disease activity burden as measured by AMSG., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Nitrate pollution in terrestrial and aquatic ecosystems in global agricultural areas poses an environmental concern. However, there is limited understanding of hydrogeological controls on the behavior of nitrogen compounds in unsaturated zones. Here, Self-Organizing Map and multiple isotopes approaches (δ 15 N-NO 3 - , δ 18 O-NO 3 - , and δ 15 N-NH 4 + ) were used to investigate the sources, transport and transformation of N-species in the unsaturated zone in an alluvial-lacustrine plain, southeast China. The results revealed significant spatial heterogeneity in soil texture and physicochemical properties with vertically four soil geochemical and N-species zones (high NO₃⁻, high Fe(Ⅲ) and Mn, low ionic, and high NH₄⁺ contents), dominated by agricultural input, soil minerals and redox conditions. Nitrate in the unsaturated zone primarily originated from fertilizers and soil nitrogen. Excess nitrogen fertilizers infiltrated into the soil, where mineralization, nitrification, and dissimilatory nitrate reduction to ammonium (DNRA) acted as key mechanisms for nitrogen transformation. The change in the depositional environment from the plain to the lakeshore area led to nitrification gradual decrease and DNRA significant increase. Consequently, a conceptual model of reactive transport of N-species, influenced by hydrogeologic conditions and biogeochemical processes, was proposed. This study provides a new insight into the nitrate behaviors in unsaturated zone and contributes to groundwater nitrogen management strategies., 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 Elsevier B.V. All rights reserved.)

Nitrous oxide (N 2 O) emissions from paddy soils, particularly from the rice rhizosphere, significantly contribute to agricultural greenhouse gas outputs. This study explores N 2 O emission dynamics in rhizosphere (R) and non-rhizosphere (NR) soils from two distinct paddy types (JR and YC) during the primary rice growth stages (tillering, jointing, heading, and grain-filling). Cumulative N 2 O emissions were measured at 688.56, 762.90, 831.20, and 1072.32 µg N kg -1 for JR-NR, JR-R, YC-NR, and YC-R, respectively. Notably, JR-R and YC-R exhibited increases in cumulative N 2 O emissions by up to 20.04% and 28.23%, respectively, compared to their NR counterparts at different growth stages. These enhanced emissions were primarily associated with microbial genera Nitrosospira and Nitrosospirae , and influenced by factors such as electrical conductivity (EC) and available potassium (AK). The soil organic carbon to total nitrogen ratio (C/N) was a key determinant influencing Nitrosospira abundance. Additionally, nitrification inhibitors (NIs) demonstrated a substantial reduction in N 2 O emissions, with a decrease of 92.37% in JR-R and 91.93% in YC-R at selected growth stages, showing more pronounced effects compared to NR soils. These findings highlight the efficacy of NIs in significantly mitigating N 2 O emissions, particularly in rhizosphere soils. Variations in the efficiency of NIs across different soil types and growth stages suggest that optimizing application timing and developing tailored soil-specific strategies could further enhance the effectiveness of NIs in mitigating N 2 O emissions from paddy fields. This research provides essential insights for developing targeted mitigation strategies to reduce N 2 O emissions in rice cultivation and contributes to sustainable agricultural practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhang, Lu, Li, Liao, Wang, Zhang and Yang.)

Chinese bayberry ( Myrica rubra or Morella rubra ) is a valuable fruit, yet the mechanism of its flesh segment development is not well understood. Using paraffin sectioning, we investigated the flower buds of the 'Biqi' and 'Zaojia' varieties, revealing that the flesh segment development in these Chinese bayberry varieties involved the formation of a primordium outside the ovary wall, the establishment of a simple columnar structure, and the formation of the primary flesh segment. Assessment of endogenous hormone levels indicated the significant reductions in jasmonic acid (JA) and indole-3-acetic acid (IAA) levels at the critical stages of flesh segment development. Correlation analysis highlighted the essential roles of IAA, JA, abscisic acid (ABA), and gibberellins in the flesh segment developmental process, underscoring the complex interactions driven primarily by the IAA, JA, and ABA networks. Gene modules positively correlated with flesh segment development were identified using transcriptome-based weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) were enriched in plant hormone signal transduction pathways, particularly for upregulated genes associated with auxin and JA signaling. Key genes predicted to be involved in flesh segment development included LAX2 and LAX3 (auxin transport), JAZ6 (JA signaling repression), and KAN1 and KAN4 (regulating multiple hormonal signaling pathways). Quantitative real-time polymerase chain reaction (qRT-PCR) validation confirmed that the expression trends for these genes were consistent across both varieties, particularly for CRC , SEP1 , SEP3 , IAA7 , and JAZ6 . Immunofluorescence localization studies revealed that auxin was primarily distributed in the central vascular bundle and outer cells of the flesh segment. This uneven auxin distribution might contribute to the unique morphology of flesh segments. Overall, this study provides insights into the hormonal regulation and genetic factors involved in the development of Chinese bayberry flesh segments.

Cuproptosis, a newly suggested mechanism of controlled cellular demise, which has been extensively associated with aspects of occurrence and development in breast cancer. The aim of this study was to conduct a comprehensive multi-group bioinformatics analysis based on the expression of cuproptosis-related genes (CRGs) to identify novel breast cancer subtypes to guide clinical practice. We collected TCGA-BRCA and GSE42568 datasets to investigate the expression patterns of CRGs in breast cancer. Consensus cluster analysis was performed to identify distinct subtypes. Subsequently, an investigation was carried out to examine the disparities between CRGclusters through functional enrichment analysis. Finally, we examined microsatellite instability, tumor mutation burden, drug sensitivity, infiltration of immune cells and cancer cell stemness across different CRGclusters. We identified two subtypes, where CRGcluster S2 exhibits a poorer prognosis compared to CRGcluster S1. Moreover, CRGcluster S2 demonstrated lower immune infiltration scores, higher cancer cell stemness index, and increased tumor mutation burden relative to CRGcluster S1, with the most frequently mutated gene being ATP7A. Notably, breast cancer chemotherapy drugs such as docetaxel, doxorubicin, and paclitaxel exhibited reduced sensitivity towards CRGcluster S2 when compared to CRGcluster S1. We have identified two CRGclusters in breast cancer that could serve as potential therapeutic targets and warrant further investigation in clinical trial studies for breast cancer., Competing Interests: Declarations. Ethics approval and consent to participate: The samples utilized in this study were obtained from publicly available online databases, thus exempting the need for ethical approval. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Pulsed electromagnetic fields (PEMFs) therapy was extensively investigated to treat wound healing, which is a highly metabolically demanding process. However, the effect of PEMFs on energy metabolism in wound healing remains largely unexplored. Therefore, our study aims to demonstrate the role of PEMFs on energy metabolism in wound healing., Methods: Scratch-wound healing assay and cell viability assay were performed for the in vitro study of the effect of PEMFs on cell migration and viability. Seahorse assay was conducted for energy metabolism analysis while holo-tomographic microscopy for fine changes of L929 cells. Mitochondrial membrane potential assay and intracellular reactive oxygen species (ROS) and pH assay were performed for analyzing the changes of mitochondrial function., Results: PEMFs with specific parameter (4mT, 80 Hz) promoted cell migration and viability. Glycolysis stress and mitochondria stress test revealed that PEMFs-exposed L929 cells was highly glycolytic for energy generation. Besides, PEMFs enhanced intracellular acidification and maintained low level of intracellular ROS in L929 cells. Compared to control group, much more vesicles were generated and then transported to regions close to the nuclear in L929 cells treated with PEMFs., Conclusions: Our major findings revealed for the first time that PEMFs induce metabolic reprogramming of fibroblast shifting from mitochondrial respiration to glycolysis, accompanied with an increase of vesicular transport, which is closely related to wound healing in vitro., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cerebral malaria (CM) is a severe encephalopathy caused by Plasmodium parasite infection, resulting in thousands of annual deaths and neuro-cognitive sequelae even after anti-malarial drugs treatment. Despite efforts to dissect the mechanism, the cellular transcriptomic reprogramming within the spatial context remains elusive. Here, we constructed single-cell and spatial transcriptome atlases of experimental CM (ECM) male murine brain tissues with or without artesunate (ART) treatment. We identified activated inflammatory endothelial cells during ECM, characterized by a disrupted blood-brain barrier, increased antigen presentation, and leukocyte adhesion. We also observed that inflammatory microglia enhance antigen presentation pathway such as MHC-I to CD8 + cytotoxic T cells. The latter underwent an inflammatory state transition with up-regulated cytokine expression and cytotoxic activity. Multi-omics analysis revealed that the activated interferon-gamma response of injured neurons during ECM and persisted after ART treatment. Overall, our research provides valuable resources for understanding malaria parasite-host interaction mechanisms and adjuvant therapy development., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Iridium (Ir) is recognized to have extremely high catalytic activity in the hydrogen evolution reaction (HER). However, there are still technical challenges in maximizing the utilization of Ir atoms in the catalytic reaction process through dimensional regulation strategies. Herein, an innovative strategy is utilized to fabricate porous phosphorus-doped iridium (P-Ir) with a 2D structure, specifically the reduction of 1T phase-IrO 2 (1T-IrO 2 ) nanosheets using phosphine gas. The optimized P-Ir achieves an overpotential of 17.2 mV (vs RHE without iR-correction) in 0.5 m H 2 SO 4 during the HER process, outperforming benchmark Pt/C (27.0 mV) and most reported Ir-based electrocatalysts. During the long-term stability tests, P-Ir maintains stable operation for more than 100 h at both -10 and -100 mA cm -2 , respectively. Moreover, the HER activity and transient potential scanning results of Ir-based phosphides prove that doping P atoms in the Ir lattice promotes the reaction kinetic rate and charge transport capacity during hydrogen evolution. Theoretical calculations reveal that P atoms doping weakens the adsorption energy of H intermediates (H*) by regulating the d-band center of the Ir sites. Simultaneously, the desorption process of H* is also facilitated by forming a special bridged-H* bond structure, eventually accelerating the HER kinetics., (© 2025 Wiley‐VCH GmbH.)

Ethnopharmacological Relevance: Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI)., Aim of the Study: This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice., Materials and Methods: FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1β, IL-6, TNF-α through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages., Results: FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus., Conclusion: Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome., 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 © 2024. Published by Elsevier B.V.)

This study reports a novel ratiometric fluorescence sensor based on a tetraphenylethylene-bipyridine covalent organic framework (TPE-Bpy-COF) for the sensitive detection of Cu 2+ , leveraging the unique coordination properties of the bipyridine moieties. The interaction between Cu 2+ and the nitrogen atoms in the bipyridine units induces fluorescence quenching at 500 nm through an efficient host-guest electron transfer mechanism, where excited-state electrons from the COF framework are transferred to the vacant orbitals of Cu 2+ . Upon excitation at 410 nm, the sensor exhibits a primary emission peak at 500 nm, which is quenched in the presence of Cu 2+ , while an overtone peak at 820 nm remains stable, serving as an internal reference for ratiometric measurements and significantly enhancing the accuracy and reliability of the sensor. The detection limit for Cu 2+ is 0.1 μM, with the dual-emission system and the strong affinity of the bipyridine units for Cu 2+ , further improving the sensor's sensitivity and selectivity. Additionally, the sensor demonstrated excellent recovery rates in real water samples, confirming its practical applicability in environmental monitoring.

How pathogens inhibit transplant tolerance remains unclear. Here, we found that Pseudomonas aeruginosa infection, but not other common bacterial respiratory infections, increases antibody-mediated rejection (AMR) risk in recipients of lung transplants. To explore this relationship, we performed orthotopic lung transplants in mice, infected recipients with P. aeruginosa , and observed for the development of AMR. Intravital two-photon microscopy showed that P. aeruginosa rapidly invaded bronchial-associated lymphoid tissues, which resulted in acute lymphocytotoxicity, including the death of forkhead box P3 (Foxp3) + CD4 + T cells that are required to suppress AMR. P. aeruginosa -mediated AMR required expression of the type III secretion system (T3SS), which injects exotoxins into the cell cytoplasm. Through a combination of mutagenesis and epitope tagging experiments, we revealed that T3SS exotoxin T ADP ribosyl-transferase activity was sufficient for graft-resident Foxp3 + CD4 + T cell apoptosis, leading to myeloid differentiation primary response 88 (Myd88)-dependent generation of T-box expressed in T cells (T-bet)- and C-X-C motif chemokine receptor 3 (CXCR3)-positive germinal center and memory B cells with high donor antigen avidity. We also found that T-bet + and CXCR3 + B cells were elevated in biopsies from recipients of lung transplants who were diagnosed with AMR. In mice, CXCR3 deficiency restricted to B cells or CXCR3 blockade prevented AMR despite P. aeruginosa infection. Our work has identified a previously unrecognized role of bacterial virulence in lung allograft rejection and suggests potential strategies to prevent AMR for those at high risk of P. aeruginosa infection after transplant.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with different immunophenotypes, morphological features, clinical presentations, and outcomes. Therefore, the diversity of NENs can easily confuse clinicians and lead to misdiagnosis. This article reports a case of a rectal NEN (r-NEN) growing within a lipoma with ulcerative lesions, which had been mistaken for rectal cancer. Fortunately, an experienced surgeon questioned the initial diagnosis (rectal cancer) after combining the results of a colonoscopic biopsy and the digital anorectal examination, thus enabling the patient to avoid unnecessary surgery. Through the review of this case and relevant literature, we further analyze the growth pattern of NENs and lipomas. Additionally, we hope to enhance clinicians' awareness of a NEN that grew insidiously within a lipoma with surface ulcerative lesions, to make accurate diagnoses and treatments in time., Competing Interests: Declarations. Conflict of interest: X. Zhang, H. Duan, S. Yue, L. Gong and F. Liao declare that they have no competing interests. Ethical standards: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Purpose: Shear-induced platelet activation and aggregation (SIPA) play crucial roles in arterial thrombosis. Piezo1 is a mechanosensitive calcium channel that promotes platelet hyperactivation under pathological high-shear conditions. This study explores the function of platelet Piezo1 in SIPA and arterial thrombosis, and the inhibitory effects and mechanisms of ginsenoside Rb1 on these processes., Experimental Approach: Transgenic mice with platelet-specific Piezo1 deficiency (Piezo1 ΔPlt ) were used to elucidate the role of platelet Piezo1 in SIPA and arterial thrombosis. A microfluidic channel system was employed to assess platelet aggregation, calcium influx, calpain activity, talin cleavage, integrin αIIbβ3 activation and P-selectin expression under shear flow. Cellular thermal shift assay was used to determine binding between Rb1 and Piezo1. Folts-like model in mice was used to evaluate antithrombotic effects of Rb1., Key Results: Piezo1 deficiency in platelets reduced platelet activation and aggregation induced by a high shear rate of 4000 s -1 and attenuated arterial thrombosis induced by Folts-like mouse model. Rb1 inhibited SIPA with an IC 50 of 10.8 μM. Rb1 inhibited shear-induced Ca 2+ -dependent platelet activation and aggregation, as well as thrombus formation in Folts-like model in Piezo1 fl/fl mice. Rb1 significantly improved thermal stability of Piezo1 in platelets by binding to Piezo1. Treatment of Piezo1 ΔPlt mice with Rb1 did not exhibit further inhibitory effects on SIPA and thrombosis., Conclusion and Implications: Platelet Piezo1 is essential for SIPA and arterial thrombosis induced by high shear. Rb1 exerted anti-platelet and anti-thrombotic effects at high shear rates via Piezo1 channels, providing a potential candidate as antiplatelet therapeutic agent., (© 2025 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The intrinsic performance of an electrocatalyst can be reinforced by constructing appropriate epitaxial interfaces, where the modulated electronic states and adsorption/desorption behaviors are conductive to enhancing electrocatalytic activity. Herein, nickel-nickelous hydroxide epitaxial interface supported on nickel foam (Ni-Ni(OH) 2 /NF) with epitaxial growth of nickel nanoparticles on the surface of nickelous hydroxide nanoribbons is devised for alkaline hydrogen evolution reaction (HER). Notably, the Ni-Ni(OH) 2 /NF reveals excellent electrocatalytic activity of alkaline HER (158 mV @ 100 mA cm -2 ), along with robust stability (90 % activity retention after 150 h continuous test at 200 mA cm -2 ). Theoretical simulations disclose the tuned interface electronic structure and accelerated water dissociation around the epitaxial nickel-nickelous hydroxide interface result in efficient electrochemical activity toward alkaline hydrogen evolution., 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 © 2024 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) exert critical functions in colorectal cancer development. In this work, we wanted to elucidate the functional role and regulatory mechanism of circ&#95;0007351 in colorectal cancer. For quantification of circ&#95;0007351, microRNA (miR)-5195-3p and G Protein-coupled receptor class C group 5 member A (GPRC5A), a qRT-PCR, immunoblotting or immunohistochemistry assay was performed. Effects of circ&#95;0007351/miR-5195-3p/GPRC5A cascade were evaluated by determining cell viability, proliferation, colony formation, motility, and invasion. Relationships among variables were assessed by dual-luciferase reporter assay. Animal studies were performed to evaluate circ&#95;0007351's function in the growth of xenograft tumors. Circ&#95;0007351 was markedly up-regulated in colorectal cancer tissues and cells. Down-regulation of circ&#95;0007351 hindered cell growth, migration and invasiveness. Also, circ&#95;0007351 depletion exerted a suppressive function in colorectal cell xenograft growth in vivo. Mechanistically, circ&#95;0007351 sponged miR-5195-3p to sequester miR-5195-3p. Reduction of available miR-5195-3p neutralized the effects of circ&#95;0007351 down-regulation on cell phenotypes. MiR-5195-3p directly targeted and inhibited GPRC5A. Circ&#95;0007351 regulated GPRC5A expression by sponging miR-5195-3p. Moreover, the effects of circ&#95;0007351 down-regulation on cell functional phenotypes were due to in part the reduction of GPRC5A expression. Our findings show that circ&#95;0007351 down-regulation impedes proliferation, motility, and invasiveness in colorectal cancer cells at least in part via the regulation of the miR-5195-3p/GPRC5A cascade, highlighting that circ&#95;0007351 inhibition may have a potential therapeutic value for colorectal cancer., Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The clinical efficacies of Ulcerative colitis (UC) are far from satisfactory. Fucoxanthin (FUC) is a marine carotenoid that is abundant in seaweed and microalgae. It has been reported that FUC can possess anti-inflammatory and antioxidant. However, its mechanism and role in UC is yet to be clarified. This study aimed to investigate the protective effect and potential mechanism of FUC extracted from the diatom Phaeodactylum tricornutm on dextran sodium sulfate (DSS) -induced colitis., Methods: Animal UC model was induced by DSS and cellular model was established by TNF-α. Immunohistochemical staining, Western blot, RT-qPCR, and immunofluorescence were used to assess the inflammatory responses and epithelial barrier in vivo and in vitro models., Results: The results showed that FUC attenuates DSS-induced colitis by ameliorating the epithelial mucosal barrier. Moreover, FUC possessed antioxidant and anti-inflammatory effects on NCM460 cells. JAK/STAT activator RO8191 could reverse these changes., Conclusion: FUC exerted anti-inflammatory and antioxidant effects via the JAK2/STAT3 signaling pathway, and served as a potential therapeutic agent for the treatment of UC., 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 © 2024. Published by Elsevier Inc.)

Although photodynamic therapy (PDT) has great potential for treating severely infected wounds, it is restricted by the short lifetime, limited diffusion distance of reactive oxygen species (ROS), and incomplete contact with bacteria. Herein, we report a novel nanosized ionic porous organic polymer (TPAPy-IPOP) based on the triphenylamine (TPA) moiety. Strong electron-deficient cationic groups were introduced into TPA to construct the donor-acceptor (D-A) system, in which the photoelectric effect of TPAPy-IPOP was greatly enhanced, and it was easily excited to produce ROS under irradiation with visible light. The introduction of cations not only facilitated bacterial adsorption by TPAPy-IPOP via electrostatic attraction, which was more conducive to killing bacteria by ROS, but also inactivated bacteria by the cations directly. The nanosized TPAPy-IPOP remained suspended in water for several months and could be sprayed onto various substrates to form a durable coating with excellent antibacterial properties. The in vivo results proved that the silk fibroin/polyvinyl alcohol non-woven fabric (SF/PVA) coated with TPAPy-IPOP could create and maintain a sterile microenvironment at a wound site. The rapid reduction in inflammation resulting from its bactericidal action accelerated the wound healing rate. Collectively, this design is expected to offer a generalizable approach for developing novel antibacterial therapeutic photosensitizers, especially for infected wound treatment., 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 © 2024 Elsevier Inc. All rights reserved.)

The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood. SARS-CoV-2 N protein mutations were analyzed in Delta, Omicron, and original strains. Two mutations with a methionine (M) residue at site 203 and a tyrosine (Y) residue at site 377 of the N protein were found in Delta strain but not in Omicron and original strains, and promoted SARS-CoV-2 infection therein. Those mutations, R203M and D377Y, enhanced the inhibitory impact of N protein on the impairment of RIG-I-mediated antiviral signaling, such as IRF3 phosphorylation and IFN-β activation. The viral RNA-binding activity of N protein was promoted by these mutations, effectively attenuating the recognition and interaction of RIG-I with viral RNA compared to the original or other variants. The R203M/D377Y mutations thus enhanced the suppressive activity of the N protein on RIG-I-mediated interferon induction both in vitro and in vivo, which in turn promoted viral replication. This study helps to understand the variability of SARS-CoV-2 in regulating host immunity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Remote photoplethysmography (rPPG) achieves non-contact heart rate monitoring by detecting subtle skin color variations in facial videos, offering significant potential in healthcare, fitness, and security applications.However, accurately extracting rPPG signals in complex environments-especially under variable lighting and motion artifacts-remains challenging. The main difficulties are capturing spatio-temporal dynamics and modeling long-term dependencies across channels. To address these limitations, we propose MaKAN-Mixer, a novel end-to-end network designed to enhance the robustness and accuracy of rPPG signal extraction. First, MaKAN-Mixer integrates a Hybrid of Eulerian Video Magnification and Temporal Shift Module Amplification (HETA) to amplify subtle physiological signals and enhance temporal information without relying on explicit region-of-interest (ROI) selection. Additionally, we propose the Mamba-KAN Fusion Module (MKFM), which leverages Mamba's ability to efficiently model long-term dependencies in temporal sequences. By incorporating the Kolmogorov-Arnold Network (KAN) for effective channel mixing, MKFM ensures the comprehensive fusion of relevant spatio-temporal features across different channels. Finally, we employ a KAN Feedforward Neural Network (KFN) to capture complex, nonlinear, and periodic physiological patterns, improving heart rate estimation. Extensive experiments conducted on four benchmark datasets demonstrate that MaKAN-Mixer achieves superior performance in both intra- and cross-dataset testing, exhibiting exceptional robustness in challenging scenarios, particularly with compressed video data and complex environments. In comparison to the best-performing existing method, which reported RMSE values of 0.78/0.47/4.57/6.81 on the four datasets, MaKAN-Mixer significantly improves the RMSE to 0.66/0.40/0.32/6.25, highlighting its effectiveness across diverse conditions. Furthermore, novel visualization techniques were employed for qualitative validation of the results, underscoring its potential for accurate, real-world rPPG monitoring.

Background: Ambient artificial intelligence offers promise for improving documentation efficiency and reducing provider burden through clinical note generation. However, challenges persist in workflow integration, compliance, and widespread adoption. This study leveraged a Learning Health System (LHS) framework to align research and operations using a hybrid effectiveness-implementation protocol, embedded as pragmatic trial operations within the electronic health record (EHR)., Methods: An alpha phase was conducted to pilot technical integration, refine workflows, and determine sample size in planning for a beta phase designed as a pragmatic randomized controlled trial with the Stanford Professional Fulfillment Index (PFI) as primary outcome. During alpha, bi-directional governance was established between IS operations and LHS team with multidisciplinary workgroups for analytics, technical, documentation, and user experience. Ambient AI was embedded into the EHR using Fast Healthcare Interoperability Resources (FHIR), with real-time data dashboards tracking utilization and documentation accuracy for operations and research. Performance metrics were monitored serially using a difference-in-differences (DiD) analysis to detect drift caused by software workflow changes., Results: The alpha phase, designed as Type 1 Hybrid, informed a 24-week beta phase stepped-wedge trial with 90% power to detect changes in PFI. Across the alpha phase, the weighted median of average provider Ambient AI utilization was 65.4% following Plan-Do-Study-Act cycles addressing organizational feasibility and task-dependent adoption. During initial implementation, a workflow issue caused discrepancies between ICD-10 diagnosis entries and note content, reducing accuracy from 79% to 35% (p < 0.01). After implementing a new note template and provider training, accuracy returned to pre-intervention levels. DiD did not detect significant drifts in work outside of work or time in notes two weeks before and after the new note template. Beta phase enrollment achieved its targeted 66 providers across eight specialties, initiating on schedule., Conclusions and Relevance: We provide a novel playbook for integrating Generative AI platforms in healthcare, combining pragmatic trial operations, human-centered design, and real-time monitoring to advance evidence-based implementation., Clinicaltrialsgov Id: NCT06517082.