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Abstract Traumatic brain injury (TBI) is one of the leading causes of disability and mortality, which was classified as low-altitude TBI and high-altitude TBI. A large amount of literature shows that high-altitude TBI is associated with more severe neurological impairments and higher mortality rates compared to low-altitude TBI, due to the special environment of high-altitude hypoxia. However, the role of high-altitude hypoxia in the pathogenesis of TBI remains unclear. In order to deeply investigate this scientific issue, we constructed a high-altitude hypoxic TBI model at different altitudes and used animal behavioral assessments (Modified neurological severity score, rotarod test, elevated plus maze test) as well as histopathological analyses (brain gross specimens, brain water content, Evans blue content, hypoxia inducible factor-1α, Hematoxylin-Eosin staining and ROS detection) to reveal its underlying principles and characteristics. We found that with higher altitude, TBI-induced neurological deficits were more severe and the associated histopathological changes were more significant. Single-nuclear RNA sequencing was subsequently employed to further reveal differential gene expression profiles in high-altitude TBI. We found a significant increase in ferroptosis of astrocytes in cases of high-altitude TBI compared to those at low-altitude TBI. Analyzing transcription factors in depth, we found that Bach1 plays a crucial role in regulating key molecules that induce ferroptosis in astrocytes following high-altitude TBI. Down-regulation of Bach1 can effectively alleviate high-altitude TBI-induced neurological deficits and histopathological changes in mice. In conclusion, high-altitude hypoxia may significantly enhance the ferroptosis of astrocytes and aggravate TBI by up-regulating Bach1 expression. Our study provides a theoretical foundation for further understanding of the mechanism of high-altitude hypoxic TBI and targeted intervention therapy.

Abstract Background Tertiary lymphoid structures (TLS) correlate with tumour prognosis and immunotherapy responses in gastric cancer (GC) studies. However, understanding the complex and diverse immune microenvironment within TLS requires comprehensive analysis. Methods We examined the prognostic impact of TLS within the tumour core (TC) of 59 GC patients undergoing immunotherapy. Multispectral fluorescence imaging was employed to evaluate variations in immune cell infiltration across different TLS sites among 110 GC patients, by quantifying immune cell density and spatial characteristics. We also generated a single-cell transcriptomic atlas of TLS-positive (n = 4) and TLS-negative (n = 8) microenvironments and performed spatial transcriptomics (ST) analysis on two samples. Results TLS presence in the TC significantly correlated with improved immune-related overall survival (P = 0.049). CD8+LAG-3−PD-1+TIM-3−, CD4+PD-L1+, and CD4+FoxP3− T cell densities were significantly higher in the TLS within TC compared to tumour and stromal regions. Immune cells within TLS exhibited closer intercellular proximity than those outside TLS. Five key density and spatial characteristics of immune cells within TLS in the TC were selected to develop the Density and Spatial Score risk model. Single-cell RNA sequencing revealed strong intercellular interactions in the presence of TLS within the microenvironment. However, TLS-absent environment facilitated tumour cell interactions with immune cells through MIF- and galectin-dependent pathways, recruiting immunosuppressive cells. ST analysis confirmed that T and B cells co-localise within TLS, enhancing immune response activation compared to cancer nests and exerting a strong anti-tumour effect. Conclusions TLS presence facilitates frequent cell-to-cell communication, forming an active immune microenvironment, highlighting the prognostic value of TLS.

Abstract The reduction of cellular PD-L1 abundance through lysosomal degradation is recognized as essential for effective and sustained targeting of PD-L1-dependent immune evasion in cancer. While Hsc70 can interact with PD-L1 to promote its lysosomal degradation, the overexpression of CMTM6 competitively inhibits this interaction, leading to the blockade of PD-L1 lysosomal degradation. To overcome this issue, a meso chimeric peptide PEPPDL1 was designed to specifically bind the PD-1 binding domain of PD-L1 instead of the Hsc70/CMTM6 binding domain, while also binding to Hsc70 to facilitate the dragging of PD-L1 into Hsc70-mediated chaperone-mediated autophagy (CMA), thereby achieving lysosomal degradation. In order to enable internalization into tumor cells, supramolecular engineering techniques were employed through terminal modification involving sulfydryl and monovalent gold ion (Au(I)), both facilitating self-assembly of modified PEPPDL1 into supramolecular nanospheres termed CTAC-PDL1 driven by aurophilic interaction. Furthermore, based on bioinformatics analysis of mRNA expression data from 30 types of tumors obtained from TCGA database, malignant melanoma was identified as the most suitable indication for CTAC-PDL1 due to its specific characteristics of tumor immune. As expected, CTAC-PDL1 effectively reactivated Hsc70-mediated lysosomal degradation of PD-L1 and consequently restored anti-tumor T cell immunity in a B16F10-derived mouse model of malignant melanoma while maintaining a favorable safety profile. Overall, this work not only presents an alternative approach for targeting PD-L1-dependent cancer immune evasion, but also provides a modularized strategy for discovering specific regulators for target proteins in various diseases.

Highlights A three-dimensional multiscale liquid metal/polyacrylonitrile evaporator is fabricated through wet spinning and assembly. The evaporator exhibits an outstanding water evaporation rate of 2.66 kg m−2 h−1 with a solar energy efficiency of 96.5% under one sun irradiation. The evaporator demonstrates a superior purification performance for seawater and sewage under light irradiation.

As the eutrophication of the water body becomes more and more serious, the algae in the water body grow in large quantities and eventually form harmful algal blooms, causing great harm to the marine ecosystem. Therefore, how to quickly and accurately identify algae and make precautions becomes the key to solving this problem. Currently, more than tens of thousands of microalgae species are known around the world, but publicly available data are sparse, many of the species are characterized similarly to each other, and it is currently challenging to train an effective classification model with limited data. Existing few-shot learning classification algorithms that utilize meta-learning for metrics can be a good solution to this problem. In this paper, an AlgaeClass_Net algorithm that combines an improved multi-scale feature fusion with a feature enhancement module is proposed for the fine-grained features of microalgae. Furthermore, it utilizes a metric learning approach to classify few-shot microalgae by calculating the distances between the feature vectors of samples in the query set and the feature vectors of samples in the support set. The experimental results showed that the method achieves 78.55% and 91.20% classification accuracies under different tasks of 5-way 1-shot and 5-way 5-shot, respectively, with an improvement of 3.51% and 4.97% on the suboptimal model, respectively. It provides new research ideas for the identification of marine microalgae and the development and utilization of marine renewable energy.

Abstract Background Individuals with neurofibromatosis type 1 (NF1) frequently report psychosocial problems, among which internalizing and externalizing symptoms are the most poorly understood due to limited research and inconsistent evidence. This hinders the overall attendance of their psychosocial needs and has a major impact on their quality of life. Thus, this systematic review and meta-analysis was conducted to synthesize existing findings on the degree to which individuals with NF1 experience internalizing and externalizing symptoms, compared with the unaffected population, and explore moderators of the group disparities. Methods Scopus, PsycINFO, Web of Science, PubMed, and ProQuest were searched from inception to March 26th, 2024, which identified 59 eligible studies (N of NF1 = 3182, mean ages 2.38 to 46.4 years). Hedges’ g was calculated for differences in internalizing and externalizing symptoms between the NF1 group and the unaffected controls. Study effect sizes were pooled using robust variance estimation and random-effects models. Moderators of group differences were tested using meta-regression. Results Random-effects meta-analyses indicated that compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression. Conclusions Findings highlight the importance of promptly recognizing internalizing and externalizing symptoms in individuals with NF1 for timely interventions. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development. Other implications for future research were also discussed. Systematic review registration The study protocol of this meta-analysis was registered at PROSPERO (CRD42023478258).

Abstract Background Large language models (LLMs) are increasingly utilized in healthcare settings. Postoperative pathology reports, which are essential for diagnosing and determining treatment strategies for surgical patients, frequently include complex data that can be challenging for patients to comprehend. This complexity can adversely affect the quality of communication between doctors and patients about their diagnosis and treatment options, potentially impacting patient outcomes such as understanding of their condition, treatment adherence, and overall satisfaction. Materials and methods This study analyzed text pathology reports from four hospitals between October and December 2023, focusing on malignant tumors. Using GPT-4, we developed templates for interpretive pathology reports (IPRs) to simplify medical terminology for non-professionals. We randomly selected 70 reports to generate these templates and evaluated the remaining 628 reports for consistency and readability. Patient understanding was measured using a custom-designed pathology report understanding level assessment scale, scored by volunteers with no medical background. The study also recorded doctor-patient communication time and patient comprehension levels before and after using IPRs. Results Among 698 pathology reports analyzed, the interpretation through LLMs significantly improved readability and patient understanding. The average communication time between doctors and patients decreased by over 70%, from 35 to 10 min (P

Abstract Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but the underlying molecular interactions remain unclear. This study aims to identify the molecular mechanisms of ERS in AS pathogenesis to inform innovative diagnostic approaches and therapeutic targets for managing AS. GSE28829 and GSE43292—human early and advanced carotid atherosclerotic tissue samples—were obtained from the Gene Expression Omnibus database. Endoplasmic reticulum stress-related genes (ERSRGs) were obtained from GeneCards. Differential gene expression and weighted gene co-expression network analyses were conducted to identify genes associated with atherosclerosis, and intersection with ER-related genes revealed three ERSRGs (i.e. CTSB, LYN, and CYBB) associated with advanced atherosclerotic plaque. These three ERSRGs exhibited associations with various immune cells. Additionally, the three ERSRGs were upregulated in human atherosclerotic tissues, mouse models of progressive atherosclerotic lesions, and in vitro macrophage models. In conclusion, this study identified CTSB, LYN, and CYBB as potentially critical ERSRGs associated with advanced atherosclerotic plaque, demonstrating their good diagnostic utility and offering novel insights into the potential pathobiology of AS progression, paving the way for exploring innovative therapeutic targets.

Abstract Background Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29% of the cohort, which suggests pleural infection as the predominant etiology of pleural effusion in China. Medical thoracoscopy (MT) combined with intrapleural injection of Urokinase holds significant therapeutic value for patients with early to moderate-stage empyema. However, there remains a lack of high-quality evidence regarding the efficacy and safety of combining MT with intrapleural injection of Urokinase administration in patients with pleural infections. Methods This study is a prospective, multicenter, randomized controlled clinical trial involving patients with pleural infections. The intervention involves medical thoracoscopy. The control group receives conventional treatment involving intrapleural urokinase injection followed by chest tube placement for drainage. The study outcomes include efficacy and health economic benefits. The estimated minimum sample size for each group is 64 cases, totaling 128 cases. The study groups are delineated as follows: patients in group A receives intrapleural urokinase injection followed by chest tube placement for drainage, while patients in group B undergoes MT to remove multiple septa and necrotic tissue followed by chest tube placement for drainage, and then intrapleural urokinase injection the day after MT. It is recommended that the diameter of the chest tube be 12–14 F, with three daily flushes of 30 ml normal saline to ensure optimal drainage. Subsequently, comprehensive statistical analyses will be conducted to compare treatment effects and complications across all groups, ultimately leading to conclusive findings. Discussion The study is the first prospective, multicenter clinical trial on the efficacy and safety of medical thoracoscopy combined with intrapleural urokinase injection for the treatment of pleural infection. This study aims to offer clinical guidance for the management of pleural infection. Registration number ChiCTR2300078352 (Registration Date: 2023/12/06).

Abstract Research on the aetiology of neural tube defects (NTDs) has made progress in recent years. However, the molecular mechanism of apolipoproteins underlying NTDs development remains unclear. This study aimed to investigate the function of apolipoprotein M (ApoM) in the pathogenesis of NTDs and its underlying mechanisms. We demonstrated that ApoM expression was reduced in the spinal cord samples of rat models and human fetuses with NTDs respectively. Specifically, lack of ApoM resulted in reduced cytosolic localization of Elavl2 and caused Nnt mRNA degradation, which further led to impaired cell homeostasis by suppressing PINK1-PRKN-mediated mitophagy and promoting apoptosis and subsequent NTDs formation. Moreover, Zic3 directly interacted with the promoter of ApoM and activated its transcription. Lastly, intra-amniotic delivery of adenoviral recombinant Zic3 or ApoM could promote mitophagy and alleviate apoptosis in spinal cords of NTDs. Collectively, these findings highlight the important role of the Zic3-ApoM-Elavl2-Nnt axis in cellular homeostasis during neural tube development, thereby revealing an intracellular molecular regulatory mechanism of ApoM, providing a mechanistic basis for understanding embryonic neural development, and offering experimental evidence for potential therapeutic targets for NTDs.

Abstract Malignant pleural mesothelioma (MPM) is a rare form of thoracic malignancy with a poor prognosis. Pleural effusion (PE) occurs in the majority of patients with MPM; however, its impact on MPM outcomes remains controversial. We searched for eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database, and clinicopathological information and outcomes were collected. Cox proportional hazard regression analyses were utilized to evaluate the association of PE and other factors with overall survival (OS) and cancer-specific survival (CSS) in patients with MPM. A total of 4185 patients were extracted from the SEER database from 2000 to 2021. The median age of the cohort was 73 years, with a predominance of male patients and epithelioid MPM as the main histological subtype. Univariate Cox regression revealed associations between PE, age, sex, marital status, histology, stage, and treatment with both OS and CSS. Besides, multivariate analyses indicated that PE was independently associated with poorer OS and CSS in patients with MPM, regardless of age, sex, histology, stage, and treatment. Subgroup analyses suggested that PE has a remarkable impact on patients undergoing surgery. PE might serve as an independent prognostic factor in patients with MPM, especially in surgery recipients. Consequently, the development of pleural effusion in these patients should receive increased attention. Future studies are needed to validate these findings, particularly concerning the effect of PE in other clinical settings, such as immunotherapy.

Abstract Biochar and organic fertilizer substitution have been utilized to improve crop yields and promote sustainable agricultural development. However, few studies have focused on how biochar and organic fertilizer substitution regulate the diversities of bacterial meta-communities and sub-communities (i.e., habitat specialists and generalists) within soil aggregates on the Loess Plateau. A field experiment, containing six treatments, namely no fertilizer (CK), no fertilizer plus 104 kg ha−1 biochar (CK + B), traditional N fertilizer (TF, 150 kg N ha−1), traditional N fertilizer plus 104 kg ha−1 biochar (TF + B), organic fertilizer replacing (OF), and organic fertilizer replacing plus 104 kg ha−1 biochar (OF + B), was adopted to explore the influences of biochar and organic fertilizer substitution on the size distribution, nutrient levels, extracellular enzymatic stoichiometry, bacterial meta-community and sub-community diversities, structures, ecological networks, and assembly processes within bulk soil, large macro-aggregates (> 2 mm), small macro-aggregates (0.25–2 mm), and micro-aggregates (

Abstract Objective Depression is a common comorbidity in cardiovascular disease (CVD), and both conditions are associated with chronic inflammation. The systemic immune-inflammation index (SII) has emerged as a promising marker of systemic inflammation, but its role in association with depressive symptoms, particularly in the context of CVD, remains unclear. This study aims to investigate the association of SII with depressive symptoms in individuals with and without CVD using cross-sectional data from NHANES (2005–2016). Methods A total of 29,479 participants from the National Health and Nutrition Examination Survey (NHANES) 2005–2016 waves were included. Depressive symptoms were assessed through Patient’s Health Questionnaire (PHQ-9). SII was calculated as the platelet count × neutrophil count/lymphocyte count. In order to determine the relationships between SII and depressive symptoms in participants with and without CVD, binary logistic regression model and smooth curve fitting were used. We also performed sensitivity analyses and subgroup analysis. Results The total prevalence of depressive symptoms was 8.73% among the 29,479 participants analyzed. After adjusting for confounding factors, a higher SII was significantly associated with increased depressive symptoms in the total population (OR per SD increase: 1.101, 95% CI: 1.060–1.144, P

Kinases have a pivotal role in phosphorylation and kinase dysregulation has been implicated in the occurrence and progression of various diseases. By mid-2024 the Food and Drug Administration had approved 81 small-molecule kinase inhibitors targeting greater than 30 kinases, providing substantial clinical benefits for patients with cancer and other diseases. However, many reported kinase inhibitors exhibit poor target selectivity, limited solubility, and issues with drug resistance. To address these challenges medicinal chemists have used a macrocyclization strategy to optimize these molecules and three macrocyclic kinase inhibitors (lorlatinib [ALK/ROS1], pacritinib [Flt3/JAK2], and repotrectinib [TRK/ROS1]) have received FDA approval. The macrocyclization strategy is now widely used to enhance kinase inhibitory activity, overcome drug resistance caused by point mutations, improve kinase selectivity, and optimize drug-like properties. In this review we provide a comprehensive overview of the utilization of macrocyclization in the optimization of kinase inhibitors by detailing the structural modification process from lead compounds to macrocyclic molecules that has been applied in recent years. In addition, we discuss the limitations of existing macrocyclic kinase inhibitors and propose key considerations for the development of improved macrocyclic molecules. We aim for this review to offer valuable insights for future advances in kinase inhibitor development.

Abstract Acute Myeloid Leukemia (AML) with KMT2A rearrangements (KMT2Ar), found on chromosome 11q23, is often called KMT2A-rearranged AML (KMT2Ar-AML). This variant is highly aggressive, characterized by rapid disease progression and poor outcomes. Growing knowledge of epigenetic changes, especially lactylation, has opened new avenues for investigation and management of this subtype. Lactylation plays a significant role in cancer, inflammation, and tissue regeneration, but the underlying mechanisms are not yet fully understood. This research examined the influence of lactylation on gene expression within KMT2Ar-AML, initially identifying twelve notable lactylation-dependent differentially expressed genes (DEGs). Using advanced machine learning techniques, six key lactylation-associated genes (PFN1, S100A6, CBR1, LDHB, LGALS1, PRDX1) were identified as essential for prognostic evaluation and linked to relevant disease pathways. The study also suggested PI3K inhibitors and Pevonedistat as possible therapeutic options to modulate immune cell infiltration. Our findings confirm the critical role of lactylation in KMT2Ar-AML and identify six key genes that may serve as biomarkers for diagnosis and treatment. In addition to highlighting the need for further validation in clinical settings, these findings contribute to our understanding of KMT2Ar-AML’s molecular mechanisms.

Abstract Objectives To develop and validate the performance of CT-based radiomics models for predicting the prognosis of acute pancreatitis. Methods All 344 patients (51 ± 15 years, 171 men) in a first episode of acute pancreatitis (AP) were retrospectively enrolled and randomly divided into training (n = 206), validation (n = 69), and test (n = 69) sets with the ratio of 6:2:2. The patients were dichotomized into good and poor prognosis subgroups based on follow-up CT and clinical data. The radiomics features were extracted from contrast-enhanced CT. Logistic regression analysis was applied to analyze clinical-radiological features for developing clinical and radiomics-derived models. The predictive performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results Eight pancreatic and six peripancreatic radiomics features were identified after reduction and selection. In the training set, the AUCs of clinical, pancreatic, peripancreatic, radiomics, and combined models were 0.859, 0.800, 0.823, 0.852, and 0.899, respectively. In the validation set, the AUCs were 0.848, 0.720, 0.746, 0.773, and 0.877, respectively. The combined model exhibited the highest AUC among radiomics-based models (pancreatic, peripancreatic, and radiomics models) in both the training (0.899) and validation (0.877) sets (all p

Abstract Transient stability assessment (TSA) plays an important role in ensuring the reliable operation of power systems. With the popularity of phasor measurement units (PMUs), data‐driven TSA methods have been widely concerned. However, the performance of TSA model may deteriorate when data loss occurs due to PMU failure. This paper proposes an adaptive assessment method for transient stability of power systems considering PMU data loss. First, considering the importance of temporal features, a collection of PMU clusters is constructed to minimize the failure risk and maintain full observability of the whole buses of the grid. Secondly, a weighted integrated assessment model based on PMU clusters is constructed by using an improved eXplainable Convolutional neural network for Multivariate time series classification (XCM) as a TSA classifier. The model can make full use of time series information to carry out adaptive TSA and maintain the robustness of the assessment performance even when PMU failure occurs. Finally, it is verified in a modified IEEE 39‐bus system with wind power and solar power. The effect of the proposed method shows high accuracy and strong anti‐noise interference ability in case of data loss.

Abstract Aims The aim of this study was to explore whether continuous infusion causing lubrication can effectively alleviate pain during male urethral catheterization. Methods This prospective, multicenter, double-blinded study included 190 male patients scheduled for urethral catheterization. Patients were randomly allocated into four groups: Group A: the catheter was lubricated with paraffin; Group B: the catheter was lubricated with compound lidocaine gel; Group C: the pump continuously infusing with sterilized water; Group D: the pump continuously infusing with 2% lidocaine. The primary outcome was the visual analogue scale (VAS) scores. Statistical analysis system (SAS) (version 9.4) was used to perform all the statistical analyses. Significance for all results was set at P

Abstract Aim To evaluate the medication-related burden (MRB) of patients with late-life depression (LLD) and its influencing factors in China using the Living with Medicines Questionnaire-3 (LMQ-3), providing reference for reducing the MRB of those patients. Method A cross-sectional study was conducted between September 2023 and January 2024 on 588 patients with LLD. LMQ-3 and MRB factors questionnaire were used for data collection. The distribution of variables was assessed using descriptive analysis, while analyses of Mann-Whitney and Kruskal-Wallis were performed to evaluate inter-group differences. To explore the MRB among patients with LLD and influencing factors, multiple linear regression analysis was performed. Results The median (IQR) LMQ-3 score of 588 participants was 102 (18), indicating a moderate MRB level. Regression analysis revealed a significant trend toward higher perceived burden among patients aged 70–79 years old, living in rural areas, receiving more medical insurance settlements, using all cash, taking more than 5 drugs each time, and taking medicine more than 3 times a day (p

Abstract Background Intrauterine adhesion (IUA) is a common cause of clinically refractory infertility, and there exists significant heterogeneity in the treatment outcomes among IUA patients with the similar severity after transcervical resection of adhesion(TCRA). The underlying mechanism of different treatment outcomes occur remains elusive, and the precise contribution of various cell subtypes in this process remains uncertain. Results Here, we performed single-cell transcriptome sequencing on 10 human endometrial samples to establish a single-cell atlas differences between patients who responded to estrogen therapy and those who did not. The results showed increased infiltration of immune cells such as monocyte macrophages, T cells, and natural killer (NK) cells in patients who did not respond to estrogen therapy. Our findings indicate that distinct fibroblast subsets are implicated in the modulation of the Wnt, Hippo, and Hedgehog signaling pathways, as evidenced by functional enrichment analyses. This may have implications for the therapeutic efficacy in patients with IUA. Furthermore, we delineated the markers and transcriptional status of different macrophage subsets and identified two cell clusters, CXCL10high and CCL4L2high macrophage subsets, which are intimately associated with inflammation and fibrosis. The state of fibrosis and inflammatory response in human endometrial tissues with disparate treatment outcomes is revealed, and providing evidence to clarify the underlying determinants of sensitivity to estrogen therapy. Conclusions We described the transcriptional status of different cell subtypes in the two groups of patients, providing new ideas for exploring the molecular mechanism of the difference in the effectiveness of estrogen therapy in patients, and providing theoretical basis for providing precise and individualized treatment plans for IUA patients.

Abstract In response to the challenges faced by the Coati Optimization Algorithm (COA), including imbalance between exploration and exploitation, slow convergence speed, susceptibility to local optima, and low convergence accuracy, this paper introduces an enhanced variant termed the Adaptive Coati Optimization Algorithm (ACOA). ACOA achieves a balanced exploration–exploitation trade-off through refined exploration strategies and developmental methodologies. It integrates chaos mapping to enhance randomness and global search capabilities and incorporates a dynamic antagonistic learning approach employing random protons to mitigate premature convergence, thereby enhancing algorithmic robustness. Additionally, to prevent entrapment in local optima, ACOA introduces an Adaptive Levy Flight strategy to maintain population diversity, thereby improving convergence accuracy. Furthermore, underperforming individuals are eliminated using a cosine disturbance-based differential evolution strategy to enhance the overall quality of the population. The efficacy of ACOA is assessed across four dimensions: population diversity, exploration–exploitation balance, convergence characteristics, and diverse strategy variations. Ablation experiments further validate the effectiveness of individual strategy modules. Experimental results on CEC-2017 and CEC-2022 benchmarks, along with Wilcoxon rank-sum tests, demonstrate superior performance of ACOA compared to COA and other state-of-the-art optimization algorithms. Finally, ACOA’s applicability and superiority are reaffirmed through experimentation on five real-world engineering challenges and a complex urban three-dimensional unmanned aerial vehicle (UAV) path planning problem.

ObjectiveAiming at the significant features of high-resolution synthetic aperture radar (SAR) ship targets with multiple scenes, multi-scale and dense arrangements, and the problem of the blurring of target edge details due to coherent noise in the imaging process, a high-resolution SAR ship detection method is proposed with joint wavelet thresholding and fast non-local mean (F-NLM) de-noising. MethodsFirst, wavelet thresholding and F-NLM de-noising modules are utilized to preprocess the SAR image and reduce the sea clutter noise, enhance the detailed features and edge information of the detection target, and make the extracted features more discriminative. Next, a YOLOv7 detection algorithm combined with a bi-directional feature pyramid network (Bi-FPN) is selected to effectively aggregate the multi-scale features and further improve the model's accuracy. ResultsThe experimental results show that the average precision of ship detection using the de-noised dataset D-SSDD can reach 98.69% and the false alarm rate is reduced to 2.37%.ConclusionsIt is clear that the proposed high-resolution SAR ship detection method not only homogenizes the background clutter to improve the image quality, but also improves the interactivity of multi-scale feature information to ensure precise and accurate target detection.

Abstract Purpose To assess bone mineral density (BMD) in middle-aged individuals in Shanghai, in order to improve awareness of osteopenia and osteoporosis screening. Methods The clinical data of 1107 permanent residents of Shanghai aged 40–60 years were collected using a random cluster sampling method. Osteoporosis questionnaire survey and BMD test were conducted. Mann-Whitney U and Chi-square test were used to compare sex, age and body mass index at different stages of bone mass, and Pearson test was used to conduct correlation analysis. Logistic regression was used to analyze the influencing factors. Results The detection rates of osteopenia and osteoporosis were 59% and 12.5% respectively, and bone mineral density was correlated with sex, age, and body mass index (P

Abstract Cuproptosis, a newly identified form of cell death, has drawn increasing attention for its association with various cancers, though its specific role in colorectal cancer (CRC) remains unclear. In this study, transcriptomic and clinical data from CRC patients available in the TCGA database were analyzed to investigate the impact of cuproptosis. Differentially expressed genes linked to cuproptosis were identified using Weighted Gene Co-Expression Network Analysis (WGCNA). Key genes were further refined through LASSO regression and random forest approaches, culminating in the development of a prognostic model comprising six critical genes. The predictive accuracy of the model was validated using two independent external datasets. This model effectively stratified patients into high- and low-risk groups, which exhibited significant differences in disease stage, immune landscape, tumor mutational burden, and therapeutic response, underscoring the robustness of the model. P4HA1 was identified as a key gene of interest, where downregulation was found to inhibit tumor progression in single-cell sequencing analyses and in vitro experiments. Additionally, suppression of P4HA1 enhanced the sensitivity of CRC cells to the cuproptosis inducer elesclomol (ES), potentially through oxidative stress mechanisms. In conclusion, this study proposes a prognostic model based on six cuproptosis-related genes that could aid in personalizing CRC treatment. Furthermore, P4HA1 emerges as a promising therapeutic target.

Abstract Pyroptosis, an inflammatory regulated cell death (RCD) mechanism, is characterized by cellular swelling, membrane rupture, and subsequent discharge of cellular contents, exerting robust proinflammatory effects. Recent studies have significantly advanced our understanding of pyroptosis, revealing that it can be triggered through inflammasome- and caspase-independent pathways, and interacts intricately with other RCD pathways (e.g., pyroptosis, necroptosis, ferroptosis, and cuproptosis). The pathogenesis of pulmonary fibrosis (PF), including idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, involves a multifaceted interplay of factors such as pathogen infections, environmental pollutants, genetic variations, and immune dysfunction. This chronic and progressive interstitial lung disease is characterized by persistent inflammation, extracellular matrix (ECM) accumulation, and fibrotic alveolar wall thickening, which potentially contribute to deteriorated lung function. Despite recent advances in understanding pyroptosis, the mechanisms by which it regulates PF are not entirely elucidated, and effective strategies to improve clinical outcomes remain unclear. This review strives to deliver a comprehensive overview of the biological functions and molecular mechanisms of pyroptosis, exploring its roles in the pathogenesis of PF. Furthermore, it examines potential biomarkers and therapeutic agents for anti-fibrotic treatments.

Viral hepatitis is one of the leading infectious diseases contributing to the global increase in mortality and posing a serious threat to global public health. In 2016, the World Health Organization (WHO) proposed the goal of eliminating the significant public health threat of viral hepatitis by 2030. This article provides a summary of the current status of viral hepatitis and relevant literature, reports on the progress made in eliminating viral hepatitis in recent years, both nationally and internationally, and describes the global prevalence of viral hepatitis. It also discusses the actions and progress made by different countries in eliminating viral hepatitis, as well as the challenges they face. The aim is to provide a reference for international and national efforts to eliminate viral hepatitis.

Molecular aromatic corrosion inhibitors are frequently applied to slow down the corrosion of iron, its alloys and numerous other metallic materials. This case study with three representative aromatic inhibitors and a pure iron electrode aims at the verification of the reported conclusions regarding these inhibitors and at the verification and comparison of electrochemical corrosion assessment methods with attention to differences between iron alloys (steels) and pure iron possibly related to the presence/absence of alloying elements and non-iron impurities.

Microstructure can play a vital role in defining mechanical properties of metallic materials. To elucidate this correlation in the case of Ti–15Mo–3Nb–3Al-0.2Si (TB8) alloy, herein, we designed various microstructures via heat treatment exploring the effects of grain size, precipitates and segregation on crack initiation behavior during tensile tests in metastable β-Ti alloy. After solution treatment at 830 °C, the TB8 alloy with equiaxed β grain displayed a good fracture elongation of 30.2 ± 0.63%. The adiabatic shearing band and β→α phase transformation were activated to increase the compatible deformation capability during tensile testing; however, the phase transformation caused the stress concentration in the boundary, resulting in crack initiation. For the samples prepared using solution and low aging at 440 °C, large grain, elements segregation at grain boundary and incomplete precipitates induced a slight reduction in ultimate tensile strength and elongation. After solution and aging at 520 °C, the short-rod or/and lamellar α phase precipitated in β grain effectively enhancing ultimate tensile strength (1398.71 ± 15.6 MPa). The increased boundaries provided the interface or precipitation strengthening effect, but high-density dislocations were also accumulated at the β/α interface, causing unstable deformation and crack initiation. These findings advance our understanding of the correlation between microstructure and crack initiation, and provide a basis for designing and customizing the mechanical properties of metastable β-Ti alloy.

Abstract Background Dexamethasone has been widely used in treating severe COVID-19 patients due to its anti-inflammatory properties. However, its long-term impact on mortality remain unclear. Objective To evaluate the effect of dexamethasone on short-term (28-day) and long-term (1-year) mortality in hospitalized COVID-19 patients and to explore its efficacy across different respiratory support. Methods A retrospective cohort study was conducted using the MIMIC-IV (v3.0) database. A total of 576 confirmed COVID-19 patients were included, with 288 patients receiving dexamethasone and 288 not receiving it, matched by propensity scores. Survival analyses assessed the impact of dexamethasone on mortality, and subgroup analyses were performed based on the type of respiratory support received. Results After propensity score matching, dexamethasone treatment was associated with reduced mortality at both 28 days (adjusted HR 0.67, 95% CI 0.46–0.99, P = 0.045) and 1 year (adjusted HR 0.66, 95% CI 0.47–0.92, P = 0.014). Subgroup analysis revealed differential treatment effects by respiratory support type (P for interaction = 0.001 at 28 days and 0.004 at 1 year). The survival benefit was most pronounced in patients receiving NIV (28-day adjusted HR 0.15, 95% CI 0.05–0.42, P

FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processes, including proliferation, differentiation, and survival. Alterations in FGFR1 can lead to constitutive activation of signaling pathways that drive oncogenesis by promoting uncontrolled cell division, inhibiting apoptosis, and enhancing the metastatic potential of cancer cells. This article reviews the activation mechanisms and signaling pathways of FGFR1 and provides a detailed exposition of the types of FGFR1 aberration. Furthermore, we have compiled a comprehensive overview of current therapies targeting FGFR1 aberration in cancer, aiming to offer new perspectives for future cancer treatments by focusing on drugs that address specific FGFR1 alterations.

Abstract Impending myasthenic crisis (IMC) is an emergent situation requiring aggressive management to prevent patients from developing myasthenic crisis (MC) in patients with myasthenia gravis (MG). Efgartigimod has been proved to be well tolerated and efficacious in MG patients. The present study aimed to compare the efficacy of efgartigimod and intravenous immunoglobulin (IVIg) in rescuing IMC. IMC patients treated with efgartigimod or IVIg were retrospectively enrolled. The primary outcome was determined as the mean change in MG activities of daily living (MG-ADL) score from baseline to week 1 and 4 after treatment, respectively. Safety was assessed based on medical records during the hospitalization to monitor the adverse events. A total of 9 patients treated with efgartigimod and 10 patients treated with IVIg were enrolled. There were no significant differences in the clinical characteristics at baseline between the two groups (P > 0.05). Compared with the IVIg group, the efgartigimod group had a greater reduction in the MG-ADL score at week 1 (P = 0.035) and week 4 (P = 0.005). One patient in the efgartigimod group had an upper respiratory infection. These findings suggest that efgartigimod is a treatment option for IMC in addition to IVIg and plasma exchange.

Abstract Background This study utilizes a Knowledge, Attitude, and Practice (KAP) questionnaire to investigate the awareness of medical professionals in the Ningxia region regarding research integrity and their attitudes towards academic misconduct. A comprehensive analysis of the factors contributing to academic misconduct is performed, with the aim of providing insights for the formulation of policies to enhance research integrity. Methods This study is a cross-sectional study. It performed between May 2023 and October 2023, and the questionnaires were distributed and collected through Wenjuanxing and WeChat platforms. The research employs a self-designed KAP survey questionnaire distributed online for clinical doctors and nurses in hospital, faculty members in medical higher education institutions, and undergraduates enrolled in medical schools in the Ningxia region. Results A total of 1013 valid questionnaires were collected, with a majority of participants (76.2%) having received training in research integrity. The survey results indicate that a significant majority of participants (75.04%) cannot tolerate academic misconduct. More than 70% of respondents believe that the main reasons for academic misconduct are a lack of understanding of academic ethical norms, a deficiency in personal integrity awareness, individual inadequacy in research capabilities, and excessive pressure. When it comes to measures for academic misconduct reduction, over 70% of individuals believe that strengthening research integrity training, improving the assessment methods for research outcomes, and enhancing personal research capabilities can decrease instances of academic misconduct. Most respondents demonstrated a basic understanding of research integrity and maintained a resistant attitude towards academic misconduct. However, there exists an insufficient awareness of certain forms of academic misconduct. The study recommends implementing multifaceted measures to enhance the ethical awareness and attitudes of researchers. Conclusion In this study, a KAP questionnaire was administered to clinicians, nurses, medical faculty and students to find out their understanding of research integrity and their attitudes towards academic misconduct. Most of the respondents had a negative attitude towards academic misconduct, but their understanding of research integrity could be improved. Furthermore, university teachers’ understanding of research integrity and their attitudes towards academic misconduct were better than other groups, and university students had lower scores in this area, so it is recommended to take various measures to improve their understanding of research integrity.

Abstract The development of thermoelectric devices provides an ideal solution for self-sustaining Internet of Things (IoT) applications. However, existing thermoelectric devices face issues such as low integration levels and poor stability. To address these challenges, this paper presents a novel method for fabricating flexible thermoelectric devices using Ag2Se/MgAgSb, which combines MEMS lithographic lift-off techniques to achieve precise control over the dimensions of the thermoelectric functional layer while also reducing fabrication costs. The optimal cell dimensions were identified through simulations. The device achieved an open circuit voltage of 0.49 mV at a temperature difference of 50 K. Additionally, the output power density of the Ag₂Se/MgAgSb flexible Y-type thermoelectric device reached 3.39 µW/m² at a temperature difference of 5 K. The device also demonstrated excellent flexibility; even after being bent 800 times around a glass rod with a diameter of 4 mm, its conductivity decreased by only 12%. Furthermore, it maintained stability under high humidity conditions. This work offers a novel strategy for the miniaturization and large-area controllable fabrication of flexible and reliable thermoelectric devices, as well as an enhancement in their reliability.

Introduction We aimed to explore the prognostic value of the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio in non-surgical patients with type 2 diabetes hospitalized for heart failure. Material and methods Using a large electronic medical record-based cohort of diabetes in China (WECODe), we gathered data on non-surgical hospitalized patients with type 2 diabetes and heart failure from 2011 to 2019. Baseline AST/ALT ratio was calculated. The primary outcomes were all-cause death within 30 days after discharge, composite cardiac events, major acute kidney injury, and major systemic infection. A multivariable Cox proportional regression model was utilized to evaluate the association between the AST/ALT ratio and outcomes. Results This retrospective cohort included 8,073 patients (39.4% women) with type 2 diabetes hospitalized for heart failure. The median age was 71 years. Higher AST/ALT ratio was associated with higher risks of poor endpoints (with per standard deviation increment in AST/ALT ratio, for death within 30 days after discharge: adjusted hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21 to 1.50; for composite cardiac events: HR, 1.18, 95% CI: 1.06 to 1.31). Compared to patients in the lowest quartile for the AST/ALT ratio, those in the highest quartile have elevated risk of death within 30 days after discharge and major systemic infection (HRs [95% CIs]: 1.61 [1.18 to 2.19] and 1.28 [1.06 to 1.56], respectively). Subgroup analyses and sensitivity analyses confirmed the robustness of the findings. Conclusions Type 2 diabetes patients hospitalized for heart failure with the AST/ALT ratio in the highest quartile face a poor short-term prognosis.

Molecular inhibitors added to the corrosive medium attacking metallic materials are a well-established way of combating corrosion. The inhibitive action proceeds via adsorption of the inhibitor on the surface to be protected. Aromatic building blocks in the inhibitor play a major role in its protective action, and further details like substituents, heteroatoms, and molecular geometry contribute. An overview focused on aromatic inhibitors is provided, aiming at the identification of particularly promising inhibitors and their mode of action. Directions for further research and development are pointed out in the conclusion.

Objective(s): Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF’s hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity. Materials and Methods: Fifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected. Results: The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes. Conclusion: In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF’s toxicity to the liver.

Abstract Aims The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all‐cause death in hospitalized HFpEF patients. Methods and results Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database‐HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio > 0.0%), moderate HR dropping group (−15%

Abstract Introduction Several risk scores have been proposed to predict venous thromboembolism (VTE) in hospitalized patients. However, their predictive performances in lung cancer patients receiving immune checkpoint inhibitors (ICIs) is unclear. We aimed to validate and compare their performances of the Caprini, Padua and Khorana risk scores in lung cancer patients receiving ICIs. Methods This was a retrospective cohort study of patients with lung cancer treated with ICIs at West China Hospital between January 2018 and March 2022. The primary outcome was VTE during 12 months of follow-up from the first day of treatment with ICIs. The predictive performances of risk scores was determined using receiver operating characteristic (ROC) curve analysis. Results Among the 1115 eligible patients with lung cancer who received ICIs, 105 patients (9.4%) experienced VTE during the 12-month follow-up period. There was a statistically significant difference in the cumulative incidence of VTE between the different risk levels as determined by Caprini and Padua scores (all P

Abstract Background Although the imaging manifestations of pulmonary sarcoidosis have been described in detail in previous studies, a consensus has not been reached on the imaging presentation of non-specific interstitial pneumonia (NSIP) lookalike pattern as a distinct pattern in the diagnosis of pulmonary sarcoidosis in high-resolution computed tomography (HRCT). No cases of pulmonary sarcoidosis comorbid with NSIP have been reported. Case presentation A 53-year-old male presented to the hospital with a five-year history of recurrent coughing up sputum and a four-year history of shortness of breath. In addition to the typical features of pulmonary sarcoidosis, the patient’s HRCT also showed unexpected interstitial changes in the lower lobes of both lungs, suggesting an NSIP pattern. Histopathology of the lung tissue in this region confirmed well-formed noncaseating epithelioid granulomas and pathological modifications of NSIP. After a rigorous exclusion diagnosis combining the patient’s clinical features, radiological and pathological findings, we diagnosed this patient with pulmonary sarcoidosis comorbid with NSIP. Conclusions This suggests that NSIP may act as a rare comorbidity of pulmonary sarcoidosis thereby resulting in the patient’s HRCT presenting differently from routine sarcoidosis imaging.

Abstract Background Cutaneous infections caused by non-tuberculous mycobacteria (NTM) are extremely rare, particularly when they are localized to the facial area. This condition presents significant diagnostic challenges due to its unusual presentation and the need for precise microbiological identification. Case Presentation A two-year-old male patient presented with a progressively enlarging reddish-brown mass on the left side of his face. Despite the absence of systemic symptoms, the lesion’s growth warranted investigation due to its growth. Ultrasonography showed a hypoechoic mass in the dermis, indicating an underlying abscess. The subsequent aspiration resulted in pale yellow pus, which upon testing and culture, confirmed the presence of Mycobacterium avium complex infection, a species of NTM. This case exemplifies the synergy between imaging modalities and microbiological analysis, highlighting the crucial role of both in achieving favorable clinical outcomes in patients with suspected cutaneous NTM infections. Ultrasound can expedite diagnosis, improve treatment planning, and enhance patient care by enabling targeted interventions and monitoring response to therapy in these scenarios. However, it is the combination of pathogen-specific diagnostics that ensures accurate etiological attribution and appropriate antimicrobial stewardship. Conclusion Although rare, facial cutaneous infections caused by NTM still deserve thorough investigation to determine the exact cause. Ultrasound is used to identify cutaneous lesions, measure their extent, and guide surgical procedures. The ultimate diagnosis is based on microbiological confirmation.

Abstract Background TOBAMOVIRUS MULTIPLICATION 1 (TOM1) and its homolog TOBAMOVIRUS MULTIPLICATION 3 (TOM3) play a prominent role in the multiplication of tobacco mosaic virus (TMV) in higher plants. Although homologs of NtTOM1/TOM3 genes have been identified in several plant species, little is known about the characteristics and functions of NtTOM1/TOM3 at the genome-wide level in tobacco (Nicotiana tabacum L.). Results In this study, we performed genome-wide identification and expression pattern analysis of the tobacco NtTOM1/TOM3 gene family. Twelve NtTOM1/TOM3 genes were identified and classified into four groups based on phylogenetic analysis. Sequence and conserved domain analyses showed that all these genes contained a specific DUF1084 domain. Expression pattern analysis showed that NtTOM1a, NtTOM1b, NtTOM1d, NtTOM3a, NtTOM3b, and NtTOM3d were induced by TMV at 1-, 3-, and 9 dpi, whereas the expression of other genes was not responsive to TMV at the early infection stage. TMV virion accumulation showed no obvious difference in either nttom1a or nttom3a mutants compared with the wild type. However, the virus propagation was significantly, but not completely, inhibited in the nttom1atom3a double mutant, indicating that other gene family members may function redundantly, such as NtTOM1b and NtTOM1d. In addition, overexpression of NtTOM1a or NtTOM3a also inhibited the TMV replication to some extent. Conclusions The present study performed genome-wide analysis of the NtTOM1/TOM3 gene family in tobacco, and identified NtTOM1a and NtTOM3a as important genes involved in TMV multiplication based on functional analysis. These results provide a theoretical basis for further improving TMV resistance in tobacco.

Abstract Objectives This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response. Methods This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis. Results In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p

Abstract Coronary artery disease (CAD), a critical condition resulting from systemic inflammation, metabolic dysfunction, and gut microbiota dysbiosis, poses a global public health challenge. ALW-II-41-27, a specific inhibitor of the EphA2 receptor, has shown anti-inflammatory prosperities. However, the impact of ALW-II-41-27 on atherosclerosis has not been elucidated. This study aimed to examine the roles of pharmacologically inhibiting EphA2 and the underlying mechanism in ameliorating atherosclerosis. ALW-II-41-27 was administered to apoE−/− mice fed a high-fat diet via intraperitoneal injection. We first discovered that ALW-II-41-27 led to a significant reduction in atherosclerotic plaques, evidenced by reduced lipid and macrophage accumulation, alongside an increase in collagen and smooth muscle cell content. ALW-II-41-27 also significantly lowered plasma and hepatic cholesterol levels, as well as the colonic inflammation. Furthermore, gut microbiota was analyzed by metagenomics and plasma metabolites by untargeted metabolomics. ALW-II-41-27-treated mice enriched Enterococcus, Akkermansia, Eggerthella and Lactobaccilus, accompanied by enhanced secondary bile acids production. To explore the causal link between ALW-II-41-27-associated gut microbiota and atherosclerosis, fecal microbiota transplantation was employed. Mice that received ALW-II-41-27-treated mouse feces exhibited the attenuated atherosclerotic plaque. In clinical, lower plasma DCA and HDCA levels were determined in CAD patients using quantitative metabolomics and exhibited a negative correlation with higher monocytes EphA2 expression. Our findings underscore the potential of ALW-II-41-27 as a novel therapeutic agent for atherosclerosis, highlighting its capacity to modulate gut microbiota composition and bile acid metabolism, thereby offering a promising avenue for CAD.

Abstract Acquired drug resistance is a major challenge in the management of cancer, which underscores the need for discovery and development of novel therapeutic strategies. We report here the mechanism of the anti-cancer activity of a small coordinate complex composed of the rare earth metal praseodymium (Pr) and mercaptopyridine oxide (MPO; pyrithione). Exposure of cancer cells to relatively low concentrations of the conjugate Pr-MPO (5 µM) significantly impairs cell survival in a p53-independent manner and irrespective of the drug resistant phenotype. Mechanistically, Pr-MPO-induced cell death is caspase-independent, not inhibitable by necrostatin, but associated with the appearance of autophagy markers. However, further analysis revealed incomplete autophagic flux, thus suggesting altered integrity of lysosomal machinery. Supporting the lysosomal targeting activity are data demonstrating increased lysosomal Ca2+ accumulation and alkalinization, which coincides with cytosolic acidification (drop in pHc from 7.75 to 7.00). In parallel, an increase in lysosomal activity of glycosidase alpha acid (GAA), involved in passive glycogen breakdown, correlates with rapid depletion of glucose stores upon Pr-MPO treatment. This is associated with swift cataplerosis of TCA cycle intermediates, loss of NAD+/NADH and increase in pyruvate dehydrogenase (PDH) activity to compensate for pyruvate loss. Addition of exogenous pyruvate rescued cell survival. Notably, lysosomal impairment and metabolic catastrophe triggered by Pr-MPO are suggestive of Zn2+-mediated cytotoxicity, which is confirmed by the ability of Zn2+ chelator TPEN to block Pr-MPO-mediated anti-tumor activity. Together, these results highlight the ability of the small molecule lanthanide conjugate to target the cells’ waste clearing machinery as well as mitochondrial metabolism for Zn2+-mediated execution of cancer cells, which could have therapeutic potential against cancers with high metabolic activity.

Abstract Background Anemone shikokiana (Makino) Makino is a perennial herb of the genus Anemone in the family Ranunculaceae. Endemic to the Shandong Peninsula in China and Shikoku Island in Japan, it is a rare and endangered plant with a narrow, disjunct distribution. It is threatened with extinction and is in urgent need of conservation. Evaluating the genetic diversity of species, revealing the population genetic structure and gene flow, and inferring the population history are of great importance for species conservation, especially for rare and endangered plants. Results In our study, 73 samples from eight wild populations in China were sequenced by Super-GBS, yielding a total of 40.59 G clean reads and 52,231 SNPs. Based on the obtained SNP data set, we evaluated the population genetic diversity, genetic structure, and gene flow of A. shikokiana. A low level of genetic diversity was found (He = 0.1925, Ho = 0.1422). The neighbor-joining (NJ) tree, principal component analysis and ADMIXTURE analysis suggested that these 73 A. shikokiana could be considered as two groups. Pairwise genetic differentiation coefficients (Fst) indicated that genetic differentiation was lower between adjacent populations and higher between geographically separated populations. The gene flow between Kunyu Mountain and Lao Mountain was very low. However, neither of the two regions showed evidence of Isolation by Distance. Conclusions Here, we revealed the population genetic structure and gene flow of A. shikokiana from the Shandong Peninsula, China. This research provides valuable genetic resources for A. shikokiana and contributes to the scientific and effective conservation of the species.

Abstract Background The gut microbiota is a key regulator of bone metabolism. Investigating the relationship between the gut microbiota and bone remodeling has revealed new avenues for the treatment of bone-related disorders. Despite significant progress in understanding gut microbiota-bone interactions in mammals, research on avian species remains limited. Birds have unique bone anatomy and physiology to support egg-laying. However, whether and how the gut microbiota affects bone physiology in birds is still unknown. In this study, we utilized laying hens as a research model to analyze bone development patterns, elucidate the relationships between bone and the gut microbiota, and mine probiotics with osteomodulatory effects. Results Aging led to a continuous increase in bone mineral density in the femur of laying hens. The continuous deposition of medullary bone in the bone marrow cavity of aged laying hens led to significant trabecular bone loss and weakened bone metabolism. The cecal microbial composition significantly shifted before and after sexual maturity, with some genera within the class Clostridia potentially linked to postnatal bone development in laying hens. Four bacterial strains associated with bone development, namely Blautia coccoides CML164, Fournierella sp002159185 CML151, Anaerostipes caccae CML199 (ANA), and Romboutsia lituseburensis CML137, were identified and assessed in chicks with low bacterial loads and chicken primary osteoblasts. Among these, ANA demonstrated the most significant promotion of bone formation both in vivo and in vitro, primarily attributed to butyrate in its fermentation products. A long-term feeding experiment of up to 72 weeks confirmed that ANA enhanced bone development during sexual maturity by improving the immune microenvironment of the bone marrow in laying hens. Dietary supplementation of ANA for 50 weeks prevented excessive medullary bone deposition and mitigated aging-induced trabecular bone loss. Conclusions These findings highlight the beneficial effects of ANA on bone physiology, offering new perspectives for microbial-based interventions for bone-related disorders in both poultry and possibly extending to human health. Video Abstract Graphical Abstract

Abstract Phytochrome-interacting factors (PIFs) are a subgroup of transcription factors within the basic helix-loop-helix (bHLH) family, playing a crucial role in integrating various environmental signals to regulate plant growth and development. Despite the significance of PIFs in these processes, a comprehensive genome-wide analysis of PIFs in conifers has yet to be conducted. In this investigation, three PtPIF genes were identified in Chinese pine, categorized into three subgroups, with conserved motifs indicating the presence of the APA/APB motif and bHLH domain in the PtPIF1 and PtPIF3 proteins. Phylogenetic analysis revealed that the PtPIF1 and PtPIF3 proteins belong to the PIF7/8 and PIF3 groups, respectively, and were relatively conserved among gymnosperms. Additionally, a class of PIF lacking APA/APB motif was identified in conifers, suggesting its function may differ from that of traditional PIFs. The cis-elements of the PtPIF genes were systematically examined, and analysis of PtPIF gene expression across various tissues and under different light, temperature, and plant hormone conditions demonstrated similar expression profiles for PtPIF1 and PtPIF3. Investigations into protein-protein interactions and co-expression networks speculated the involvement of PtPIFs and PtPHYA/Bs in circadian rhythms and hormone signal transduction. Further analysis of transcriptome data and experimental validation indicated an interaction between PtPIF3 and PtPHYB1, potentially linked to diurnal rhythms. Notably, the study revealed that PtPIF3 may be involved in gibberellic acid (GA) signaling through its interaction with PtDELLAs, suggesting a potential role for PtPIF3 in mediating both light and GA responses. Overall, this research provides a foundation for future studies investigating the functions of PIFs in conifer growth and development.

Abstract Surface acoustic wave (SAW) tweezers are a promising multifunctional micromanipulation method that controls microscale targets via patterned acoustic fields. Owing to their device structure and bonding process, most SAW tweezers have limitations in terms of controlling the position and motion of the acoustic traps, as they generate an acoustic field with a fixed region and adjust the manipulation effects via signal modulation. To address this challenge, we propose movable SAW tweezers with a multilayer structure, achieving dynamic control of their wave field and acoustic trap positions; we demonstrate their precise manipulation functions, such as translation, in-plane rotation, out-of-plane rotation, and cluster formation, on a wide spectrum of samples, including particles, bubbles, droplets, cells, and microorganisms. Our method not only improves the degree of freedom and working range of SAW tweezers but also allows for precise and selective manipulation of microtargets via microtools and localized wavefields. Owing to their flexibility, versatility, and biocompatibility, the movable SAW tweezers can be a practical platform for achieving arbitrary manipulation of microscale targets and have the potential to play significant roles in biomedical microrobotics.