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Abstract Pyroptosis, a lytic form of cell death mediated by the gasdermin family, is characterized by cell swelling and membrane rupture. Inducing pyroptosis in cancer cells can enhance antitumor immune responses and is a promising strategy for cancer therapy. However, excessive pyroptosis may trigger the development of inflammatory diseases due to immoderate and continuous inflammatory reactions. Nanomaterials and nanobiotechnology, renowned for their unique advantages and diverse structures, have garnered increasing attention owing to their potential to induce pyroptosis in diseases such as cancer. A nano-delivery system for drug-induced pyroptosis in cancer cells can overcome the limitations of small molecules. Furthermore, nanomedicines can directly induce and manipulate pyroptosis. This review summarizes and discusses the latest advancements in nanoparticle-based treatments with pyroptosis among inflammatory diseases and cancer, focusing on their functions and mechanisms and providing valuable insights into selecting nanodrugs for pyroptosis. However, the clinical application of these strategies still faces challenges owing to a limited understanding of nanobiological interactions. Finally, future perspectives on the emerging field of pyroptotic nanomaterials are presented. Graphical abstract

With the acceleration of urbanization, urban rail transit systems have become one of the most important modes of transportation in modern cities. Urban rail transit systems operate in enclosed or semi-enclosed environments, characterized by poor air circulation and high passenger flow. During the period of high incidence of respiratory infectious diseases in autumn and winter, air quality and pathogenic microorganism monitoring in public places have attracted much attention. This article provided a detailed introduction to air pollutants and their sources related to urban rail transit, including chemical pollutants, such as particulate matter and gaseous pollutants, and microbial aerosols. Based on identified air pollutants related to urban rail transit, this paper reviewed the research progress on air quality monitoring technologies for chemical pollution factors and microbial aerosols. Finally, a summary of the health effects of chemical pollutants and microbial aerosols was provided, along with suggestions for monitoring and improving air quality tailored to the characteristics of urban rail transit systems. Through a review of previous studies, carrying out research on air quality monitoring technologies and associated health effects related to urban rail transit is of great significance and values for air quality management, urban development, and public health.

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

Abstract Background Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study. Methods Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75–94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test. Results Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults. Conclusion Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults.

Abstract Background Early prediction of pathological complete response (pCR) is important for deciding appropriate treatment strategies for patients. In this study, we aimed to quantify the dynamic characteristics of dynamic contrast-enhanced magnetic resonance images (DCE-MRI) and investigate its value to improve pCR prediction as well as its association with tumor heterogeneity in breast cancer patients. Methods The DCE-MRI, clinicopathologic record, and full transcriptomic data of 785 breast cancer patients receiving neoadjuvant chemotherapy were retrospectively included from a public dataset. Dynamic features of DCE-MRI were computed from extracted phase-varying radiomic feature series using 22 CAnonical Time-sereis CHaracteristics. Dynamic model and radiomic model were developed by logistic regression using dynamic features and traditional radiomic features respectively. Various combined models with clinical factors were also developed to find the optimal combination and the significance of each components was evaluated. All the models were evaluated in independent test set in terms of area under receiver operating characteristic curve (AUC). To explore the potential underlying biological mechanisms, radiogenomic analysis was implemented on patient subgroups stratified by dynamic model to identify differentially expressed genes (DEGs) and enriched pathways. Results A 10-feature dynamic model and a 4-feature radiomic model were developed (AUC = 0.688, 95%CI: 0.635–0.741 and AUC = 0.650, 95%CI: 0.595–0.705) and tested (AUC = 0.686, 95%CI: 0.594–0.778 and AUC = 0.626, 95%CI: 0.529–0.722), with the dynamic model showing slightly higher AUC (train p = 0.181, test p = 0.222). The combined model of clinical, radiomic, and dynamic achieved the highest AUC in pCR prediction (train: 0.769, 95%CI: 0.722–0.816 and test: 0.762, 95%CI: 0.679–0.845). Compared with clinical-radiomic combined model (train AUC = 0.716, 95%CI: 0.665–0.767 and test AUC = 0.695, 95%CI: 0.656–0.714), adding the dynamic component brought significant improvement in model performance (train p

During the installation of a cable oil terminal, it is easy to leave scratches on the main insulation owing to uneven forces when removing the semi-conductive layer. Scratch defects cause field intensity distortion, which leads to partial discharge and insulation failure. This study attempts to establish a simulation model of a 220 kV cable terminal to determine the effect of the length, depth, and position of the scratch on the maximum field strength at the defect. The simulation and experiment demonstrate that the maximum field strength at the defect increases with greater length and decreases as the depth increases. Therefore, a prediction method for the terminal defect field strength based on a multivariate nonlinear regression model was proposed in this study. When the defect is located at 20 mm from the root of the stress cone, the maximum field strength is 14.5 MV/m when the length and depth are 2 mm and 1 mm, respectively. The maximum field strength at the defect was predicted based on the length, depth, and position of the scratch defect to evaluate the severity of the defect.

Objective: To assess the consistency of liquid biopsy and histologic analysis for detecting epidermal growth factor receptor (EGFR) gene mutations in patients with advanced non-small cell lung cancer (NSCLC). Methods: The PubMed, Cochrane Library, and CNKI et al. databases were searched to collect studies comparing liquid biopsy and histopathologic specimens. The EGFR mutation status was extracted from the studies, and meta-analysis was carried out using Stata 12.0 software. Results: We included 22 studies of 3359 NSCLC patients. In the meta-analysis, eight papers with a sample size of size 50 %, showing that literature that did not include the T790M mutation was more heterogeneous. The combined diagnostic effect size of 34 in the exon 19 group was smaller than that in the group with no exon 19, with an I2>50 %. There was substantial heterogeneity in both the exon 19 group and the non-exon 19 group. The group with the L858R mutation had a greater diagnostic effect size of 28, lower I2, and less heterogeneity than the group without the L858R mutation. The exon 21 group had a larger pooled diagnostic effect size of 66, a smaller I2, and less heterogeneity than the group without exon 21. Conclusion: Liquid biopsy and histologic analysis have high concordance for detecting EGFR mutations in NSCLC. Liquid biopsy can provide an alternative technology for individualized treatment and monitoring of minimal residual disease (MRD) in advanced NSCLC patients with EGFR tyrosine kinase inhibitor-sensitive and drug resistance (T790M) mutations.

G protein-coupled receptor-associated sorting protein 2 (GPRASP2) deficiency has been implicated in immunological inflammation, cancers, and neurological disorders. Our previous work revealed that the pathogenic mutation in GPRASP2 was responsible for X-linked recessive syndromic hearing loss (SHL). Given the specific high expression of GPRASP2 in the spiral ganglion, GPRASP2 likely contributes to the maintenance and functionality of neurons, potentially playing a role in synaptic transmission. The impact of GPRASP2 deficiency on spiral ganglion cells (SGCs) and their underlying pathogenic mechanisms will be investigated in this study. The primary culture of SGCs obtained from mouse cochleae was treated with Gprasp2-targeting short hairpin RNA (Gprasp2-shRNA) via lentivirus infection. The results showed that GPRASP2 deficiency enhanced SGCs apoptosis and decreased cell viability. Meanwhile, a significant abnormality of mitochondrial morphology and decreased membrane potential were observed in GPRASP2-deficient SGCs. These effects could be mitigated by treatment with the mitochondrial division inhibitor 1 (Mdivi-1). In addition to enhancing SGCs apoptosis and decreasing cell viability, GPRASP2 deficiency also inhibited the development of SGCs in mouse cochlear explant culture. Our study further revealed that this deficiency resulted in increased phosphorylation of AMPK and activation of the AMPK/DRP1 pathway, promoting SGCs apoptosis. These findings provide insight into the pathogenic mechanisms by which GPRASP2 deficiency is implicated in auditory dysfunction.

Diabetes mellitus(DM) stands as a multifaceted metabolic disorder marked by heightened blood glucose levels and an elusive pathogenesis.Hypoxia-inducible factor-1(HIF-1) emerges as a pivotal transcription factor triggered within hypoxic environments.Its involvement in the pathogenesis of diabetes and its complications is instrumental, as it orchestrates the hypoxia adaptive response, governs glucose and lipid metabolism, and influences the function of islet β cells.This article meticulously examines the structural and functional aspects of HIF-1, shedding light on its role in the pathogenesis of diabetes and associated complications.By unraveling these intricate connections, it not only enhances our understanding of the disease but also propels innovative avenues for the exploration of novel preventive and therapeutic strategies for diabetes and its complications.

Abstract Recently, the following global-best strategy and discussion mechanism have been prevailing to solve the slow convergence and the low optimization accuracy in the brain storm optimization (BSO) algorithm. However, the traditional BSO algorithm also suffers from the problem that it is easy to fall into local optimum. Therefore, this work innovatively designed the chaotic difference step strategy. This strategy introduced four commonly used chaotic maps and difference step to expand the population search space to improve the situation. Moreover, opposition-based learning thought was innovatively adopted into the BSO algorithm. The thought aims to generate the opposition-based population, increase the search density, and make the algorithm out of the local optimum as soon as possible. In summary, this work proposed a global-best brain storm optimization algorithm based on the chaotic difference step and opposition-based learning (COGBSO). According to the CEC2013 benchmark test suit, 15 typical benchmark functions were selected, and multiple sets of simulation experiments were conducted on MATLAB. The COGBSO algorithm was also compared to recent competitive algorithms based on the complete CEC2018 benchmark test suit. The results demonstrate that the COGBSO outperforms BSO and other improved algorithms in solving complex optimization problems.

Osteoarthritis (OA) is one of the fast-growing disability-related diseases worldwide, which has significantly affected the quality of patients' lives and brings about substantial socioeconomic burdens in medical expenditure. There is currently no cure for OA once the bone damage is established. Unfortunately, the existing radiological examination is limited to grading the disease's severity and is insufficient to precisely diagnose OA, detect early OA or predict OA progression. Therefore, there is a pressing need to develop novel approaches in medical image analysis to detect subtle changes for identifying early OA development and rapid progressors. Recently, radiomics has emerged as a unique approach to extracting high-dimensional imaging features that quantitatively characterise visible or hidden information from routine medical images. Radiomics data mining via machine learning has empowered precise diagnoses and prognoses of disease, mainly in oncology. Mounting evidence has shown its great potential in aiding the diagnosis and contributing to the study of musculoskeletal diseases. This paper will summarise the current development of radiomics at the crossroads between engineering and medicine and discuss the application and perspectives of radiomics analysis for OA diagnosis and prognosis. The translational potential of this article: Radiomics is a novel approach used in oncology, and it may also play an essential role in the diagnosis and prognosis of OA. By transforming medical images from qualitative interpretation to quantitative data, radiomics could be the solution for precise early OA detection, progression tracking, and treatment efficacy prediction. Since the application of radiomics in OA is still in the early stages and primarily focuses on fundamental studies, this review may inspire more explorations and bring more promising diagnoses, prognoses, and management results of OA.

Monoterpenoids are typically present in the secretory tissues of higher plants, and their biosynthesis is catalyzed by the action of monoterpene synthases (MTSs). However, the knowledge about these enzymes is restricted in a few plant species. MTSs are responsible for the complex cyclization of monoterpene precursors, resulting in the production of diverse monoterpene products. These enzymatic reactions are considered exceptionally complex in nature. Therefore, it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid products. In our study, we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene products. By focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic, monocyclic and bicyclic products in MTSs, we observed that even a single amino acid mutation can change the specificity and diversity of MTS products, which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation changing. Notably, residues N340, I448, and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene cations. Alterations in these residues, either directly or indirectly, can impact the synthesis of single monoterpenes or their mixtures. By revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs, it will be possible to reasonably design and engineer different catalytic activities into existing MTSs, laying a foundation for the artificial design and industrial application of MTSs.

Abstract Background The genus Libanotis Haller ex Zinn, nom. cons., a contentious member of Apiaceae, encompasses numerous economically and medicinally significant plants, comprising approximately 30 species distributed across Eurasia. Despite many previous taxonomic insights into it, phylogenetic studies of the genus are still lacking. And the establishment of a robust phylogenetic framework remains elusive, impeding advancements and revisions in the taxonomic system for this genus. Plastomes with greater variability in their genetic characteristics hold promise for building a more robust Libanotis phylogeny. Results During our research, we sequenced, assembled, and annotated complete plastomes for twelve Libanotis species belong to three sections and two closely related taxa. We conducted a comprehensive comparative analysis through totally thirteen Libanotis plastomes for the genus, including an additional plastome that had been published. Our results suggested that Libanotis plastome was highly conserved between different subclades, while the coding regions were more conserved than the non-coding regions, and the IR regions were more conserved than the single copy regions. Nevertheless, eight mutation hotspot regions were identified among plastomes, which can be considered as candidate DNA barcodes for accurate species identification in Libanotis. The phylogenetic analyses generated a robustly framework for Libanotis and revealed that Libanotis was not a monophyletic group and their all three sections were polygenetic. Libanotis schrenkiana was sister to L. sibirica, type species of this genus, but the remainders scattered within Selineae. Conclusion The plastomes of Libanotis exhibited a high degree of conservation and was effective in enhancing the support and resolution of phylogenetic analyses within this genus. Based on evidence from both phylogeny and morphology, we propose the recognition of "Libanotis sensu stricto" and provide taxonomic recommendations for other taxa that previously belonged to Libanotis. In conclusion, our study not only revealed the phylogenetic position and plastid evolution of Libanotis, but also provided new insights into the phylogeny of the family Apiaceae and phylogenetic relationships within the tribe Selineae.

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Abstract Type 2 diabetes (T2D)-related fragility fractures represent an increasingly tough medical challenge, and the current treatment options are limited. Mechanical loading is essential for maintaining bone integrity, although bone mechano-responsiveness in T2D remains poorly characterized. Herein, we report that exogenous cyclic loading-induced improvements in bone architecture and strength are compromised in both genetically spontaneous and experimentally-induced T2D mice. T2D-induced reduction in bone mechano-responsiveness is directly associated with the weakened Ca2+ oscillatory dynamics of osteocytes, although not those of osteoblasts, which is dependent on PPARα-mediated specific reduction in osteocytic SERCA2 pump expression. Treatment with the SERCA2 agonist istaroxime was demonstrated to improve T2D bone mechano-responsiveness by rescuing osteocyte Ca2+ dynamics and the associated regulation of osteoblasts and osteoclasts. Moreover, T2D-induced deterioration of bone mechano-responsiveness is blunted in mice with osteocytic SERCA2 overexpression. Collectively, our study provides mechanistic insights into T2D-mediated deterioration of bone mechano-responsiveness and identifies a promising countermeasure against T2D-associated fragility fractures.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract Plants usually produce defence metabolites in non-active forms to minimize the risk of harm to themselves and spatiotemporally activate these defence metabolites upon pathogen attack. This so-called two-component system plays a decisive role in the chemical defence of various plants. Here, we discovered that Panax notoginseng, a valuable medicinal plant, has evolved a two-component chemical defence system composed of a chloroplast-localized β-glucosidase, denominated PnGH1, and its substrates 20(S)-protopanaxadiol ginsenosides. The β-glucosidase and its substrates are spatially separated in cells under physiological conditions, and ginsenoside hydrolysis is therefore activated only upon chloroplast disruption, which is caused by the induced exoenzymes of pathogenic fungi upon exposure to plant leaves. This activation of PnGH1-mediated hydrolysis results in the production of a series of less-polar ginsenosides by selective hydrolysis of an outer glucose at the C-3 site, with a broader spectrum and more potent antifungal activity in vitro and in vivo than the precursor molecules. Furthermore, such β-glucosidase-mediated hydrolysis upon fungal infection was also found in the congeneric species P. quinquefolium and P. ginseng. Our findings reveal a two-component chemical defence system in Panax species and offer insights for developing botanical pesticides for disease management in Panax species.

Abstract Background Omental metastasis is the major cause of ovarian cancer recurrence and shortens patient survival, which can be largely attributed to the dynamic evolution of the fertile metastatic microenvironment driven by cancer cells. Previously, we found that adipose-derived mesenchymal stem cells (ADSCs) undergoing a phenotype shift toward cancer-associated fibroblasts (CAFs) participated in the orchestrated omental premetastatic niche for ovarian cancer. Here, we aim to elucidate the underlying mechanisms. Methods Small extracellular vesicles were isolated from ovarian cancer cell lines (ES-2 and its highly metastatic subline, ES-2-HM) and patient ascites using ultracentrifugation. Functional experiments, including Transwell and EdU assays, and molecular detection, including Western blot, immunofluorescence, and RT–qPCR, were performed to investigate the activation of ADSCs in vitro. High-throughput transcriptional sequencing and functional assays were employed to identify the crucial functional molecules inducing CAF-like activation of ADSCs and the downstream effector of miR-320a. The impact of extracellular vesicles and miR-320a-activated ADSCs on tumor growth and metastasis was assessed in subcutaneous and orthotopic ovarian cancer xenograft mouse models. The expression of miR-320a in human samples was evaluated using in situ hybridization staining. Results Primary human ADSCs cocultured with small extracellular vesicles, especially those derived from ES-2-HM, exhibited boosted migration, invasion, and proliferation capacities and elevated α-SMA and FAP levels. Tumor-derived small extracellular vesicles increased α-SMA-positive stromal cells, fostered omental metastasis, and shortened the survival of mice harboring orthotopic ovarian cancer xenografts. miR-320a was abundant in highly metastatic cell-derived extracellular vesicles, evoked dramatic CAF-like transition of ADSCs, targeted the 3′-untranslated region of integrin subunit alpha 7 and attenuated its expression. miR-320a overexpression in ovarian cancer was associated with omental metastasis and shorter survival. miR-320a-activated ADSCs facilitated tumor cell growth and omental metastasis. Depletion of integrin alpha 7 triggered CAF-like activation of ADSCs in vitro. Video Abstract Conclusions miR-320a in small extracellular vesicles secreted by tumor cells targets integrin subunit alpha 7 in ADSCs and drives CAF-like activation, which in turn facilitates omental metastasis of ovarian cancer. Graphical Abstract

ABSTRACTDifferences in human mobility reflect temporal variations and spatial differences in urban spaces, including regional functions, physical environments, and geographical sentiments. Accurately quantifying these differences is critical for understanding and managing cities. However, existing measurement methods overlook the spatial distribution of population movement, which limits the ability to compare spatial differences in human mobility. Separate treatment of the spatial distribution, flux, and distance of human movement increases the complexity and uncertainty of understanding geographic phenomena. Therefore, we propose a flow-based location measure, termed the mobility difference index (MDI), that fuses multidimensional movement characteristics to quantify temporal variations and spatial differences in human mobility. The method quantifies the differences in human mobility by calculating the minimum transformation cost between two sets of origin-destination flows based on optimal transport theory. Simulation experiments confirmed the advantage of the MDI in perceiving the multidimensional characteristics of human movement, particularly regarding spatial distribution. We examined mobile signaling and positioning data from Wuhan and found that the proposed MDI could effectively identify the spatial and temporal dependencies of variations in human mobility and heterogeneous effects of spatial semantics and distance on spatial differences in human mobility.

BackgroundPatients with carotid atherosclerotic stenosis (CAS) often have varying degrees of cognitive decline. However, there is little evidence regarding how brain morphological and functional abnormalities impact the cognitive decline in CAS patients. This study aimed to determine how the brain morphological and functional changes affected the cognitive decline in patients with CAS.MethodsThe brain morphological differences were analyzed using surface and voxel-based morphometry, and the seed-based whole-brain functional connectivity (FC) abnormalities were analyzed using resting-state functional magnetic resonance imaging. Further, mediation analyses were performed to determine whether and how morphological and FC changes affect cognition in CAS patients.ResultsThe CAS-MCI (CAS patients with mild cognitive impairment) group performed worse in working memory, verbal fluency, and executive time. Cortical thickness (CT) of the left postcentral and superiorparietal were significantly reduced in CAS-MCI patients. The gray matter volume (GMV) of the right olfactory, left temporal pole (superior temporal gyrus) (TPOsup.L), left middle temporal gyrus (MTG.L), and left insula (INS.L) were decreased in the CAS-MCI group. Besides, decreased seed-based FC between TPOsup.L and left precuneus, between MTG.L and TPOsup.L, and between INS.L and MTG.L, left middle frontal gyrus, as well as Superior frontal gyrus, were found in CAS-MCI patients. Mediation analyses demonstrated that morphological and functional abnormalities fully mediated the association between the maximum degree of carotid stenosis and cognitive function.ConclusionMultiple brain regions have decreased GMV and CT in CAS-MCI patients, along with disrupted seed-based FC. These morphological and functional changes play a crucial role in the cognitive impairment in CAS patients.

Objective: Knee replacement (KR) is the last-resort treatment for knee osteoarthritis. Although radiographic evidence of tibiofemoral joint has been widely adopted for prognostication, patellofemoral joint has gained little attention and may hold additional value for further improvements. We aimed to quantitatively analyse patellofemoral joint through radiomics analysis of lateral view radiographs for improved KR risk prediction. Design: From the Multicenter Osteoarthritis Study dataset, we retrospectively retrieved the initial-visit lateral left knee radiographs of 2943 patients aged 50 to 79. They were split into training and test cohorts at a 2:1 ratio. A comprehensive set of radiomic features were extracted within the best-performing subregion of patellofemoral joint and combined into a radiomics score (RadScore). A KR risk score, derived from Kellgren-Lawrence grade (KLG) of tibiofemoral joint and RadScore of patellofemoral joint, was developed by multivariate Cox regression and assessed using time-dependent area under receiver operating characteristic curve (AUC). Results: While patellofemoral osteoarthritis (PFOA) was insignificant during multivariate analysis, RadScore was identified as an independent risk factor (multivariate Cox p-value < 0.001) for KR. The subgroup analysis revealed that RadScore was particularly effective in predicting rapid progressor (KR occurrence before 30 months) among early- (KLG < 2) and mid-stage (KLG ​= ​2) patients. Combining two joints radiographic information, the AUC reached 0.89/0.87 for predicting 60-month KR occurrence. Conclusions: The RadScore of the patellofemoral joint on lateral radiographs emerges as an independent prognostic factor for improving KR prognosis prediction. The KR risk score could be instrumental in managing progressive knee osteoarthritis interventions.

Background: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. Objectives: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. Methods: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. Results: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. Discussion: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

This paper investigates how tourists develop adaptive perceptions in response to pandemic situations and how these perceptions influence their international travel decision-making toward a COVID-19-shaken destination in the new normal era. The survey was administered to Chinese potential international tourists and 608 questionnaires were utilized in data analysis. The results revealed the indirect effect of COVID-19 risk perception on travel intention first through cognitive image and then through affective image. Cognitive and affective images were identified as mediators of these interrelationships. The findings also showed that COVID-19 displayed varying effects on tourists with different past travel experiences. By unveiling factors influencing individuals’ travel decision-making in the new normal era, this study provides a theoretical basis for understanding the psychological and behavioral effects caused by a pandemic; delineating the underlying mechanism of the COVID-19 risk perception effect on international travel decision-making; expanding the research on destination image by clarifying the mediating roles of cognitive and affective images and their relation; providing timely and insightful implications for post-pandemic tourism recovery.

Myostatin (Mstn) was reported to be involved in multiple biological processes including the regulation of skeletal muscle growth, lipid metabolism and reproduction in vertebrates, therefore, it might play an essential role in the fine balance between growth and reproduction. In order to clarify the roles of Mstn in fish reproduction, we systematically investigated the gonadal development and fertility of mstnb mutants in Nile tilapia (Orochromis niloticus). In the present study, mstnb was found to be expressed in the different cell types of gonads by fluorescence in situ hybridization (FISH). Mutation of mstnb resulted in excessive proliferation of phase II follicles in the ovaries while the numbers of phase III follicles were significantly reduced at 210 days after hatching (dah). Interestingly, significant decline of cyp19a1a gene expression, the serum 17β-estradiol (E2), vitellogenin (VTG) were detected at 210 dah. At 360 dah, the ovarian development of mstnb-/- XX tilapia was partially recovered and female fish spawn regularly, however, they were subfertile and produced the poor-quality eggs with significantly lower offspring survival rate. The dramatic up-regulation of cyp19a1a gene expression and serum E2 level at 360 dah might account for the recovery of ovarian development. In mstnb-/- males, excessive proliferation of spermatogonia and retardation of testicular differentiation were found throughout the whole development stages. In mstnb-/- males, evident declines of gonadosomatic index (GSI), cyp11b2 gene expression, and 11-Ketotestosterone (11-KT) were detected at 210 dah, while the mRNA level of cyp11b2 and serum 11-KT level were significantly upregulated at 360 dah. However, mstnb-/- males were infertile since mutation of mstnb gene led to excessive increase of apoptosis of testicular cells and spermiation obstacle. Taken together, these results indicated that Mstn might be an essential regulator for the maintenance of fish fertility.

Abstract Objective As a single‐transmembrane protein of the FXYD family, FXYD6 plays different roles under physiological and pathological status, especially in the nervous system. This study aims to identify FXYD6 as a biomarker for glioma, by analyzing its expression and methylation patterns. Methods Using TCGA and GTEx datasets, we analyzed FXYD6 expression in various tissues, confirming its levels in normal brain and different glioma grades via immunoblotting and immunostaining. FXYD6 biological functions were explored through enrichment analysis, and tumor immune infiltration was assessed using ESTIMATE and TIMER algorithms. Pearson correlation analysis probed FXYD6 associations with biological function‐related genes. A glioma detection model was developed using FXYD6 methylation data from TCGA and GEO. Consistently, a FXYD6 methylation‐based prognostic model was constructed for glioma via LASSO Cox regression. Results FXYD6 was observed to be downregulated in GBM and implicated in a range of cellular functions, including synapse formation, cell junctions, immune checkpoint, ferroptosis, EMT, and pyroptosis. Hypermethylation of specific FXYD6 CpG sites in gliomas was identified, which could be used to build a diagnostic model. Additionally, FXYD6 methylation‐based prognostic model could serve as an independent factor as well. Conclusions FXYD6 is a promising biomarker for the diagnosis and prognosis of glioma, with its methylation‐based prognostic model serving as an independent factor. This highlights its potential in clinical application for glioma management.

Abstract Background Para-dichlorobenzene (p-DCB) exposure associated with oxidative stress has indeed raised public concerns. However, whether p-DCB is linked with metabolic syndrome (MetS) remains unclear. We hypothesized that higher exposure to p-DCB would be linked with a higher risk of MetS in the U.S population. This study aimed to examine the associations of exposure to p-DCB with MetS prevalence. Methods We included 10,428 participants (5,084 men and 5,344 women), aged ≥ 20 years, from the National Health and Nutrition Examination Survey (2003–2016). The cases of MetS were diagnosed by NCEP/ATPIII. Logistic regression models were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of MetS prevalence. Moreover, the mix associations of p-DCB metabolites were assessed using quantile sum (WQS) regression and quantile g-computation (qgcomp) methods. Results We documented 2,861 (27.1%) MetS cases. After adjustment for the potential risk factors, the ORs (95% CI) of MetS prevalence across the quartile of urinary 2,5-dichlorophenol (2,5-DCP) were 1.09 (0.93-1.28), 1.22 (1.00-1.49), and 1.34 (1.04-1.73). Moreover, 2,5 DCP is significantly associated with a higher prevalence of abdominal obesity [ORQ4vsQ1 (95% CI): 1.23 (1.03-1.48)]. The WQS and qgcomp index also showed significant associations between p-DCB metabolites and MetS. Moreover, we further examined that 2,5 DCP was correlated with higher systolic blood pressure (r = 0.022, P = 0.027), waist circumference (r = 0.099, P

Abstract Inflammatory bowel disease (IBD) is a common immune-mediated condition with its molecular pathogenesis remaining to be fully elucidated. This study aimed to deepen our understanding of the role of FUT2 in human IBD, by studying a new surrogate gene Sec1, a neighboring gene of Fut2 and Fut1 that co-encodes the α 1,2 fucosyltransferase in mice. CRISPR/Cas9 was used to prepare Sec1 knockout (Sec1 −/− ) mice. IBD was induced in mice using 3% w/v dextran sulphate sodium. Small interfering RNA (siRNA) was employed to silence Sec1 in murine colon cancer cell lines CT26.WT and CMT93. IBD-related symptoms, colonic immune responses, proliferation and apoptosis of colon epithelial cells were assessed respectively to determine the role of Sec1 in mouse IBD. Impact of Sec1 on the expression of death receptor 5 (DR5) and other apoptosis-associated proteins were determined. Sec1 knockout was found to be associated with deterioration of IBD in mice and elevated immune responses in the colonic mucosa. Silencing Sec1 in CT26.WT and CMT93 cells led to greater secretion of inflammatory cytokines IL-1β, IL-6 and TNF-α. Cell counting kit 8 (CCK8) assay, flow cytometry and TUNEL detection suggested that Sec1 expression promoted the proliferation of colon epithelial cells, inhibited cell apoptosis, reduced cell arrest in G0/G1 phase and facilitated repair of inflammatory injury. Over-expression of DR5 and several apoptosis-related effector proteins was noticed in Sec1 −/− mice and Sec1-silenced CT26.WT and CMT93 cells, supporting a suppressive role of Sec1 in cell apoptosis. Our results depicted important regulatory roles of Sec1 in mouse IBD, further reflecting the importance of FUT2 in the pathogenesis of human IBD.

Abstract Background Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. Methods A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. Results The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH. Conclusions Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Abstract Image perturbation is a promising technique to assess radiomic feature repeatability, but whether it can achieve the same effect as test–retest imaging on model reliability is unknown. This study aimed to compare radiomic model reliability based on repeatable features determined by the two methods using four different classifiers. A 191-patient public breast cancer dataset with 71 test–retest scans was used with pre-determined 117 training and 74 testing samples. We collected apparent diffusion coefficient images and manual tumor segmentations for radiomic feature extraction. Random translations, rotations, and contour randomizations were performed on the training images, and intra-class correlation coefficient (ICC) was used to filter high repeatable features. We evaluated model reliability in both internal generalizability and robustness, which were quantified by training and testing AUC and prediction ICC. Higher testing performance was found at higher feature ICC thresholds, but it dropped significantly at ICC = 0.95 for the test–retest model. Similar optimal reliability can be achieved with testing AUC = 0.7–0.8 and prediction ICC > 0.9 at the ICC threshold of 0.9. It is recommended to include feature repeatability analysis using image perturbation in any radiomic study when test–retest is not feasible, but care should be taken when deciding the optimal feature repeatability criteria.

Background: Plastic-based products are ubiquitous due to their tremendous utility in our daily lives. Nanoplastic (NP) and microplastic (MP) pollution has become a severe threat to the planet and is a growing concern. It has been widely reported that polystyrene (PS) MPs are severely toxic to the male reproduction system, with effects including decreased sperm parameters, impaired spermatogenesis, and damaged testicular structures. However, the molecular mechanisms for impaired spermatogenesis remain poorly understood. Methods: C57BL/6 male mice were treated with PS-NPs (80 nm) and PS-MPs (5 μm) by oral gavage every day for 60 days. A series of morphological analyses were completed to explore the influence of PS-NP and PS-MP exposure on the testes. Compared to other cell types in the seminiferous tubule, PS-NP and PS-MP exposure can lead to decreased spermatocytes. Then, more refined molecular typing was further performed based on gene expression profiles to better understand the common and specific molecular characteristics after exposure to PS-NPs and PS-MPs. Results: There were 1794 common DEGs across the PS-NP groups at three different doses and 1433 common DEGs across the PS-MP groups at three different doses. GO and KEGG analyses of the common DEGs in the PS-NP and PS-MP groups were performed to enrich the common and specific functional progress and signaling pathways, including 349 co-enriched GO entries and 13 co-enriched pathways. Moreover, 348 GO entries and 33 pathways were specifically enriched in the PS-NP group, while 526 GO entries and 15 pathways were specifically enriched in the PS-MPs group. Conclusions: PS-NPs were predominantly involved in regulating retinoic acid metabolism, whereas PS-MPs primarily influenced pyruvate metabolism and thyroid hormone metabolism. Our results highlight the different molecular mechanisms of PS-NPs and PS-MPs in the impairment of spermatogenesis in male mammals for the first time, providing valuable insights into the precise mechanisms of PS-NPs and PS-MPs in male reproduction.

This study aims to evaluate the repeatability of radiomics and dosiomics features via image perturbation of patients with cervical cancer. A total of 304 cervical cancer patients with planning CT images and dose maps were retrospectively included. Random translation, rotation, and contour randomization were applied to CT images and dose maps before radiomics feature extraction. The repeatability of radiomics and dosiomics features was assessed using intra-class correlation of coefficient (ICC). Pearson correlation coefficient (r) was adopted to quantify the correlation between the image characteristics and feature repeatability. In general, the repeatability of dosiomics features was lower compared with CT radiomics features, especially after small-sigma Laplacian-of-Gaussian (LoG) and wavelet filtering. More repeatable features (ICC > 0.9) were observed when extracted from the original, Large-sigma LoG filtered, and LLL-/LLH-wavelet filtered images. Positive correlations were found between image entropy and high-repeatable feature number in both CT and dose (r = 0.56, 0.68). Radiomics features showed higher repeatability compared to dosiomics features. These findings highlight the potential of radiomics features for robust quantitative imaging analysis in cervical cancer patients, while suggesting the need for further refinement of dosiomics approaches to enhance their repeatability.

Radiomics, which integrates the comprehensive characterization of imaging phenotypes with machine learning algorithms, is increasingly recognized for its potential in the diagnosis and prognosis of oncological conditions. However, the repeatability and reproducibility of radiomic features are critical challenges that hinder their widespread clinical adoption. This review aims to address the paucity of discussion regarding the factors that influence the reproducibility and repeatability of radiomic features and their subsequent impact on the application of radiomic models. We provide a synthesis of the literature on the repeatability and reproducibility of CT/MR-based radiomic features, examining sources of variation, the number of reproducible features, and the availability of individual feature repeatability indices. We differentiate sources of variation into random effects, which are challenging to control but can be quantified through simulation methods such as perturbation, and biases, which arise from scanner variability and inter-reader differences and can significantly affect the generalizability of radiomic model performance in diverse settings. Four suggestions for repeatability and reproducibility studies are suggested: (1) detailed reporting of variation sources, (2) transparent disclosure of calculation parameters, (3) careful selection of suitable reliability indices, and (4) comprehensive reporting of reliability metrics. This review underscores the importance of random effects in feature selection and harmonizing biases between development and clinical application settings to facilitate the successful translation of radiomic models from research to clinical practice.

The global population aging poses new challenges in allocating care facilities for the elderly. This demographic trend also influences economic development and the quality of urban life. However, current research focuses on the supply of elderly care facilities and primarily uses administrative divisions as a scale, resulting in low spatiotemporal sensitivity in evaluating the spatial equilibrium of elderly care facilities (SEECF). The relationship between the SEECF and economic development is not clear. In response to these problems, we proposed a spatial equilibrium model of elderly care facilities with high spatiotemporal sensitivity (SEM-HSTS) and explored the spatiotemporal associations between the SEECF and economic development. Considering the spatial accessibility rate of elderly care services (SARecs) and the spatiotemporal supply–demand ratio for elderly care services (STSDRecs), two types of supply–demand relationship factors were constructed. Then, a spatiotemporal accessibility of medical services (STAms) factor was obtained based on a modified two-step floating catchment area (M2SFCA) method. On this basis, the SEM-HSTS was constructed based on the theory of coordinated development. Further, a panel threshold model was employed to evaluate the influence relationships among population aging, SEECF, and gross domestic product (GDP) in different phases. Finally, spatial autocorrelation and Geodetector explored the spatial associations between SEECF and GDP across complex urban land use categories (ULUC). The experimental results at a 100-m grid scale showed that the SEM-HSTS exhibited higher spatiotemporal heterogeneity than the classical accessibility method, with elevated spatiotemporal sensitivity. Effectively identified various spatial imbalances, such as undersupply and resource waste. The panel model captured phased relationship changes, showing that SEECF had inhibitory and promotional effects on GDP in pre- and post-aging societies, with stronger effects as balance approached. Moreover, the combined interaction of ULUC and GDP had a more significant influence on SEECF than any individual factor, with GDP exerting a more significant influence. This study provides an empirical basis for creating resource-efficient elderly care facility systems and optimizing layouts.

In this paper, we develop a multi-objective integrated optimization method for feeder buses of rail transit based on realistic considerations. We propose a bus stop selection method that considers the influence of shared motorcycles, which can score the importance of alternative bus stops and select those with the highest scores as objectives. The objective of the model in this paper is to minimize both the travel costs of passengers and the operating costs of the bus company. This is achieved by optimizing feeder bus routes, the frequency of departures, and interchange discounts to enhance the connectivity between feeder buses and rail transit. In addition, to ensure the feasibility of generated routes in the real road network, a genetic algorithm encoded with priority is used to solve this model. We use the Xingyao Road subway station in Kunming as an example, and the results show that the optimization method is effective.

A physics-based low frequency noise (LFN) model for AlxGa1−xN/GaN high electron mobility transistors (HEMTs) is proposed in this article. By treating the distributed low-density surface donor states as the responsible mechanism and exhibiting charge neutrality in combination with the electric field across the barrier layer, a compact expression for Schottky barrier height (SBH) capturing the physics behind the variations of AlxGa1−xN layer thickness is profiled, which incorporates the effect of strain relaxation caused by high Al fraction. Furthermore, the SBH is applied to develop VTH and IDS. The LFN model, dominated by the fluctuations of carriers and drain current in the channel caused by the trapping/detrapping process, is subsequently obtained. It is indicated that the larger threshold voltage, higher drain current, and normalized noise are observed by our model with respect to the traditional SBH expressed only by an interpolated linear function of x. The drain current noise behavior showing the 1/f spectrum down to very low frequencies is seriously subjected to the barrier thickness-dependent SBH of AlxGa1−xN/GaN HEMTs. The accuracy of the proposed model is also verified by comparison with the experimental results from different devices.

Summary: Neoadjuvant chemotherapy (NACT) is a therapeutic option for locally advanced cervical cancer (LACC) patients. This study was aimed to identify potential liquid biopsy biomarkers to monitor the NACT response. Through targeted next-generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) and tumor tissue DNA (ttDNA) taken from LACC patients undergoing platinum-based NACT, 64 genes with mutations emerge during NACT in the non-responders but none in the responders. Among them, the PBRM1, SETD2, and ROS1 mutations were frequently detected in the ctDNA and ttDNA of the non-responders, and mutant PBRM1 was associated with poorer survival of patients. In vitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

Background and purposeA notable prevalence of subarachnoid hemorrhage is evident among patients with anterior choroidal artery aneurysms in clinical practice. To evaluate the risk of rupture in unruptured anterior choroidal artery aneurysms, we conducted a comprehensive analysis of risk factors and subsequently developed two nomograms.MethodsA total of 120 cases of anterior choroidal artery aneurysms (66 unruptured and 54 ruptured) from 4 medical institutions were assessed utilizing computational fluid dynamics (CFD) and digital subtraction angiography (DSA). The training set, consisting of 98 aneurysms from 3 hospitals, was established, with an additional 22 cases from the fourth hospital forming the external validation set. Statistical differences between the two data sets were thoroughly compared. The significance of 9 clinical baseline characteristics, 11 aneurysm morphology parameters, and 4 hemodynamic parameters concerning aneurysm rupture was evaluated within the training set. Candidate selection for constructing the nomogram models involved regression analysis and variance inflation factors. Discrimination, calibration, and clinical utility of the models in both training and validation sets were assessed using area under curves (AUC), calibration plots, and decision curve analysis (DCA). The DeLong test, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed to compare the effectiveness of classification across models.ResultsTwo nomogram models were ultimately constructed: model 1, incorporating clinical, morphological, and hemodynamic parameters (C + M + H), and model 2, relying primarily on clinical and morphological parameters (C + M). Multivariate analysis identified smoking, size ratio (SR), normalized wall shear stress (NWSS), and average oscillatory shear index (OSIave) as optimal candidates for model development. In the training set, model 1 (C + M + H) achieved an AUC of 0.795 (95% CI: 0.706 ~ 0.884), demonstrating a sensitivity of 95.6% and a specificity of 54.7%. Model 2 (C + M) had an AUC of 0.706 (95% CI: 0.604 ~ 0.808), with corresponding sensitivity and specificity of 82.4 and 50.3%, respectively. Similarly, AUCs for models 1 and 2 in the external validation set were calculated to be 0.709 and 0.674, respectively. Calibration plots illustrated a consistent correlation between model evaluations and real-world observations in both sets. DCA demonstrated that the model incorporating hemodynamic parameters offered higher clinical benefits. In the training set, NRI (0.224, p = 0.007), IDI (0.585, p = 0.002), and DeLong test (change = 0.089, p = 0.008) were all significant. In the external validation set, NRI, IDI, and DeLong test statistics were 0.624 (p = 0.063), 0.572 (p = 0.044), and 0.035 (p = 0.047), respectively.ConclusionMultidimensional nomograms have the potential to enhance risk assessment and patient-specific treatment of anterior choroidal artery aneurysms. Validated by an external cohort, the model incorporating clinical, morphological, and hemodynamic features may provide improved classification of rupture states.

Vaccinium species have great significance as fruit crops due to their economic and food values. Here we report the chloroplast genome of V. oxycoccos. The chloroplast genome of V. oxycoccos was 177,088 bp in length with a GC content of 36.74%. LSC, SSC, and IR regions were 104,139 bp, 3031 bp, and 34,959 bp in length, respectively. The chloroplast genome contained 105 different genes, including 73 protein-coding genes, 4 rRNA genes, and 28 tRNA genes. The phylogenetic analysis indicated that V. oxycoccos was closely related to V. microcarpum in the family Ericaceae. This chloroplast genome not only enriches the genome information of Vaccinium, but also will be useful in the evolution study of the family Ericaceae.

Artificial intelligence (AI) is developing rapidly and has found widespread applications in medicine, especially radiotherapy. This paper provides a brief overview of AI applications in radiotherapy, and highlights the research directions of AI that can potentially make significant impacts and relevant ongoing research works in these directions. Challenging issues related to the clinical applications of AI, such as robustness and interpretability of AI models, are also discussed. The future research directions of AI in the field of medical physics and radiotherapy are highlighted.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Lung adenocarcinoma (LUAD) is the most widespread cancer in the world, and its development is associated with complex biological mechanisms that are poorly understood. Here, we revealed a marked upregulation in the mRNA level of C1orf131 in LUAD samples compared to non-tumor tissue samples in The Cancer Genome Atlas (TCGA). Depletion of C1orf131 suppressed cell proliferation and growth, whereas it stimulated apoptosis in LUAD cells. Mechanistic investigations revealed that C1orf131 knockdown induced cell cycle dysregulation via the AKT and p53/p21 signalling pathways. Additionally, C1orf131 knockdown blocked cell migration through the modulation of epithelial–mesenchymal transition (EMT) in lung adenocarcinoma. Notably, we identified the C1orf131 protein nucleolar localization sequence, which included amino acid residues 137–142 (KKRKLT) and 240–245 (KKKRKG). Collectively, C1orf131 has potential as a novel therapeutic marker for patients in the future, as it plays a vital role in the progression of lung adenocarcinoma.

To tackle the problem of the brain storm optimization (BSO) algorithm’s suboptimal capability for avoiding local optima, which contributes to its inadequate optimization precision, we developed a flock decision mutation approach that substantially enhances the efficacy of the BSO algorithm. Furthermore, to solve the problem of insufficient BSO algorithm population diversity, we introduced a strategy that utilizes the good point set to enhance the initial population’s quality. Simultaneously, we substituted the K-means clustering approach with spectral clustering to improve the clustering accuracy of the algorithm. This work introduced an enhanced version of the brain storm optimization algorithm founded on a flock decision mutation strategy (FDIBSO). The improved algorithm was compared against contemporary leading algorithms through the CEC2018. The experimental section additionally employs the AUV intelligence evaluation as an application case. It addresses the combined weight model under various dimensional settings to substantiate the efficacy of the FDIBSO algorithm further. The findings indicate that FDIBSO surpasses BSO and other enhanced algorithms for addressing intricate optimization challenges.

Background: A healthy, well-balanced diet plays an essential role in respiratory diseases. Since micronutrient deficiency is relatively common in patients with chronic obstructive pulmonary disease (COPD), micronutrient supplementation might have the beneficial health effects in those patients. This systematic review and meta-analysis aimed to demonstrate the impact of micronutrient supplementation on the lung function of patients with COPD. Methods: The PubMed, Cochrane Library, and Web of Science databases were searched from their corresponding creation until February 2024. Search terms included ‘chronic obstructive pulmonary disease’, ‘COPD’, ‘micronutrients’, ‘dietary supplements’, ‘vitamins’, ‘minerals’, and ‘randomized controlled trials’. Meta-analysis was performed to evaluate the effects of micronutrient supplementation alone or complex on lung function in patients with COPD. Results: A total of 43 RCTs fulfilled the inclusion criteria of this study. Meta-analysis revealed that vitamin D supplementation could significantly improve FEV1% (WMDdifferences between baseline and post-intervention (de): 6.39, 95% CI: 4.59, 8.18, p < 0.01; WMDpost-intervention indicators (af): 7.55, 95% CI: 5.86, 9.24, p < 0.01) and FEV1/FVC% (WMDde: 6.88, 95%CI: 2.11, 11.65, WMDaf: 7.64, 95% CI: 3.18, 12.10, p < 0.001), decrease the odds of acute exacerbations, and improve the level of T-cell subsets, including CD3+%, CD4+%, CD8+%, and CD4+/CD8+% (all p < 0.01). The effects of compound nutrients intervention were effective in improving FEV1% (WMDde: 8.38, 95%CI: 1.89, 14.87, WMDaf: 7.07, 95%CI: −0.34, 14.48) and FEV1/FVC% (WMDde: 7.58, 95% CI: 4.86, 10.29, WMDaf: 6.00, 95% CI: 3.19, 8.81). However, vitamin C and vitamin E supplementation alone had no significant effects on lung function (p > 0.05). Conclusions: Micronutrient supplementation, such as vitamin D alone and compound nutrients, has improved effect on the lung function of patients with COPD. Therefore, proper supplementation with micronutrients would be beneficial to stabilize the condition and restore ventilation function for COPD patients.

Abstract Background The immunohistochemical test (IHC) of HER2 and HR can provide prognostic information and treatment guidance for invasive breast cancer patients. We aimed to develop noninvasive image signatures ISHER2 and ISHR of HER2 and HR, respectively. We independently evaluate their repeatability, reproducibility, and association with pathological complete response (pCR) to neoadjuvant chemotherapy. Methods Pre-treatment DWI, IHC receptor status HER2/HR, and pCR to neoadjuvant chemotherapy of 222 patients from the multi-institutional ACRIN 6698 trial were retrospectively collected. They were pre-separated for development, independent validation, and test–retest. 1316 image features were extracted from DWI-derived ADC maps within manual tumor segmentations. ISHER2 and ISHR were developed by RIDGE logistic regression using non-redundant and test–retest reproducible features relevant to IHC receptor status. We evaluated their association with pCR using area under receiver operating curve (AUC) and odds ratio (OR) after binarization. Their reproducibility was further evaluated using the test–retest set with intra-class coefficient of correlation (ICC). Results A 5-feature ISHER2 targeting HER2 was developed (AUC = 0.70, 95% CI 0.59 to 0.82) and validated (AUC = 0.72, 95% CI 0.58 to 0.86) with high perturbation repeatability (ICC = 0.92) and test–retest reproducibility (ICC = 0.83). ISHR was developed using 5 features with higher association with HR during development (AUC = 0.75, 95% CI 0.66 to 0.84) and validation (AUC = 0.74, 95% CI 0.61 to 0.86) and similar repeatability (ICC = 0.91) and reproducibility (ICC = 0.82). Both image signatures showed significant associations with pCR with AUC of 0.65 (95% CI 0.50 to 0.80) for ISHER2 and 0.64 (95% CI 0.50 to 0.78) for ISHER2 in the validation cohort. Patients with high ISHER2 were more likely to achieve pCR to neoadjuvant chemotherapy with validation OR of 4.73 (95% CI 1.64 to 13.65, P value = 0.006). Low ISHR patients had higher pCR with OR = 0.29 (95% CI 0.10 to 0.81, P value = 0.021). Molecular subtypes derived from the image signatures showed comparable pCR prediction values to IHC-based molecular subtypes (P value > 0.05). Conclusion Robust ADC-based image signatures were developed and validated for noninvasive evaluation of IHC receptors HER2 and HR. We also confirmed their value in predicting treatment response to neoadjuvant chemotherapy. Further evaluations in treatment guidance are warranted to fully validate their potential as IHC surrogates.

Abstract Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold. The NGOVM has a broader antitumor spectrum and a more robust oncolytic effect in a range of solid tumors. Mechanistically, two critical mutations are identified in the E2 and nsP3 genes, which accelerate the entry of M1 virus by increasing its binding to the Mxra8 receptor and antagonize antiviral responses by inhibiting the activation of PKR and STAT1 in tumor cells, respectively. Importantly, the NGOVM is well tolerated in both rodents and nonhuman primates. This study implies that directed natural evolution is a generalizable approach for developing next-generation OVs with an expanded scope of application and high safety.

Abstract Purpose Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. Methods ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5‐associated differentially expressed genes. Analyses of single‐cell RNA‐seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT‐PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. Results High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5‐associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5‐targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K‐Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p‐AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1‐targeting siRNA showed fibronectin may play a critical role on ITGA5‐mediated angiogenesis. Conclusion ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer.

Abstract Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’ anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.

Abstract Black carbon (BC) plays an important role in the climate system because of its strong warming effect, yet the magnitude of this effect is highly uncertain owing to the complex mixing state of aerosols. Here we build a unified theoretical framework to describe BC’s mixing states, linking dynamic processes to BC coating thickness distribution, and show its self-similarity for sites in diverse environments. The size distribution of BC-containing particles is found to follow a universal law and is independent of BC core size. A new mixing state module is established based on this finding and successfully applied in global and regional models, which increases the accuracy of aerosol climate effect estimations. Our theoretical framework links observations with model simulations in both mixing state description and light absorption quantification.