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Abstract Background This study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR). Methods From January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed. Results Squamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046). Conclusion The study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Objective: This study aimed to investigate the application value of virtual monoenergetic (VMI) (≤70 keV) computed tomography angiography (CTA) in imaging small cerebral vessels with dual-layer detector spectral CT. Methods: The imaging data of 52 patients who underwent head and neck CTA using Philips IQon CT were retrospectively analyzed. Conventional 120 kVp mixed energy images and 40~70 keV (10 keV interval) VMI CTA images reconstructed using spectral data were obtained. The CT value, signal-to-noise ratio (SNR), contrast noise ratio (CNR), and CT value and noise (SD) of the paravascular cerebral parenchyma at the same level were measured in the M1 segment of the middle cerebral artery. The image quality of the middle cerebral artery in volume reconstruction (VRT) and lepidopleural artery in maximum density projection (MIP) was scored by two physicians using a 5-point Likert scale. The evaluation results between the different groups were compared. Results: The CT, SNR, and CNR values of blood vessels at 40~70 keV VMI increased with a decrease in energy level, and the SD values increased slightly, with more statistically significant differences compared with conventional images. In the subjective evaluation, the VRT images in the 40 keV and 50 keV groups were 5 (5, 5) and 5 (4, 5), respectively, and the MIP image scores were 4 (3, 4) and 4 (3, 5), respectively. The subjective scores of both groups were better than those of the other groups, with no statistically significant difference. Conclusion: Virtual monoenergetic CTA technology with dual-layer spectral CT

Abstract Background Cotton serves as a primary source of natural fibers crucial for the textile industry. However, environmental elements such as drought have posed challenges to cotton cultivation, resulting in adverse impacts on both production and fiber quality. Improving cotton’s resilience to drought could mitigate yield losses and foster the expansion of cotton farming. Rab7 protein, widely present in organisms, controls the degradation and recycling of cargo, and has a potential role in biotic and abiotic tolerance. However, comprehensive exploration of the Rab7 gene family in Gossypium remains scarce. Results Herein, we identified a total of 10, 10, 20, and 20 Rab7 genes through genome-wide analysis in Gossypium arboreum, Gossypium raimondii, Gossypium hirsutum, and Gossypium barbadense, respectively. Collinearity analysis unveiled the pivotal role of whole genome or segmental duplication events in the expansion of GhRab7s. Study of gene architecture, conserved protein motifs, and domains suggested the conservation of structure and function throughout evolution. Exploration of cis-regulatory elements revealed the responsiveness of GhRab7 genes to abiotic stress, corroborated by transcriptome analysis under diverse environmental stresses. Notably, the greatly induced expression of GhRab7B3-A under drought treatment prompted us to investigate its function through virus-induced gene silencing (VIGS) assays. Silencing GhRab7B3-A led to exacerbated dehydration and wilting compared with the control. Additionally, inhibition of stomatal closure, antioxidant enzyme activities and expression patterns of genes responsive to abiotic stress were observed in GhRab7B3-A silenced plants. Conclusions This study sheds light on Rab7 members in cotton, identifies a gene linked to drought stress, and paves the way for additional investigation of Rab7 genes associated with drought stress tolerance.

Abstract Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process.

Abstract Drug repositioning is gaining attention as a method for developing new drugs due to its low cost, short cycle time, and high success rate. One important approach is to explore new uses for already marketed drugs. In this study, we utilized the strategy of drug repositioning, focusing on the Dan-Lou tablet. We predicted the efficacy of Dan-Lou tablet against non-small cell lung cancer based on gene expression similarity and verified it by in vitro experiments. Next, we performed further analysis and validation using network pharmacology, molecular docking and molecular dynamics. Based on the results, it was concluded that Dan-Lou tablet mainly acted through nine compounds, Quercetin, Luteolin, Scoparone, Isorhamnetin, Eugenol, Genistein, Coumestrol, Hederagenin, Succinic Acid, and mainly targeted CCL2, FEN1, TPI1, RMI2 by six pathways. This discovery not only provides a new idea for the development of Dan-Lou tablet but also provides useful predictive information for clinical treatment. The method we adopted has great development prospects as a way to predict the efficacy of new drugs and their main mechanisms of action, and it has a positive impact on the research and development of new drugs using drug repositioning and the modernization of traditional Chinese medicine.

Abstract Background Australia hosts over 680,000 international students, contributing $47.8 billion to the Australian economy in 2023, and Chinese students rank first among all nationalities. However, despite their considerable numbers, research focusing on their access to healthcare services is scant. This study aimed to explore barriers and supports regarding the utilisation of healthcare services among Chinese international students studying in Australia. Methods Semi-structured interviews were conducted in Chinese between October and December 2023 with 25 Chinese international students (age range, 19–30; female/male, n = 18/7; undergraduate/postgraduate/doctoral, n = 1/18/6) enrolled in three Australian universities to understand the healthcare challenges they encountered and the coping strategies they recommended. These interviews were recorded, and thematic analysis was applied to the interview data. An adapted social-ecological model was used to identify barriers and pragmatic strategies to deal with the challenges at different levels. Results Chinese international students in Australia faced healthcare barriers at different levels. Individual barriers included language and cultural disparities, lack of knowledge about the healthcare system, and reluctance to seek help. Institutional barriers involved high costs, difficulties regarding appointments, and procedures related to the referral system. Policy barriers included insurance coverage and reimbursement issues. The students interviewed for this study proposed individual-level strategies, such as trying various methods to reduce language barriers, seeking information online, and using online resources and consultations. A central appointment platform and multilingual medical service were recommended from students to medical institutions, while medical service guidance and psychological support were suggested to education institutions. Higher-level strategies were also reported, which were mainly pertaining to insurance terms and coverage for overseas students and improving the accessibility of medical information. Conclusions Our study identifies barriers to healthcare access for Chinese international students in Australia, including culture-specific challenges. To mitigate these issues, we recommend self-directed health promotion, targeted support by education institutions, enhanced cross-cultural communication and expanded telemedicine by hospitals, and attention to insurance coverage. Future research should explore optimising these approaches to improve support systems and policy frameworks.

Abstract Although many genome-wide association studies (GWAS) have confirmed the negative associations between rs401681[T] / rs402710[T] in the Cleft lip and cleft palate transmembrane protein 1 (CLPTM1L) region and lung cancer (LC) susceptibility in Caucasian and Asian populations, some other studies haven’t found these negative associations. The purpose of this study is to clarify the associations between them and LC, as well as the differences in these associations between patients of different ethnicities (Caucasians and Asians), LC subtypes and smoking status. Relevant literatures published before July 7, 2023 in PubMed, EMbase, Web of Science, MEDLINE were searched through the Internet. Statistical analysis of data was performed in Revman 5.3, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias were performed in Stata 14.0. TSA software was performed for the trial sequential analysis (TSA) tests to assess the stability of the results. Registration number: CRD42023407890. A total of 41 literatures (containing 44 studies: 16 studies in Caucasians and 28 studies in Asians) were included in this meta-analysis, including 126476 LC patients and 191648 healthy controls. The results showed that the T allele variants of rs401681 and rs402710 were negatively associated with the risk of LC (rs401681[T]: [OR] = 0.87, 95% CI [0.86, 0.88]; rs402710[T]: [OR] = 0.88, 95% CI [0.86, 0.89]), and the negative associations were stronger in Caucasians than in Asians (Subgroup differences: I2 > 50%). In LC subtypes, the rs401681[T] was negatively associated with the risk of Non-small-cell lung carcinoma (NSCLC), Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) (P 50%). The rs402710[T] was negatively associated with the risk of NSCLC, LUAD and LUSC (P

Abstract Background The cycle threshold (Ct) value is inversely proportional to the number of copies of the target region in a sample, suggesting that a low Ct value indicates a high pathogen load. The relationship between Ct value and clinical presentation in children with pertussis is not well-defined. Methods We investigated the relationships between the Ct value of nasopharyngeal samples positive for Bordetella pertussis deoxyribonucleic acid via real-time polymerase chain reaction (PCR), collected from children on admission and their adult family members between May 2022 and March 2024 at Hangzhou Children’s Hospital, China. The study focused on the correlation between Ct value and clinical presentation in children with pertussis. Results The Ct value was positively correlated with age (r = 0.362, P = 0.001). The mean Ct value for children with pertussis was 28.0 (range: 22.0–32.0), which was lower than the 32.0 (range: 30.0–34.0) observed in adults. Ct value was inversely correlated with length of stay, an indicator of disease severity (r = -0.356, P = 0.001). Logistic regression analyses revealed that both Ct value (OR: 0.891, 95% CI: 0.799–0.993, P = 0.036) and white blood cell count (OR: 1.127, 95% CI: 1.005–1.263, P = 0.040) were independently associated with severity of pertussis. Conclusions Real-time PCR Ct values at initial diagnosis for pertussis may potentially predict severe disease outcomes in children.

Abstract Large datasets are required to develop Artificial Intelligence (AI) models in AI powered smart farming for reducing farmers’ routine workload, this paper contributes the first large lion-head goose dataset GooseDetect l i o n , which consists of 2,660 images and 98,111 bounding box annotations. The dataset was collected with 6 cameras deployed in a goose farm in Chenghai district of Shantou city, Guangdong province, China. Images sampled from videos collected during July 9 -10 in 2022 were fully annotated by a team of fifty volunteers. Compared with another 6 well known animal datasets in literature, our dataset has higher capacity and density, which provides a challenging detection benchmark for main stream object detectors. Six state-of-the-art object detectors have been selected to be evaluated on the GooseDetect l i o n , which includes one two-stage anchor-based detector, three one-stage anchor-based detectors, as well as two one-stage anchor-free detectors. The results suggest that the one-stage anchor-based detector You Only Look Once version 5 (YOLO v5) achieves the best overall performance in terms of detection precision, model size and inference efficiency.

Abstract Background Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by glioblastoma stem cells (GSCs). The interplay between GSCs and immunosuppressive microglia plays crucial roles in promoting the malignant growth of GBM; however, the molecular mechanisms underlying this crosstalk are unclear. This study aimed to investigate the role of POSTN in maintaining GSCs and the immunosuppressive phenotype of microglia. Methods The expression of POSTN in GBM was identified via immunohistochemistry, quantitative real-time PCR, and immunoblotting. Tumorsphere formation assay, Cell Counting Kit-8 assay and immunofluorescence were used to determine the key role of POSTN in GSC maintenance. ChIP-seq and ChIP-PCR were conducted to confirm the binding sequences of β-catenin in the promoter region of FOSL1. Transwell migration assays, developmental and functional analyses of CD4+ T cells, CFSE staining and analysis, enzyme-linked immunosorbent assays and apoptosis detection tests were used to determine the key role of POSTN in maintaining the immunosuppressive phenotype of microglia and thereby promoting the immunosuppressive tumor microenvironment. Furthermore, the effects of POSTN on GSC maintenance and the immunosuppressive phenotype of microglia were investigated in a patient-derived xenograft model and orthotopic glioma mouse model, respectively. Results Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway. In addition to its intrinsic effects on GSCs, POSTN can recruit microglia and upregulate CD70 expression in microglia through the αVβ3/PI3K/AKT/NFκB pathway, which in turn promotes Treg development and functionality and supports the formation of an immunosuppressive tumor microenvironment. In both in vitro models and orthotopic mouse models of GBM, POSTN depletion disrupted GSC maintenance, decreased the recruitment of immunosuppressive microglia and suppressed GBM growth. Conclusion Our findings reveal that POSTN plays critical roles in maintaining GSCs and the immunosuppressive phenotype of microglia and provide a new therapeutic target for treating GBM.

Currently, polylactic acid (PLA) is an attractive alternative to polypropylene (PP) because of its biodegradability. This study introduces a novel modification strategy for PLA by creating a multifunctional ionization layer with ionic salts. This approach achieves humidity sensing, reliable antibacterial properties, and excellent degradability simultaneously. The modified PLA textile sensor exhibits high sensitivity to respiratory humidity (0.92 at 90% RH), with ultrafast response (0.12 s) and recovery times (0.16 s). Additionally, the textile demonstrates excellent antibacterial performance against both E. coli (99.9%) and S. aureus (99.9%) after 1 h of contact. It also shows notable biodegradability with a weight loss rate of 60.38% after 30 days. Also, the ionic salt mechanism is explained through dynamic ionization interactions attributed to the modified ionic salts, which feature both long-chain alkanes and active ions. This work presents a new method to enhance the respiratory detection and antibacterial performance of biodegradable masks.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Peri-implant diseases, characterized by inflammatory conditions affecting peri-implant tissues, encompass peri-implant mucositis and peri-implantitis. Peri-implant mucositis is an inflammatory lesion limited to the mucosa around an implant, while peri-implantitis extends from the mucosa to the supporting bone, causing a loss of osseointegration. For non-surgical treatments, we tested the null hypothesis that the presence or absence of air-polishing made no difference. The study focused on randomized controlled trials (RCTs) comparing air-polishing with mechanical or ultrasonic debridement, evaluating outcomes such as bleeding on probing (BOP), probing depth (PD), plaque index/plaque score (PI/PS), clinical attachment level (CAL), bone loss, and mucosal recession (MR). Two independent reviewers conducted data extraction and quality assessments, considering short-term (

AbstractContext Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.Objective This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.Materials and methods 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.Results Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.Discussion and conclusion The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.Trial registration ChiCTR2300076136, retrospectively registered.

Analyzing the vast amount of omics data generated comprehensively by high-throughput sequencing technology is of utmost importance for scientists. In this context, we propose HiOmics, a cloud-based platform equipped with nearly 300 plugins designed for the comprehensive analysis and visualization of omics data. HiOmics utilizes the Element Plus framework to craft a user-friendly interface and harnesses Docker container technology to ensure the reliability and reproducibility of data analysis results. Furthermore, HiOmics employs the Workflow Description Language and Cromwell engine to construct workflows, ensuring the portability of data analysis and simplifying the examination of intricate data. Additionally, HiOmics has developed DataCheck, a tool based on Golang, which verifies and converts data formats. Finally, by leveraging the object storage technology and batch computing capabilities of public cloud platforms, HiOmics enables the storage and processing of large-scale data while maintaining resource independence among users.

Abstract Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate the local activation of pulmonary and colon eosinophils within the inflammatory microenvironment. Leveraging transcriptional sequencing, we identify TGF-β as a putative regulator of eosinophil activation, leading to the secretion of granule proteins, including peroxidase. Genetic deletion of TGF-β receptors on eosinophils resulted in the inhibition of peroxidase synthesis, affirming the significance of TGF-β signaling in eosinophil activation. Using models of HDM-induced asthma and DSS-induced colitis, we demonstrate the indispensability of TGF-β-driven eosinophil activation in both disease contexts. Notably, while TGF-β signaling did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates a distinct pattern of eosinophil activation within inflammatory responses, highlighting the pivotal role of TGF-β signaling in regulating eosinophil behavior. These findings deepen our comprehension of eosinophil-related pathophysiology and may pave the way for targeted therapeutic approaches in allergic and inflammatory diseases.

Abstract Objective This study aimed to identify a quantitative index for optical coherence tomography (OCT) images to discriminate tumours from surrounding tissues. Subjects and methods Based on OCT measurements, mean grey values were determined from 432 locations on fifty-four human tissue specimens (eighteen cancerous, para-cancerous, and normal tissues each). These results were histologically evaluated by hematoxylin and eosin staining (H&E). Results The mean grey values of oral squamous cell carcinoma (OSCC) measurements were significantly different from those of the surrounding healthy tissue (p value

Abstract Recent studies have demonstrated that finely tuned deep neural networks (DNNs) are susceptible to adversarial attacks. Conventional physical attacks employ stickers as perturbations, achieving robust adversarial effects but compromising stealthiness. Recent innovations utilise light beams, such as lasers and projectors, for perturbation generation, allowing for stealthy physical attacks at the expense of robustness. In pursuit of implementing both stealthy and robust physical attacks, the authors present an adversarial catoptric light (AdvCL). This method leverages the natural phenomenon of catoptric light to generate perturbations that are both natural and stealthy. AdvCL first formalises the physical parameters of catoptric light and then optimises these parameters using a genetic algorithm to derive the most adversarial perturbation. Finally, the perturbations are deployed in the physical scene to execute stealthy and robust attacks. The proposed method is evaluated across three dimensions: effectiveness, stealthiness, and robustness. Quantitative results obtained in simulated environments demonstrate the efficacy of the proposed method, achieving an attack success rate of 83.5%, surpassing the baseline. The authors utilise common catoptric light as a perturbation to enhance the method's stealthiness, rendering physical samples more natural in appearance. Robustness is affirmed by successfully attacking advanced DNNs with a success rate exceeding 80% in all cases. Additionally, the authors discuss defence strategies against AdvCL and introduce some light‐based physical attacks.

Objective: This study focused on the identification and activity analysis of antioxidant active peptides in walnut dregs protein hydrolysates. Methods: Protein was extracted from walnut meal by fractionation method, and five kinds of proteolytic enzymes, including trypsin, papain, neutral protease, alkaline protease and flavor protease, were used to hydrolyze the proteins. The antioxidant activity of trypsin hydrolysate （TH）, papain hydrolysate （PH）, dispase hydrolysate （DH）, alcalase hydrolysate （AH） and flavourzyme hydrolysate （FPH） were evaluated and compared. The in vitro antioxidant activity of different concentrations of AH was determined by the detection indexes of DPPH free radical scavenging rate, ABTS free radical scavenging rate and hydroxyl free radical scavenging rate. The sequences of all peptides in AH were identified by LC-MS/MS technology, and the potential antioxidant active peptides of walnut were screened by PeptideRanker, BIOPEP-UWM database and molecular docking tool AutoDock1.5.6, and the two antioxidant active peptides were obtained. The above two peptides were simulated with Keap1 protein, and the antioxidant activity of the two antioxidant peptides was analyzed by using the zebrafish embryo oxidative damage model. Results: The optimal scavenging rates of AH with better antioxidant activity among the five enzymatic hydrolysates were （71.56±0.75）%, （60.63±0.45）% and （98.63±0.06）%, respectively. LC-MS/MS was identified by computer analysis to obtain two active ALWPF and PLRWPF peptides, both of which could bind to the active sites of Keap1 protein, with binding energies of -9.2 and -9.6 kJ/mol, respectively. The safe concentrations of zebrafish embryos treated with ALWPF and PLRWPF peptides ranged from 0～50 μg/mL and 0～30 μg/mL, respectively. Conclusion: Two antioxidant peptides were obtained from walnut meal, and the antioxidant effects of them were verified by zebrafish embryo model. The results of this study can provide a basis for the in-depth utilization of walnut protein.

Abstract Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe–loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence. Graphical Abstract

Abstract Background To evaluate the performances of several advanced deep convolutional neural network models (AlexNet, VGG, GoogLeNet, ResNet) based on ensemble learning for recognizing chronic gingivitis from screening oral images. Methods A total of 683 intraoral clinical images acquired from 134 volunteers were used to construct the database and evaluate the models. Four deep ConvNet models were developed using ensemble learning and outperformed a single model. The performances of the different models were evaluated by comparing the accuracy and sensitivity for recognizing the existence of gingivitis from intraoral images. Results The ResNet model achieved an area under the curve (AUC) value of 97%, while the AUC values for the GoogLeNet, AlexNet, and VGG models were 94%, 92%, and 89%, respectively. Although the ResNet and GoogLeNet models performed best in classifying gingivitis from images, the sensitivity outcomes were not significantly different among the ResNet, GoogLeNet, and Alexnet models (p>0.05). However, the sensitivity of the VGGNet model differed significantly from those of the other models (p

Abstract Background Oral Squamous Cell Carcinoma (OSCC) presents significant diagnostic challenges in its early and late stages. This study aims to utilize preoperative MRI and biochemical indicators of OSCC patients to predict the stage of tumors. Methods This study involved 198 patients from two medical centers. A detailed analysis of contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) MRI were conducted, integrating these with biochemical indicators for a comprehensive evaluation. Initially, 42 clinical biochemical indicators were selected for consideration. Through univariate analysis and multivariate analysis, only those indicators with p-values less than 0.05 were retained for model development. To extract imaging features, machine learning algorithms in conjunction with Vision Transformer (ViT) techniques were utilized. These features were integrated with biochemical indicators for predictive modeling. The performance of model was evaluated using the Receiver Operating Characteristic (ROC) curve. Results After rigorously screening biochemical indicators, four key markers were selected for the model: cholesterol, triglyceride, very low-density lipoprotein cholesterol and chloride. The model, developed using radiomics and deep learning for feature extraction from ceT1W and T2W images, showed a lower Area Under the Curve (AUC) of 0.85 in the validation cohort when using these imaging modalities alone. However, integrating these biochemical indicators improved the model’s performance, increasing the validation cohort AUC to 0.87. Conclusion In this study, the performance of the model significantly improved following multimodal fusion, outperforming the single-modality approach. Clinical relevance statement This integration of radiomics, ViT models, and lipid metabolite analysis, presents a promising non-invasive technique for predicting the staging of OSCC.

Abstract Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Abstract With business process optimization, technological advancement, equipment capability enhancement, and other means, the Railway Passenger Service Department in China is consistently working to improve the efficiency and convenience of passenger entry and exit procedures at railway stations. Concerning passengers’ checkout, not only conventional identification approaches based on manual control, identification card, and magnetic thermal paper ticket are supported, but also a recent contactless identification process based on face recognition is applied in some stations. To further improve the contactless identification ability for checkout, an advanced contactless checkout process based on gait-augmented face recognition is innovatively put forward, in which a weakly-supervised body segmentation network named Dwsegnet and an improved GaitSet model are proposed. Through comparison with various models, the effectiveness of both Dwsegnet and the improved GaitSet is validated. Specifically, the contactless identification rate of gait-augmented face recognition is improved by 2.31% when compared to single-modal face recognition, which demonstrates the superiority of the proposed process.

Abstract Background Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. Methods We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. Results We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. Conclusions Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.

Abstract Background Learning to perform strabismus surgery is an essential aspect of ophthalmologists’ surgical training. Automated classification strategy for surgical steps can improve the effectiveness of training curricula and the efficient evaluation of residents’ performance. To this end, we aimed to develop and validate a deep learning (DL) model for automated detecting strabismus surgery steps in the videos. Methods In this study, we gathered 479 strabismus surgery videos from Shanghai Children’s Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, spanning July 2017 to October 2021. The videos were manually cut into 3345 clips of the eight strabismus surgical steps based on the International Council of Ophthalmology’s Ophthalmology Surgical Competency Assessment Rubrics (ICO-OSCAR: strabismus). The videos dataset was randomly split by eye-level into a training (60%), validation (20%) and testing dataset (20%). We evaluated two hybrid DL algorithms: a Recurrent Neural Network (RNN) based and a Transformer-based model. The evaluation metrics included: accuracy, area under the receiver operating characteristic curve, precision, recall and F1-score. Results DL models identified the steps in video clips of strabismus surgery achieved macro-average AUC of 1.00 (95% CI 1.00–1.00) with Transformer-based model and 0.98 (95% CI 0.97-1.00) with RNN-based model, respectively. The Transformer-based model yielded a higher accuracy compared with RNN-based models (0.96 vs. 0.83, p

Abstract Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age‐related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia‐targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia‐induced pathways to enhance healthy aging and reduce the burden of age‐related diseases.

We analyze the properties of relativistic (>700 keV) electron precipitation (REP) events measured by the low-Earth-orbit (LEO) POES/MetOp constellation of spacecraft from 2012 through 2023. Leveraging the different profiles of REP observed at LEO, we associate each event with its possible driver: waves or field line curvature scattering (FLCS). While waves typically precipitate electrons in a localized radial region within the outer radiation belt, FLCS drives energy-dependent precipitation at the edge of the belt. Wave-driven REP is detected at any MLT sector and L shell, with FLCS-driven REP occurring only over the nightside–a region where field line stretching is frequent. Wave-driven REP is broader in radial extent on the dayside and accompanied by proton precipitation over 03–23 MLT, either isolated or without a clear energy-dependent pattern, possibly implying that electromagnetic ion cyclotron (EMIC) waves are the primary driver. Across midnight, both wave-driven and FLCS-driven REP occur poleward of the proton isotropic boundary. On average, waves precipitate a higher flux of >700 keV electrons than FLCS. Both contribute to energy deposition into the atmosphere, estimated of a few MW. REP is more associated with substorm activity than storms, with FLCS-driven REP and wave-driven REP at low L shells occurring most often during strong activity (SML* < −600 nT). A preliminary analysis of the Solar Wind (SW) properties before the observed REP indicates a more sustained (∼5 h) dayside reconnection for FLCS-driven REP than for wave-driven REP (∼3 h). The magnetosphere appears more compressed during wave-driven REP, while FLCS-driven REP is associated with a faster SW of lower density. These findings are useful not only to quantify the contribution of >700 keV precipitation to the atmosphere but also to shed light on the typical properties of wave-driven vs FLCS-driven precipitation which can be assimilated into physics-based and/or predictive radiation belt models. In addition, the dataset of ∼9,400 REP events is made available to the community to enable future work.

Summary: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe inflammatory condition that remains refractory; however, its molecular mechanisms are largely unknown. Previous studies have shown numerous compounds containing 4-indolyl-2-aminopyrimidine that display strong anti-inflammatory properties. In our research, we identified that a 4-Indole-2-Arylaminopyrimidine derivative named “IAAP” suppressed lipopolysaccharide (LPS)-induced inflammation. Immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified that IAAP interacts with a lysosomal cysteine protease, cathepsin L (CTSL), and restrains its activity. The nuclear factor kappa B (NF-κB) family plays a central role in controlling innate immunity. Canonical NF-κB activation, such as stimulation with lipopolysaccharide (LPS), typically involves the degradation of A20. We observed that IAAP suppression of CTSL prevented the LPS-induced degradation of A20, thereby ameliorating NF-κB activation. This study identifies CTSL as a crucial regulator of A20/NF-κB signaling and suggests IAAP as a potential lead compound for developing drugs to treat ALI/ARDS.

ABSTRACT: Recently, poultry industry has been seeking antibiotic residue-free poultry products and safe nutritious feed additives. Whether rosemary ultrafine powder (RUP) affects productive performance by regulating the intestinal microbiome of aged layers remains unclear. Here, we investigated the effects of dietary RUP supplementation on the production performance, egg quality, antioxidant capacity, intestinal microbial structure, and metabolome of aged hens. The results indicate that RUP had no significant effect on production performance but significantly enhanced Thick albumen height, Haugh unit, yolk color (P < 0.05), daily feed intake, and qualified egg rate. Serum content of non-esterified fatty acids, catalase, and glutathione peroxidase increased significantly (P < 0.05). Furthermore, the liver total protein content was significantly increased (P < 0.05). 16S rRNA sequence analysis revealed that RUP significantly impacted both α- and β-diversity of the caecum microbiota. Linear discriminant analysis of effect size and random forest identified Bacteroides, Muribaculum, Butyricimonas, Odoribacter, and Prevotella as biomarkers in groups A and B. In comparing groups A and C, Barnesiella, Turicibacter, and Acholeplasma were critical bacteria, while comparing groups A and D highlighted Barnesiella and Candidatus Saccharimonas as differential bacteria. FAPROTAX analysis of the caecum microbiota revealed that the functional genes associated with harmful substance biodegradation were significantly increased in the RUP-fed group. Based on Spearman correlation analysis, alterations in microbial genera were associated with divergent metabolites. In summary, dietary RUP can improve egg quality and antioxidant capacity and regulate the intestinal microbiome and metabolome in aged breeders. Therefore, RUP can potentially be used as a feed additive to extend breeder service life at an appropriate level of 1.0 g/kg.

ABSTRACT: The microbiomes of the reproductive tract play a crucial role in the egg production and quality and reproductive health of laying hens. Speckled eggs are characterized by shells with brown spots of varying sizes and commonly produced by brown-shelled laying hens. Speckles reduce the economic value of eggs. However, the relationship between oviduct and cloacal microbiomes and the presence of speckled eggs in laying hens remains unclear. In this study, we collected samples from the reproductive tracts (uterus, vagina, and cloaca) of hens laying speckled eggs and those laying normal eggs and compared their microbial structures and relative abundances through 16S rRNA sequencing. We found that the microbial community structure in the reproductive tracts of the hens laying speckled eggs was similar to that in the reproductive tracts of the hens laying normal eggs; however, the relative abundances of Clostridium in the uterus and Turicibacter and Gallibacterium in the vagina of the hens from the speckled group (7.27%, 6.83% and 0.10%, respectively) were significantly higher than those in the normal group (2.00%, 0% and 0%, respectively [P < 0.05]). Additionally, 8, 24, and 11 bacterial taxa in the uterus, vagina, and cloaca were different between the groups of hens laying speckled and normal eggs. At the same time, Clostridium in the uterus may be associated with eggshell speckles. However, further investigations are necessary to understand the functions of these microbiota in the reproductive tracts of laying hens. This study provides novel insights into methods for reducing the occurrence of speckled eggs in laying hens.

ABSTRACT: The development and maturation of follicles are intricately linked to egg production and reproductive performance of chickens. Granulosa cells death directly affects the development and maturation of follicles, thereby impacting the reproductive performance of hens. Ferroptosis is a new type of cell death, it is unknown how it affects the growth and development of chicken follicles. In this study, RNA-seq analysis revealed significant differences in the expression of ferroptosis-related genes between normal follicles and atretic follicles, suggesting a potential role for ferroptosis in follicle growth and development. In addition, we found that ubiquitin-specific protease 13 (USP13) was significantly upregulated in atrophic follicles. Overexpression of USP13 results in depletion of glutathione (GSH), peroxidation of lipids, accumulation of iron, and activation of ferroptosis in chicken granulosa cells. In contrast, USP13 knockdown significantly inhibited ferroptosis events. Mechanistically, USP13 prevents the degradation of autophagy related 7 (ATG7) by deubiquitinating it, thereby enhancing the stability of ATG7 protein and ultimately promoting ferroptosis. In conclusion, this study elucidates the crucial role of the USP13-ATG7 axis in regulating ferroptosis in chicken follicle granulosa cells, thereby presenting a novel avenue for molecular breeding research in chickens.

Salmonella enterica ser. Typhimurium is a common pathogen that poses a considerable public health threat, contributing to severe gastrointestinal diseases and widespread foodborne illnesses. The virulence of S. Typhimurium is regulated by quorum sensing (QS) and the type III secretion system (T3SS). This study investigated the inhibitory effects and anti-QS activity of epigallocatechin gallate (EGCG), which is a bioactive ingredient found in green tea, on the virulence of S. Typhimurium. In vitro bacterial experiments demonstrated that EGCG inhibited the production of autoinducers, biofilm formation, and flagellar activity by downregulating the expression of AI-1, AI-2, Salmonella pathogenicity islands (SPI)-1, SPI-2, and genes related to flagella, fimbriae, and curli fibers. In a mouse model of S. Typhimurium-induced enteritis, EGCG considerably reduced intestinal colonization by S. Typhimurium and alleviated intestinal damage. In conclusion, EGCG protects the intestines of mice infected with S. Typhimurium by inhibiting QS-induced virulence gene expression, demonstrating its potential as a therapeutic agent for controlling S. Typhimurium infections.

This study aims to investigate the impact of sentiment and policy on the volatility of educational stock prices by using HAR (Heterogeneous Auto Regressive) and LSTM (Long Short-Term Memory) models. We construct a weighted educational index volatility composed of nine publicly traded educational companies from the Shenzhen Stock Exchange and Shanghai Stock Exchange, and analyze the impact of sentiment and policy variables on the volatility of educational stock prices. We use OLS regression models and LSTM prediction models to analyze the data by developing various of models to investigate the impact of sentiment, education policies and their intersection effect. The empirical results show that the sentiment index and policy index have significant impacts on different time horizons of educational stock price volatility. The LSTM model confirms the effectiveness of including sentiment and policy variables in predicting educational stock price volatility. These findings carry several practical implications, particularly for investors, education-listed companies, and policymakers. And this study contributes to the literature by providing new evidence on the impact of sentiment and policy on the volatility of educational stock prices and by demonstrating the usefulness of combining HAR and LSTM models in predicting stock price volatility.

The increasing demand for tea has resulted in the swift expansion of tea plantations, leading to significant alterations in the local ecosystem. This has garnered considerable attention. However, research on rationally modifying land use structures (LUSs) in specialized tea regions to achieve a balance with ecosystem services (ESs) and enhance their synergistic effects remains limited. In this study, we quantified the values of water yield (WY), soil conservation (SC), carbon storage (CS), and habitat quality (HQ) by the InVEST model, utilized K-means clustering to categorize the LUSs of the village areas in Anxi County from 2010 to 2020, and then investigated the influences of the LUSs on the ESs by the improvement of the constraint line tool, according to which we utilized the ecosystem services trade-off degree (ESTD) and the Pearson correlation coefficient to explore the trade-offs and synergies among ecosystem services. The findings indicated that: (1) LUSs in Anxi County are tea garden structure (TS), forest land-tea garden structure (FTS), and construction land-cropland-tea garden structure (CCTS); (2) In LUSs, to achieve a balance among WY, SC, CS, and HQ, the dominant land use proportions were as follows: 0.5 for tea plantations in TS; a range of 0.55–0.6 for forest land and 0.05–0.1 for tea plantations in FTS; and CCTS, 0.25–0.3 for built-up land, 0–0.1 for cropland, and 0.2 for tea plantations; (3) The trade-offs and synergies of ESs vary across different LUSs. The synergy is particularly evident in FTS. Increasing the quantity of forest area is helpful in enhancing the synergy of ESs. This study offers an analysis of the effect of LUSs on ESs and their interconnections in specialized tea planting regions. It serves as a valuable insight into informing urban planning for future land usage and ecological conservation efforts.

The 2A12 aluminum alloy, renowned for its exceptional mechanical properties, encounters significant limitations in applications involving abrasive environments or frequent contact with other surfaces due to its inadequate wear resistance. This shortcoming substantially reduces the service life of components and escalate maintenance costs, highlighting the urgent need for advanced surface modification techniques. This study meticulously investigates the influence of nanoceramic particle size and content on the wear resistance of micro-arc oxidation (MAO) coatings, a surface modification technique renowned for forming dense, adherent ceramic layers on aluminum alloys. The systematic experimentation revealed that the incorporation of 150 nm α-Al2O3 nanoparticles into the MAO matrix achieves an optimal dispersion, leading to a substantial enhancement in wear resistance. The sample with a 5 g/L concentration of 150 nm α-Al2O3 nanoparticles doping in the MAO electrolyte demonstrated the lowest mass loss, underscoring its enhanced wear resistance. The enhanced microstructure, enriched with hard ceramic phases such as α-Al2O3 and mullite, plays a pivotal role in withstanding wear. Moreover, this study identified that an optimal balance of surface roughness and coating thickness is essential for achieving enhanced wear resistance. The findings of this research provide a strategy for the design of wear-resistant coatings tailored for high-performance applications across aerospace, automotive, and general engineering industries. By optimizing the particle size and concentration in MAO coatings, this study paves the way for the development of durable materials capable of thriving in demanding environments, thereby extending the service life and reducing maintenance requirements of components.

IntroductionLong-duration commuting is widely recognized for its significant influence on health. However, while research has traditionally focused on direct impacts, there remains a critical need to explore the nonlinear dynamics of this relationship. This study aims to deepen our understanding of how behavioral preferences and built environments contribute to these complex interactions.MethodsThis study was conducted in Jinan, China’s most congested city, using data from the “Jinan Residents Commuting Survey” of 1,755 participants aged 19 to 59. We applied Generalized Propensity Score Matching (GPSM) to explore the nonlinear effects of commuting time on self-rated health, adjusting for participants’ sociodemographic characteristics. Variables related to active commuting, physical activity, and perceived built environment were also examined for their potential moderating effects.ResultsCommuting for less than 21 minutes enhances health, but negative effects intensify and peak at 60 minutes. Heterogeneity analysis reveals that women and older adults, especially those with higher incomes, are more susceptible to long commutes, experiencing a delayed onset of adverse effects. While active commuting offers health benefits, it may exacerbate health issues if prolonged. Conversely, regular physical activity consistently improves health outcomes related to commuting. Additionally, factors like residential greenery and walkability help alleviate commuting-related stress, improving the overall commuting-health dynamic.DiscussionThis study clarifies the commuting-health relationship by identifying key time thresholds and the positive effects of active commuting and physical activity on mitigating longer commute impacts. The findings inform healthier commuting behaviors and offer practical guidelines for urban planning and policy-making to enhance commuter well-being.

IntroductionThe aim of this study was to investigate the effects of blood flow-restrictive resistance training (BFR-RT) on improving metabolic abnormalities, blood pressure (BP), obesity, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk in middle-aged patients with type 2 diabetes mellitus (T2DM).MethodWe conducted a parallel-group, single blind randomized controlled trial. Participants who met the inclusion criteria were randomly divided into control group, BFR-RT group and aerobic exercise (AE) group. Control group received health education and follow-up; Two exercise groups received supervised collective training for a period of six months, three times per week. AE group trained at moderate-intensity for 60 minutes each time, while BFR-RT group trained at low-intensity for 40 minutes each time. The primary outcomes were change in 10-year ASCVD risk index and level, and the secondary outcomes included changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), blood lipids, BP, and obesity level within and across the three groups at baseline, the third and sixth months of intervention.ResultAmong 93 individuals (control group, n=31; AE, n=30; BFR-RT, n=32) were analyzed. At baseline, there were no significant differences in various indicators among the three groups (p>0.05). After intervention, the 10-year ASCVD risk index and risk level of both exercise groups significantly decreased compared to the control group and baseline (p0.05).ConclusionBFR-RT could reduce the 10-year ASCVD risk in middle-aged T2DM patients for by improving metabolic abnormalities, BP and obesity, and its effect was similar to that of moderate-intensity AE.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.

Magnetoencephalography (MEG) is a noninvasive imaging technique used in neuroscience and clinical research. The source estimation of MEG involves solving a highly underdetermined inverse problem, which requires additional constraints to restrict the solution space. Traditional methods tend to obscure the extent of the sources. However, an accurate estimation of the source extent is important for studying brain activity or preoperatively estimating pathogenic regions. To improve the estimation accuracy of the extended source extent, the spatial constraint of sources is employed in the Bayesian framework. For example, the source is decomposed into a linear combination of validated spatial basis functions, which is proved to improve the source imaging accuracy. In this work, we further construct the spatial properties of the source using the diagonal covariance bases (DCB), which we summarize as the source imaging method SI-DCB. In this approach, specifically, the covariance matrix of the spatial coefficients is modeled as a weighted combination of diagonal covariance basis functions. The convex analysis is used to estimate noise and model parameters under the Bayesian framework. Extensive numerical simulations showed that SI-DCB outperformed five benchmark methods in accurately estimating the location and extent of patch sources. The effectiveness of SI-DCB was verified through somatosensory stimulation experiments performed on a 31-channel OPM-MEG system. The SI-DCB correctly identified the source area where each brain response occurred. The superior performance of SI-DCB suggests that it can provide a template approach for improving the accuracy of source extent estimations under a sparse Bayesian framework.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

In recent years, with the emergence of resistance to traditional antibiotics and the growing interest in the development of natural antimicrobials, natural antimicrobial peptides have received extensive attention. Among them, plant-derived antimicrobial peptides have the characteristics of low drug resistance, wide antibacterial spectrum and low toxicity, and because of rich cysteine residues, they can form multiple disulfide bonds, so they have high chemical, thermal and enzymatic hydrolysis stability. In this paper, the classification of plant antimicrobial peptides and the methods of extracting and screening antimicrobial peptides from plant sources were reviewed. The potential applications of plant antimicrobial peptides in the field of food were emphasized, and the screening and future applications of these plant antimicrobial peptides in the field of food were prospected.

Abstract Zintl phases typically exhibit low lattice thermal conductivity, which are extensively investigated as promising thermoelectric candidates. While the significance of Zintl anionic frameworks in electronic transport properties is widely recognized, their roles in thermal transport properties have often been overlooked. This study delves into KCdSb as a representative case, where the [CdSb4/4]− tetrahedrons not only impact charge transfer but also phonon transport. The phonon velocity and mean free path, are heavily influenced by the bonding distance and strength of the Zintl anions Cd and Sb, considering the three acoustic branches arising from their vibrations. Furthermore, the weakly bound Zintl cation K exhibits localized vibration behaviors, resulting in strong coupling between the high‐lying acoustic branch and the low‐lying optical branch, further impeding phonon diffusion. The calculations reveal that grain boundaries also contribute to the low lattice thermal conductivity of KCdSb through medium‐frequency phonon scattering. These combined factors create a glass‐like thermal transport behavior, which is advantageous for improving the thermoelectric merit of zT. Notably, a maximum zT of 0.6 is achieved for K0.84Na0.16CdSb at 712 K. The study offers both intrinsic and extrinsic strategies for developing high‐efficiency thermoelectric Zintl materials with extremely low lattice thermal conductivity.

Ovarian transplantation presents significant advantages for the preservation of female fertility. Nonetheless, a substantial number of follicles are apoptosis during the process of ovarian tissue transplantation as a result of ischemic conditions. This study aimed to assess whether adipose-derived mesenchymal stem cells combined with urinary bladder matrix (ADSC/UBM) confer a greater therapeutic benefit compared to ADSCs alone. To achieve this, ADSC/UBM was applied during the autotransplantation of rat ovaries. Thirty rats were divided into five sets of six: the untreated control group (Normal), the oophorectomy group, the autograft group, the autograft + ADSCs group (ADSC), and the autograft + ADSC/UBM group (ADSC/UBM). After transplantation, the number of follicles in the ADSC/UBM group was significantly higher than that in the autograft group. Angiogenesis was enhanced following ADSC/UBM transplantation. Follicle-stimulating hormone (FSH) levels were significantly lower, and Anti-Müllerian hormone (AMH) levels were significantly higher in rats in the ADSC/UBM group than in the Autograft group. The apoptosis rate in the ADSC/UBM group decreased. The estrous cycle in the ADSC/UBM group recovered more quickly than the ADSC group. The data indicate that UBM improves ADSC retention in graft ovaries and aids in permanently restoring ovarian function, making ADSC/UBM a promising option for ovarian transplantation.

BackgroundSepsis is marked by a dysregulated immune response to infection. Calcineurin inhibitors (CNIs), commonly used as immunosuppressants, have unique properties that may help mitigate the overactive immune response in sepsis, potentially leading to better patient outcomes. This study aims to assess whether CNIs improve prognosis in septic patients and to evaluate any associated adverse reactions.MethodsWe utilized the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database to identify septic patients who were treated with CNIs and those who were not. Propensity score matching (PSM) was employed to balance baseline characteristics between the CNI user group and the non-user group. The primary outcome was 28-day mortality, analyzed using the Kaplan-Meier method and Cox proportional hazard regression models to examine the relationship between CNI use and patient survival.ResultsFrom the MIMIC-IV database, 22,517 septic patients were identified. After propensity score matching, a sample of 874 patients was analyzed. The CNI group exhibited a significantly lower 28-day mortality risk compared to the non-user group (HR: 0.26; 95% CI: 0.17, 0.41) in the univariate Cox hazard analysis. Kaplan-Meier survival curves also demonstrated a significantly higher 28- and 365-day survival rate for CNI users compared to non-users (log-rank test p-value = 0.001). No significant association was found between CNI use and an increased risk of new-onset infection (p = 0.144), but an association with mild hypertension (P < 0.001) and liver injury (P < 0.001) was observed.ConclusionThe use of calcineurin inhibitors was associated with reduced short- and long-term mortality in septic patients without an increased incidence of new-onset infections, hyperkalemia, severe hypertension, or acute kidney injury (AKI). However, CNI use may lead to adverse effects, such as liver injury and mild hypertension.

IntroductionArtificial intelligence is already widely utilized in gastroenterology. This study aims to comprehensively evaluate the research hotspots and development trends within the field of AI in gastroenterology by employing bibliometric techniques to scrutinize geographical distribution, authorship, affiliated institutions, keyword usage, references, and other pertinent data contained within relevant publications.MethodsThis investigation compiled all pertinent publications related to artificial intelligence in the context of gastrointestinal polyps and digestive endoscopy from 2003 to 2023 within the Web of Science Core Collection database. Furthermore, the study harnessed the tools CiteSpace, VOSviewer, GraphPad Prism and Scimago Graphica for visual data analysis. The study retrieved a total of 2,394 documents in the field of AI in digestive endoscopy and 628 documents specifically related to AI in digestive tract polyps.ResultsThe United States and China are the primary contributors to research in both fields. Since 2019, studies on AI for digestive tract polyps have constituted approximately 25% of the total AI digestive endoscopy studies annually. Six of the top 10 most-cited studies in AI digestive endoscopy also rank among the top 10 most-cited studies in AI for gastrointestinal polyps. Additionally, the number of studies on AI-assisted polyp segmentation is growing the fastest, with significant increases in AI-assisted polyp diagnosis and real-time systems beginning after 2020.DiscussionThe application of AI in gastroenterology has garnered increasing attention. As theoretical advancements in AI for gastroenterology have progressed, real-time diagnosis and detection of gastrointestinal diseases have become feasible in recent years, highlighting the promising potential of AI in this field.

Background: Nano titanium dioxides (TiO2) are widely used in drug development, food additives and packaging materials. Although several studies have demonstrated the poisonousness of TiO2 in vivo and in vitro, the underlying molecular mechanisms have not been fully revealed. Methods: Characterization of TiO2 by FTIR, XRD, TEM and DLS. The NCM460 cell line, representing normal colon epithelial cells, was utilized as a model to assess the impact of TiO2 nanoparticles (TiO2-NPs) on cell proliferation and apoptosis. The potential molecular mechanisms underlying its toxic effects were investigated through transcriptome analysis, RT-qPCR, and western blot experiments. Results: The particle size of the TiO2-NPs used is about 25 nm, which has typical characteristics of anatase. TiO2-NPs at a concentration of 30–60 μg/mL will cause changes in colon cell morphology, decreased proliferation ability, and increased number of apoptotic cells. TiO2-NPs at a concentration of 6 μg/mL did not significantly modify the transcriptome expression profile of colon cells; while 30 μg/mL had a significant effect, leading to up-regulation of gene expression. The differentially expressed genes predominantly modulate the MAPK signaling pathway, TNF signaling pathway, cytokine-cytokine receptor interaction, and other related pathways. Further, western blot analysis revealed that higher concentrations of TiO2-NPs (30–60 μg/mL) could up-regulate the expression of P53, P21 and Bax, while down-regulating the expression of Bcl2 by regulating the MAPK (ERK, P38) signaling pathway. Simultaneously, it also promoted the decreased in Fos protein expression and inhibited the phosphorylation of Jun and Fos. Conclusion: This study demonstrates that TiO2-NPs may exert potential toxic effects on colon cells, and therefore the intake of TiO2-NPs should be strictly regulated in practical applications.

Introduction6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is highly expressed in several cancers and plays important roles during the whole pathological process of cancer. It is also involved in chemoresistance, while the intrinsic mechanism needs to be further revealed.MethodsThe different responses to cisplatin (DDP) between wild type (WT) and DDP-resistant (DDR) colorectal cancer (CRC) cells were analyzed by several assays. Coumarin conjugated DDP (CP-DDP) was utilized to trace the distribution of DDP. Pharmacological and genetic methods were used to deprive autophagy and PFKFB3, and the effects were investigated. The mouse xenograft model was performed to confirm the effect of the PFKFB3 inhibitor on reversing DDP resistance.ResultsDDR cells showed a lower capacity for apoptosis upon DDP treatment, but exhibited higher levels of autophagy and PFKFB3. CP-DDP partly co-localized with LC3, and its content lessened faster in DDR cells. Deprivation of both autophagy and PFKFB3 attenuated CP-DDP elimination, and reversed the DDP resistance. Moreover, PFKFB3 inhibition reduced DDP-induced autophagy. PFKFB3 inhibitor in combination with DDP led to a remarkable reduction in tumor growth in vivo.DiscussionsInhibition of PFKFB3 reduced the autophagy induced by DDP, and therefore extended the retention time of CP-DDP. Meanwhile, PFKFB3 deprivation reversed the DDP resistance and made it a potent therapeutic target for CRC.

ObjectiveTo investigate the relationship between post-traumatic growth, morbidity stigma and readiness for discharge in post-operative thyroid cancer patients.Methods422 post-operative thyroid cancer patients from three tertiary care hospitals in Hunan and Tianjin were surveyed using the General Information Questionnaire, the Post-traumatic Growth Scale, the Readiness for Discharge Scale, and the Social Influence Scale.ResultsDischarge readiness positively predicted the level of post-traumatic growth in thyroid cancer patients (P < 0.01), and morbidity stigma negatively predicted post-traumatic growth (P < 0.01), with morbidity stigma playing a mediated role between discharge readiness and post-traumatic growth.ConclusionsReadiness for discharge can positively predict post-traumatic growth, and morbidity stigma plays a mediating role between readiness for discharge and post-traumatic growth. It is suggested that clinical and nursing staff should strengthen patients’ discharge readiness guidance and education, help patients and their families establish an effective feedback mechanism for disease condition and psychological cognitive condition, focus on reducing patients’ sense of shame, and improve patients’ physical and mental health.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Pulmonary vascular remodeling and inflammation play an important role in the hypoxic-induced lung diseases. Our previous investigations showed that peptide from yak milk residues could alleviate inflammation. In this study, our results suggest that peptide (LV) from yak milk residues peptide had protective effect of lung in the animal models of hypoxic-induced lung injury. LV Gavage could improve pulmonary vascular remodeling in the lung tissues of hypoxic mice. A comprehensive analysis of metabolomics and transcriptomics revealed that 5-KETE, 8,9-EET, and 6-keto-prostaglandin F1a might be potential targets to prevent lung injury in the hypoxic mice. These metabolites can be regulated by MAPK/VEGF and inflammatory pathways. Our data indicated that LV treatment could inhibit apoptosis and inflammation via Nrf2/NF-κB/MAPK/PHD-2 pathway and protected hypoxic-induced lung epithelial cells injury. Taken together, our results suggest that LV provides a novel therapeutic clue for the prevention of hypoxia-induced lung injury and inflammation-related lung diseases.