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Abstract In the general population, there is limited evidence for the associations between hand eczema (HE) and lifestyle factors, and between the severity of HE and quality of life. This study aimed to estimate the risk factors for the incidence of HE in the general population and the risk factors for the severity of HE. A cross-sectional questionnaire was administered to 121 HE patients in a hospital from December 2018 to December 2019 in Wuhan. The severity of HE was significantly associated with working with wet hands more than 5 h per day and chapped skin. Sixty-seven patients have positive patch test results. Working with wet hands for more than 5 h per day and chapped skin were the most common and significant risk factors for HE. Working hours with wet hands per day was an independent risk factor for the hand eczema severity index and dermatology life quality index, and there was a significant positive correlation between chapped skin and the severity of hand eczema and higher transepidermal water loss (TEWL). The results also revealed a significant positive correlation between the severity of HE and the impact on quality of life and the severity of TEWL. Prolonged wet hand work can lead to a higher rate of severe hand eczema in the general population. HE can be relieved by reducing the wet hand working time and hand moisturizing.

Abstract Image hiding is a task that embeds secret images in digital images without being detected. The performance of image hiding has been greatly improved by using the invertible neural network. However, current image hiding methods are less robust in the face of Joint Photographic Experts Group (JPEG) compression. The secret image cannot be extracted from the stego image after JPEG compression of the stego image. Some methods show good robustness for some certain JPEG compression quality factors but poor robustness for other common JPEG compression quality factors. An image‐hiding network (RIHINNet) that is robust to all common JPEG compression quality factors is proposed. First of all, the loss function is redesigned; thus, the secret image is hidden as much as possible in the area that is less likely to be changed after JPEG compression. Second, the classifier is designed, which can help the model to select the extractor according to the range of JPEG compression degree. Finally, the interval robustness of the secret image extraction is improved through the design of a denoising module. Experimental results show that this RIHINNet outperforms other state‐of‐the‐art image‐hiding methods in the face of JPEG compressed noise with random compression quality factors, with more than 10 dB peak signal‐to‐noise ratio improvement in secret image recovery on ImageNet, COCO and DIV2K datasets.

Abstract Due to the increasing sophistication of face forgery techniques, the images generated are becoming more and more realistic and difficult for human eyes to distinguish. These face forgery techniques can cause problems such as fraud and social engineering attacks in facial recognition and identity verification areas. Therefore, researchers have worked on face forgery detection studies and have made significant progress. Current face forgery detection algorithms achieve high detection accuracy within-dataset. However, it is difficult to achieve satisfactory generalization performance in cross-dataset scenarios. In order to improve the cross-dataset detection performance of the model, this paper proposes a multi-feature fusion network based on two-stream extraction and multi-scale enhancement. First, we design a two-stream feature extraction module to obtain richer feature information. Secondly, the multi-scale feature enhancement module is proposed to focus the model more on information related to the current sub-region from different scales. Finally, the forgery detection module calculates the overlap between the features of the input image and real images during the training phase to determine the forgery regions. The method encourages the model to mine forgery features and learns generic and robust features not limited to a particular feature. Thus, the model achieves high detection accuracy and performance. We achieve the AUC of 99.70% and 90.71% on FaceForensics++ and WildDeepfake datasets. The generalization experiments on Celeb-DF-v2 and WildDeepfake datasets achieve the AUC of 80.16% and 65.15%. Comparison experiments with multiple methods on other benchmark datasets confirm the superior generalization performance of our proposed method while ensuring model detection accuracy. Our code can be found at: https://github.com/1241128239/MFNet .

Objective To evaluate the performance of a blood nucleic acid testing kit, construct a consistency assessment system, and analyze the influencing factors of the test results. Methods A total of 18 644 samples of voluntary blood donors in our center were collected, and 189 double positive samples of hepatitis B surface antigen (HBsAg) by ELISA were eliminated, and the remaining 18 455 samples were tested for HBV DNA in parallel with the test reagent and the control reagent (Roche Company). Samples with inconsistent results were confirmed with third-party reagents (Grifols Company, with the sensitivity of HBV DNA, HCV RNA and HIV RNA of 4.5 IU/mL, 2.4 IU/mL and 17.3 IU/mL by single reagent, which were significantly better than other reagents), and the consistency between the two methods was compared. Results No HCV RNA or HIV RNA positive samples were detected in this study. Among the 18 455 samples in initial test, 12 were positive with consistent results, 18 378 were negative with consistent results, and 65 were with inconsistent results between the test reagent and the control reagent, with positive concordance rate, negative concordance rate and concordance rate of the two reagents at 85.17%, 99.66% and 99.65%, respectively. In order to further clarify the infection of 65 inconsistent samples, five qualitative tests of hepatitis B and single NAT were conducted to comprehensively evaluate the infection. The results showed that there were 60 positive samples with consistent results, 18 371 negative samples with consistent results, and 24 samples with inconsistent results between the test reagent and the control reagent, with positive concordance rate, negative concordance rate and the concordance rate for the two reagents at 86.96%, 99.92% and 99.87%, respectively. The Kappa value was 0.83, and the Youden index was 0.40. The ROC curve was plotted with the false-positive rate (1-specificity) as the horizontal coordinate and the true-positive rate (sensitivity) as the vertical coordinate, and the area under the ROC curve was 0.705. 189 double-positive samples were selected for conformance testing, and the Ct values of the test reagent and the control reagent were analyzed and fitted linearly, with correlation coefficient r=0.972. A Bland-Altman model was constructed with the mean value of the logarithm of the quantitative values of the test reagent and the control reagent as the horizontal coordinate and the difference as the vertical coordinate, and 96.30% of the difference values of the test reagents were within the confidence interval. Conclusion The construction of the consistency evaluation system showed that the test reagent has similar detection efficiency with the control reagent, and is suitable for HBV DNA routine screening, which can effectively ensure the safety and effectiveness of blood screening.

Abstract Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.

Abstract Image hiding is a task that hides secret images into cover images. The purposes of image hiding are to ensure the secret images are invisible to the human and the secret images can be recovered. The current state‐of‐the‐art steganography methods run the risk of secret information leakage. A safe image hiding network (SIHNet) is presented to reduce the leakage of secret information. Based on some phenomena of image hiding methods which use invertible neural network, a reversible secret image processing (SIP) module is proposed to make the secret images suitable for hiding and make the stego images leak less secret information. Besides, a reversible lost information hiding (LIH) module is used to hide the lost information into the cover images, thus the method can recover the secret images better than the method that uses random noise to replace the lost information. Experimental results show that SIHNet outperforms other state‐of‐the‐art methods on the PSNR and SSIM values of the recovered secret images and the stego images. Besides, residual images of other state‐of‐the‐art methods all contain information about secret images while residual images of SIHNet leak almost no secret information. Thus the method can prevent the listener of transmission channel from obtaining the information of the secret image through the residual image, which means SIHNet performs better in security than other state‐of‐the‐art methods.

Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract

Abstract Background As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats. Methods PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg− 1·wk− 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined. Results Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9. Conclusion Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2.

Abstract Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.

This study examined how Eucommia ulmoides flavonoids (EUF) protect against intestinal oxidative stress induced by deoxynivalenol (DON) in weaned piglets. Forty weaned piglets were randomly assigned to four dietary groups for a period of 14 days. The piglets were fed a control diet (Control) or the Control diet supplemented with 100 mg EUF/kg (EUF group), 4 mg DON/kg diet (DON group) or both (EUF+DON group) in a 2×2 factorial design. DON-challenged piglets on the EUF-supplemented diet showed significant improvements in growth performance. They also had notably lower serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) compared to those not receiving supplementation (P0.05). Piglets challenged with DON and fed a diet supplemented with EUF showed significantly lower levels of interleukin-8 (IL-8) and interferon-γ (IFN-γ) mRNA and protein expression in serum and intestinal tissues compared to those in the DON group (P < 0.05). The EUF+DON group significantly increased the serum levels of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and total antioxidative capability enzymes compared to the DON group (P

ObjectiveThis study aims to examine nursing professional pride levels in blood purification center nurses, explore its relationship with adversity quotient and grit, and identify influencing factors.MethodsUsing convenience sampling, this study selected 231 nurses from blood purification centers at 11 tertiary hospitals in China during July to August 2023 as research subjects. A general data survey questionnaire, nurse professional pride scale, nurse adversity quotient self-assessment scale, and the Oviedo resilience scale were employed for the investigation. The results were statistically analyzed using descriptive analysis, t-tests, one-way ANOVA, Pearson correlation analysis, and multiple stepwise linear regression analysis.ResultsIn the blood purification center, the average scores were as follows: nursing professional pride (69.53 ± 15.21), adversity quotient (132.90 ± 41.10), and grit (30.95 ± 10.54). There was a significant positive correlation between nursing professional pride, adversity quotient, and grit (P < 0.001). Multiple linear regression analysis (n = 231) revealed that education background, professional title, average monthly income, adversity quotient, and grit significantly influenced nursing professional pride (P < 0.001). The R2 value indicates that this study accounted for 76.2% of the total variance in nursing professional pride.ConclusionThe findings of this study indicate that blood purification center nurses have a moderate level of nursing professional pride. The level of nursing professional pride can be enhanced by focusing on factors such as adversity quotient and grit.RegistrationThis study was approved by the Ethics Committee of Pidu District People's Hospital, Chengdu, China (2021 No. 231). All participants were informed of the relevant information and research purposes before their participation. Participants were also required to independently and anonymously complete the questionnaires.

The challenge of understanding the interaction between trace elements and microbial life is critical for assessing environmental and ecological impacts. Nevertheless, cysteine (Cys), a low molecular weight thiol substance prevalent in the ecosystem, is able to influence the fate of certain trace elements, which increases the complexity of the interaction between trace elements and microorganisms. Therefore, we chose Cys, selenite and the model methanogenic archaeon Methanosarcina acetivorans C2A as research targets, and comprehensively explored the intricate role of Cys in modulating the biological effects of selenite on M. acetivorans C2A in terms of population growth, methane production and oxidative stress. Our results demonstrate that Cys significantly exacerbates the inhibitory effects of selenite on growth and methane production in M. acetivorans C2A. This increased toxicity is linked to heightened membrane permeability and oxidative stress, with a marked upregulation in reactive oxygen species and changes in NADPH levels. Transcriptomic analysis reveals alterations in genes associated with transmembrane transport and methanogenesis. Intriguingly, we also observed a potential interaction between selenite and phosphate transmembrane transporters, suggesting a novel pathway for selenite entry into cells. These findings highlight the complex interplay between trace elements and microbial processes, with significant implications for understanding environmental risks and developing remediation strategies.

Background: This study aimed to introduce and evaluate a new treatment method for rectus sheath hematoma: ultrasound-guided suction using negative pressure, curettage, and percutaneous drainage. Methods: This retrospective study involved five patients with rectus sheath hematoma rectus sheath hematoma who had cesarean sections. For all patients, ultrasound revealed that the maximum diameter of their hematoma exceeded 70 mm. We summarized and analyzed the therapeutic effects of five patients and introduced the procedure, technical points, precautions, advantages, and indications of the procedure. Results: In all five patients, hematoma area was significantly reduced as confirmed by ultrasound at follow-up, and all patients’ abdominal pain were significantly relieved. No complications, including bleeding or infection, were detected at both the 2-h postoperative and 3-day follow-up assessments. The hematoma volume reduction rates were 90 %, 67 %, 81 %, 68 %, and 70 % at three days re-examinations, and 99 %, 96 %, 98 %, 98 %, and 90 % at the 30-day follow-up. Conclusion: The removal of rectus sheath hematoma by suction using negative pressure can prevent patients from undergoing abdominal wall exploration, offering a less invasive alternative while potentially achieving comparable therapeutic effect to surgical hematoma removal in certain cases. This treatment method shows potential for clinical application, particularly in relatively young and healthy postpartum women, and is expected to be popularized and applied in clinical practice.

Abstract High‐grade serous tubo‐ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP‐ribose) polymerase inhibitors (PARPis) and anti‐PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single‐cell RNA and single‐cell T‐cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRβ+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tregs, whereas HRP tumors are enriched with HDAC1‐expressing epithelial cells, indolent CAFs, M2 macrophages, and bystander CD4+/CD8+ T cells. Significantly, customized therapies are proposed. For HRD patients, targeting FGFR1+PDGFRβ+ myCAFs via tyrosine kinase inhibitors, targeting Tregs via anti‐CCR8 antibodies/TNFRSF4 stimulation, and targeting CXCL13+ exhausted T cells by blocking PDCD1/CTLA‐4/LAG‐3/TIGIT are proposed. For HRP patients, targeting indolent CAFs, targeting M2 macrophages via CSF‐1/CSF‐1R inhibitors, targeting bystander T cells via tumor vaccines, and targeting epithelial cells via HDAC inhibitors. The study provides comprehensive insights into HRD and HRP TIME and tailored therapeutic approaches, addressing the challenges of PARPi‐resistant HRD and refractory HRP tumors.

IntroductionPasteurella multocida is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of P. multocida. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.MethodsIn this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain C48-1 of P. multocida, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a PMCNA_RS00975 gene mutant of P. multocida strain C48-1 was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within P. multocida. The recombinant protein PMCNA_RS00975 of P. multocida was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.ResultsThe mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of P. multocida. Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages.DiscussionThis study identified a novel virulence factor in the C48-1 strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against P. multocida.

Abstract Objective This study aimed to evaluate the effect of fence tray matching care (FTMC) in bracket bonding by measuring excess adhesive, as well as linear and angular deviations, and by comparing it with the half-wrapped tray (HWT). Materials and methods An intraoral scanner was used to acquire data on the maxillary dental arch of a patient with periodontitis.Furthermore, 20 maxillary dental arch models were 3D printed. Using 3Shape, PlastyCAD software, and 3D printing technology, 10 FTMC (method I) and HWT (method II) were obtained. By preoperative preparation, intraoperative coordination, and postoperative measurement, the brackets were transferred from the trays to the 3D-printed maxillary dental arch models. Additionally, the bracket’s excess adhesive as well as linear and angular deviations were measured, and the differences between the two methods were analyzed. Results Excess adhesive was observed in both methods, with FTMC showing less adhesive (P

Abstract In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in β-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. β-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic β-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.

Deposition pattern and path-planning deposition strategy have significant impacts on the deformation and residual stress of components during a wire-arc additive manufacturing (WAAM) process. This work comparatively addressed the influence of weaving and non-weaving deposition patterns on the distributions of residual stress and warping deformation during a single-bead-on-plate WAAM process. Further, four path strategies with different deposition sequences (in-out and out-in) and deposition directions (alternate and consistent) were designed for a weaving WAAM process of disc part, and their impacts on temperature history, warping deformation, and residual stress were comparatively analyzed through thermal-mechanical coupling finite element (FE) method. Simulation and experiment results manifest that, compared to the non-weaving pattern, the weaving deposition pattern results in more uniform deformation and lower residual stress on the deposited plate due to wider and shallower molten pool. Comparison results for the four deposition path strategies in the weaving WAAM process of disc part suggest that the out-in deposition sequence exhibits faster heat dissipation and uniform temperature field during the cooling stage, resulting in reduced warping deformation and residual stress on the workpiece. Moreover, uniform deformation is observed across path strategies employing alternate deposition direction. The out-in alternate deposition path strategy was identified as the optimal choice for the weaving WAAM process of disc part. Finally, physical experiments validated the simulated warping deformation of disc parts under different deposition path strategies. This work contributes to the design and optimization of weaving WAAM process for disc-shaped components.

In this study, we developed a new prognostic model for glioblastoma (GBM) based on an integrated machine learning algorithm. We used univariate Cox regression analysis to identify prognostic genes by combining six GBM cohorts. Based on the prognostic genes, 10 machine learning algorithms were integrated into 117 algorithm combinations, and the artificial intelligence prognostic signature (AIPS) with the greatest average C-index was chosen. The AIPS was compared with 10 previously published models by univariate Cox analysis and the C-index. We compared the differences in prognosis, tumor immune microenvironment (TIME), and immunotherapy sensitivity between the high and low AIPS score groups. The AIPS based on the random survival forest algorithm with the highest average C-index (0.868) was selected. Compared with the previous 10 prognostic models, our AIPS has the highest C-index. The AIPS was closely linked to the clinical features of GBM. We discovered that patients in the low score group had improved prognoses, a more active TIME, and were more sensitive to immunotherapy. Finally, we verified the expression of several key genes by western blotting and immunohistochemistry. We identified an ideal prognostic signature for GBM, which might provide new insights into stratified treatment approaches for GBM patients.

Medicinal herbs can be used for the development of antioxidant and anticancer platforms. However, the mechanisms by which the bioactive materials show these properties remain largely unclear. Also, a detailed understanding of the interaction between small compounds and carrier proteins like albumin can provide useful information about the regulation of their stability and circulation time properties. In this paper, the interaction of rhamnazin (C17H14O7), an O-methylated flavonol exists in Rhamnus petiolaris, with human serum albumin (HSA) was investigated. Also, the antioxidant and anti-lung cancer effects of rhamnazin were assessed. The results showed that a static rhamnazin-HSA complex was formed by the contribution of hydrophobic forces, which led to an increase in the content of the α-helix structure of HSA. Cellular assays revealed that rhamnazin (10 µM) recovered cell viability in human proximal renal tubular epithelial cells (HK2) reduced by H2O2 (0.5 mM) through reduction of ROS, restoration of CAT and SOD activities and GSH content, regulation of Bax, Bcl-2, and caspase-3. Moreover, the anti-lung cancer data demonstrated that rhamnazin induced apoptosis on lung adenocarcinoma A549 cells associated with a p53-dependent manner via overexpression of apoptotic Bax and caspase-3 and down-regulation of anti-apoptotic Bcl-2. To summarize, the potential binding of rhamnazin and HSA, as well as its antioxidant/anticancer properties, are critical for understanding the solubility and stability of this bioactive compound in plasma, as well as its therapeutic implications.

Abstract Chronic obstructive pulmonary disease (COPD) is a persistent and progressive disorder characterized by airway or alveolar abnormalities, commonly leading to pulmonary hypertension (PH). This clinical observational study investigates the therapeutic mechanisms of Bufei Huoxue capsules (BHC) in treating PH in patients with COPD‐linked PH (COPD‐PH) using network pharmacology and molecular docking methods, and assesses the therapeutic efficacy and safety of BHCs. The active compounds and their target proteins in BHCs were sourced from the Traditional Chinese Medicine Systems Pharmacology database, with additional target proteins derived from the GeneCards and OMIM databases. An active network was constructed using Cytoscape 3.7.1, and interaction networks were established. Intersecting targets underwent Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Metascape database. Network pharmacology and molecular docking studies demonstrated favorable binding affinities of BHC active ingredients, such as quercetin, bavachalcone, and isobavachin, for key targets including PTGS1, ESR1, and PTGS2. Gene Ontology enrichment analysis highlighted the involvement of these targets in processes such as the positive regulation of locomotion, the transmembrane receptor protein tyrosine kinase signaling pathway, and peptidyl‐tyrosine phosphorylation. KEGG pathway analysis indicated their roles in pathways related to cancer, AGE‐RAGE signaling in diabetic complications, and prostate cancer. BHCs exhibit therapeutic effects on COPD‐PH through multi‐component, multi‐target, and multi‐pathway interactions. This clinical observational study confirms the efficacy and safety of BHCs in improving cardiac and pulmonary functions, enhancing exercise tolerance, and elevating the quality of life in patients with COPD‐PH.

Image preprocessing models are usually employed as the preceding operations of high‐level vision tasks to improve the performance. The adversarial attack technology makes both these models face severe challenges. Prior research is focused solely on attacking single object detection models, without considering the impact of the preprocessing models (multifocus image fusion) on adversarial perturbations within the object detection system. Multifocus image fusion models work in conjunction with the object detection models to enhance the quality of the images and improve the capability of object detection system. Herein, the problem of attacking object detection system that utilizes multifocus image fusion as its preprocessing models is addressed. To retain the attack capabilities of adversarial samples against as many perturbations as possible, new attack method called adaptive retention attack (ARA) is proposed. Additionally, adversarial perturbations concentration mechanism and image selection mechanism, which, respectively, enhance the transferability and attack capability of ARA‐generated adversarial samples. Extensive experiments have demonstrated the feasibility of the ARA. The results confirm that the ARA method can successfully bypass multifocus image fusion models to attack the object detection model.

BackgroundT lymphocytes in tumor microenvironment play a pivotal role in the anti-tumor immunity, and the memory of T cells contributes to the long-term protection against tumor antigens. Compared to solid tumors, studies focusing on the T-cell differentiation in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment remain limited.Patients and methodsFresh BM specimens collected from 103 adult AML patients at diagnosis and 12 healthy donors (HDs) were tested T-cell differentiation subsets by multi-parameter flow cytometry.ResultsCD4 and CD8 T-cell compartments had different constituted profiles of T-cell differentiated subsets, which was similar between AML patients and HDs. Compared to HDs, AML patients as a whole had a significantly higher proportion of CD8 effector T cells (Teff, P = 0.048). Moreover, the T-cell compartment of AML patients with no DNMT3A mutations skewed toward terminal differentiation at the expense of memory T cells (CD4 Teff: P = 0.034; CD8 Teff: P = 0.030; CD8 memory T: P = 0.017), whereas those with mutated DNMT3A had a decrease in CD8 naïve T (Tn) and CD4 effector memory T cells (Tem) as well as an increase in CD4 central memory T cells (Tcm) (P = 0.037, 0.053 and 0.053). Adverse ELN genetic risk correlated with a lower proportion of CD8 Tn. In addition, the low proportions of CD4 Tem and CD8 Tn independently predicted poorer relapse-free survival (RFS, HR [95%CI]: 5.7 (1.4–22.2), P = 0.017 and 4.8 [1.3–17.4], P = 0.013) and event-free survival (EFS, HR [95% CI]: 3.3 (1.1–9.5), P = 0.029; 4.0 (1.4–11.5), P = 0.010), respectively.ConclusionsAML patients had abnormal profiles of BM T-cell differentiation subsets at diagnosis, which was related to DNMT3A mutations. The low proportions of CD4 Tem and CD8 Tn predicted poor outcomes.

BackgroundBrain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of “ineffective or futile recanalization” after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain.MethodsThis single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio (n = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes.DiscussionThis study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT.Clinical trial registrationhttps://www.chictr.org.cn/. Identifier ChiCTR 2300077052.

ObjectiveThis study systematically reviews and meta-analyzes existing risk prediction models for diabetic kidney disease (DKD) among patients with type 2 diabetes, aiming to provide references for scholars in China to develop higher-quality risk prediction models.MethodsWe searched databases including China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, Embase, and the Cochrane Library for studies on the construction of DKD risk prediction models among type 2 diabetes patients, up until 28 December 2023. Two researchers independently screened the literature and extracted and evaluated information according to a data extraction form and bias risk assessment tool for prediction model studies. The area under the curve (AUC) values of the models were meta-analyzed using STATA 14.0 software.ResultsA total of 32 studies were included, with 31 performing internal validation and 22 reporting calibration. The incidence rate of DKD among patients with type 2 diabetes ranged from 6.0% to 62.3%. The AUC ranged from 0.713 to 0.949, indicating the prediction models have fair to excellent prediction accuracy. The overall applicability of the included studies was good; however, there was a high overall risk of bias, mainly due to the retrospective nature of most studies, unreasonable sample sizes, and studies conducted in a single center. Meta-analysis of the models yielded a combined AUC of 0.810 (95% CI: 0.780–0.840), indicating good predictive performance.ConclusionResearch on DKD risk prediction models for patients with type 2 diabetes in China is still in its initial stages, with a high overall risk of bias and a lack of clinical application. Future efforts could focus on constructing high-performance, easy-to-use prediction models based on interpretable machine learning methods and applying them in clinical settings.RegistrationThis systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a recognized guideline for such research.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024498015.

Background: Inflammation and subsequent mitochondrial dysfunction and cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1 (RIPK1) activated dynamin-related protein 1 (DRP1) in a NLRPyrin domain containing 3 (NLRP3) inflammasome-dependent fashion and Hypoxia-Inducible Factor (HIF)-1α play key roles in the process. This study determined how phenothiazine drugs (chlorpromazine and promethazine (C + P)) with the hypothermic and normothermic modality impacts the RIPK1/RIPK3-DRP1 and HIF-1α pathways in providing neuroprotection. Methods: A total of 150 adult male Sprague-Dawley rats were subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. 8 mg/kg of C + P was administered at onset of reperfusion. Infarct volumes, mRNA and protein expressions of HIF-1α, RIPK1, RIPK3, DRP-1, NLRP3-inflammation and cytochrome c-apoptosis were assessed. Apoptotic cell death, infiltration of neutrophils and macrophages, and mitochondrial function were evaluated. Interaction between RIPK1/RIPK3 and HIF-1α/NLRP3 were determined. In SH-SY5Y cells subjected to oxygen/glucose deprivation (OGD), the normothermic effect of C + P on inflammation and apoptosis were examined. Results: C + P significantly reduced infarct volumes, mitochondrial dysfunction (ATP and ROS concentration, citrate synthase and ATPase activity), inflammation and apoptosis with and without induced hypothermia. Overexpression of RIPK1, RIPK3, DRP-1, NLRP3-inflammasome and cytochrome c-apoptosis were all significantly reduced by C + P at 33 °C and the RIPK1 inhibitor (Nec1s), suggesting hypothermic effect of C + P via RIPK1/RIPK3-DRP1pathway. When body temperature was maintained at 37 °C, C + P and HIF-1α inhibitor (YC-1) reduced HIF-1α expression, leading to reduction in mitochondrial dysfunction, NLRP3 inflammasome and cytochrome c-apoptosis, as well as the interaction of HIF-1α and NLRP3. These were also evidenced in vitro, indicating a normothermic effect of C + P via HIF-1α. Conclusion: Hypothermic and normothermic neuroprotection of C + P involve different pathways. The normothermic effect was mediated by HIF-1α, while hypothermic effect was via RIPK1/RIPK3-DRP1 signaling. This provides a theoretical basis for future precise exploration of hypothermic and normothermic neuroprotection.