Synergistic corrosion inhibition of 4-hydroxypyridine and halogen ions: Insights from interfacial nonlinear spectroscopy.

4-Hydroxypiridine (4-HPy) is a green chemistry corrosion inhibitor for low-carbon steel, valued for its environmental compatibility and low toxicity. Despite lower initial effectiveness than 4-mercapto/4-aminopyridine, 4-HPy's performance is markedly enhanced by halogen ions. By employing second harmonic generation (SHG) spectroscopy combined with electrochemical methods, Raman spectroscopy, atomic force microscopy, x-ray photoelectron spectroscopy, and in situ UV spectroscopy, this study elucidates the synergistic enhancement mechanism of 4-HPy with Cl-, Br-, and I- in 0.5 mol/L HCl solution. Time-dependent SHG measurements showed a two-step process of rapid adsorption and subsequent orientation change, with a proposed mechanism to interpret the temporal changes in SHG intensity. Deducing the adsorption kinetic equations and their application to the experimental data yields the adsorption rate (kad) and orientation change rate (Kre). Halogens reduce the orientation angle of 4-HPy, facilitating its adsorption on the substrate surface and effectively inhibiting corrosion via distinct mechanisms. Cl- and Br- ions primarily adsorb onto the metal surface, forming an adsorption film that not only enhances the subsequent adsorption of 4-HPy but also provides a protective effect for the metal surface. Conversely, I- forms mainly complexes with 4-HPy in solution, co-adsorbs onto the metal surface, and demonstrates a significant synergistic effect. This study revealed the synergistic efficacy hierarchy among halogen ions, with the order 4HPy + NaCl < 4HPy + NaBr < 4HPy + NaI. This study enhances our molecular-level understanding of the synergistic mechanism between halogen ions and corrosion inhibitors and provides valuable insights for designing and developing effective corrosion inhibitors.

Targeting Lactate: An Emerging Strategy for Macrophage Regulation in Chronic Inflammation and Cancer.

Lactate accumulation and macrophage infiltration are pivotal features of both chronic inflammation and cancer. Lactate, once regarded merely as an aftereffect of glucose metabolism, is now gaining recognition for its burgeoning spectrum of biological roles and immunomodulatory significance. Recent studies have evidenced that macrophages display divergent immunophenotypes in different diseases, which play a pivotal role in disease management by modulating macrophage polarization within the disease microenvironment. The specific polarization patterns of macrophages in a high-lactate environment and their contribution to the progression of chronic inflammation and cancer remain contentious. This review presents current evidence on the crosstalk of lactate and macrophage in chronic inflammation and cancer. Additionally, we provide an in-depth exploration of the pivotal yet enigmatic mechanisms through which lactate orchestrates disease pathogenesis, thereby offering novel perspectives to the development of targeted therapeutic interventions for chronic inflammation and cancer.

Immunoglobulin M-based local production in skin-associated lymphoid tissue of flounder (Paralichthys olivaceus) initiated by immersion with inactivated Edwardsiella tarda.

Fish skin, the mucosal site most exposed to external antigens, requires protection by an efficient local mucosal immune system. The mucosal reserve of IgM is recognized as an immune strategy that blocks pathogen invasion to maintain homeostasis, whereas the mechanism of skin-associated local IgM production induced by mucosal antigens is not well know. In this study, we found that the skin of flounder (Paralichthys olivaceus) was equipped with the immune cellular and molecular basis for processing mucosal antigens and triggering local specific responses, i.e., CD4+ Zap-70+ T cells, CD4- Zap-70+ T/NK cells, IgM+ MHCII+ B cells, PNA+ MHCII+ antigen-presenting cells, UEA-1+ WGA+ and UEA-1+ WGA- antigen-sampling cells, as well as secreted IgM and pIgR, as demonstrated by indirect immunofluorescence assay using different antibodies and lectins. After immersion immunization with inactivated Edwardsiella tarda, qPCR assay displayed up-regulation of immune-related genes in flounder skin. Flow cytometry analysis and EdU labeling demonstrated that the mucosal inactivated vaccine induced local proliferation and increased amounts of cutaneous IgM+ B cells. Skin explant culture proved the local production of specific IgM in the skin, which could bind to the surface of E. tarda. ELISA, laser scanning confocal microscopy, and western blot revealed that, in addition to the elevated IgM levels, pIgR protein level was significantly up-regulated in skin tissue and surface mucus containing the pIgR (secretory component, SC)-tetrameric IgM complex, indicating that mucosal vaccine stimulated up-regulation of IgM and pIgR, which were secreted as a complex into skin mucus to exert the protective effects as secretory IgM. These findings deepen the understanding of IgM-based local responses in the mucosal immunity of teleosts, which will be critical for subsequent investigation into the protective mechanism of mucosal vaccines for fish health.

Secondary rhinoplasty for unilateral cleft lip nasal deformity using the complex of autologous costal cartilage and fascia grafts.

BACKGROUND: Secondary unilateral cleft lip nasal deformity is a prevalent condition in the world, and surgical repair remains a formidable challenge. The objective of the study is to investigate functionally and aesthetically outcomes of a new technique using a complex of autologous costal cartilage and fascia grafts to repair the secondary unilateral cleft lip nasal deformity. METHODS: First, the autologous costal cartilage and fascia were harvested from a total of 34 patients with secondary unilateral cleft lip nasal deformity, who were undergoing treatments at the First Affiliated Hospital of Xi'an Jiaotong University from April 2020 to June 2023. Then, the cartilage was sub-divided into 6 pieces and placed on the depressed alar base, nasal columella, lower lateral cartilage, and nasal tip. At the same time, the fascia was trimmed to cover the nasal tip cap graft and augment the dorsum of the nose. Patient outcomes were assessed through subjective evaluation and objective anthropometric measurements. In addition, associated complications were also examined. RESULTS: All were primary healing incisions, and no patients were encountered with any clinical complications. We found that the overall mean score of the Independent Rhinoplasty Outcome Score (IROS) was very good during the subjective assessment. Also, the objective measurements indicated an excellent nasal symmetry. Furthermore, both functionally and aesthetically satisfactory outcomes were obtained in all the patients during long-time follow-up. CONCLUSIONS: Secondary rhinoplasty using the complex of autologous costal cartilage and fascia grafts is a safe and effective approach for unilateral cleft lip nasal deformity repair.

Exosomes from adipose-derived stem cells overexpressing microRNA-671-3p promote fat graft angiogenesis and adipogenic differentiation.

Exosomes from adipose-derived stem cells (ADSCs) have been demonstrated to benefit angiogenesis, wound healing, and fat grafting. Small noncoding RNAs such as microRNA (miRNA) and circular RNA play critical roles in mediating the function of ADSCs-derived exosomes. However, the underlying mechanisms have not been fully elucidated. In this study, we investigated the function and mechanism of human ADSCs-derived exosomes (hADSCs-Exo) in promoting fat graft angiogenesis and adipogenic differentiation. hADSCs-Exo were isolated and identified, and treatment with hADSCs-Exo enhanced fat graft angiogenesis and adipogenic differentiation in a mouse fat graft implantation model. We found that hADSCs-Exo overexpressed miR-671-3p and promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and invasion. Bioinformatics analysis and luciferase reporter assay validated that TMEM127 is a direct target of miR-671-3p. Rescue experiments demonstrated that TMEM127 overexpression partially antagonized the function of hADSCs-Exo in vitro, such as suppressing HUVEC cell proliferation, migration, and invasion. Moreover, TMEM127 overexpression abrogated the function of hADSCs-Exo on fat graft angiogenesis and adipogenic differentiation. Taken together, our findings demonstrate that miR-671-3p-overexpressing exosomes from ADSC promote fat graft angiogenesis and adipogenic differentiation, which highlights the potential of targeting the ADSC-Exosomes-miR-671-3p/TMEM127 axis to improve outcome of fat graft and tissue engineering regenerative medicine.

Multiparametric MRI Radiomics With Machine Learning for Differentiating HER2-Zero, -Low, and -Positive Breast Cancer: Model Development, Testing, and Interpretability Analysis.

BACKGROUND: MRI radiomics has been explored for three-tiered classification of breast cancer HER2 expression (i.e., HER2-zero, HER2-low, or HER2-positive), although understanding of how such models reach their predictions is lacking. OBJECTIVE: To develop and test multiparametric MRI radiomics machine-learning models for differentiating three-tiered HER2 expression levels in patients with breast cancer, and to explain the contributions of model features through local and global interpretations using SHapley Additive exPlanation (SHAP) analysis. METHODS: This retrospective study included 737 patients (mean age, 54.1±10.6 years) with breast cancer from two centers (center 1: n=578; center 2: n=159), who underwent breast MRI and had HER2 expression determined after excisional biopsy. Analysis entailed two tasks: differentiating HER2-negative (i.e., HER2-zero or HER2-low) from HER2-positive tumors (task 1), and differentiating HER2-zero from HER2-low tumors (task 2). For each task, patients from center 1 were randomly assigned in 7:3 ratio to training (task 1: n=405; task 2: n=284) or internal test (task 1: n=173; task 2: n=122) sets; those from center 2 formed an external test set (task 1: n=159; task 2: n=105). Radiomics features were extracted from early-phase dynamic contrast-enhanced images (DCE), T2-weighted images (T2WI), and DWI. For each task, a support vector machine (SVM) was used for feature selection; a multiparametric radiomics score (radscore) was computed using feature weights from SVM correlation coefficients; conventional MRI and combined models were constructed; and model performances were evaluated. SHAP analysis was used to provide local and global interpretations for model outputs. RESULTS: In the external test set, for task 1, AUCs for the conventional MRI model, radscore, and combined model were 0.624, 0.757, and 0.762, respectively; for task 2, AUC for radscore was 0.754, and no conventional MRI model or combined model could be constructed. SHAP analysis identified early-phase DCE features as having the strongest influence for both tasks; T2WI features also had a prominent role for task 2. CONCLUSION: The findings indicate suboptimal performance of MRI radiomics models for noninvasive characterization of HER2 expression. CLINICAL IMPACT: The study provides an example of the use of SHAP interpretation analysis to better understand predictions of imaging-based machine learning models.

Fluorescent cellulose hydrogels based on corn stalk of double sulfhydryl functional group modification for Hg(II) removal and detection.

Ions of mercury, one of the most hazardous heavy metals in nature, pose serious risks to the environment and human health. Blue sulfur-doped carbon dots (SCDs) from corn stalks were utilized as material. The SCDs were incorporated into a carboxylated hydrogel modified with sulfur, and a compound gel (SCDs-KTOCS gel) was successfully fabricated for simultaneous fluorescence detection and Hg(II) adsorption. This enabled the effective identification and removal of Hg(II) from contaminated water. The chemical content, fluorescence properties, and adsorption behaviors of the SCDs-KTOCS-gels were analyzed. The results demonstrate that the SCDs-KTOCS-gels exhibited effective Hg(II) adsorption (193 mg/g) and an extensive linear spectrum for Hg(II) fluorescence emission (150-500 mg/L; detection limit = 1.5668 mg/L). The adsorption values fit well with the Temkin models and pseudo-second-order kinetics. Additionally, Hg(II) detection and adsorption in the SCDs-KTOCS-gels were examined. By exchanging the existing probe for a suitable one that fits various relevant applications, this study suggests an environmentally friendly and sustainable method of producing materials for removing and detecting Hg(II) and constructing a fluorescence hydrogel for the detection and adsorption of different metals.

Activatable Near-Infrared Fluorescence Probe for Hypochlorous Acid Detection in Early Diagnosis of Keloids.

Keloids represent pathologic conditions characterized by the presence of hyalinized collagen bundles and chronic inflammatory reactions. Recently, increased ROS production and disrupted apoptosis mechanisms in keloids have been reported, although the detailed mechanisms remain unclear. Herein, we developed a specific fluorescence probe, Pro-NBS, to investigate ClO- levels in keloids. The probe demonstrated high specificity for ClO- over other ROS and exhibited a strong linear detection relationship. Based on its performance, we focused on the TGF-ß pathway in the development of keloids. ROS upregulation was observed in keloid-derived fibroblasts. Using ClO- as an intrinsic overexpression marker, our probe effectively distinguished between normal fibroblasts and keloid-derived fibroblasts both in vitro and in vivo. Furthermore, Pro-NBS showed potential for monitoring the progression and evaluating the systematic therapy of abnormal scarring or keloids.

Age difference in the connection between systemic inflammatory response and metabolic syndrome.

BACKGROUND: This research aims to investigate the connection between systemic inflammatory response and Metabolic Syndrome (MetS) across different age groups, with the aim of proposing more targeted recommendations. METHODS: This study enrolled 15,959 adults from the 2001-2018 National Health and Nutrition Examination Survey(NHANES) of whom 6,739 were diagnosed with MetS.After dividing Systemic Immune-Inflammation Index (SII) into four quartiles, Kruskal-Wallis test and weighted chi-square test was employed to assess statistical differences. Weighted multivariable logistic regression analysis, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were employed to examine the relationship between SII and MetS. RESULTS: Our study revealed that SII exhibits a quantitative association with MetS (OR=1.56; 95% CI: 1.37-1.79; p < 0.001). Elevated SII is an independent risk factor for the five components of MetS. Different age group and alcohol consumption status could modify the connection between SII and MetS. This connection was statistically significant in the 18-65 age group but not in the elderly subgroup (OR = 1.08; 95% CI: 0.95-1.23; p = 0.248). Multiple imputation confirmed the robustness of our results. Moreover, the connection exhibits an inverted U-shaped curve. CONCLUSIONS: Our research highlights the predictive significance of SII in forecasting the incidence of MetS in young and middle-aged population. The differences in inflammatory mechanisms across various age groups necessitate further research for exploration.

[AI-HIP system for prosthesis size, global femoral offset and osteotomy in total hip arthroplasty].

OBJECTIVE: To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty (THA) and its influence on clinical outcomes. METHODS: A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system (AI-HIP group), including 16 males and 20 females, aged from 43 to 81 years old with an average of (62.2±10.9) years old. According to the matching principle, 36 patients who were planned by the traditional template method at the same period were selected as the control group, including 16 males and 20 females, aged from 40 to 80 years old with an average of (60.9±12.1) years old. The accuracy between two groups of prostheses were compared, as well as the combined eccentricity difference between preoperative planning and postoperative practice, lower limb length difference, osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect. Harris score and visual analogue scale (VAS) were used to evaluate clinical efficacy. RESULTS: Both groups were followed up for 12 to 18 months with an average of (14.5±2.1) months. The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%, 100%, 58.3%, 88.9%, respectively, which were better than 44.4%, 83.3%, 33.3%, 66.7% in control group (P<0.05). There was no statistical significance in planning of femoral head prosthesis size (P>0.05). The actual combined eccentricity difference and combined eccentricity difference (practical-planning) in AI-HIP group were 1.0(0.2, 2.4) mm and 1.1(-2.1, 3.2) mm, respectively;which were better than 3.0 (1.4, 4.9) mm and 3.5 (-1.6, 6.5) mm in control group (P<0.05). There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter (P>0.05). In AI-HIP group, the actual difference of lower extremity length after surgery, the difference of lower extremity length (practical-planning), osteotomy height from the upper margin of lesser trochanter (practical-planning), actual topshoulder distance after surgery, and topshoulder distance (practical-planning) were 1.5 (0.2, 2.8), 1.1 (-0.3, 2.2), 2.1(-2.3, 4.1), (15.3±4.1), 2.2(-4.8, 0.3) mm, respectively;which were better than control group of 2.6(1.3, 4.1), 2.5 (0.3, 3.8), 5.8(-2.4, 7.7), (13.0±4.3), -5.7(-9.4, -2.2) mm(P<0.05). At final follow-up, there were no significant differences in Harris scores of pain, function, deformity, total scores and VAS between two groups (P>0.05). The range of motion score was 4.8±0.6 in AI-HIP group, which was higher than that in control group (4.4±0.8)(P<0.05). CONCLUSION: Compared with traditional template planning, AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk, restoring joint eccentricity, planning lower limb length, osteotomy height and top shoulder distance on the first unilateral THA, and the clinical follow-up effect is satisfactory.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Robust optical multi-image encryption with lossless decryption Recovery Based on phase recombination and vector decomposition.

Image encryption is crucial for protecting image privacy and ensuring security. Encrypting large batches of images of different types and sizes simultaneously with losslessly decryption is often necessary. This paper proposes an optical asymmetric multi-image encryption algorithm to meet these demands. First, plaintext images are converted into one-dimensional pixels and blocked. Image information, image count, and pixels are stored in corresponding areas and reassembled. Unit equal-modulus vector decomposition (UEMD) and phase truncation generate the ciphertext image and keys. The decrypted image is reconstructed from the ciphertext's information and quantity areas. Asymmetric encryption with different keys for encryption and decryption enhances security, while UEMD ensures lossless recovery and robustness. Experiments demonstrate the proposed algorithm's efficiency in encrypting multiple grayscale and color images of varying sizes, providing high security, and lossless recovery. This technology offers superior protection for sensitive image data, enhancing encryption system practicality and digital security.

TACE Combined with Portal Vein Tumor Thrombus 125I Seed Implantation in the Treatment of HCC with Hepatic Arterioportal Shunts.

Background and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS. Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed. Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02). Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.

Functional characterisation of BnaA02.TOP1α and BnaC02.TOP1α involved in true leaf biomass accumulation in Brassica napus L.

Leaves, as primary photosynthetic organs essential for high crop yield and quality, have attracted significant attention. The functions of DNA topoisomerase 1α (TOP1α) in various biological processes, including leaf development, in Brassica napus remain unknown. Here, four paralogs of BnaTOP1α, namely BnaA01.TOP1α, BnaA02.TOP1α, BnaC01.TOP1α and BnaC02.TOP1α, were identified and cloned in the B. napus inbred line 'K407'. Expression pattern analysis revealed that BnaA02.TOP1α and BnaC02.TOP1α, but not BnaA01.TOP1α and BnaC01.TOP1α, were persistently and highly expressed in B. napus true leaves. Preliminary analysis in Arabidopsis thaliana revealed that BnaA02.TOP1α and BnaC02.TOP1α paralogs, but not BnaA01.TOP1α and BnaC01.TOP1α, performed biological functions. Targeted mutations of four BnaTOP1α paralogs in B. napus using the CRISPR-Cas9 system revealed that BnaA02.TOP1α and BnaC02.TOP1α served as functional paralogs and redundantly promoted true leaf number and size, thereby promoting true leaf biomass accumulation. Moreover, BnaA02.TOP1α modulated the levels of endogenous gibberellins, cytokinins and auxins by indirectly regulating several genes related to their metabolism processes. BnaA02.TOP1α directly activated BnaA03.CCS52A2 and BnaC09.AN3 by facilitating the recruitment of RNA polymerase II and modulating H3K27me3, H3K36me2 and H3K36me3 levels at these loci and indirectly activated the BnaA08.PARL1 expression, thereby positively controlling the true leaf size in B. napus. Additionally, BnaA02.TOP1α indirectly activated the BnaA07.PIN1 expression to positively regulate the true leaf number. These results reveal the important functions of BnaTOP1α and provide insights into the regulatory network controlling true leaf biomass accumulation in B. napus.

Bioaccessibility and bioavailability of exogenous and endogenous toxic substances in traditional Chinese medicine and their significance in risk assessment.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke.

Rationale: Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear. Methods: Surface-enhanced Raman spectroscopy (SERS) and liquid chromatography-mass spectrometry (LC‒MS) analysis of clinical serum samples from 69 controls and 51 ischemic stroke patients who underwent reperfusion within 24 hours were performed to identify differentially abundant metabolites. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) and then intravenously injected with hypoxanthine. The infarct area was evaluated via tetrazolium chloride (TTC) staining, and behavior tests were conducted. Blood-brain barrier (BBB) leakage was assessed by Evans blue and IgG staining. Human blood vessel organoids were used to investigate the mechanism of hypoxanthine-induced pyroptosis of endothelial cells. Results: SERS and LC‒MS revealed the metabolic profiles of serum from stroke patients and controls with high sensitivity, speed and accuracy. Hypoxanthine levels were significantly elevated in the acute stage of ischemic stroke in both patients and mice (p < 0.001 after Bonferroni correction). In addition, increasing hypoxanthine increased the infarct area and aggravated BBB leakage and neurobehavioral deficits in mice after ischemic stroke. Further mechanistic studies using endothelial cells, human blood vessel organoids, and stroke mice demonstrated that hypoxanthine-mediated gasdermin E (GSDME)-dependent pyroptosis of endothelial cells occurs through intracellular Ca2+ overload. Conclusion: Our study identified hypoxanthine as an important metabolite that induces vascular injury and BBB disruption in stroke through triggering GSDME-dependent pyroptosis of endothelial cells.

Feature matching based on local windows aggregation.

The core goal of feature matching is to establish correspondences between two images. Current methods without detectors achieve impressive results but often focus on global features, neglecting regions with subtle textures and resulting in fewer matches in areas with weak textures. This paper proposes a feature-matching method based on local window aggregation, which balances global features and local texture variations for more accurate matches, especially in weak-texture regions. Our method first applies a local window aggregation module to minimize irrelevant interference using window attention, followed by global attention, generating coarse and fine-grained feature maps. These maps are processed by a matching module, initially obtaining coarse matches via the nearest neighbor principle. The coarse matches are then refined on fine-grained maps through local window refinement. Experimental results show our method surpasses state-of-the-art techniques in pose estimation, homography estimation, and visual localization under the same training conditions.

A Robust Deep Learning Method with Uncertainty Estimation for the Pathological Classification of Renal Cell Carcinoma Based on CT Images.

This study developed and validated a deep learning-based diagnostic model with uncertainty estimation to aid radiologists in the preoperative differentiation of pathological subtypes of renal cell carcinoma (RCC) based on computed tomography (CT) images. Data from 668 consecutive patients with pathologically confirmed RCC were retrospectively collected from Center 1, and the model was trained using fivefold cross-validation to classify RCC subtypes into clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). An external validation with 78 patients from Center 2 was conducted to evaluate the performance of the model. In the fivefold cross-validation, the area under the receiver operating characteristic curve (AUC) for the classification of ccRCC, pRCC, and chRCC was 0.868 (95% CI, 0.826-0.923), 0.846 (95% CI, 0.812-0.886), and 0.839 (95% CI, 0.802-0.88), respectively. In the external validation set, the AUCs were 0.856 (95% CI, 0.838-0.882), 0.787 (95% CI, 0.757-0.818), and 0.793 (95% CI, 0.758-0.831) for ccRCC, pRCC, and chRCC, respectively. The model demonstrated robust performance in predicting the pathological subtypes of RCC, while the incorporated uncertainty emphasized the importance of understanding model confidence. The proposed approach, integrated with uncertainty estimation, offers clinicians a dual advantage: accurate RCC subtype predictions complemented by diagnostic confidence metrics, thereby promoting informed decision-making for patients with RCC.

Polyvalent Glycomimetic-Gold Nanoparticles Revealing Critical Roles of Glycan Display on Multivalent Lectin-Glycan Interaction Biophysics and Antiviral Properties.

Multivalent lectin-glycan interactions (MLGIs) are widespread and vital for biology, making them attractive therapeutic targets. Unfortunately, the structural and biophysical mechanisms of several key MLGIs remain poorly understood, limiting our ability to design spatially matched glycoconjugates as potential therapeutics against specific MLGIs. We have recently demonstrated that natural oligomannose-coated nanoparticles are powerful probes for MLGIs. They can provide not only quantitative affinity and binding thermodynamic data but also key structural information (e.g, binding site orientation and mode) useful for designing glycoconjugate therapeutics against specific MLGIs. Despite success, how designing parameters (e.g., glycan type, density, and scaffold size) control their MLGI biophysical and antiviral properties remains to be elucidated. A synthetic pseudodimannose (psDiMan) ligand has been shown to selectively bind to a dendritic cell surface tetrameric lectin, DC-SIGN, over some other multimeric lectins sharing monovalent mannose specificity but having distinct cellular functions. Herein, we display psDiMan polyvalently onto gold nanoparticles (GNPs) of varying sizes (e.g., ∼5 and ∼13 nm, denoted as G5- and G13 psDiMan hereafter) to probe how the scaffold size and glycan display control their MLGI properties with DC-SIGN and the closely related lectin DC-SIGNR. We show that G5/13 psDiMan binds strongly to DC-SIGN, with sub-nM K ds, with affinity being enhanced with increasing scaffold size, whereas they show apparently no or only weak binding to DC-SIGNR. Interestingly, there is a minimal, GNP-size-dependent, glycan density threshold for forming strong binding with DC-SIGN. By combining temperature-dependent affinity and Van't Hoff analyses, we have developed a new GNP fluorescence quenching assay for MLGI thermodynamics, revealing that DC-SIGN-Gx-psDiMan binding is enthalpy-driven, with a standard binding ΔH 0 of ∼ -95 kJ mol-1, which is ∼4-fold that of the monovalent binding and is comparable to that measured by isothermal titration calorimetry. We further reveal that the enhanced DC-SIGN affinity with Gx-psDiMan with increasing GNP scaffold size is due to reduced binding entropy penalty and not due to enhanced favorable binding enthalpy. We further show that DC-SIGN binds tetravalently to a single Gx-psDiMan, irrespective of the GNP size, whereas DC-SIGNR binding is dependent on GNP size, with no apparent binding with G5, and weak cross-linking with G13. Finally, we show that Gx-psDiMans potently inhibit DC-SIGN-dependent augmentation of cellular entry of Ebola pseudoviruses with sub-nM EC50 values, whereas they exhibit no significant (for G5) or weak (for G13) inhibition against DC-SIGNR-augmented viral entry, consistent to their MLGI properties with DC-SIGNR in solution. These results have established Gx-psDiMan as a versatile new tool for probing MLGI affinity, selectivity, and thermodynamics, as well as GNP-glycan antiviral properties.

Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases.

BACKGRUOUND: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. METHODS: In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. RESULTS: Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05). CONCLUSION: The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.