Dynamin-related protein 1 mediates the therapeutic effect of isoliquiritigenin in diabetic intimal hyperplasia via regulation of mitochondrial fission.

Phenotypic shift of vascular smooth muscle cells (VSMCs) plays a key role in intimal hyperplasia, especially in patients with diabetes mellitus (DM). This study aimed to investigate the role of dynamin-related protein 1 (DRP1) in mitochondrial fission-mediated VSMC phenotypic shift and to clarify whether DRP1 is the therapeutic target of isoliquiritigenin (ISL). Wire injury of carotid artery or platelet-derived growth factor treatment was performed in DM mice or high-glucose cultured human aortic smooth muscle cells (HASMCs), respectively. The effects of DRP1 silencing on DM-induced intimal hyperplasia were investigated both in vivo and in vitro. Phenotypic shift of HASMCs was evaluated by detection of reactive oxygen species (ROS) generation, cell viability, and related protein expressions. The effects of ISL on DM-induced intimal hyperplasia were evaluated both in vivo and in vitro. DRP1 silencing and ISL treatment attenuated DM-induced intimal hyperplasia with reduced ROS generation, cell viability, and VSMC dedifferentiation. The GTPase domain of DRP1 protein played a critical role in mitochondrial fission in DM-induced VSMC phenotypic shift. Cellular experiments showed that ISL inhibited mitochondrial fission and reduced the GTPase activity of DRP1, which was achieved by the directly binding to K216 of the DRP1 GTPase domain. ISL attenuated mouse intimal hyperplasia by reducing GTPase activity of DRP1 and inhibiting mitochondrial fission in vivo. In conclusion, increased GTPase activity of DRP1 aggregated DM-induced intimal hyperplasia by increasing mitochondrial fission-mediated VSMC phenotypic shift. ISL attenuated mouse intimal hyperplasia by reducing DRP1 GTPase activity and inhibiting mitochondrial fission of VSMCs.

Glucagon-like peptide-1 receptor agonist exendin 4 ameliorates diabetes-associated vascular calcification by regulating mitophagy through the AMPK signaling pathway.

BACKGROUND: Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. MATERIALS AND METHODS: The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and ß-glycerophosphate (ß-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. RESULTS: In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/ß-GP-induced VSMCs. In HG/ß-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/ß-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. CONCLUSION: EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.

The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of ß-glucan by resetting TAMs.

Anti-CD40 antibodies (Abs) have been shown to induce antitumor T-cell responses. We reported that the engineered agonistic anti-CD40 Ab (5C11, IgG4 isotype) recognized human CD40 antigen expressed on a human B lymphoblastoid cell line as well as on splenic cells isolated from humanized CD40 mice. Of note, a single high dosage of 5C11 was able to prohibit tumor growth in parallel with an increase in the population of infiltrated CD8+ T cells. Furthermore, the antitumor effects of 5C11 were enhanced in the presence of ß-glucan along with an increase in the population of infiltrated CD8+ T cells. In addition, the numbers of CD86+ TAMs and neutrophils were elevated in the combination of 5C11 and ß-glucan compared with either 5C11 or ß-glucan alone. Furthermore, the abundance of Faecalibaculum, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and ß-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and ß-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and ß-glucan could be a promising therapeutic strategy for cancer patients.

Uncovering the Pre-Deterioration State during Disease Progression Based on Sample-Specific Causality Network Entropy (SCNE).

Complex diseases do not always follow gradual progressions. Instead, they may experience sudden shifts known as critical states or tipping points, where a marked qualitative change occurs. Detecting such a pivotal transition or pre-deterioration state holds paramount importance due to its association with severe disease deterioration. Nevertheless, the task of pinpointing the pre-deterioration state for complex diseases remains an obstacle, especially in scenarios involving high-dimensional data with limited samples, where conventional statistical methods frequently prove inadequate. In this study, we introduce an innovative quantitative approach termed sample-specific causality network entropy (SCNE), which infers a sample-specific causality network for each individual and effectively quantifies the dynamic alterations in causal relations among molecules, thereby capturing critical points or pre-deterioration states of complex diseases. We substantiated the accuracy and efficacy of our approach via numerical simulations and by examining various real-world datasets, including single-cell data of epithelial cell deterioration (EPCD) in colorectal cancer, influenza infection data, and three different tumor cases from The Cancer Genome Atlas (TCGA) repositories. Compared to other existing six single-sample methods, our proposed approach exhibits superior performance in identifying critical signals or pre-deterioration states. Additionally, the efficacy of computational findings is underscored by analyzing the functionality of signaling biomarkers.

Automated prediction of isthmus areas in scar-related atrial tachycardias using artificial intelligence.

INTRODUCTION: Ablation of scar-related reentrant atrial tachycardia (SRRAT) involves identification and ablation of a critical isthmus. A graph convolutional network (GCN) is a machine learning structure that is well-suited to analyze the irregularly-structured data obtained in mapping procedures and may be used to identify potential isthmuses. METHODS: Electroanatomic maps from 29 SRRATs were collected, and custom electrogram features assessing key tissue and wavefront properties were calculated for each point. Isthmuses were labeled off-line. Training data was used to determine the optimal GCN parameters and train the final model. Putative isthmus points were predicted in the training and test populations and grouped into proposed isthmus areas based on density and distance thresholds. The primary outcome was the distance between the centroids of the true and closest proposed isthmus areas. RESULTS: A total of 193 821 points were collected. Thirty isthmuses were detected in 29 tachycardias among 25 patients (median age 65.0, 5 women). The median (IQR) distance between true and the closest proposed isthmus area centroids was 8.2 (3.5, 14.4) mm in the training and 7.3 (2.8, 16.1) mm in the test group. The mean overlap in areas, measured by the Dice coefficient, was 11.5 ± 3.2% in the training group and 13.9 ± 4.6% in the test group. CONCLUSION: A GCN can be trained to identify isthmus areas in SRRATs and may help identify critical ablation targets.

CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age.

Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer+CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02-restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age.

Robust, high-density lesion mapping in the left atrium with near-infrared spectroscopy.

Significance: Radiofrequency ablation (RFA) procedures for atrial fibrillation frequently fail to prevent recurrence, partially due to limitations in assessing extent of ablation. Optical spectroscopy shows promise in assessing RFA lesion formation but has not been validated in conditions resembling those in vivo. Aim: Catheter-based near-infrared spectroscopy (NIRS) was applied to porcine hearts to demonstrate that spectrally derived optical indices remain accurate in blood and at oblique incidence angles. Approach: Porcine left atria were ablated and mapped using a custom-fabricated NIRS catheter. Each atrium was mapped first in phosphate-buffered saline (PBS) then in porcine blood. Results: NIRS measurements showed little angle dependence up to 60 deg. A trained random forest model predicted lesions with a sensitivity of 81.7%, a specificity of 86.1%, and a receiver operating characteristic curve area of 0.921. Predicted lesion maps achieved a mean structural similarity index of 0.749 and a mean normalized inner product of 0.867 when comparing maps obtained in PBS and blood. Conclusions: Catheter-based NIRS can precisely detect RFA lesions on left atria submerged in blood. Optical parameters are reliable in blood and without perpendicular contact, confirming their ability to provide useful feedback during in vivo RFA procedures.

Improving the productivity of gibberellic acid by combining small-molecule compounds-based targeting technology and transcriptomics analysis in Fusarium fujikuroi.

Gibberellic acid (GA3), produced industrially by Fusarium fujikuroi, stands as a crucial plant growth regulator extensively employed in the agriculture filed while limited understanding of the global metabolic network hinders researchers from conducting rapid targeted modifications. In this study, a small-molecule compounds-based targeting technology was developed to increase GA3 production. Firstly, various small molecules were used to target key nodes of different pathways and the result displayed that supplement of terbinafine improved significantly GA3 accumulation, which reached to 1.08 g/L. Subsequently, lipid and squalene biosynthesis pathway were identified as the key pathways influencing GA3 biosynthesis by transcriptomic analysis. Thus, the strategies including in vivo metabolic engineering modification and in vitro supplementation of lipid substrates were adopted, both contributed to an enhanced GA3 yield. Finally, the engineered strain demonstrated the ability to achieve a GA3 yield of 3.24 g/L in 5 L bioreactor when utilizing WCO as carbon source and feed.

A novel tRNA-derived fragment tRF-3023b suppresses inflammation in RAW264.7 cells by targeting Cul4a through NF-κB signaling.

The role of transfer RNA (tRNA)-derived fragment (tRF) in various diseases has been established. However, the effect of tRF-3023b on inflammation remains unclear. Inflammation was imitated in RAW264.7 cells by adding Lipopolysaccharide (LPS). Cells were first divided into control, LPS, and LPS + Bulleyaconitine A (BLA) groups. The contents of TNF-α, IL-6, and MCP-1 were quantified using ELISA. The levels of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), and the phosphorylation of nuclear factor-kappa B (NF-κB)-P65 (p-P65) were detected by Western blotting. RNA sequencing was utilized to find differentially expressed tRFs (DE-tRFs) among three groups. The levels of various tRFs were checked by quantitative real-time PCR (qRT-PCR). Cell cycle and apoptosis were checked by flow cytometry. Dluciferase reporter assay was applied to predict and confirm the interaction between tRF-3023b and Cullin 4A (Cul4a), subsequently RNA pull-down followed by mass spectrometry analysis were conducted. BLA treatment decreased the contents of TNF-α, IL-6, MCP-1, and the expression levels of COX2, iNOS, p-P65. We found 6 DE-tRFs in LPS + BLA group compared to LPS group, tRF-3023b was high expression in control and BLA groups, and the lowest in LPS group. Cul4a was a direct target of tRF-3023b. tRF-3023b mimic affected the cell cycle distribution, promoted cells apoptosis, and suppressed the TNF-α, IL-6, MCP-1, COX2, iNOS and p-P65. The suppression of Cul4a affected the cell cycle distribution, resulted in an increase of cell apoptosis while a decrease of TNF-α, IL-6, MCP-1, COX2, iNOS and p-P65. Furthermore, Cul4a overexpression reversed the effect of tRF-3023b mimic. Cul4a knockdown reversed the effect of tRF-3023b inhibitor. Our study positions tRF-3023b as a compelling candidate, through its interaction with Cul4a, the underlying mechanism on inflammation maybe related to NF-κB pathway. The study provides a basis for exploring new therapeutic strategies for inflammation.

Bacterial bioburden of duodenoscope elevator mechanism in different reprocessing stages.

Over the past decade, infections linked to duodenoscopes have become a significant concern, primarily due to the intricate design of the elevator mechanism. Currently, there is limited evidence regarding the bacterial contamination level of the elevator mechanism after clinical use and throughout its various reprocessing stages. This study utilized the swab culture technique to examine the bacterial contamination on the duodenoscope elevator mechanism after clinical use and after 3 reprocessing stages at a Center of tertiary hospital. Our findings revealed severe bacterial contamination after clinical usage, emphasizing that the effectiveness of manual cleaning greatly influences the subsequent high-level disinfection quality.

Comprehensive evaluation of the risk system for heavy metals in the rehabilitated saline-alkali land.

A comprehensive assessment of the heavy metal system in the rehabilitated saline-alkali land holds significant importance, as the in-situ remediation process utilizing amendments substantially alters the initial physicochemical properties of the soil, which could lead to the migration or reactivation of previously stabilized heavy metals. In this context, the present study aims to evaluate the heavy metal content and health risk within the improved saline-alkali soil-plant system. Moreover, a comprehensive evaluation based on the TOPSIS-RSR method is carried out to accurately gauge the soil health status. The findings indicate that the modification process has an impact on the concentrations of heavy metals in the soil and crops, causing either an increase or decrease. However, the level of heavy metal pollution in the improved saline-alkali soil and rape remains within safe limits. The results of the migration of heavy metals after amendment application indicated that the migration of heavy metals in the soil was influenced by the properties of the heavy metals, the composition of the amendment, and leaching. Furthermore, the total non-carcinogenic hazard quotients in the soil and rape were within the safe threshold for all populations. The findings provided novel insights into the status and risk assessment of the pollution of improved saline-alkali soil.

Effective strategies for reclamation of saline-alkali soil and response mechanisms of the soil-plant system.

The combination of amendments has emerged as a potential strategy to efficiently alleviate salt stress in saline-alkali soil. However, knowledge regarding how to optimize the proportion of different amendment materials, comprehensively assess the contribution of each component, and clarify the response mechanisms of the amendment-saline-alkali soil-plant system is incomplete. Based on this, we conducted a pot experiment to evaluate the improvement effect of the combined application of different amendment materials at varying levels and the contribution of the amendment components to alleviating salt stress. Overall, T6 exhibited the most significant improvement effect on the physicochemical and biological properties of the saline-alkali soil and promoted the growth of oilseed rape, with the levels of 2.0 % phosphogypsum, 2.0 % humic acid, 0.25 % bentonite, and 0.03 % sodium carboxymethyl cellulose. Compared with the control group, the EC decreased by 1.51 % to 33.49 %, the soil salt content dropped by 11.40 % to 35.46 %, and the soil soluble Na + concentration significantly declined by 39.47 % to 63.20 %. Additionally, the soil nutrient content and soil microbial community structure were enhanced in treatment groups. Meanwhile, amendments alleviated salt stress in the oilseed rape plant by activating anti-oxidative enzymes and osmoregulatory substances such as soluble sugar and proline, thus improving their ability to remove reactive oxygen species (ROS). The anti-oxidative enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly increased, with an increase of 10.68 % (SOD, T2) ∼207.31 % (CAT, T6) compared to the control group. The structural equation modeling (SEM) analysis and simulation experiments indicated that the amendment components synergically promoted the amelioration effect on salt stress, and effectively improved soil properties, which affected the response of oilseed rape to soil environment. This research paper provides the relevant reference for the combined application of different amendment materials for soil reclamation.

Succession of endophytic fungi and rhizosphere soil fungi and their correlation with secondary metabolites in Fagopyrum dibotrys.

Golden buckwheat (Fagopyrum dibotrys, also known as F. acutatum) is a traditional edible herbal medicinal plant with a large number of secondary metabolites and is considered to be a source of therapeutic compounds. Different ecological environments have a significant impact on their compound content and medicinal effects. However, little is known about the interactions between soil physicochemical properties, the rhizosphere, endophytic fungal communities, and secondary metabolites in F. dibotrys. In this study, the rhizosphere soil and endophytic fungal communities of F. dibotrys in five different ecological regions in China were identified based on high-throughput sequencing methods. The correlations between soil physicochemical properties, active components (total saponins, total flavonoids, proanthocyanidin, and epicatechin), and endophytic and rhizosphere soil fungi of F. dibotrys were analyzed. The results showed that soil pH, soil N, OM, and P were significantly correlated with the active components of F. dibotrys. Among them, epicatechin, proanthocyanidin, and total saponins were significantly positively correlated with soil pH, while proanthocyanidin content was significantly positively correlated with STN, SAN, and OM in soil, and total flavone content was significantly positively correlated with P in soil. In soil microbes, Mortierella, Trechispora, Exophiala, Ascomycota_unclassified, Auricularia, Plectosphaerella, Mycena, Fungi_unclassified, Agaricomycetes_unclassified, Coprinellus, and Pseudaleuria were significantly related to key secondary metabolites of F. dibotrys. Diaporthe and Meripilaceae_unclassified were significantly related to key secondary metabolites in the rhizome. This study presents a new opportunity to deeply understand soil-plant-fungal symbioses and secondary metabolites in F. dibotrys, as well as provides a scientific basis for using biological fertilization strategies to improve the quality of F. dibotrys.

Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study.

Introduction: Previous research has reported that the gut microbiota performs an essential role in sleep through the microbiome-gut-brain axis. However, the causal association between gut microbiota and sleep remains undetermined. Methods: We performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression. Results: In forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis. Discussion: In conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.

Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma.

B7-H3 (immunoregulatory protein B7-homologue 3) is overexpressed in many cancer cells with limited expression in normal tissues, considered to be a promising target for tumor therapeutics. Clinical trials of antibody-drug conjugates (ADCs) against different targets for glioblastoma have been investigated and showed potent efficacies. In this study, we developed a homogeneous ADC 401-4 with a drug-to-antibody ratio (DAR) of 4, which was prepared by conjugation of Monomethyl auristatin E (MMAE) to a humanized anti-B7-H3 mAb 401, through a divinylsulfonamide-mediated disulfide re-bridging approach. In vitro studies, 401-4 displayed specific killing against B7-H3-expressing tumors and was more effective in cells with higher levels of B7-H3 for different glioblastoma cells. 401-4 was furthered labeled with Cy5.5 to yield a fluorescent conjugate 401-4-Cy5.5. The in vivo imaging studies showed that the conjugate accumulated in tumor regions and exhibited the ability to target-specific delivery. In addition, significant antitumor activities for 401-4 was observed against U87-derived tumor xenografts in a dose dependent manner.

CD226 identifies functional CD8+T cells in the tumor microenvironment and predicts a better outcome for human gastric cancer.

It is well-known that CD226 serves as a critical activating receptor on various immune cells, such as lymphocytes and monocytes, and it is suggested to promote anti-tumor immunity in the tumor microenvironment (TME). Herein, we showed a crucial regulatory role of CD226 in CD8+T cell-mediated anti-tumor response in TME of human gastric cancer (GC). Specifically, the increased CD226 expression in cancer tissues was significantly associated with better clinical outcomes in GC patients. Moreover, the increased infiltrating CD226+CD8+T cells and the increased ratio of infiltrating CD226+CD8+T cells in CD8+T subpopulation within cancer tissues could also be valuable prognostic predictors for GC patients. Mechanically, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis revealed that the chromatin accessibility of CD226 in CD4+ and CD8+TILs was significantly higher than that in CD8+T cells in normal tissues. Further analysis showed that CD8+TILs highly expressed immune checkpoint molecules, such as TIGIT, LAG3, and HAVCR2, which means CD8+TILs are more exhausted. In addition, our multi-color immunohistochemical staining (mIHC) revealed that GC patients with higher frequency of IFN-γ+CD226+CD8+TILs showed poorer prognosis. Combined with the single-cell transcriptome sequencing (scRNA-seq) data analysis, we found that the expressions of IFN-γ and TIGIT in CD8+TILs were significantly and positively correlated. The expression of TIGIT in IFN-γ+CD226+CD8+TILs was higher, while that in IFN-γ-CD226+CD8+TILs was significantly lower. The correlation analysis showed that the expression of CD226 was positively correlated with the score of effector T cells but negatively correlated with that of immunosuppressive factors, such as Tregs and tumor-associated macrophages (TAMs). Collectively, we showed that the frequency of CD226+CD8+TILs was an excellent prognostic predictor for GC patients. Our findings provided insights into the interaction pattern between co-stimulatory receptor CD226 and tumor cells as well as the infiltrating immune cells in the TME in GC.

Prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUND: Tissue-resident CD8+T cells (CD103+CD8+T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the proliferation and effector function of tissue-resident CD103+CD8+T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated. METHODS: In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8+T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell-cell communication between tumor-infiltrating CD103+CD8+T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data. RESULTS: Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8+T cells in human HCC and ICC. Elevated CD8+T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8+T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103+CD8+T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8highCD103high had a better OS, and the CD8lowCD103low group tended to have a poorer prognosis in ICC. Evaluation of the CD103+CD8+T-cell ratio in CD8+T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103+CD8+T cells over total CD8+T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103+CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103+CD8+T cells over total CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103+CD8+T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion. CONCLUSION: The CD103+ tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103+CD8+T cells might be helpful in assessing the on-treatment response of liver cancer.

Cardiac Adipose Tissue Segmentation via Image-Level Annotations.

Automatically identifying the structural substrates underlying cardiac abnormalities can potentially provide real-time guidance for interventional procedures. With the knowledge of cardiac tissue substrates, the treatment of complex arrhythmias such as atrial fibrillation and ventricular tachycardia can be further optimized by detecting arrhythmia substrates to target for treatment (i.e., adipose) and identifying critical structures to avoid. Optical coherence tomography (OCT) is a real-time imaging modality that aids in addressing this need. Existing approaches for cardiac image analysis mainly rely on fully supervised learning techniques, which suffer from the drawback of workload on labor-intensive annotation process of pixel-wise labeling. To lessen the need for pixel-wise labeling, we develop a two-stage deep learning framework for cardiac adipose tissue segmentation using image-level annotations on OCT images of human cardiac substrates. In particular, we integrate class activation mapping with superpixel segmentation to solve the sparse tissue seed challenge raised in cardiac tissue segmentation. Our study bridges the gap between the demand on automatic tissue analysis and the lack of high-quality pixel-wise annotations. To the best of our knowledge, this is the first study that attempts to address cardiac tissue segmentation on OCT images via weakly supervised learning techniques. Within an in-vitro human cardiac OCT dataset, we demonstrate that our weakly supervised approach on image-level annotations achieves comparable performance as fully supervised methods trained on pixel-wise annotations.

Automated analysis framework for in vivo cardiac ablation therapy monitoring with optical coherence tomography.

Radiofrequency ablation (RFA) is a minimally invasive procedure that is commonly used for the treatment of atrial fibrillation. However, it is associated with a significant risk of arrhythmia recurrence and complications owing to the lack of direct visualization of cardiac substrates and real-time feedback on ablation lesion transmurality. Within this manuscript, we present an automated deep learning framework for in vivo intracardiac optical coherence tomography (OCT) analysis of swine left atria. Our model can accurately identify cardiac substrates, monitor catheter-tissue contact stability, and assess lesion transmurality on both OCT intensity and polarization-sensitive OCT data. To the best of our knowledge, we have developed the first automatic framework for in vivo cardiac OCT analysis, which holds promise for real-time monitoring and guidance of cardiac RFA therapy..

Bibliometric Analysis of Post-Stroke Pain Research Published from 2012 to 2021.

Background and Purpose: Pain is one of the most common symptoms in patients after stroke. It is a distressing experience that affects patients' quality of life, and it is highly prevalent in clinical practice. The pathogenesis mechanisms of PSP are not so clear, and there is currently a lack of effective medical treatments, hence it is necessary to establish a sufficient understanding of this disease. Limited number of studies have applied bibliometric methods to systematically analyze studies on post-stroke pain. This study aimed to systematically analyze scientific studies conducted worldwide on post-stroke pain from 2012 to 2021 to evaluate global trends in this field using a bibliometric analysis. Methods: Publications related to post-stroke pain from 2012 to 2021 were obtained from the Web of Science Core Collection database. Bibliometrics Biblioshiny R-package software was used to analyze the relationship of publication year with country, institution, journals, authors, and keywords and to generate variant visual maps to show annual publications, most relevant countries, authors, sources, keywords, and top-cited articles. Results: In this study, 5484 papers met the inclusion criteria. The annual growth rate of publications was 5.13%. The USA had the highest number of publications (1381, 25.2%) and citations (36,395), and the University of Toronto had the highest number of papers (156, 2.8%). "Stroke", "management", "pain", "risk", "prevalence", "ischemic stroke", "risk factors", "disease", "diagnosis" and "therapy" are the top 10 keywords. Conclusion: The global research interest regarding PSP has maintained growing over the past ten years. Both central post stroke pain and hemiplegic shoulder pain are the hottest research subjects. Further investigations are needed in order to reveal the mystery of the pathophysiologic mechanisms of CPSP, and high-quality well-designed trials of potential treatments of CPSP and HSP are also needed.