M2-Type Macrophages and Cancer-Associated Fibroblasts Combine to Promote Colorectal Cancer Liver Metastases.

Purpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells. Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases. Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis. Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research.

Background: Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Methods: Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. Results: The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. Conclusion: This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

Circulating microRNAs in association with pancreatic cancer risk within 5 years.

Early detection is critical for improving pancreatic cancer prognosis. Our study aims to identify circulating microRNAs (miRNAs) associated with pancreatic cancer risk. The two-stage study used plasma samples collected ≤5 years prior to cancer diagnosis, from case-control studies nested in five prospective cohort studies. The discovery stage included 185 case-control pairs from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Replication stage samples comprised 277 pairs from Shanghai Women's Health Study/Shanghai Men's Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study. Seven hundred and ninety-eight miRNAs were measured using the NanoString nCounter Analysis System. Odds ratios (OR) and 95% confidence intervals (CI) for per 10% change in miRNAs in association with pancreatic cancer risk were derived from conditional logistic regression analysis in discovery and replication studies, separately, and then meta-analyzed. Stratified analysis was conducted by age at diagnosis (<65/≥65 years) and time interval between sample collection and diagnosis (≤2/>2 years). In the discovery stage, 120 risk associated miRNAs were identified at p < .05. Three were validated in the replication stage: hsa-miR-199a-3p/hsa-miR-199b-3p, hsa-miR-767-5p, and hsa-miR-191-5p, with respective ORs (95% CI) being 0.89 (0.84-0.95), 1.08 (1.02-1.13), and 0.90 (0.85-0.95). Five additional miRNAs, hsa-miR-640, hsa-miR-874-5p, hsa-miR-1299, hsa-miR-22-3p, and hsa-miR-449b-5p, were validated among patients diagnosed at ≥65 years, with OR (95% CI) of 1.23 (1.09-1.39), 1.33 (1.16-1.52), 1.25 (1.09-1.43), 1.28 (1.12-1.46), 0.76 (0.65-0.89), and 1.22 (1.07-1.39), respectively. The miRNA targets were enriched in pancreatic carcinogenesis/progression-related pathways. Our study suggests that circulating miRNAs may identify individuals at high risk for pancreatic cancer ≤5 years prior to diagnosis, indicating its potential utility in cancer screening and surveillance.

Insights into the phage community structure and potential function in silage fermentation.

The virus that infects bacteria known as phage, plays a crucial role in the biogeochemical cycling of nutrients. However, the community structure and potential functions of phages in silage fermentation remain largely unexplored. In this study, we utilized viral metagenomics (viromics) to investigate the types, lifestyles, functions, and nutrient utilization patterns of phages in silage. Our findings indicated a high prevalence of annotated phages belonging to Caudovirales and Geplafuvirales, as well as unclassified phages in silage. The predominant host types for these phages were Campylobacterales and Enterobacterales. Virulent phages dominated the silage environment due to their broader range of hosts and enhanced survival capabilities. All identified phages present in silage were found to be non-pathogenic. Although temperate and virulent phages carried distinct genes associated with nutrient cycling processes, the shared genes (prsA) involved in carbon metabolism underscore the potential significance of phages in regulating carbon metabolism in silage. Overall, our findings provide a valuable foundation for further exploring the complex interactions between phages and microorganisms in regulating silage fermentation quality.

A photo-responsive self-healing hydrogel loaded with immunoadjuvants and MoS2 nanosheets for combating post-resection breast cancer recurrence.

Tumor recurrence after surgical resection remains a significant challenge in breast cancer treatment. Immune checkpoint blockade therapy, as a promising alternative therapy, faces limitations in combating tumor recurrence due to the low immune response rate. In this study, we developed an implantable photo-responsive self-healing hydrogel loaded with MoS2 nanosheets and the immunoadjuvant R837 (PVA-MoS2-R837, PMR hydrogel) for in situ generation of tumor-associated antigens at the post-surgical site of the primary tumor, enabling sustained and effective activation of the immune response. This PMR hydrogel exhibited potential for near-infrared (NIR) light response, tissue adhesion, self-healing, and sustained adjuvant release. When implanted at the site after tumor resection, NIR irradiation triggered a photothermal effect, resulting in the ablation of residual cancer cells. The in situ-generated tumor-associated antigens promoted dendritic cell (DC) maturation. In a mouse model, PMR hydrogel-mediated photothermal therapy combined with immune checkpoint blockade effectively inhibited the recurrence of resected tumors, providing new insights for combating post-resection breast cancer recurrence.

Intra-fractional geometric and dose/volume metric variations of magnetic resonance imaging-guided stereotactic radiotherapy of prostate bed after radical prostatectomy.

Background and purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods: Nineteen patients who received 30-34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9-76.8 %) and a median MDA of 5.1 mm (IQR 3.4-7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0-4.8 %). DSC was 0.97 (IQR 0.94-0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8-100 %) to 99.6 % (IQR 93.9-100 %). Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

Matrimeres are systemic nanoscale mediators of tissue integrity and function.

Tissue barriers must be rapidly restored after injury to promote regeneration. However, the mechanism behind this process is unclear, particularly in cases where the underlying extracellular matrix is still compromised. Here, we report the discovery of matrimeres as constitutive nanoscale mediators of tissue integrity and function. We define matrimeres as non-vesicular nanoparticles secreted by cells, distinguished by a primary composition comprising at least one matrix protein and DNA molecules serving as scaffolds. Mesenchymal stromal cells assemble matrimeres from fibronectin and DNA within acidic intracellular compartments. Drawing inspiration from this biological process, we have achieved the successful reconstitution of matrimeres without cells. This was accomplished by using purified matrix proteins, including fibronectin and vitronectin, and DNA molecules under optimal acidic pH conditions, guided by the heparin-binding domain and phosphate backbone, respectively. Plasma fibronectin matrimeres circulate in the blood at homeostasis but exhibit a 10-fold decrease during systemic inflammatory injury in vivo . Exogenous matrimeres rapidly restore vascular integrity by actively reannealing endothelial cells post-injury and remain persistent in the host tissue matrix. The scalable production of matrimeres holds promise as a biologically inspired platform for regenerative nanomedicine.

Highly Selective Pb(II) Adsorption by DTPA-Functionalized Graphene Oxide/Carboxymethyl Cellulose Aerogel.

Graphene oxide (GO) exhibits a strong adsorption capacity for the removal of heavy metal ions from liquids, making it a topic of increasing interest among researchers. However, a significant challenge persists in the preparation of graphene oxide-based adsorbents that possess both high structural stability and excellent adsorption capacity. In this paper, a green and environmentally friendly ternary composite aerogel based on graphene was successfully synthesized. The adsorption capacity of graphene oxide was enhanced through diethylenetriaminepentaacetic acid modification, while the incorporation of composite carboxymethyl cellulose improved the structural stability of the composite aerogel in liquid. The composite aerogel demonstrates robust interactions between its components and features a multiscale porous structure. Adsorption tests conducted with Pb(II) revealed that the GO/DTPA/CMC (GDC) composite aerogel exhibits a favorable adsorption capacity. The study of adsorption kinetics and isotherms indicated that the adsorption process follows the quasi-secondary adsorption model and Freundlich adsorption model, suggesting a chemical multilayer adsorption mechanism, and the maximum adsorption capacity for Pb(II) ions was 521.917 mg/g based on the quasi-quadratic kinetic model fitting. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) analyses, performed before and after adsorption, confirmed that the adsorption of Pb(II) primarily occurs through chelation, complexation, proton exchange, and electrostatic interactions between ions and active sites such as hydroxyl and carboxyl groups. This study presents an innovative strategy for simultaneously enhancing the adsorption properties of graphene oxide-based composite aerogels and ensuring solution stability.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Mapping of a Major-Effect Quantitative Trait Locus for Seed Dormancy in Wheat.

The excavation and utilization of dormancy loci in breeding are effective endeavors for enhancing the resistance to pre-harvest sprouting (PHS) of wheat varieties. CH1539 is a wheat breeding line with high-level seed dormancy. To clarify the dormant loci carried by CH1539 and obtain linked molecular markers, in this study, a recombinant inbred line (RIL) population derived from the cross of weak dormant SY95-71 and strong dormant CH1539 was genotyped using the Wheat17K single-nucleotide polymorphism (SNP) array, and a high-density genetic map covering 21 chromosomes and consisting of 2437 SNP markers was constructed. Then, the germination percentage (GP) and germination index (GI) of the seeds from each RIL were estimated. Two QTLs for GP on chromosomes 5A and 6B, and four QTLs for GI on chromosomes 5A, 6B, 6D and 7A were identified. Among them, the QTL on chromosomes 6B controlling both GP and GI, temporarily named QGp/Gi.sxau-6B, is a major QTL for seed dormancy with the maximum phenotypic variance explained of 17.66~34.11%. One PCR-based diagnostic marker Ger6B-3 for QGp/Gi.sxau-6B was developed, and the genetic effect of QGp/Gi.sxau-6B on the RIL population and a set of wheat germplasm comprising 97 accessions was successfully confirmed. QGp/Gi.sxau-6B located in the 28.7~30.9 Mbp physical position is different from all the known dormancy loci on chromosomes 6B, and within the interval, there are 30 high-confidence annotated genes. Our results revealed a novel QTL QGp/Gi.sxau-6B whose CH1539 allele had a strong and broad effect on seed dormancy, which will be useful in further PHS-resistant wheat breeding.

Injectable self-assembled GDF5-containing dipeptide hydrogels for enhanced tendon repair.

Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

Integrating historical patterns and future trends for ecological management zone identification and validation: A case study in Beijing, China.

Ecological management zones (EMZs) are pivotal in improving the management of ecosystem services (ESs) and promoting sustainable regional development. In this study, we developed a comprehensive framework aimed at identifying EMZs and substantiating their efficacy through the amalgamation of historical evolutionary patterns and future trends. We applied this framework to Beijing, China, and selected five vital ESs for the study area namely, water yield (WY), carbon sequestration (CS), habitat quality (HQ), soil conservation (SC) and water purification (WP). The framework involves two key components. Firstly, the identification of EMZs is based on the historical evolution of five types of ESs and the dynamic assessment of ES bundles. Subsequently, it enables a simulation of various scenarios to predict future alterations in land use and ESs, thereby validating the effectiveness of the identified EMZs. Our findings reveal notable spatial heterogeneity among different ESs, and that CS, HQ, SC, and WP exhibited synergies, while WY and showed trade-offs with the remaining four types of ESs. Based on an analysis of ES bundle evolution trajectories, we identified four types of EMZs: ecological conservation zone, ecological restoration zone, ecological transition zone and sustainable construction zone. Through strategic EMZ planning, it becomes possible to augment the area of forestland and grassland, alleviate the contradiction between arable land and construction land, and enhance the supply of various ESs. The proposed framework not only offers a novel perspective on the scientific management of ESs but also furnishes decision-makers and planners with an intuitive understanding of the tangible benefits associated with EMZ planning.

Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

A Practical Tool for Measuring Home-Based Cardiac Rehabilitation Self-Management Behavior: A Multiphase Cross-Sectional Study.

BACKGROUND: Optimal self-management is the key to home-based cardiac rehabilitation for patients with heart disease. At present, there is a lack of a specific assessment tool to evaluate the home-based cardiac rehabilitation self-management behavior in patients with heart disease. Therefore, the aim of this study was to develop the Home-Based Cardiac Rehabilitation Self-Management Scale and validate its psychometric properties among patients with coronary heart disease. METHODS AND RESULTS: A multiphase cross-sectional study was conducted that study covered 3 phases: (1) item generation and revision, (2) item evaluation and preliminary exploration, and (3) assessment of the psychometric properties of the scale. A scale with 21 items was developed to measure the home-based cardiac rehabilitation self-management behavior. The content validity index of the scale was 0.980. In exploratory factor analysis, the 5-factor structure supported by eigenvalues and screen plot explained 74.326% of the total variation. In confirmatory factor analysis, all fitting indicators were acceptable, further supporting the construct validity of the scale. The criterion validity of the scale was 0.783. In the reliability analysis, the Cronbach's α coefficient of the scale was 0.882, with a dimensionality range of 0.780 to 0.936. The split-half reliability coefficient and test-retest reliability coefficient were 0.774 and 0.770, respectively. CONCLUSIONS: This study is the first to develop and validate a practical tool. This scale can comprehensively and accurately assess the self-management behavior of patients with heart disease in a home-based cardiac rehabilitation environment.

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway.

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.

Protopanaxadiol Targeting Membrane Induces HepG2 Cell Apoptosis Via Raft-like Formation and Tubulation Disruption.

Protopanaxadiol (PPD), which has a molecular structure similar to cholesterol, is a potent anticancer agent that has been proposed to target the lipid membrane for the pharmacological effects. However, the underlying mechanism by which PPD modulates the cell membrane leading to cancer cell death is not be fully understood. In this work, we used single cell infrared spectroscopy, scanning electron microscopy and confocal microscopy to investigate the effects of PPD on human hepatocellular carcinoma (HepG2) cells, focusing on the change in membrane structure. We found that PPD significantly reduced the number of membrane tubules over the course of treatment. Interestingly, the addition of PPD could promote the formation of lipid raft-like domains (PPD rafts) and even restore the domain disruption caused by methyl-beta-cyclodextrin depletion of membrane cholesterol. In addition, PPD pre-treatment may increase the induction effect of FasL, which impairs cell viability, although it does not appear to be beneficial for Fas clustering in the PPD rafts. Collectively, these results highlight a non-classical mechanism by which PPD induces HepG2 apoptosis by directly affecting the physical properties of the cell membrane, providing a novel insight into understanding membrane-targeted therapy.

[Characteristics, Sources Apportionment, and Health Risks of PM2.5-bound PAHs and Their Derivatives Before and After Heating in Zibo City].

Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are a global problem that influences the environment and threatens human health. To investigate the characteristics, sources, and health risk assessment of PM2.5-bound PAHs and their derivatives, PM2.5 were collected at an urban site in Zibo from November 5 to December 26, 2020, and the concentrations of 16 conventional PAHs, nine NPAHs, and five OPAHs in PM2.5 were analyzed using gas chromatography-mass spectrometry. Source apportionment of PAHs and their derivatives was conducted using diagnostic ratios and a PMF model, and the health risks of PAHs and their derivatives to adult men and women were evaluated using the source-dependent incremental lifetime cancer risk (ILCR) model. The results showed that the average concentrations of ∑16pPAHs, ∑9NPAHs, and ∑5OPAHs in PM2.5 of Zibo City during the sampling period were (41.61 ± 13.40), (6.38 ± 5.70), and (53.20 ± 53.47) ng·m-3, respectively. The concentrations of the three PAHs increased significantly after heating, which were 1.31, 2.04, and 5.24 times larger than those before heating. During the sampling period, Chr, BaP, and BaA were the dominant components of pPAHs; 9N-Ant and 2N-Flt + 3N-Flt were the dominant components of NPAHs; and ATQ and BZO were the dominant components of OPAHs. Source apportionment results showed that motor vehicles were the main source of PAHs and their derivatives in PM2.5 before heating, whereas after heating, the main sources were the mixed source of coal and biomass combustion and secondary formation. The total BaP equivalent (TEQ) was 14.5 ng·m-3 during the sampling period, and the TEQ increased significantly after heating, which was approximately 1.2 times of that before heating. Assisted by the individual PAH source apportionment results, the ILCR of PM2.5-boundPAHs and NPAHs in Zibo City had a certain potential carcinogenic risk for adult males (1.06 × 10-5) and females (9.32 × 10-6). Among them, the health risks of PAHs from gasoline vehicles, diesel vehicles, and coal/biomass combustion were significantly higher than those from other emission sources.

Semi or fully automatic tooth segmentation in CBCT images: a review.

Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.