Unsupervised Bayesian Generation of Synthetic CT from CBCT Using Patient-Specific Score-Based Prior.

BACKGROUND: Cone-beam computed tomography (CBCT) scans, performed fractionally (e.g., daily or weekly), are widely utilized for patient alignment in the image-guided radiotherapy (IGRT) process, thereby making it a potential imaging modality for the implementation of adaptive radiotherapy (ART) protocols. Nonetheless, significant artifacts and incorrect Hounsfield unit (HU) values hinder their application in quantitative tasks such as target and organ segmentations and dose calculation. Therefore, acquiring CT-quality images from the CBCT scans is essential to implement online ART in clinical settings. PURPOSE: This work aims to develop an unsupervised learning method using the patient-specific diffusion model for CBCT-based synthetic CT (sCT) generation to improve the image quality of CBCT. METHODS: The proposed method is in an unsupervised framework that utilizes a patient-specific score-based model as the image prior alongside a customized total variation (TV) regularization to enforce coherence across different transverse slices. The score-based model is unconditionally trained using the same patient's planning CT (pCT) images to characterize the manifold of CT-quality images and capture the unique anatomical information of the specific patient. The efficacy of the proposed method was assessed on images from anatomical sites including head and neck (H&N) cancer, pancreatic cancer, and lung cancer. The performance of the proposed CBCT correction method was evaluated using quantitative metrics including mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and normalized cross-correlation (NCC). Additionally, the proposed algorithm was benchmarked against two other unsupervised diffusion model-based CBCT correction algorithms.

The transcriptomic and spatial organization of telencephalic GABAergic neuronal types.

The telencephalon of the mammalian brain comprises multiple regions and circuit pathways that play adaptive and integrative roles in a variety of brain functions. There is a wide array of GABAergic neurons in the telencephalon; they play a multitude of circuit functions, and dysfunction of these neurons has been implicated in diverse brain disorders. In this study, we conducted a systematic and in-depth analysis of the transcriptomic and spatial organization of GABAergic neuronal types in all regions of the mouse telencephalon and their developmental origins. This was accomplished by utilizing 611,423 single-cell transcriptomes from the comprehensive and high-resolution transcriptomic and spatial cell type atlas for the adult whole mouse brain we have generated, supplemented with an additional single-cell RNA-sequencing dataset containing 99,438 high-quality single-cell transcriptomes collected from the pre- and postnatal developing mouse brain. We present a hierarchically organized adult telencephalic GABAergic neuronal cell type taxonomy of 7 classes, 52 subclasses, 284 supertypes, and 1,051 clusters, as well as a corresponding developmental taxonomy of 450 clusters across different ages. Detailed charting efforts reveal extraordinary complexity where relationships among cell types reflect both spatial locations and developmental origins. Transcriptomically and developmentally related cell types can often be found in distant and diverse brain regions indicating that long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons. Additionally, we find various spatial dimensions of both discrete and continuous variations among related cell types that are correlated with gene expression gradients. Lastly, we find that cortical, striatal and some pallidal GABAergic neurons undergo extensive postnatal diversification, whereas septal and most pallidal GABAergic neuronal types emerge simultaneously during the embryonic stage with limited postnatal diversification. Overall, the telencephalic GABAergic cell type taxonomy can serve as a foundational reference for molecular, structural and functional studies of cell types and circuits by the entire community.

Research trends and hotspots of myositis ossificans: a bibliometric analysis from 1993 to 2022.

Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively. Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022. The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field. Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP. This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

Identification of anoikis-related gene signatures and construction of the prognosis model in prostate cancer.

Background: One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated. Methods: Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub). Results: 113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa. Conclusion: We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

Presenilin deficiency enhances tau phosphorylation and its secretion.

Alzheimer's disease (AD) is characterized by the accumulation of abnormally folded amyloid ß-protein (Aß) in the brain parenchyma and phosphorylated tau in neurons. Presenilin (PS, PSEN) 1 and PS2 are essential components of γ-secretase, which is responsible for the cleavage of amyloid precursor protein (APP) to generate Aß. PSEN mutations are associated with tau aggregation in frontotemporal dementia, regardless of the presence or absence of Aß pathology. However, the mechanism by which PS regulates tau aggregation is still unknown. Here, we found that tau phosphorylation and secretion were significantly increased in PS double-knock-out (PS1/2-/-) fibroblasts compared with wild-type fibroblasts. Tau-positive vesicles in the cytoplasm were significantly increased in PS1/2-/- fibroblasts. Active GSK-3ß was increased in PS1/2-/- fibroblasts, and inhibiting GSK3ß activity in PS1/2-/- fibroblasts resulted in decreased tau phosphorylation and secretion. Transfection of WT human PS1 and PS2 reduced the secretion of phosphorylated tau and active GSK-3ß in PS1/2-/- fibroblasts. However, PS1D257A without γ-secretase activity did not decrease the secretion of phosphorylated tau. Furthermore, nicastrin deficiency also increased tau phosphorylation and secretion. These results suggest that deficient PS complex maturation may increase tau phosphorylation and secretion. Thus, our studies discover a new pathway by which PS regulates tau phosphorylation/secretion and pathology independent of Aß and suggest that PS serves as a potential therapeutic target for treating neurodegenerative diseases involving tau aggregation.

Multi-Enzyme Cascade Nanoreactors for High-Throughput Immunoassay: Transitioning Concept in Lab to Application in Community.

In this work, we reported a cholesterol oxidase (Chox)-loaded platinum (Pt) nanozyme with the collaborative cascade nanoreactor for the construction of nanozyme-enzyme-linked immunosorbent assay (N-ELSA) models to realize high-throughput rapid evaluation of cancer markers. Considering the high specific surface area and manipulable surface sites, ZIF-8 was used as a substrate for natural enzyme and nanozyme loading. The constructed ZIF-8-Pt nanozyme platform exhibited efficient enzyme-like catalytic efficiency with a standard corrected activity of 60.59 U mg-1, which was 12 times higher than that of the ZIF-8 precursor, and highly efficient photothermal conversion efficiency (∼35.49%). In N-ELISA testing, developed multienzyme photothermal probes were immobilized in microplates based on antigen-antibody-specific reactions. Cholesterol was reacted in a cascade to reactive oxygen radicals, which attacked 3,3',5,5'-tetramethylbenzidine, causing it to oxidize and color change, thus exhibiting highly enhanced efficient photothermal properties. Systematic temperature evaluations were performed by a hand-held microelectromechanical system thermal imager under the excitation of an 808 nm surface light source to determine the cancer antigen 15-3 (CA15-3) profiles in the samples. Encouragingly, the temperature signal from the microwells increased with increasing CA15-3, with a linear range of 2 mU mL-1 to 100 U mL-1, considering it to be the sensor with the widest working range for visualization and portability available. This work provides new horizons for the development of efficient multienzyme portable colorimetric-photothermal platforms to help advance the community-based process of early cancer detection.

Mode-locking and wavelength-tuning of a NPR fiber laser based on optical speckle.

Passively mode-locked fiber lasers based on nonlinear polarization rotation (NPR) have been widely used due to their ability to produce short pulses with high peak power. Nevertheless, environmental perturbations can influence the mode-locked state, making it a challenge for the practical implementation. Therefore, researchers are searching for assessment criteria to quickly assist and maintain mode-locking of NPR fiber lasers. Speckle patterns containing spectral information can be generated when the laser transmits through a scattering medium, which can serve as indicators of the mode-locked state. The mode-locked regions are confined to the area close to the minimum texture contrast of speckle patterns. Based on these characteristics, we manually simulate the automatic mode-locking (AML). In addition, we utilize convolutional neural networks (CNNs) to recognize speckle patterns of wavelength tunable lasers and determine the center wavelength.

Fluorine-18 Prostate-Specific Membrane Antigen-1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Bavachinin, a main compound of Psoraleae Fructus, facilitates GSDMD-mediated pyroptosis and causes hepatotoxicity in mice.

Psoraleae Fructus (PF, Psoralea corylifolia L.), a traditional medicine with a long history of application, is widely used clinically for the treatment of various diseases. However, the reports of PF-related adverse reactions, such as hepatotoxicity, phototoxic dermatitis, and allergy, are increasing year by year, with liver injury being the mostly common. Our previous studies have demonstrated that PF and its preparations can cause liver injury in lipopolysaccharide (LPS)-mediated susceptibility mouse model, but the mechanism of PF-related liver injury is unclear. In this study, we showed that PF and bavachinin, a major component of PF, can directly induce the expression of caspase-1 and interleukin-1ß (IL-1ß), indicating that PF and bavachinin can directly triggered the activation of inflammasome. Furthermore, pretreatment with NLR family pyrin domain-containing 3 (NLRP3), NLR family CARD domain containing 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome inhibitors, containing MCC950, ODN TTAGGG (ODN) and carnosol, all significantly reversed bavachinin-induced inflammasome activation. Mechanistically, bavachinin dose-dependently promote Gasdermin D (GSDMD) post-shear activation and then induce mitochondrial reactive oxygen species (mtROS) production and this effect is markedly inhibited by pretreatment with N-Acetylcysteine amide (NAC). In addition, combination treatment of LPS and bavachinin significantly induced liver injury in mice, but not LPS or bavachinin alone, and transcriptome analysis further validated these results. Thus, PF and bavachinin can induce the activation of inflammasome by promoting GSDMD cleavage and cause hepatotoxicity in mice. Therefore, PF, bavachinin, and PF-related preparations should be avoided in patients with inflammasome activation-associated diseases.

Evidence that spatial scale and environment factors explain grassland community assembly in woodland-grassland ecotones.

How communities of living organisms assemble has long been a central question in ecology. The impact of habitat filtering and limiting similarity on plant community structures is well known, as both processes are influenced by individual responses to environmental fluctuations. Yet, the precise identifications and quantifications of the potential abiotic and biotic factors that shape community structures at a fine scale remains a challenge. Here, we applied null model approaches to assess the importance of habitat filtering and limiting similarity at two spatial scales. We used 63 natural vegetation plots, each measuring 5 × 5 m, with three nested subplots measuring 1 × 1 m, from the 2021 field survey, to examine the alpha diversity as well as beta diversity of plots and subplots. Linear mixed-effects models were employed to determine the impact of environmental variables on assembly rules. Our results demonstrate that habitat filtering is the dominant assembly rules at both the plot and subplot levels, although limiting similarity assumes stronger at the subplot level. Plot-level limiting similarity exhibited a positive association with fine-scale partitioning, suggesting that trait divergence originated from a combination of limiting similarity and spatial partitioning. Our findings also reveal that the community assembly varies more strongly with the mean annual temperature gradient than the mean annual precipitation. This investigation provides a pertinent illustration of non-random assembly rules from spatial scale and environmental factors in plant communities in the loess hilly region. It underscores the critical influence of spatial and environmental constraints in understanding the assembly of plant communities.

A dicoumarol-graphene oxide quantum dot polymer inhibits porcine reproductive and respiratory syndrome virus through the JAK-STAT signaling pathway.

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission. Methods: In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials. Results: Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-ß (IFN-ß) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs. Discussion: These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.

A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer.

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Identification of core genes shared by ischemic stroke and myocardial infarction using an integrated approach.

BACKGROUND: Both ischemic stroke (IS) and myocardial infarction (MI) are caused by vascular occlusion that results in ischemia. While there may be similarities in their mechanisms, the potential relationship between these 2 diseases has not been comprehensively analyzed. Therefore, this study explored the commonalities in the pathogenesis of IS and MI. METHODS: Datasets for IS (GSE58294, GSE16561) and MI (GSE60993, GSE61144) were downloaded from the Gene Expression Omnibus database. Transcriptome data from each of the 4 datasets were analyzed using bioinformatics, and the differentially expressed genes (DEGs) shared between IS and MI were identified and subsequently visualized using a Venn diagram. A protein-protein interaction (PPI) network was constructed using the Interacting Gene Retrieval Tool database, and identification of key core genes was performed using CytoHubba. Gene Ontology (GO) term annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the shared DEGs were conducted using prediction and network analysis methods, and the functions of the hub genes were determined using Metascape. RESULTS: The analysis revealed 116 and 1321 DEGs in the IS and MI datasets, respectively. Of the 75 DEGs shared between IS and MI, 56 were upregulated and 19 were downregulated. Furthermore, 15 core genes - S100a12, Hp, Clec4d, Cd163, Mmp9, Ormdl3, Il2rb, Orm1, Irak3, Tlr5, Lrg1, Clec4e, Clec5a, Mcemp1, and Ly96 - were identified. GO enrichment analysis of the DEGs showed that they were mainly involved in the biological functions of neutrophil degranulation, neutrophil activation during immune response, and cytokine secretion. KEGG analysis showed enrichment in pathways pertaining to Salmonella infection, Legionellosis, and inflammatory bowel disease. Finally, the core gene-transcription factor, gene-microRNA, and small-molecule relationships were predicted. CONCLUSION: These core genes may provide a novel theoretical basis for the diagnosis and treatment of IS and MI.

Spatial proximity and gene function: a new dimension in prokaryotic gene association network analysis with 3D-GeneNet.

Understanding the biological functions and processes of genes, particularly those not yet characterized, is crucial for advancing molecular biology and identifying therapeutic targets. The hypothesis guiding this study is that the 3D proximity of genes correlates with their functional interactions and relevance in prokaryotes. We introduced 3D-GeneNet, an innovative software tool that utilizes high-throughput sequencing data from chromosome conformation capture techniques and integrates topological metrics to construct gene association networks. Through a series of comparative analyses focused on spatial versus linear distances, we explored various dimensions such as topological structure, functional enrichment levels, distribution patterns of linear distances among gene pairs, and the area under the receiver operating characteristic curve by utilizing model organism Escherichia coli K-12. Furthermore, 3D-GeneNet was shown to maintain good accuracy compared to multiple algorithms (neighbourhood, co-occurrence, coexpression, and fusion) across multiple bacteria, including E. coli, Brucella abortus, and Vibrio cholerae. In addition, the accuracy of 3D-GeneNet's prediction of long-distance gene interactions was identified by bacterial two-hybrid assays on E. coli K-12 MG1655, where 3D-GeneNet not only increased the accuracy of linear genomic distance tripled but also achieved 60% accuracy by running alone. Finally, it can be concluded that the applicability of 3D-GeneNet will extend to various bacterial forms, including Gram-negative, Gram-positive, single-, and multi-chromosomal bacteria through Hi-C sequencing and analysis. Such findings highlight the broad applicability and significant promise of this method in the realm of gene association network. 3D-GeneNet is freely accessible at https://github.com/gaoyuanccc/3D-GeneNet.

Lightweight, Elastic, and Superhydrophobic Multifunctional Organic-Inorganic Fibrous Aerogels for Efficient Oily Wastewater Purification and Electromagnetic Microwave Absorption.

Lightweight and robust aerogels with multifunctionality are highly desirable to meet the technological demands of current society. Herein, we designed lightweight, elastic, and superhydrophobic multifunctional organic-inorganic fibrous hybrid aerogels which were assembled with organic aramid nanofibers and inorganic hierarchical porous carbon fibers. Thanks to the organic-inorganic fiber hybridization strategy, the optimal aerogels possessed remarkable compressibility and elasticity. Benefiting from the microscopic hierarchical porous structure of carbon fibers and the macroscopic macroporous lamellar structure of aerogels, the optimal aerogels exhibited superb lightweight property, conspicuous electromagnetic microwave absorption ability, and outstanding oily wastewater purification capacity. As for electromagnetic microwave absorption, it achieved a strong reflection loss of -41.8 dB, and the effective absorption bandwidth reached 6.86 GHz. Besides, the oil adsorption capacity for trichloromethane reached as high as 93.167 g g-1 with a capacity retention of 95.6% after 5 cycles. Meanwhile, it could act as a gravity-driven separation membrane to continuously separate trichloromethane from a trichloromethane-water mixture with a high flux of 7867.37 L·m-2·h-1, even for surfactant-stabilized water-in-n-heptane emulsions of 3794.94 L·m-2·h-1. Such a strategy might shed some light on the construction of multifunctional aerogels toward broader applications.

"Abraxane-Like" Radiosensitizer for In Situ Oral Cancer Therapy.

Radiotherapy plays a vital role in cancer therapy. However, the hypoxic microenvironment of tumors greatly limits the effectiveness, thus it is crucial to develop a simple, efficient, and safe radiosensitizer to reverse hypoxia and ameliorate the efficacy of radiotherapy. Inspired by the structure of canonical nanodrug Abraxane, herein, a native HSA-modified CaO2 nanoparticle system (CaO2-HSA) prepared by biomineralization-induced self-assembly is developed. CaO2-HSA will accumulate in tumor tissue and decompose to produce oxygen, altering the hypoxic condition inside the tumor. Simultaneously, ROS and calcium ions will lead to calcium overload and further trigger immunogenic cell death. Notably, its sensitizing enhancement ratio (SER = 3.47) is much higher than that of sodium glycididazole used in the clinic. Furthermore, in animal models of in situ oral cancer, CaO2-HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy-metal free biosafety, the CaO2-HSA-based radiosensitizer holds enormous potential for oral cancer therapy.

Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease.

BACKGROUND: Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD. METHODS: Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. RESULTS: Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. CONCLUSIONS: Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Identification of a disulfidptosis-related prognostic signature for prediction of the effect of treatment in patients with endometrial carcinoma.

Background: Disulfide, an essential compounds family, has diverse biological activity and can affect the dynamic balance between physiological and pathological states. A recently published study found that aberrant accumulation of disulfide had a lethal effect on cells. This mechanism of cell death, named disulfidptosis, differs from other known cell death mechanisms, including cuproptosis, apoptosis, necroptosis, and pyroptosis. The relationship between disulfidptosis and development of cancer, in particular endometrial carcinoma, remains unclear. Methods: To address this knowledge gap, we performed a preliminary analysis of samples from The Cancer Genome Atlas database. The samples were divided equally into a training group and a test group. A total of 2308 differentially expressed genes were extracted, and 11 were used to construct a prognostic model. Results: Based on the risk score calculated using the prognostic model, the samples were divided into a high-risk group and a low-risk group. Survival time, tumor mutation burden, and microsatellite instability scores differed significantly between the two groups. Furthermore, a between-group difference in treatment effect was predicted. Comparison with other models in the literature indicated that this prognostic model had better predictive anility. Conclusion: The results of this study provide a general framework for understanding the relationship between disulfidptosis and endometrial cancer that could be used for clinical evaluation and selection of appropriate personalized treatment strategies.

Vesicle Hydrogels Formed from the Perfluorononanoic Acid/Tetradecyl Dimethylaminoxide Oxide System.

Vesicle hydrogels are supramolecular structures formed by the self-assembly of surfactant molecules in solution, which have great application prospects. The phase behavior of perfluorononanoic acid (C8F17COOH) and an amphoteric hydrocarbon surfactant, tetradecyl dimethylaminoxide (C14DMAO), in an aqueous solution has been studied. By changing the mixing ratio and concentration of C8F17COOH and C14DMAO, the phase diagram of the system was drawn, and interestingly, a hydrogel composed of polyhedral and spherical vesicles was successfully constructed. The formation mechanism of the polyhedral and spherical vesicle hydrogel was studied by differential scanning calorimetry (DSC), small-angle X-ray diffraction (XRD), wide-angle X-ray scattering (WAXS), and 1H nuclear magnetic resonance (1H NMR) measurements, and the rheological properties and influencing factors of the hydrogel were systematically investigated. The formation of the vesicle hydrogels in this system was considered to be caused by the "cocrystallization" of two surfactant molecular chains.

The combined effects of polystyrene of different sizes and cadmium in mouse kidney tissues.

Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100 nm and/or 1 µm) and Cd for 25 days.The results showed that PS at 100 nm caused more severe oxidative damage and cell apoptosis than PS at 1 µm. Combined exposure to PS at both 100 nm and 1 µm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100 nm vs. 1 µm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100 nm PS+1µm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.