Fast Solution Blow Spinning of Lotus-Leaf-Inspired SiO2 Nanofiber Sponge for High Efficiency Purification.

Massive production of SiO2 nanofibers with both high durability and exceptional performance remains a significant challenge. Herein, a novel approach was introduced to achieve the massive production of SiO2 nanofibers with lotus-leaf-inspired surfaces by combining solution blowing spinning (SBS) and the polymer-derived ceramics method. Based on the SBS technique, three types of precursor nanofiber products were fast spined with methyl silsesquioxane polymer and polymethyl hydrogen siloxane employed as Si sources. The flow rate of the SBS spined Si-based ceramic nanofibers was enhanced to 20 mL·h-1. Furthermore, through the integration of hydrophobic-oleophilic SiO2 nanoparticles into the precursor solution, SiO2 nanofibers with lotus-leaf nanoprotrusion surfaces were fabricated. Nanoparticle-decorated SiO2 fibers demonstrated excellent hydrophobicity (138.3°), compression resilience (∼60%), proficiency in organic pollutant adsorption, high-temperature resistance (∼1100 °C), and outstanding thermal insulation properties (thermal conductivity of 0.0165 W·(m·K)-1).

Unraveling the intrinsic mechanism behind the retention of arsenic in the co-gasification of coal and sewage sludge: Focus on the role of Ca and Fe compounds.

Minimizing the emission of arsenic (As) is one of the urgent problems during co-gasification of Shenmu coal (SM) and sewage sludge (SS). The intrinsic mechanism of As retention was obtained by analyzing the effect of different SM addition ratios on the As form transformation during co-gasification at 1000 °C under CO2 atmosphere. The results showed that the addition of SM effectively promoted the enrichment of As in the co-gasified residues. Especially, the best As retention rate of 65.71% was achieved with the 70 wt% addition ratio of SM. The addition of SM promoted the adsorption and chemical oxidation of As(III) to the less toxic As(V) through the coupling of Ca and Fe compounds in the co-gasified residues. XRD and XPS results indicated that Fe2O3 adsorbed As2O3(g) after partial conversion to Fe3O4 by the Boudouard reaction, while part of As2O3 was oxidized to As2O5 by lattice oxygen. Finally, the generated As2O5 was successively trapped by CaO and Fe2O3 to form stable Ca3(AsO4)2 and FeAsO4. HRTEM and TEM analysis comprehensively proved that As(III) was stabilized by the lattice cage of CaAl2Si2O8. In conclusion, the co-oxidation of Ca and Fe compounds and lattice stabilization simultaneously played a crucial role in the retention of As2O3(g) during co-gasification.

IGF-1 Induces Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Promoting SOX4 via the MAPK/ERK Pathway.

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.

SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming.

Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.

Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner.

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

PURPOSE: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. STUDY DESIGN: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. RESULTS: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. CONCLUSIONS: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

Octadecyl-fibrous mesoporous silica nanospheres coated 96-blade thin-film microextraction for high-throughput analysis of phthalic acid esters in food and migration from food packages.

A high-throughput sample pre-treatment method combined with high-performance liquid chromatography (HPLC) was developed to analyze phthalates (PAEs) in food and food contact package samples. Thin film microextraction (TFME) in 96-blade format was used to pre-treat 96 samples simultaneously. Octadecyl groups functionalized fibrous mesoporous silica nanospheres, namely C18-FMSNs, were synthesized and used as TFME coating material. The coating was fabricated by spraying a slurry of C18-FMSNs and polyacrylontrile (PAN) mixture with a commercial portable spraypen. The prepared C18-FMSNs/PAN coatings exhibited good reproducibility, repeatability and reusability. The optimized TFME conditions for PAEs consisted of extraction at pH 4.0 for 50 min, and desorption by methanol/acetonitrile (25/75, V/V) for 40 min. The pretreatment time for each sample was approximately 1.3 min. This TFME-HPLC method showed good linearity for eight PAEs within the concentration range of 0.5-1000 ng mL-1, with the coefficients higher than 0.9972. The limits of detection and quantification were 0.096-0.26 ng mL-1 and 0.32-0.86 ng mL-1, respectively. The intra-day and inter-day RSD % were below 6.6 % and 8.4 %, respectively, indicating good precision. The PAEs analysis in real samples showed that dibutyl phthalate (DBP) of 2.3 ± 0.3 ng mL-1 and di-(2-ethylhexyl) phthalate (DEHP) of 5.5 ± 0.8 ng mL-1 in boxed milk, dimethyl phthalate (DMP) of 12.6 ± 0.8 ng mL-1, DBP of 3.2 ± 0.4 ng mL-1and DEHP of 14.3 ± 0.7 ng mL-1 in the simulated water migration of plastic box, as well as DMP of 19.0 ± 0.6 ng mL-1, DBP of 25.6 ± 0.9 ng mL-1 and DEHP of 49.5 ± 2.8 ng mL-1 in the simulated ethanol migration of plastic box were determined, respectively. In addition, the detection of PAEs in all the real samples showed good recovery ranging from 85.6 to 110 % and lower RSDs % (<7.2 %).

Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a "cold cancer" for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy. MATERIALS AND METHODS: We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens. RESULTS: In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens. CONCLUSION: Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.

Clinical significance of the C-reactive protein-to-bilirubin ratio in patients with ulcerative colitis.

Background: Ulcerative colitis (UC) is a chronic relapsing remitting disease of the colon. Appropriate monitoring of the disease status is necessary for patients to adopt optimal therapy and obtain a better prognosis. Finding an ideal non-invasive biomarker, which is suitable for long-term monitoring in clinical settings will bring a significant benefit to the individualized management of patients with UC. The aim of this study is to determine the clinical significance of a novel optimizing serological biomarker by integrating C-reactive protein (CRP) and bilirubin levels in monitoring disease activity. Methods: A total of 182 patients with UC were retrospectively enrolled. Clinical characteristics and laboratory parameters of the subjects were retrieved from the electronic medical record database of our hospital. The CRP-to-bilirubin ratio (CBR) was computed for clinical activity of UC defined by the partial Mayo score and endoscopic activity by the Mayo endoscopic score (MES). Results: CBR was significantly elevated in patients with UC than that in healthy controls. Patients with clinically or endoscopically active UC showed evidently higher CBR levels compared to those with inactive disease, even in a subset of patients with normal CRP levels. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CBR was higher than that of CRP or bilirubin alone for determining clinical remission and endoscopic mucosal improvement. Furthermore, CBR levels were significantly decreased when patients achieved mucosal improvement compared with when they had active endoscopic inflammation. Conclusion: CBR could be useful to reflect disease activity in patients with UC.

Venetoclax Overcomes Sorafenib Resistance in Acute Myeloid Leukemia by Targeting BCL2.

Sorafenib, a kinase inhibitor, has shown promising therapeutic efficacy in a subset of patients with acute myeloid leukemia (AML). However, despite its clinical effectiveness, sorafenib resistance is frequently observed in clinical settings, and the mechanisms underlying this resistance as well as effective strategies to overcome it remain unclear. We examined both single-cell and bulk transcription data in sorafenib-resistant and control AML patients and integrated a sorafenib resistance gene signature to predict the sensitivity of AML cells and the clinical outcomes of AML patients undergoing sorafenib therapy. In addition, our drug sensitivity analysis of scRNA-seq data using deconvolution methods showed that venetoclax was effective in targeting sorafenib-resistant AML cells. Mechanistically, sorafenib was found to activate the JAK-STAT3 pathway and upregulate BCL2 expression in sorafenib-resistant AML cells. This upregulation of BCL2 expression rendered the cells vulnerable to the BCL2 inhibitor venetoclax. In conclusion, we developed a platform to predict sorafenib resistance and clinical outcomes in AML patients after therapy. Our findings suggest that the combination of sorafenib and venetoclax could be an effective therapeutic strategy for AML treatment.

Comprehensive assessment of the anterior segment in refraction corrected OCT based on multitask learning.

Anterior segment diseases are among the leading causes of irreversible blindness. However, a method capable of recognizing all important anterior segment structures for clinical diagnosis is lacking. By sharing the knowledge learned from each task, we proposed a fully automated multitask deep learning method that allows for simultaneous segmentation and quantification of all major anterior segment structures, including the iris, lens, cornea, as well as implantable collamer lens (ICL) and intraocular lens (IOL), and meanwhile for landmark detection of scleral spur and iris root in anterior segment OCT (AS-OCT) images. In addition, we proposed a refraction correction method to correct for the true geometry of the anterior segment distorted by light refraction during OCT imaging. 1251 AS-OCT images from 180 patients were collected and were used to train and test the model. Experiments demonstrated that our proposed network was superior to state-of-the-art segmentation and landmark detection methods, and close agreement was achieved between manually and automatically computed clinical parameters associated with anterior chamber, pupil, iris, ICL, and IOL. Finally, as an example, we demonstrated how our proposed method can be applied to facilitate the clinical evaluation of cataract surgery.

Fecal calprotectin as an intestinal inflammation marker is elevated in glaucoma.

Objective: The aim of this study was to investigate the potential association between glaucoma and fecal calprotectin. Methods: A total of 144 glaucomatous patients and 66 healthy controls were enlisted for this study. The fecal calprotectin was assessed using enzyme-linked immunosorbent assay. Results: The median fecal calprotectin levels were significantly elevated in glaucoma (73.67 vs 41.97 µg/g; p < 0.001), primary angle-closure glaucoma (76.85 µg/g; p < 0.001) and primary open-angle glaucoma (69.29 µg/g; p = 0.016) groups compared with controls. A notable proportion of the glaucoma (24%; p < 0.001), primary angle-closure glaucoma (21%; p < 0.001) and primary open-angle glaucoma (24%; p < 0.001) subgroups exhibited highly abnormal fecal calprotectin levels (≥250 µg/g). Conclusion: Elevated fecal calprotectin might indicate potential intestinal inflammation in glaucoma.

Tunable Chromic Properties of Viologen-Metal Polymers Modulated by Coordination Modes for Inkless Erasable Printing.

Inkless and erasable printing (IEP) based on chromic materials holds great promise to alleviate environmental and sustainable problems. Metal-organic polymers (MOPs) are bright platforms for constructing IEP materials. However, it is still challenging to design target MOPs with excellent specific functions rationally due to the intricate component-structure-property relationships. Herein, an effective strategy was proposed for the rational design IEP-MOP materials. The stimuli-responsive viologen moiety was introduced into the construction of MOPs to give it potential chromic behaviors and two different coordination models (i. e. bilateral coordination model, M1 ; unilateral coordinated model, M2 ) based on the same viologen ligand were designed. Aided by theoretical calculations, model M1 was recommended secondarily as a more suitable system for IEP materials. Along this line, two representative viologen-ZnII MOPs 1 and 2 with models M1 and M2 were synthesized successfully. Experiments exhibit that 1 does have quicker stimuli response, stronger color contrast and longer radical lifetime compared to 2. Significantly, the obtained 1-IEP media brightly inherits the excellent chromic characteristics of 1 and the flexibility of the paper at the same time, which achieves most daily printing requirements, as well as enough resolution and durability to be used in identification by smart device.

Gut-licensed ß7+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma.

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.

Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC.

BACKGROUND: A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. METHODS: A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. RESULTS: Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. CONCLUSION: PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.

Clinical Utility of the Neutrophil-to-Bilirubin Ratio in the Detection of Disease Activity in Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a chronic relapsing remitting form of inflammatory bowel disease (IBD). Current disease monitoring includes evaluation of symptoms, fecal calprotectin, and colonoscopy. Due to limited availability of the latter two modalities in China, we sought a readily available, inexpensive, disease monitoring laboratory assessment. We recently identified a novel serological index (the neutrophil-to-bilirubin ratio, NBR) for monitoring disease activity in Crohn's disease. However, the clinical significance has not been evaluated in UC. Here, we aimed to verify the hypothesis that NBR might be useful in monitoring clinical and endoscopic activity in patients with UC. Methods: To test our hypothesis, we conducted a single-center, retrospective study including a total of 188 patients with UC and 145 non-IBD controls. NBR was calculated to determine its practical value in monitoring disease activity (including clinical and endoscopic activity). Disease activity of UC was determined by the partial Mayo score and the Mayo endoscopic score (MES) system. Results: NBR was significantly higher in patients with UC than that in controls (12.10, IQR: 9.85-16.69 versus 5.06, IQR: 3.94-6.55; p < 0.001) and showed positive correlations with clinical and endoscopic disease activity in UC. Additionally, NBR was significantly lower in patients with endoscopic mucosal healing (MH) than that in those without endoscopic MH (8.81, IQR: 6.67-11.67 versus 13.51, IQR: 11.04-18.71; p < 0.001). Serial evaluation of NBR in a subset of patients demonstrated that NBR was significantly decreased during the MH stage compared with that during the endoscopically active stage. Conclusion: Our study suggests that NBR may be a promising candidate for assessing disease activity in UC, with potential for widespread clinical use and significant clinical implications.

Piezochromism and Conductivity Modulations under High Pressure by Manipulating the Viologen Radical Concentration.

Manipulating the radical concentration to modulate the properties in solid multifunctional materials is an attractive topic in various frontier fields. Viologens have the unique redox capability to generate radical states through reversible electron transfer (ET) under external stimuli. Herein, taking the viologens as the model, two kinds of crystalline compounds with different molecule-conjugated systems were designed and synthesized. By subjecting the specific model viologens to pressure, the cross-conjugated 2-X all exhibit much higher radical concentrations, along with more sensitive piezochromic behaviors, compared to the linear-conjugated 1-X. Unexpectedly, we find that the electrical resistance (R) of 1-NO3 decreased by three orders of magnitude with the increasing pressure, while that in high-radical-concentration 2-NO3 remained almost unchanged. To date, such unusual invariant conductivity has not been documented in molecular-based materials under high pressure, breaking the conventional wisdom that the generations of radicals are beneficial to improve conductivity. We highlight that adjusting the molecular conjugation modes can be used as an effective way to regulate the radical concentrations and thus modulate properties rationally.

Automatic measurement of anterior chamber angle parameters in AS-OCT images using deep learning.

The early assessment of angle closure is of great significance for the timely diagnosis and treatment of primary angle-closure glaucoma (PACG). Anterior segment optical coherence tomography (AS-OCT) provides a fast and non-contact way to evaluate the angle close using the iris root (IR) and scleral spur (SS) information. The objective of this study was to develop a deep learning method to automatically detect IR and SS in AS-OCT for measuring anterior chamber (AC) angle parameters including angle opening distance (AOD), trabecular iris space area (TISA), trabecular iris angle (TIA), and anterior chamber angle (ACA). 3305 AS-OCT images from 362 eyes and 203 patients were collected and analyzed. Based on the recently proposed transformer-based architecture that learns to capture long-range dependencies by leveraging the self-attention mechanism, a hybrid convolutional neural network (CNN) and transformer model to encode both local and global features was developed to automatically detect IR and SS in AS-OCT images. Experiments demonstrated that our algorithm achieved a significantly better performance than state-of-the-art methods for AS-OCT and medical image analysis with a precision of 0.941, a sensitivity of 0.914, an F1 score of 0.927, and a mean absolute error (MAE) of 37.1±25.3 µm for IR, and a precision of 0.805, a sensitivity of 0.847, an F1 score of 0.826, and an MAE of 41.4±29.4 µm for SS, and a high agreement with expert human analysts for AC angle parameter measurement. We further demonstrated the application of the proposed method to evaluate the effect of cataract surgery with IOL implantation in a PACG patient and to assess the outcome of ICL implantation in a patient with high myopia with a potential risk of developing PACG. The proposed method can accurately detect IR and SS in AS-OCT images and effectively facilitate the AC angle parameter measurement for pre- and post-operative management of PACG.

A Bayesian model to identify multiple expression patterns with simultaneous FDR control for a multi-factor RNA-seq experiment.

It is often of research interest to identify genes that satisfy a particular expression pattern across different conditions such as tissues, genotypes, etc. One common practice is to perform differential expression analysis for each condition separately and then take the intersection of differentially expressed (DE) genes or non-DE genes under each condition to obtain genes that satisfy a particular pattern. Such a method can lead to many false positives, especially when the desired gene expression pattern involves equivalent expression under one condition. In this paper, we apply a Bayesian partition model to identify genes of all desired patterns while simultaneously controlling their false discovery rates (FDRs). Our simulation studies show that the common practice fails to control group specific FDRs for patterns involving equivalent expression while the proposed Bayesian method simultaneously controls group specific FDRs at all settings studied. In addition, the proposed method is more powerful when the FDR of the common practice is under control for identifying patterns only involving DE genes. Our simulation studies also show that it is an inherently more challenging problem to identify patterns involving equivalent expression than patterns only involving differential expression. Therefore, larger sample sizes are required to obtain the same target power to identify the former types of patterns than the latter types of patterns.

A Ferroptosis-Inducing and Leukemic Cell-Targeting Drug Nanocarrier Formed by Redox-Responsive Cysteine Polymer for Acute Myeloid Leukemia Therapy.

Ferroptosis is an alternative strategy to overcome chemoresistance, but effective therapeutic approaches to induce ferroptosis for acute myeloid leukemia (AML) treatment are limited. Here, we developed glutathione (GSH)-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an efficient ferroptosis inducer and chemotherapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4, a GSH-dependent hydroperoxidase, to cause lipid peroxidation and ferroptosis in AML cells. Furthermore, GCFN-loaded paclitaxel (PTX@GCFN) targeted AML cells and spared normal hematopoietic cells to limit the myeloablation side effects caused by paclitaxel. PTX@GCFN treatment extended the survival of AML mice by specifically releasing paclitaxel and simultaneously inducing ferroptosis in AML cells with restricted myeloablation and tissue damage side effects. Overall, the dual-functional GCFN acts as an effective ferroptosis inducer and a chemotherapeutic drug carrier for AML treatment.