PDIA2 has a dual function in promoting androgen deprivation therapy induced venous thrombosis events and castrate resistant prostate cancer progression.

Androgen deprivation therapy (ADT) is the first line of treatment for metastatic prostate cancer (PCa) that effectively delays the tumor progression. However, it also increases the risk of venous thrombosis event (VTE) in patients, a leading cause of mortality. How a pro-thrombotic cascade is induced by ADT remains poorly understood. Here, we report that protein disulfide isomerase A2 (PDIA2) is upregulated in PCa cells to promote VTE formation and enhance PCa cells resistant to ADT. Using various in vitro and in vivo models, we demonstrated a dual function of PDIA2 that enhances tumor-mediated pro-coagulation activity via tumor-derived extracellular vehicles (EVs). It also stimulates PCa cell proliferation, colony formation, and xenograft growth androgen-independently. Mechanistically, PDIA2 activates the tissue factor (TF) on EVs through its isomerase activity, which subsequently triggers a pro-thrombotic cascade in the blood. Additionally, TF-containing EVs can activate the Src kinase inside PCa cells to enhance the AR signaling ligand independently. Androgen deprivation does not alter PDIA2 expression in PCa cells but enhances PDIA2 translocation to the cell membrane and EVs via suppressing the clathrin-dependent endocytic process. Co-recruitment of AR and FOXA1 to the PDIA2 promoter is required for PDIA2 transcription under androgen-deprived conditions. Importantly, blocking PDIA2 isomerase activity suppresses the pro-coagulation activity of patient plasma, PCa cell, and xenograft samples as well as castrate-resistant PCa xenograft growth. These results demonstrate that PDIA2 promotes VTE and tumor progression via activating TF from tumor-derived EVs. They rationalize pharmacological inhibition of PDIA2 to suppress ADT-induced VTE and castrate-resistant tumor progression.

Bidirectional-Reinforced Carbon Fiber/Polyether-Ether-Ketone Composite Thin-Walled Pipes via Pultrusion-Winding for On-Orbit Additive Manufacturing.

Benefitting from lightweight, high strength, long life, and green recyclability, continuous fiber reinforced thermoplastic composite (CFTPC) pipes have attracted extensive interest, especially in the on-orbit additive manufacturing of structural components. However, the preparation of CFTPC pipes remains challenging due to the on-orbit limited space and high processing temperature of thermoplastic resin. Here, we report an effective approach for high performance carbon fiber/polyether-ether-ketone (CF/PEEK) thin-walled pipes via bidirectional reinforcement using the pultrusion-winding technique. The continuous fabrication of thin-walled pipes can be achieved, but the limitation by the size of core mold is also broken. The compressive and shear performance of CF/PEEK pipes with different layer designs have been studied based on experiments and simulations. With the increase in axial prepreg tape layer, the resultant CF/PEEK pipes exhibit greatly improved axial compression strength. The finite element analysis indicates that the maximum axial stress is decreased due to the axial enhancement. The flexural strength is greatly proved with pultrusion-winding cycles. The simulation confirms that the circumferential strain is effectively reduced. The high performance of bidirectional reinforced CF/PEEK pipes and the facile controllability of this approach highlight their suitability for utilization in on-orbit manufacturing of large-scale structures.

A collaborative multi-task learning method for BI-RADS category 4 breast lesion segmentation and classification of MRI images.

BACKGROUND AND OBJECTIVE: The diagnosis of BI-RADS category 4 breast lesion is difficult because its probability of malignancy ranges from 2% to 95%. For BI-RADS category 4 breast lesions, MRI is one of the prominent noninvasive imaging techniques. In this paper, we research computer algorithms to segment lesions and classify the benign or malignant lesions in MRI images. However, this task is challenging because the BI-RADS category 4 lesions are characterized by irregular shape, imbalanced class, and low contrast. METHODS: We fully utilize the intrinsic correlation between segmentation and classification tasks, where accurate segmentation will yield accurate classification results, and classification results will promote better segmentation. Therefore, we propose a collaborative multi-task algorithm (CMTL-SC). Specifically, a preliminary segmentation subnet is designed to identify the boundaries, locations and segmentation masks of lesions; a classification subnet, which combines the information provided by the preliminary segmentation, is designed to achieve benign or malignant classification; a repartition segmentation subnet which aggregates the benign or malignant results, is designed to refine the lesion segment. The three subnets work cooperatively so that the CMTL-SC can identify the lesions better which solves the three challenges. RESULTS AND CONCLUSION: We collect MRI data from 248 patients in the Second Hospital of Dalian Medical University. The results show that the lesion boundaries delineated by the CMTL-SC are close to the boundaries delineated by the physicians. Moreover, the CMTL-SC yields better results than the single-task and multi-task state-of-the-art algorithms. Therefore, CMTL-SC can help doctors make precise diagnoses and refine treatments for patients.

Combined Core Stability and Degradability of Nanomedicine via Amorphous PDLLA-Dextran Bottlebrush Copolymer for Alzheimer's Disease Combination Treatment.

Nanomedicine faces the challenges of infinite dilution, shear force, biological protein, or electrolyte competition. However, core cross-linking leads to biodegradability deficiency and brings inevitable side effects of nanomedicine on normal tissues. In order to overcome this bottleneck problem, we turn to amorphous poly(d,l)lactic acid (PDLLA)-dextran bottlebrush to emphasize the core stability of nanoparticles, and the amorphous structure offers an additional advantage of fast degradation property over the crystalline PLLA polymer. The graft density and side chain length of amorphous PDLLA together played important influence roles in controlling the architecture of nanoparticles. This effort produces structure-abundant particles, including micelles, vesicles, and large compound vesicles after self-assembly. Here, the amorphous bottlebrush PDLLA was verified to play a beneficial role in the structure stability and degradability of nanomedicines. The codelivery of the hydrophilic antioxidant of citric acid (CA), vitamin C (VC), and gallic acid (GA) via the optimum nanomedicines could effectively repair the SH-SY5Y cell damage caused by H2O2. The CA/VC/GA combination treatment repaired the neuronal function efficiently, and the cognitive abilities of senescence-accelerated mouse prone 8 (SAMP8) recovered.

Silymarin modified polysulfone hollow fiber membranes with antioxidant, anti-M1 macrophage polarization and hemocompatibility for blood purification.

Oxidative stress is highly prevalent in maintenance hemodialysis patients and increases the risk of cardiovascular morbidity and mortality. Silymarin (SM) is a natural compound extracted from plants, and has been shown to have pharmacological effects such as antioxidant, anti-inflammatory, cytoprotective, and anti-nephrotoxicity. SM-modified polysulfone (PSF) hemodialysis membranes were prepared by an immersion-precipitation phase transition method. The experimental results showed that the modified membranes effectively scavenged free radicals, significantly inhibited lipid peroxidation, and had good antioxidant stability (60 days). The PSF/SM antioxidant membranes (H-3) had no pro-inflammatory effect, which was confirmed by the result of anti-M1 macrophage polarization. Furthermore, the hemolysis rate (2%), blood cell deformation (3.7%), and inhibition of erythrocyte and platelet adhesion were improved by the SM-modified PSF membranes. All the results suggest that PSF/SM blended hollow fiber membranes are promising for application in hemodialysis membranes to improve oxidative stress status and reduce inflammation and complications in patients.

Cross-attention multi-branch CNN using DCE-MRI to classify breast cancer molecular subtypes.

Purpose: The aim of this study is to improve the accuracy of classifying luminal or non-luminal subtypes of breast cancer by using computer algorithms based on DCE-MRI, and to validate the diagnostic efficacy of the model by considering the patient's age of menarche and nodule size. Methods: DCE-MRI images of patients with non-specific invasive breast cancer admitted to the Second Affiliated Hospital of Dalian Medical University were collected. There were 160 cases in total, with 84 cases of luminal type (luminal A and luminal B and 76 cases of non-luminal type (HER 2 overexpressing and triple negative). Patients were grouped according to thresholds of nodule sizes of 20 mm and age at menarche of 14 years. A cross-attention multi-branch net CAMBNET) was proposed based on the dataset to predict the molecular subtypes of breast cancer. Diagnostic performance was assessed by accuracy, sensitivity, specificity, F1 and area under the ROC curve (AUC). And the model is visualized with Grad-CAM. Results: Several classical deep learning models were included for diagnostic performance comparison. Using 5-fold cross-validation on the test dataset, all the results of CAMBNET are significantly higher than the compared deep learning models. The average prediction recall, accuracy, precision, and AUC for luminal and non-luminal types of the dataset were 89.11%, 88.44%, 88.52%, and 96.10%, respectively. For patients with tumor size <20 mm, the CAMBNET had AUC of 83.45% and ACC of 90.29% for detecting triple-negative breast cancer. When classifying luminal from non-luminal subtypes for patients with age at menarche years, our CAMBNET model achieved an ACC of 92.37%, precision of 92.42%, recall of 93.33%, F1of 92.33%, and AUC of 99.95%. Conclusions: The CAMBNET can be applied in molecular subtype classification of breasts. For patients with menarche at 14 years old, our model can yield more accurate results when classifying luminal and non-luminal subtypes. For patients with tumor sizes ≤20 mm, our model can yield more accurate result in detecting triple-negative breast cancer to improve patient prognosis and survival.

Fibrin fiber deformation mechanisms: insights from phenomenological modeling to molecular details.

The deformation mechanism of fibrin fibers has been a long-standing challenge to uncover due to the fiber's complex structure and mechanical behaviors. In this paper, a phenomenological, bilinear, force-strain model is derived to accurately reproduce the fibrin fiber force-strain curve, and then, the phenomenological model is converted to a mechanistic model using empirical relationships developed from particle simulation data. The mechanistic model assumes that the initial linear fibrin fiber force-strain response is due to entropic extension of polypeptide chains, and the final linear response is due to enthalpic extension of protofibrils. This model is the first fibrin fiber tensile force-strain equation to simultaneously (1) reproduce the bilinear force-strain curve of fibrin fibers in tension; (2) explicitly include the number of protofibrils through the fibrin fiber cross section, persistence length of [Formula: see text]-regions, and stiffness of fibrin protofibrils; and (3) make demonstrably reasonable/accurate predictions of fibrin fiber mechanics when tempered against experimental results. The model predicted that the count of protofibrils through the cross section for the analyzed fibrin fibers is between 207 and 421, the persistence length of [Formula: see text]-regions is [Formula: see text], and the stiffness of protofibrils in a deforming fiber is [Formula: see text]. The predicted [Formula: see text]-region persistence length is within the range typical of amino acid residue lengths [Formula: see text] and the predicted protofibril stiffness is shown to correspond to half-staggered protofibrils of unfolded fibrin monomers. Our analysis supports the proposition that entropic extension of [Formula: see text]-regions could be responsible for fibrin fiber's initial force-strain stiffness and suggests a structural change in fibrin protofibrils during fibrin fiber deformation. The results from the model are compared to those from five candidate deformation mechanisms reported in the literature. Our work provides (1) strong quantitative support to a deformation mechanism that was previously supported by anecdote and qualitative argument, and (2) a model for rigorously analyzing fibrin fiber force-strain data and simulating fibrin fibers in tension.

Analysis of the Whole-Genome Sequences from an Equus Parent-Offspring Trio Provides Insight into the Genomic Incompatibilities in the Hybrid Mule.

Interspecific hybridization often shows negative effects on hybrids. However, only a few multicellular species, limited to a handful of plants and animals, have shown partial genetic mechanisms by which hybridization leads to low fitness in hybrids. Here, to explore the outcome of combining the two genomes of a horse and donkey, we analyzed the whole-genome sequences from an Equus parent-offspring trio using Illumina platforms. We generated 41.39× and 46.21× coverage sequences for the horse and mule, respectively. For the donkey, a 40.38× coverage sequence was generated and stored in our laboratory. Approximately 24.86 million alleles were discovered that varied from the reference genome. Single nucleotide polymorphisms were used as polymorphic markers for assigning alleles to their parental genomic inheritance. We identified 25,703 Mendelian inheritance error single nucleotide polymorphisms in the mule genome that were not inherited from the parents through Mendelian inheritance. A total of 555 de novo single nucleotide polymorphisms were also identified. The rate of de novo single nucleotide polymorphisms was 2.21 × 10-7 in the mule from the Equus parent-offspring trio. This rate is obviously higher than the natural mutation rate for Equus, which is also consistent with the previous hypothesis that interracial crosses may have a high mutation rate. The genes associated with these single nucleotide polymorphisms are mainly involved in immune processes, DNA repair, and cancer processes. The results of the analysis of three genomes from an Equus parent-offspring trio improved our knowledge of the consequences of the integration of parental genomes in mules.

Bioresorbable Implants in Reduction of Paediatric Zygomaticomaxillary Complex Fractures Concurrent With Internal Orbital Reconstruction.

PURPOSE: To evaluate the clinical effectiveness and safety of bioresorbable implants for treating paediatric zygomaticomaxillary complex (ZMC) fractures with concomitant orbital floor defects. METHODS: A retrospective review of paediatric patients who underwent ZMC repair with concomitant orbital floor fractures with bioresorbable implants in Shanghai Ninth People's Hospital from July 2015 to June 2019 was performed. The primary outcome measures included ocular motility, diplopia, enophthalmos, facial deformities, and restricted mouth opening, as well as complication rates. Pre- and post-operative computed tomography scans were obtained for clinical diagnosis and surgical effectiveness. RESULTS: Twenty two children were included in this study. Facial deformities were corrected in all 22 cases by surgical reconstruction postoperatively, and the average relative distance of Portals point-Zygomaxillare and Anteriornasalspine-Zygomaxillare were 1.3 ± 0.6mm ( P = 0.22) and 1.2 ± 0.5mm ( P = 0.19). The eye movement restored to normal in 13 patients. The mean amount of relative enophthalmos was 1.0 ± 0.4 mm ( P = 0.12). 12 cases had complete resolution of diplopia postoperatively at the extremes of the gaze, and 1 case presented persistent diplopia on the down gaze as before, but from level III to level I. Facial numbness was resolved completely in 6 cases, and 2 cases presented with persistent numbness but relieved significantly. The average Hounsfield units of RapidSorb plates and OrbFloor PI were 154 ± 5 and 99 ± 4 respectively on computed tomography image obtained 1 week postoperatively, which showed no obvious difference compared with 0.5 year postoperatively ( P > 0.1). Hounsfield units of implants gradually declined around 1 year postoperatively. Hounsfield units of RapidSorb plates (20 ± 1) were consistent with periorbital tissue during postoperative 2-year follow-up, and Hounsfield units of OrbFloor PI (19 ± 1) were consistent with periorbital tissue during postoperative 1.5-year follow-up. No patients had severe sequelae or implant related complications postoperatively. None of bone nonunion, malunion, infection or rejection occurred during the follow-up periods. CONCLUSIONS: Open reduction and internal fixation for the treatment of ZMC fracture have achieved significant improvement in functional and cosmetic outcomes postoperatively. Bioresorbable materials have been proved to be effective and safe in the treatment of children's ZMC and orbital wall fractures.

Prevent Drug Leakage via the Boronic Acid Glucose-Insensitive Micelle for Alzheimer's Disease Combination Treatment.

Boronic acid (BA) materials have been widely applied to glucose and oxidative stress-sensitive drug delivery for the treatment of cancer, diabetes, and Alzheimer's disease (AD). There are completely various BA-sensitive delivery conditions in different diseases. BA materials in the treatment of diabetes show better performance at a high-glucose environment than normal. In contrast, the concentration of glucose in the brain is much lower than that in the blood of AD patients. Hence, the typical glucose and oxidative stress dual-sensitive BA materials inevitably encounter drug leakage in circulation in AD. Attempts to decrease the glucose-sensitive capacity of BA materials are extremely essential for AD drug delivery. In this study, the epoxy group (electron-donating group) was introduced to increase the pKa values of BA materials by increasing the electron cloud density, and thus, the glucose-insensitive micelle (GIM) was obtained. The treatment effect and the synergism mechanism of the drug-loaded GIM micelle were studied on senescence-accelerated mouse prone 8 mice. This work provided excellent antioxidant drugs (vitamin E succinate, melatonin, and quercetin) and a glucose metabolism drug (insulin) loaded in GIM micelle for AD treatment. The discovery of the combination mechanism is enormously valuable for AD clinical research.

DNA self-assembled Au nanoparticle clusters on silver nanorod arrays for high-sensitive and multiplex detection of cancer-related biomarkers.

To sensitively detect multiple and cross-species disease-related targets from a single biological sample in a quick and reliable manner is of high importance in accurately diagnosing and monitoring diseases. Herein, a surface-enhanced Raman scattering (SERS) sensor based on a functionalized multiple-armed tetrahedral DNA nanostructure (FMTDN) immobilized silver nanorod (AgNR) array substrate and Au nanoparticle (AuNP) SERS tags is constructed to achieve both multiplex detection and enhanced sensitivity using a sandwich strategy. The sensor can achieve single, dual, and triple biomarker detections of three lung cancer-related nucleic acid and protein biomarkers, i.e., miRNA-21, miRNA-486 and carcinoembryonic antigen (CEA) in human serum. The enhanced SERS signals in multiplex detections are due to the DNA self-assembled AuNP clusters on the silver nanorod array during the assay, and the experimentally obtained relative enhancement factor ratios, 150 for AuNP dimers and 840 for AuNP trimers, qualitatively agree with the numerically calculated local electric field enhancements. The proposed FMTDN-functionalized AgNR SERS sensor is capable of multiplex and cross-species detection of nucleic acid and protein biomarkers with improved sensitivity, which has great potential for the screening and clinical diagnosis of cancer in the early stage.

Ultra-stable dextran conjugated prodrug micelles for oxidative stress and glycometabolic abnormality combination treatment of Alzheimer's disease.

Sophisticated nanomedicines are continually being developed, but big obstacles remain before they finish the drug release mission. The first challenge is rupture possibility of structure when infinite dilution, competitive reaction of electrolytes and protein in blood circulation. In addition, low responsive drug release efficiency in the lesion site remains the major challenge for clinical application of nanomedicine combination treatment. In this study, we discussed the opportunities for Alzheimer's disease (AD) combination therapy based on the thermodynamically ultra-stable dextran conjugated prodrug micelles. Dextran-nateglinide conjugated prodrug micelles (NA) and dextran-vitamin E succinate conjugated prodrug micelles (VES) presented ultra-low critical micelle concentration of ~10-5 mM and high physiological stability when challenged by NaCl, sodium dodecyl sulphate (SDS), dodecyl dimethyl benzyl ammonium chloride (DDBAC) and no rupture of structure happened. The NA/insulin polymer-drug conjugate micelles (NA/INS PDC) and VES/insulin polymer-drug conjugate micelles (VES/INS PDC) efficiently cleaved by reactive oxygen species (ROS), leading to over 80% release of the encapsulated and conjugated drugs. The combination of nateglinide and insulin, vitamin E succinate and insulin improved the glucose metabolism, reduced oxidative stress, improved the mitochondrial function and recovered the cognitive capacity of mice. This work demonstrated a paradigm for specific and high efficacy AD combination therapy.

Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1.

Myostatin (MSTN) is a negative regulator of skeletal muscle development and plays an important role in muscle development. Fluctuations in gene expression influenced by DNA methylation are critical for homeostatic responses in muscle. However, little is known about the mechanisms underlying this fluctuation regulation and myogenic differentiation of skeletal muscle. Here we report a genome-wide analysis of DNA methylation dynamics in bovine skeletal muscle myogenesis after myostatin editing. We show that, after myostatin editing, an increase in TETs (DNA demethylases) and a concomitant increase in the receptor for activated C kinase 1 (RACK1) control the myogenic development of skeletal muscle. Interestingly, enhancement of PI3K/AKT/mTOR signaling by RACK1 appears to be an essential driver of myogenic differentiation, as it was associated with an increase in myogenic differentiation marker factors (MyHC and MyoG) during muscle differentiation. Overall, our results suggest that loss of myostatin promotes the myogenic differentiation response in skeletal muscle by decreasing DNA methylation of RACK1.

[Effects of muscle derived-IL-6 on insulin resistance of skeletal muscle cells and its mechanisms].

OBJECTIVE: To study the effects of exogenous calcium-load on promoting muscle-derived IL-6 secretion, and regulating AMPK and p38MAPK signal pathway to improve insulin resistance. METHODS: C2C12 cell lines and palmitic acid-induced insulin resistance C2C12 cell lines were selected as the experimental objects. Preliminary experiment was aimed to determinate the glucose concentrations of culture solutions and observe contraction status of cells under microscope following different calcium concentrations culture 24 h. In the first official experiment, cells were divided into four groups: control group (A group, normal culture solution), IR group(B group, 0.6 mmol/L palmitic acid culture cells 24 h), 1 000 ng/ml IL-6 culture IR B group cells 48 h(IL-6+IR group) and IL-6 shRNA culture A group cells (IL-6shRNA group). In the second official experiment, cells were divided into three groups: IR group(A group), 100 µmol/L CaCl2 culture IR group cells 48 h(CaCl2+IR group) and 100 µmol/L CaCl2 and IL-6shRNA co- culture IR group cells 48 h(CaCl2+IL-6shRNA+IR group). The expression levels of GLUT4 mRNA and IL-6 mRNA were measured by real-time PCR, the protein expression levels of p-AMPK, p-p38MAPK, p-IRS-1 and p-PI-3K were measured by Western blot. RESULTS: Preliminary experiment results showed that compared with 0 µmol/L CaCl2 group, the glucose concentrations were decreased significantly after cells treated with CaCl2, at different concentrations. The cell contractions were observed under microscope and the cell contraction was most obvious treated with 100 µmol/L CaCl2. The first official experiment results showed that compared with IR group, the contents of p-AMP-activated protein kinase(p-AMPK), p-insulin receptor substrate 1(p-IRS-1), p-phosphoinositide-3 kinase(p-PI-3K), the expression level of glucose transporter 4(GLUT4) mRNA and the glucose uptake of IL-6+IR group were increased significantly(P＜0.05 or P＜0.01), the p-p38MAPK protein expression level was decreased significantly (P＜0.01) ; Compared with control group, the expression levels of p-AMPK, P-IRS-1, p-PI-3K, the expression level of GLUT4 mRNA and the glucose uptake of IL-6shRNA group were decreased significantly (P＜0.05 or P＜0.01), the p-p38MAPK protein expression level was increased significantly (P＜0.01). The second official experiment results showed that compared with IR group, the expression levels of p-AMPK, P-IRS-1, p-PI-3K, the level of GLUT4 mRNA of CaCl2+IR group were increased significantly (P＜0.05 or P＜0.01), the p-p38MAPK protein expression level was decreased significantly (P＜0.01); Compared with CaCl2+IR group, the contents of p-AMPK, P-IRS-1, p-PI-3K, the expression level of GLUT4 mRNA and the glucose uptake of CaCl2+IL-6 shRNA+IR group were decreased significantly (P＜0.05 or P＜0.01), the p-p38MAPK protein expression level was increased significantly (P＜0.01). CONCLUSION: Exogenous Ca-load can stimulate muscle cells contraction, and exercise-induced IL-6 improves insulin resistance by activating AMPK, PI-3Kand inhibiting p38MAPK signal pathway.

RNA Splicing of the Abi1 Gene by MBNL1 contributes to macrophage-like phenotype modulation of vascular smooth muscle cell during atherogenesis.

BACKGROUND: Vascular smooth muscle cells (VSMC) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind-like splicing regulator 1 (MBNL1) is a well-known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage-like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1-induced gene splicing during atherogenesis. METHODS: The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1-e10 and Abi1-Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1-induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC. RESULTS: Loss of MBNL1 was found in the macrophage-like VSMC (VSMC-M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1-Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1-Δe10, whereby Abi1-Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1-NOX1-ROS pathway, which results in increased expression of transcription factor Kruppel-like factor 4 (KLF4). While Abi1-Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage-like transdifferentiation. CONCLUSION: Loss-of-function of MBNL1 activates VSMC-M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing.

Value of breast MRI omics features and clinical characteristics in Breast Imaging Reporting and Data System (BI-RADS) category 4 breast lesions: an analysis of radiomics-based diagnosis.

BACKGROUND: The Breast Imaging Reporting and Data System (BI-RADS) category 4 breast lesions is categorized into 4A, 4B, and 4C, which reflect an increasing malignancy potential from low (2-10%) moderate (10-50%) and high (50-95%). Determining the benign and malignant of BI-RADS category 4 breast lesions is very important for accurate diagnosis and follow-up treatment. This study aimed to explore the value of breast magnetic resonance imaging (MRI) omics features and clinical characteristics in the assessment of BI-RADS category 4 breast lesions. METHODS: This retrospective study analyzed 96 lesions (39 benign and 57 malignant) from 92 patients diagnosed with MRI BI-RADS category 4 lesions in the Second Affiliated Hospital of Dalian Medical University between May 2017 and December 2019. The lesions were sub-categorized as BI-RADS 4A, 4B, or 4C based on the MRI findings. An imaging omics analysis model was applied to extract the MRI features. The positive predictive value (PPV) of each subcategory was calculated, and the area under the curve (AUC) was used to describe the efficiency for different diagnoses. Moreover, we analyzed 17 clinical indicators to assess their diagnostic value for BI-RADS category 4 breast lesions. RESULTS: The PPVs of BI-RADS 4A, 4B, and 4C were 7.1% (2/28), 41.2% (7/17), and 94.1% (48/51), respectively. The AUC, sensitivity, and specificity were 0.919, 84.2%, and 92.3%, respectively. The combination of T1-weighted images (T1WI) with dynamic contrast-enhanced (DCE) MRI yielded the best diagnostic results among all dual sequences. Two clinical indicators [progesterone receptor (PR) and Ki-67 expression] achieved an AUC almost equal to 1.0. The radiomics and redundancy reduction methods reduced the clinical data features from 1,233 to 14. CONCLUSIONS: High diagnostic performance can be achieved in distinguishing malignant breast BI-RADS category 4 lesions using the combination of T1WI and DCE in MRI. Combining the PR and Ki-67 expression variables can further improve MRI accuracy for breast BI-RADS category 4 lesions.

H2O2-Triggered Rapid Deposition of Poly(caffeic acid) Coatings: A Mechanism-Based Entry to Versatile and High-Efficient Molecular Separation.

Plant-derived polyphenol coating offers a promising route to fabricate functional surfaces for different substrate materials. However, almost all of the deposition approaches are time-consuming and involve inefficient processes, and the mechanisms behind the coating deposition are rarely understood. Herein, we report a rational methodology to achieve the rapid deposition of poly(caffeic acid) (PCA) by using H2O2 as a trigger under the assistance of copper sulfate (CuSO4). The comparative monomer structure of PCA oxidation polymerization has illustrated a significant distinction in the reaction path for PCA coating deposition which has never been reported before. Until now, the unprecedented fast velocity for polyphenol coating has been obtained, and the PCA coating exhibits excellent homogeneity, spatiotemporal tunability, and firm stability. Moreover, three different types of filtration membranes, poly(vinylidene fluoride) microfiltration membrane (PVDF MF membrane), poly(ether sulfone) (PES) ultrafiltration (UF) hollow fiber membrane, and PCA-coated PES nanofiltration (NF) membrane, are all successfully dip-coated using H2O2-triggered PCA coating. Without synthetic complexities and intricate procedures, the formation of hydrophilic and homogeneous PCA aggregates on the surface and/or inside pore walls resulted in various membranes. The as-prepared PCA-coated PVDF MF membrane demonstrates excellent oil/water separation efficiency of less than 150 ppm and a flux recovery rate of approximately 90% even after five cycles. By one-step co-deposition of PCA and poly(2-ethyl-2-oxazoline) (PEtOx) on the PES UF membrane surface, hydrophilicity and biofouling resistance are implemented for efficient protein filtration. The PES NF membrane formed by the PCA layer exhibits high mono-/divalent ion selectivity and excellent chlorine resistance. Overall, these results represent a rapid and sustainable approach to tailor PCA coatings for versatile liquid separation processes.

Dispersive Liquid-Liquid Microextraction Combined with Microwave Demulsification for Determination of FAME Residuals in Biodiesel Wastewater.

Biodiesel consists of various fatty acid methyl esters (FAMEs) that are mainly produced through transesterification of plant oil or animal fat. It is essential for biodiesel to be purified utmostly to meet its product standard before being traded, while the universal purification method has been water washing. However, water washing inevitably causes the residual of FAMEs in wastewater, which represents a loss of industrial profits. For the purpose of determination and monitoring of the FAME profile in wastewater, there is a necessity to develop a fast and reliable approach with small volume of sample in need. Hence, in this study, a combination of dispersive liquid-liquid microextraction (DLLME) and microwave demulsification is applied for the enrichment of residual FAMEs in water, followed by qualitative and quantitative analyses using gas chromatography-mass spectrometry. The results indicate that the optimal extractant in DLLME approach is toluene. And the optimal parameters are 20 mL of water sample, 80 µL of toluene as the extractant, 60 s of ultrasonic irradiation duration, 200 W of microwave power and 2 min of microwave irradiation duration. The standard curves and linear equations obtained with these conditions are used for the quantitative analysis of biodiesel wastewater, which reveals that there was 50.35 mg·L-1 of the total FAME residuals in wastewater. To the best of our knowledge, it is for the first time that the combined technique of DLLME and microwave demulsification is applied in determination of residual FAMEs in water samples. The proposed method corresponds to small volumes of sample and extractant and short analytical period. It also has the potential to be extended to the analysis of other water pollutants.

Delayed Orbital Apex Syndrome in the Post-Reconstructed Orbit.

Delayed orbital apex syndrome (OAS) is rare during orbital blowout fracture reconstruction. A 30-year-old woman fractured the right orbital floor in a fall and undergone repairing operation 2 weeks later. After severe sneezing on postoperative day 10, she gradually arose vision loss, ophthalmoplegia, ptosis with a dilated and fixed pupil within few hours, then consulted our department and was diagnosed as OAS. Computed tomography scan showed displaced implant and retrobulbar emphysema resulting in a constellation of compression to orbital apex. Therefore, an exploratory operation was engaged to reposition the implant and reduce the emphysema concurrent with mega-dose steroids. The patient regained vision immediately and resolved all symptoms at the 6 months follow-up.