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The advantages of small extracellular vesicles (sEV) in disease management have become increasingly prominent, with the main challenge lying in meeting the demands of large‐scale extraction and high‐throughput analysis, a crucial aspect in the realm of precision medicine. To overcome this challenge, an engineered on‐plate aptamer array (16×24 spots) is developed for continuous scale‐up microextraction of plasma sEV and their in situ metabolic analysis using mass spectrometry. With this integrated array strategy, metabolic profiles of sEV are acquired from the plasma of 274 antenatal or postpartum women, reducing analysis time by half (7.5 h) and sample volume by 95% (only 0.125 µL usage) compared to the traditional suspension method. Moreover, using machine learning algorithms on sEV metabolic profiles, a risk score system is constructed that accurately assesses the need for epidural analgesia during childbirth and the likelihood of post‐administration fever. The system, based on admission samples, achieves an impressive 94% accuracy. Furthermore, post‐administration fever can be identified from delivery samples, reaching an overall accuracy rate of 88%. This work offers real‐time monitoring of the childbirth process that can provide timely guidance for maternal delivery, underscoring the significance of sEV detection in large‐scale clinical samples for medicine innovation and advancement. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of using radiomics analysis of quantitative maps from synthetic MRI to preoperatively predict diffuse glioma grades, isocitrate dehydrogenase (IDH) subtypes, and 1p/19q codeletion status. Methods: Data from 124 patients with diffuse glioma were used for analysis (n = 87 for training, n = 37 for testing). Quantitative T1, T2, and proton density (PD) maps were obtained using synthetic MRI. Enhancing tumour (ET), non-enhancing tumour and necrosis (NET), and peritumoral edema (PE) regions were segmented followed by manual fine-tuning. Features were extracted using PyRadiomics and then selected using Levene/T, BorutaShap and maximum relevance minimum redundancy algorithms. A support vector machine was adopted for classification. Receiver operating characteristic curve analysis and integrated discrimination improvement analysis were implemented to compare the performance of different radiomics models. Results: Radiomics models constructed using features from multiple tumour subregions (ET + NET + PE) in the combined maps (T1 + T2 + PD) achieved the highest AUC in all three prediction tasks, among which the AUC for differentiating lower-grade and high-grade diffuse gliomas, predicting IDH mutation status and predicting 1p/19q codeletion status were 0.92, 0.95 and 0.86 respectively. Compared with those constructed on individual T1, T2, and PD maps, the discriminant ability of radiomics models constructed on the combined maps separately increased by 11, 17 and 10% in predicting glioma grades, 35, 52 and 19% in predicting IDH mutation status, and 16, 15 and 14% in predicting 1p/19q codeletion status (p < 0.05). Conclusion: Radiomics analysis of quantitative maps from synthetic MRI provides a new quantitative imaging tool for the preoperative prediction of grades and molecular subtypes in diffuse gliomas. [ABSTRACT FROM AUTHOR]

Background: Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer. Methods: This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness. Results: The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit. Conclusions: This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer. [ABSTRACT FROM AUTHOR]

Summary: In addition to inheriting the merits of interleaved parallel inverters, the internal parallel structure (IPS) inverter has the advantages of reduced circulating current and lower switching loss. Currently, however, the suppression of circulating current and output current ripple individually results in an evident increase in the number and volume of inductors. In this work, an inductor integration scheme is developed to improve the IPS inverter. Two integrated inductors are developed for different application configurations. As a result, the circulating current and output current ripple are simultaneously suppressed by an integrated inductor, making each phase of the IPS inverter to be equipped with only one integrated inductor implemented by wounding two coils on one magnetic core. The feasibility of the inductor integration scheme for the IPS inverter is experimentally verified by a downscale prototype. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials. In this study, the authors show that nanovaccines co-delivering EBV antigens and molecular adjuvants generate high levels of neutralizing antibodies targeting vulnerable EBV sites of gHgL, gB and gp42. Antibodies elicited by cocktail nanovaccine immunization provide durable protection against EBV-associated lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Platelet-derived growth factor B (PDGFB) serves as an important cytokine for cell growth and development. Tibetan sheep (Ovis aries), a unique local breed in the Qinghai–Tibet Plateau, have poor reproductive physiological characteristics, including long developmental cycles, late sexual maturity, and low fecundity, yet the mechanisms behind remain elusive. Spermatogenesis and sperm maturation are highly dynamic and multifactorial developmental processes occur in the male testis and epididymis, respectively, and thus are crucial for maintaining male reproductive function and species continuity. Despite the importance of PDGFB, its role in maintaining the development and function of the testes and epididymides in sheep remains obscure. Herein, we report, for the first time, the cloning and molecular characterization of Tibetan sheep PDGFB. Meanwhile, we investigated the gene expression pattern and subcellular localization of PDGFB in developmental testes and epididymides in Tibetan sheep. The results revealed that the Tibetan sheep PDGFB gene has a high degree of evolutionary conservation and suggested that it participates in the development and function of testicular and epididymal red blood cells, Leydig cells as well as epididymal principal cells and ciliated epithelial cells, thus contributing to the spermatogenesis and sperm maturation of Tibetan sheep. Platelet-derived growth factor B (PDGFB), as an important cellular growth factor, is widely involved in the regulation of cellular events such as cell growth, proliferation, and differentiation. Although important, the expression characteristics and biological functions in the mammalian reproductive system remain poorly understood. In this study, the PDGFB gene of Tibetan sheep was cloned by RT-PCR, and its molecular characteristics were analyzed. Subsequently, the expression of the PDGFB gene in the testes and epididymides (caput, corpus, and cauda) of Tibetan sheep at different developmental stages (3 months, 1 year, and 3 years) was examined by qRT-PCR and immunofluorescence staining. A bioinformatic analysis of the cloned sequences revealed that the CDS region of the Tibetan sheep PDGFB gene is 726 bp in length and encodes 241 amino acids with high homology to other mammals, particularly goats and antelopes. With the increase in age, PDGFB expression showed an overall trend of first decreasing and then increasing in the testis and epididymis tissues of Tibetan sheep, and the PDGFB mRNA expression at 3 months of age was extremely significantly higher than that at 1 and 3 years of age (p < 0.05). The PDGFB protein is mainly distributed in testicular red blood cells and Leydig cells in Tibetan sheep at all stages of development, as well as red blood cells in the blood vessel, principal cells, and the pseudostratified columnar ciliated epithelial cells of each epididymal duct epithelium. In addition, PDGFB protein expression was also detected in the spermatocytes of the 3-month-old group, spermatids of the 1-year-old group, spermatozoa and interstitial cells of the 3-year-old group, and loose connective tissue in the epididymal duct space in each developmental period. The above results suggest that the PDGFB gene, as an evolutionarily conserved gene, may play multiple roles in the development and functional maintenance of testicular cells (such as red blood cells, Leydig cells, and germ cells) and epididymal cells (such as red blood cells, principal cells, and ciliated epithelial cells) during testicular and epididymal development, which lays a foundation for the further exploration of the mechanisms by which the PDGFB gene influences spermatogenesis in Tibetan sheep. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process. Methods: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined. Results: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15–0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs. Conclusions: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates. [ABSTRACT FROM AUTHOR]

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based "3P model" framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning. [ABSTRACT FROM AUTHOR]

This paper delves into the Macau landfill's anti-seepage system project quality management, highlighting its environmental significance. We summarize global research and provide an overview of the project, emphasizing the importance of quality control across phases. We focus on monitoring, evaluation, and inspection methods to ensure quality objectives. Our findings contribute to environmental preservation and sustainability. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which leads to the formation of immune complex deposits in multiple organs and has heterogeneous clinical manifestations. Currently, exosomes for liquid biopsy have been applied in diagnosis and monitoring of diseases, whereas SLE discrimination based on exosomes at the metabolic level is rarely reported. Herein, we constructed a protocol for metabolomic study of urinary exosomes from SLE patients and healthy controls (HCs) with high efficiency and throughput. Exosomes were first obtained by high-performance liquid size-exclusion chromatography (HPL-SEC), and then metabolic fingerprints of urinary exosomes were extracted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with high throughput and high efficency. With the statistical analysis by orthogonal partial least-squares discriminant analysis (OPLS-DA) model, SLE patients were efficiently distinguished from HCs, the area under the curve (AUC) of the receiver characteristic curve (ROC) was 1.00, and the accuracy of the unsupervised clustering heatmap was 90.32%. In addition, potential biomarkers and related metabolic pathways were analyzed. This method, with the characteristics of high throughput, high efficiency, and high accuracy, will provide the broad prospect of exosome-driven precision medicine and large-scale screening in clinical applications. [ABSTRACT FROM AUTHOR]

Nano-sized unmanned aerial vehicles (UAVs) have been attracting growing attention from both academia and industry with their compact and versatile nature. With the size of merely several centimeters, they are particularly well-suited for executing targeted missions in confined spaces, such as tracking a single pedestrian indoors. However, due to strict constraints on payload and power consumption, the onboard computing unit of nano-UAV is limited to the microcontroller Unit (MCU), which makes the novel single object tracking algorithms not applicable on nano-UAV platform. In this paper, we present a lightweight single pedestrian tracking algorithm to meet the strict resource constraints of nano-UAV system. The algorithm consists of an object detection frontend and a motion-based tracking backend. Based on our deployment methodology, covering from dataset production, model training to layer fusion and deployment, the proposed algorithm achieves extreme complexity reduction (13 × fewer operations and 106 × less memory), and keeps good tracking performance compared with state-of-the-art (SOTA) research work. The full range of onboard experiments illustrate the efficiency our algorithm for real-time tracking (up to 43 fps). Meanwhile, both high computing efficiency (5.2 MACs/cycle) and energy efficiency (5.3 mJ/frame) are achieved and exceed similar works on nano-UAV. [ABSTRACT FROM AUTHOR]

Most vaccines are designed to attack tumor cells by activating CD4+/CD8+αβ T cells. Unfortunately, αβ T cells, which only recognize the peptide antigens in the complexes with polymorphic MHCI/II molecules, surrender to the tumor heterogenicity. As another subset of T cells, γδ T cells become salient in antitumor because of their unique immunotherapeutic roles. Herein, a tumor vaccine is developed with multivalent antigens by fusion of tumor cell membranes with lipids and successfully activated γδ T cells via microneedle inoculation. It is certified that the evoked γδ T cells synchronize with αβ T cells revitalizing tumor‐induced immunotolerance. In turn, the tumors of mice are significantly inhibited and their median survival time is prolonged considerably. Moreover, the nanovaccine inhibits tumor recurrence after resection. The therapeutic effects are corroborated with the results from TCRδ−/− mice as well as cytokine expression in tumor. [ABSTRACT FROM AUTHOR]

Extensive application of reclaimed water alleviated water scarcity obviously. Bacterial proliferation in reclaimed water distribution systems (RWDSs) poses a threat to water safety. Disinfection is the most common method to control microbial growth. The present study investigated the efficiency and mechanisms of two widely used disinfectants: sodium hypochlorite (NaClO) and chlorine dioxide (ClO2) on the bacterial community and cell integrity in effluents of RWDSs through high-throughput sequencing (Hiseq) and flow cytometry, respectively. Results showed that a low disinfectant dose (1 mg/L) did not change the bacterial community basically, while an intermediate disinfectant dose (2 mg/L) reduced the biodiversity significantly. However, some tolerant species survived and multiplied in high disinfectant environments (4 mg/L). Additionally, the effect of disinfection on bacterial properties varied between effluents and biofilm, with changes in the abundance, bacterial community, and biodiversity. Results of flow cytometry showed that NaClO disturbed live bacterial cells rapidly, while ClO2 caused greater damage, stripping the bacterial membrane and exposing the cytoplasm. This research will provide valuable information for assessing the disinfection efficiency, biological stability control, and microbial risk management of reclaimed water supply systems. [ABSTRACT FROM AUTHOR]

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy‐M‐Exo) is developed via fusing tumor‐derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T‐cell response. Moreover, the nanovaccine Hy‐M‐Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy‐M‐Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy. [ABSTRACT FROM AUTHOR]

With the system performance, volume and power restriction requirements in edge computing, single chip based on Field Programmable Gate Array (FPGA), with the characteristics of parallel execution, flexible configuration and power efficiency, is more desirable for realizing Convolutional Neural Network (CNN) acceleration. However, implementing a lightweight CNN with limited on-chip resources while maintaining high computing efficiency and utilization is still a challenging task. To achieve efficient acceleration with single chip, we implement Network-on-Chip (NoC) based on Processing Element (PE) that consists of multiple node arrays. Moreover, the computing and memory efficiencies of PE are optimized with a sharing function and hybrid memory. To maximize resource utilization, a theoretical model is constructed to explore the parallel parameters and running cycles of each PE. In the experimental results of LeNet and MobileNet, resource utilization values of 83.61% and 95.28% are achieved, where the throughput values are 53.3 Giga Operations Per Second (GOPS) and 41.9 GOPS, respectively. Power measurements show that the power efficiency is optimized to 77.25 GOPS/W and 85.51 GOPS/W on our platform, which is sufficient to realize efficient inference for edge computing. [ABSTRACT FROM AUTHOR]

Object detection has become a crucial technology in intelligent vision systems, enabling automatic detection of target objects. While most detectors perform well on open datasets, they often struggle with small-scale objects. This is due to the traditional top-down feature fusion methods that weaken the semantic and location information of small objects, leading to poor classification performance. To address this issue, we propose a novel feature pyramid network, the adaptive learnable feature pyramid network (ALFPN). Our approach features an adaptive feature inspection that incorporates learnable fusion coefficients in the fusion of different levels of feature layers, aiding the network in learning features with less noise. In addition, we construct a context-aligned supervisor that adjusts the feature maps fused at different levels to avoid scaling-related offset effects. Our experiments demonstrate that our method achieves state-of-the-art results and is highly robust for the small object detection on the TT-100K, PASCAL VOC, and COCO datasets. These findings indicate that a model's ability to extract discriminant features is positively correlated with its performance in detecting small objects. [ABSTRACT FROM AUTHOR]

With the use of Convolutional Neural Network (CNN) in the application of sensor signal processing system, it usually faces the urgent requirements of system integration, high throughput, hardware resource and energy efficiency. This paper introduces a resource efficient accelerator with general two-dimensional multiply-add array operator to focus on the characteristic of sensor signal processing, which can be applied to standard CNN, depth-wise CNN, Fully Connected (FC) layer for varied networks. Meanwhile, resource estimation model is also constructed to provide the exploration of parallel parameters for computing efficiency. Finally, a board-level verification is implemented to demonstrate the efficiency of proposed accelerator with common scene of LeNet and complex scene of MobileNetV1. Experimental results show that the Inferences Per Second (IPS) of 332225 and 1498 is realized with 100 MHz frequency. The corresponding efficiency is 88.84% and 61.09%, which outperforms other related works about CNN accelerator design in terms of signal processing. This paper is also applicable and scalable to other fields about effective acceleration research. [ABSTRACT FROM AUTHOR]

The driver's perception level and takeover performance are two major factors that result in accidents in autonomous vehicles. This study's goal is to analyze the change in drivers' perception level and its influence on takeover performance during autonomous driving. A takeover behavior test platform is implemented based on a high-fidelity driving simulator. The fog zone is selected as the takeover scenario. Thus, a 2 (takeover request time: 5 s, 10 s) by 2 (non-driving-related task: work task, entertainment task) takeover experiment was conducted. A generalized linear mixed model is developed to explore the influence of the perception level on takeover performance. The study finds out that, after the takeover request is triggered, the driver's gaze duration is shortened and the pupil area is enlarged, which is helpful for the driver to extract and understand the road information faster. Male drivers have greater perception levels than female drivers, and they prioritize leisure tasks more than professional ones. The drivers' perception level decreases when age increases. The shorter the gaze duration is, and the larger the pupil area is, the shorter the takeover response time will be. In addition, drivers' perception level has a positive effect on takeover performance. Finally, this study provides a reference for revealing the changing rules of drivers' perception level in autonomous driving, and the study can provide support for the diagnosis of takeover risks of autonomous vehicles from the perspective of human factors. [ABSTRACT FROM AUTHOR]

Fluorescence microscopy based on fluorochrome has been rapidly developed as the candidate for morphological identification of pathogenic fungi over recent years, offering superior rapidity and efficacy over traditional culture methods. However, the intrinsic quenching properties of fluorescein limit the clinical application of fluorescence imaging. Herein, we report a nano-strategy by converting a commercial fluorescein dye, fluorescent brightener-33 (FB-33), into carbon dots (FB-CDs) through a one-pot hydrothermal method. FB-CDs exhibit a chitin-targeting capacity allowing the selective recognition and ultrafast imaging of fungi within 30 s. The fluorescence quantum yield of FB-CDs is 51.6% which is 8.6-fold higher than that of commercial dye, FB-33. Moreover, FB-CDs also display superstable fluorescence signals under continuous intense light irradiation for 2 h and long-term storage for more than 2 months. The significantly improved photobleaching resistance meets the prolonged fluorescence observation and quantitative analysis of microbial samples. This work offers a novel nanoconversion strategy of commercial dyes for point-of-care testing of pathogenic organisms. [ABSTRACT FROM AUTHOR]

Objectives: Develop and evaluate a deep learning-based automatic meningioma segmentation method for preoperative meningioma differentiation using radiomic features.Methods: A retrospective multicentre inclusion of MR examinations (T1/T2-weighted and contrast-enhanced T1-weighted imaging) was conducted. Data from centre 1 were allocated to training (n = 307, age = 50.94 ± 11.51) and internal testing (n = 238, age = 50.70 ± 12.72) cohorts, and data from centre 2 external testing cohort (n = 64, age = 48.45 ± 13.59). A modified attention U-Net was trained for meningioma segmentation. Segmentation accuracy was evaluated by five quantitative metrics. The agreement between radiomic features from manual and automatic segmentations was assessed using intra class correlation coefficient (ICC). After univariate and minimum-redundancy-maximum-relevance feature selection, L1-regularized logistic regression models for differentiating between low-grade (I) and high-grade (II and III) meningiomas were separately constructed using manual and automatic segmentations; their performances were evaluated using ROC analysis.Results: Dice of meningioma segmentation for the internal testing cohort were 0.94 ± 0.04 and 0.91 ± 0.05 for tumour volumes in contrast-enhanced T1-weighted and T2-weighted images, respectively; those for the external testing cohort were 0.90 ± 0.07 and 0.88 ± 0.07. Features extracted using manual and automatic segmentations agreed well, for both the internal (ICC = 0.94, interquartile range: 0.88-0.97) and external (ICC = 0.90, interquartile range: 0.78-70.96) testing cohorts. AUC of radiomic model with automatic segmentation was comparable with that of the model with manual segmentation for both the internal (0.95 vs. 0.93, p = 0.176) and external (0.88 vs. 0.91, p = 0.419) testing cohorts.Conclusions: The developed deep learning-based segmentation method enables automatic and accurate extraction of meningioma from multiparametric MR images and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.Key Points: • A deep learning-based method was developed for automatic segmentation of meningioma from multiparametric MR images. • The automatic segmentation method enabled accurate extraction of meningiomas and yielded radiomic features that were highly consistent with those that were obtained using manual segmentation. • High-grade meningiomas were preoperatively differentiated from low-grade meningiomas using a radiomic model constructed on features from automatic segmentation. [ABSTRACT FROM AUTHOR]

Background: The primary function of testicular Leydig cells (LCs) is to produce testosterone (T). In vitro culture of the cells represents a very important approach to study androgen production and its regulations. Various methods have been developed for the enrichment of the cells from the testes. However, getting cells in large numbers with high purity and viability is still challenging. Here, we describe a new way to isolate LCs from rat testes in large quantity with high purity and viability. Methods: Enzymatic digested testicular cells from adult rats were labelled with prolactin receptor (PRLR) antibody. The positive cells were isolated by magnetic‐activated cell sorting (MACS) protocol. Purified LCs were tested in vitro for their steroidogenic (T production) and non‐steroidogenic (25‐OH‐vitamin D production and Insl3 and Cyp2r1expressions) functions in the presence of Luteinizing Hormone (LH) for up to 24 h. Results: Reanalysis of scRNA‐seq data indicates that Prlr expression is highly specific in LCs of adult rat testis. MACS procedure based on PRLR expression was able to isolate LCs with very high yield (about 106 cells/testis), high purity (about 95%) and viability (> 93%). Purified LCs retained high steroidogenic and non‐steroidogenic functions in responding to maximal LH stimulations, with more than 10‐fold increases in T production in 3 h and 42% and 103% increases in Insl3 and Cyp2r1 expressions in 24 h. Discussion and conclusion: We have established an excellent way to purify high quality LCs from adult rat testis that can serve as a useful tool to study the physiology, pharmacology and toxicology of the cells in vitro. [ABSTRACT FROM AUTHOR]

The flexible surface-enhanced Raman scattering (SERS) platform has ceaselessly propelled the development of point-of-care testing (POCT) in diverse fields. Herein, we report a facile strategy for the SERS-chemometric analysis of four β-blockers (bisoprolol, metoprolol, acebutolol and esmolol) based on a super-sticky mussel-inspired hydrogel SERS tape. The surface morphology and mechanical properties of the hydrogel tape can be easily controlled by adjusting the compositional ratio. The optimized tape with excellent toughness and adhesiveness allows efficient collection of analytes through a simple "paste and peel off" approach, further by spraying with silver nanoparticles using a household sprayer to instantly assemble a flexible SERS substrate, the analytes can then detected by a portable Raman spectrometer. This POCT strategy enables the identification and discrimination of four similar β-blockers with high sensitivity and accuracy in combination with the statistical algorithms. The developed SERS tape is finally utilized for the recognition of β-blockers in simulated urine solution, which realizes a limit of detection of 1.0 ng mL−1, revealing a promising potential of this SERS-based POCT for the clinical detection of doping abuse. [ABSTRACT FROM AUTHOR]

Diabetes and high myopia as well‐known high‐risk factors can aggravate cataracts, yet clinical coping strategy remains a bottleneck. Metabolic analysis tends to be powerful for precisely detection and mechanism exploration since most of diseases including cataracts are accompanied by metabolic disorder. Herein, a layered binary co‐ionizers assisted aqueous humor metabolic analysis tool is proposed for potentially etiological typing and detection of cataracts, including age‐related cataracts (ARC), cataracts with diabetes mellitus (CDM), and cataracts with high myopia (CHM). Startlingly, taking advantage of the optimal machine learning algorithm and all metabolic fingerprints, 100% of accuracy, precision, and recall rates are achieved for arbitrary comparison between groups. Moreover, 11, 9, and 7 key metabolites with explicit identities are confirmed as markers of discriminating CDM from ARC, CHM from ARC, and CDM from CHM, and the corresponding area under the curve values of validation cohorts are 0.985, 1.000, and 1.000. Finally, the critical impact of diabetes/high myopia on cataracts is revealed by excavating the change levels and metabolic pathways of key metabolites. This work updates the insights of prevention and treatment about cataracts at metabolic level and throws out huge surprises and progresses metabolic diagnosis toward a reality. [ABSTRACT FROM AUTHOR]

Metal–semiconductor nanocomposites have gained more and more attention as novel surface-enhanced Raman scattering (SERS) substrates due to the coupling Raman enhancement mechanism between the nanocomponents. Herein, Au@palladium oxide (Au@PdOx) nanohybrids are firstly obtained from the oxidation of Pd hexagonal nanosheets in the presence of Au ions, where the whole process takes no more than 5 min without any additional redox agent. Au@PdOx shows a sunflower-like morphology with an average size of 180 nm consisting of an Au stamen and flake-like PdOx petals. An intense electric field distribution emerges around the Au nano-stamen which endows Au@PdOx with excellent SERS activity. A maximum Raman enhancement factor of 4.7 × 107 is achieved for methylene blue with good reproducibility and reliability. [ABSTRACT FROM AUTHOR]

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice. [ABSTRACT FROM AUTHOR]

Vaccines can improve the quality of human life by preventing the burden of infectious diseases. Also, vaccination is becoming a powerful medication for preventing and treating tumors. Various vaccines have been developed based on the origin of the antigens. Herein, we focus on the subunit vaccines whose antigens are proteins or peptides. The advantage of subunit vaccines is safety for recipients; however, the immunogenicity of subunit antigens is relatively low. Nanoparticular delivery systems have been applied to improve the immunocompetence of subunit vaccines by targeting lymph nodes, and effectively present antigens to immune cells. Moreover, adding appropriate molecular adjuvants may strengthen the antigens to elicit immune response. In this perspective article, we first elucidate the characteristics of immunity induced by subunit nanovaccines and then summarize the strategies to fabricate subunit nanovaccines with delivering materials. Herein we highlight non-covalent interaction to fabricate nanoparticular subunit vaccines. [ABSTRACT FROM AUTHOR]

Exosomes are regarded as the emerging potential targets for liquid biopsy and bioprocess study owing to their abundant inclusive cargos that carry significant disease information. In addition, metabolites have been promising biomarkers for diagnosis. However, little metabolic research on exosomes is carried out by now. Herein, the mix‐crystal titania‐assisted laser desorption/ionization mass spectrometry (LDI‐MS) method is established, which features fast speed, high throughput, and efficiency, to directly extract urinary exosome metabolic patterns of healthy controls (HC) and membrane nephropathy (MN) patients. Besides, this method is also adopted to acquire the primitive urinary metabolic patterns from the same samples for comparison. By taking advantage of principal component analysis, unpaired parametric t‐test, and orthogonal partial least squares discriminant analysis on the exosome metabolic patterns, 27 significant m/z signals are filtrated, which possess more prominent differentiation capacity toward HC and MN patients (AUC = 0.942), and hold greater potential in MN diagnosis, compared to primitive urine (AUC = 0.801). The work reveals the important clinical value of exosome metabolic analysis, and paves a way to exosome‐based diagnosis at metabolomic level toward large‐scale clinical use. [ABSTRACT FROM AUTHOR]

Driving speeds are higher on freeways, and the visibility reduction occurring in freeway fog zones often increases traffic accidents. This study aims at assessing the impact of different levels of connected vehicle fog warning systems on driving behavior and safety. A connected vehicle fog warning system is developed based on driving simulators, and virtual scenes are developed based on fog zones. The connected vehicle technology includes three levels: a normal level, a level including a human-machine interface, and a level with both a human-machine interface and dynamic message signs. Speed and lateral deviation are chosen as assessment indicators and combined with sample entropy to evaluate the impact of the connected vehicle fog warning system on safety. The deceleration ratio of the warning point is used to evaluate the efficiency of the connected vehicle fog warning system. Results show that the connected vehicle fog warning system can significantly reduce driving speed, and that there are differences in the speed-reduction effectiveness for different technical levels. The connected vehicle fog warning system can reduce the lateral deviation and improve the lateral driving safety. From the perspective of change stability, speed safety entropy and lateral deviation safety entropy are increased, which indicates that the connected vehicle fog warning system will negatively impact safety because of the additional workload. Drivers' responses are more pronounced in the human-machine interface group compared to the group with dynamic message signs, where the drivers maintained a lower speed. This study provides a reference for the studies on connected vehicle technology based on driving simulators and supports the optimization, design, and evaluation of connected vehicle fog warning systems. [ABSTRACT FROM AUTHOR]

Human health is always under global spotlight, but now it suffers from severe environmental issue and various diseases. Developing highly selective and effective extraction technique for environmental pollutant removal and target protein/peptide molecules conduces to the solution of environmental contamination and early disease detection, which will promise human health to a great degree. Metal-organic frameworks (MOFs) are typical porous nanomaterials featuring rigid structure, large specific surface area, thermal and chemical stability, numerous active sites and easy functionalization. Moreover, multitudinous combination of metal centers and organic ligands often endows MOFs with structure and function diversity. Owing to such splendid merits, MOFs are able to act as advanced adsorbents for sample-pretreatment in proteomics and environmental field, which indicates great efficiency, reproducibility, convenience and cost-effectiveness. In this review, the novel design of MOFs and their applications in proteomics and environmental research are roughly summarized. We first introduce the representative researches of functional MOFs in protein post-translational modifications including glycosylation and phosphorylation, mainly focusing on hydrophilic interaction liquid chromatography (HILIC) or metal-oxide affinity chromatography (MOAC). The important role of MOFs in enzyme immobilization is also covered. Then MOF-based adsorptive removal of diverse environmental contaminants embracing plasticizers, pesticides and varied water pollutants (pharmaceutical and personal care products, organic dyes and heavy metals), in which multiple chemical and non-chemical interactions play a vital role, is emphatically discussed. Finally, we analyze the existing problems and challenges in the way of wider practical applications and put forward prospective anticipation. [ABSTRACT FROM AUTHOR]

Spermatogenesis is an efficient, complex, and highly organized proliferation and differentiation process that relies on multiple factors including testosterone produced by the Leydig cells. Although the critical role played by testosterone in spermatogenesis is well recognized, the mechanism by which it works is still not completely understood, partially due to the inability to specifically and precisely monitor testosterone-dependent changes within developing germ cells. Here we present single-cell RNA sequencing data from10,983 adult rat testicular cells after the rats were treated with ethanedimethanesulfonate, which temporarily eliminates Leydig cells. The elimination and recovery of Leydig cells represented a complete testosterone depletion and restoration cycle. The dataset, which includes all developing germ cells from spermatogonia to spermatozoa, should prove useful for characterizing developing germ cells, their regulatory networks, and novel cell-specific markers. The dataset should be particularly useful for exploring the effects of the androgen environment on the regulation of spermatogenesis. As this is the first single-cell RNA-Seq dataset for rat testes, it can also serve as a reference for future studies. Measurement(s) RNA sequence of rat testicular cells Technology Type(s) scRNA-seq Factor Type(s) Time course in weeks Sample Characteristic - Organism Sprague Dawley Rattus [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to assess the landscape of parathyroid carcinoma research during the last 22 years using machine learning and text analysis. Method: In November 2021, we obtained from PubMed all works indexed under the mesh subject line "parathyroid carcinoma". The entire set of search results was retrieved in XML format, and metadata such as title, abstract, keywords, mesh words, and year of publication were extracted for bibliometric evaluation from the original XML files. To increase the specificity of the investigation, the Latent Dirichlet allocation (LDA) topic modeling method was applied. Results: The paper analyzed 3578 papers. The volume of literature related to parathyroid cancer has been relatively flat over the past 22 years. In the field of parathyroid cancer research, the most important topic of clinical interest is the differential diagnosis. Ultrasound and MIBI are the most commonly used imaging methods for localization. In terms of basic research, the mechanisms of gene mutation and local tumor recurrence are the focus of interest. Conclusion: There are huge unmet research needs for parathyroid carcinoma. Improving the diagnosis rates of parathyroid cancer by clinicians and establishing new and reliable molecular pathological markers and new image localization techniques will continue to be the focus of future research. [ABSTRACT FROM AUTHOR]

Background: Midazolam is a neurological drug with diverse functions, including sedation, hypnosis, decreased anxiety, anterograde amnesia, brain-mediated muscle relaxation, and anticonvulsant activity. Since it is frequently used in children and adolescents for extended periods of time, there is a risk that it may affect their pubertal development. Here, we report a potential effect of the drug on the development of Leydig cells (LCs), the testosterone (T)-producing cells in the testis. Methods: Stem LCs (SLCs), isolated from adult rat testes by a magnetic-activated cell sorting technique, were induced to differentiate into LCs in vitro for 3 weeks. Midazolam (0.1–30 μM) was added to the culture medium, and the effects on LC development were assayed. Results: Midazolam has dose-dependent effects on SLC differentiation. At low concentrations (0.1–5 μM), the drug can mildly increase SLC differentiation (increased T production), while at higher concentrations (15–30 μM), it inhibits LC development (decreased T production). T increases at lower levels may be due to upregulations of scavenger receptor class b Member 1 (SCARB1) and cytochrome P450 17A1 (CYP17A1), while T reductions at higher levels of midazolam could be due to changes in multiple steroidogenic proteins. The uneven changes in steroidogenic pathway proteins, especially reductions in CYP17A1 at high midazolam levels, also result in an accumulation of progesterone. In addition to changes in T, increases in progesterone could have additional impacts on male reproduction. The loss in steroidogenic proteins at high midazolam levels may be mediated in part by the inactivation of protein kinase B/cAMP response element-binding protein (AKT/CREB) signaling pathway. Conclusion: Midazolam has the potential to affect adult Leydig cell (ALC) development at concentrations comparable with the blood serum levels in human patients. Further studies are needed to test the effects on human cells. [ABSTRACT FROM AUTHOR]

Serum N-glycan patterns from 50 Crohn's disease (CD) patients and 50 healthy controls were acquired using a carbon matrix, from which eight N-glycans with significant difference were screened out to reveal remarkale performance for CD diagnosis. This research is expected to help future glycan-based disease detection not limited to CD. [ABSTRACT FROM AUTHOR]

Currently, most Crohn's disease (CD) patients suffer from serious complications and even surgery due to delayed diagnosis; therefore, point‐of‐care diagnosis of CD is urgently required. In this work, a covalent organic framework@Au (COF‐V@Au) matrix material with excellent laser absorption is prepared, endowing metabolites with great ionization efficiency in laser desorption/ionization mass spectrometry (LDI‐MS) analysis. In addition, the COF‐V@Au matrix possesses 1093 m2 g−1 of large specific surface area and around 2 nm of average pore size, providing abundant sites and efficient structure for metabolite adsorption. Benefiting from high throughput, high sensitivity, and high ionization efficiency of COF‐V@Au assisted LDI‐MS, the extraction of serum metabolic fingerprints of CD group and healthy group is implemented. Moreover, the two groups are successfully distinguished with an area under the curve (AUC) value of 0.984 by establishing an orthogonal partial least squares discriminant analysis (OPLS‐DA) model of Crohn's patients versus healthy controls. Moreover, the expression of 25 features is determined as the prominent metabolic differences between CD patients and the controls. Furthermore, the terminal ileum and ileocolon subtypes of CD are also distinguished from healthy controls with AUC value of 0.989 and 0.991, respectively. Thus, this COF‐V@Au‐assisted LDI‐MS method is expected to be a clinical diagnostic technology in the future. [ABSTRACT FROM AUTHOR]

1T-phase niobium telluride (NbTe2) nanosheets are becoming increasingly important in emerging fields, such as spintronics, sensors and magneto-optoelectronics, due to their excellent physical and chemical properties. However, exploration on their biomedical applications are limited. Herein, ultrathin 1T-phase NbTe2 single-crystalline nanosheets with excellent photothermal performance, high drug-loading rate, near-infrared (NIR) light/acidic pH-triggered drug release, and low toxicity were developed for potentiated photothermal therapy. Importantly, they showed excellent biocompatibility in vivo and in vitro. NbTe2 nanosheets loaded with integrated stress response inhibitors (ISRIB) could achieve chemo-photothermal therapy of tumors through the ATF4–ASNS signaling axis. Ultrathin 1T-phase NbTe2 single-crystalline nanosheets with unique photothermal properties, drug loading rate and safety provide dramatic possibilities in biomedical applications, such as tissue imaging, photothermal therapeutics and pharmaceutics. [ABSTRACT FROM AUTHOR]

A hydrophilic probe is employed to enrich exosomes from three kinds of cancer cells by TiO2–phosphate interaction and exosomal glycoproteins by hydrophilic interaction in succession. The probe performs efficiently in both the enrichment processes. And the analytical results confirm that unique exosomal glycoproteins can distinguish parent exosomes from others. [ABSTRACT FROM AUTHOR]

Testicular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21lin cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21lin cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility. Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. [ABSTRACT FROM AUTHOR]

Background: Accurate prediction of recurrence is crucial for personalized treatment in breast cancer, and whether the radiomics features of ultrasound (US) could be used to predict recurrence of breast cancer is still uncertain. Here, we developed a radiomics signature based on preoperative US to predict disease-free survival (DFS) in patients with invasive breast cancer and assess its additional value to the clinicopathological predictors for individualized DFS prediction. Methods: We identified 620 patients with invasive breast cancer and randomly divided them into the training (n = 372) and validation (n = 248) cohorts. A radiomics signature was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in the training cohort and validated in the validation cohort. Univariate and multivariate Cox proportional hazards model and Kaplan–Meier survival analysis were used to determine the association of the radiomics signature and clinicopathological variables with DFS. To evaluate the additional value of the radiomics signature for DFS prediction, a radiomics nomogram combining the radiomics signature and clinicopathological predictors was constructed and assessed in terms of discrimination, calibration, reclassification, and clinical usefulness. Results: The radiomics signature was significantly associated with DFS, independent of the clinicopathological predictors. The radiomics nomogram performed better than the clinicopathological nomogram (C-index, 0.796 vs. 0.761) and provided better calibration and positive net reclassification improvement (0.147, P = 0.035) in the validation cohort. Decision curve analysis also demonstrated that the radiomics nomogram was clinically useful. Conclusion: US radiomics signature is a potential imaging biomarker for risk stratification of DFS in invasive breast cancer, and US-based radiomics nomogram improved accuracy of DFS prediction. [ABSTRACT FROM AUTHOR]

Priapism, a prolonged penile erection in the absence of sexual arousal, is common among patients with sickle cell disease (SCD). Hypogonadism is also common in patients with SCD. While the administration of exogenous testosterone reverses hypogonadism, it is contraceptive. We hypothesized that the stimulation of endogenous testosterone production decreases priapism by normalizing molecular signaling involved in penile erection without decreasing intratesticular testosterone production, which would affect fertility. Treatment of SCD mice with FGIN‐1‐27, a ligand for translocator protein (TSPO) that mobilizes cholesterol to the inner mitochondrial membrane, resulted in eugonadal levels of serum testosterone without decreasing intratesticular testosterone production. Normalized testosterone levels, in turn, decreased priapism. At the molecular level, TSPO restored phosphodiesterase 5 activity and decreased NADPH oxidase‐mediated oxidative stress in the penis, which are major molecular signaling molecules involved in penile erection and are dysregulated in SCD. These results indicate that pharmacologic activation of TSPO could be a novel, targetable pathway for treating hypogonadal men, particularly patients with SCD, without adverse effects on fertility. [ABSTRACT FROM AUTHOR]

Recently, tissue engineering has developed into a powerful tool for repairing and reconstructing damaged tissues and organs. Tissue engineering scaffolds play a vital role in tissue engineering, as they not only provide structural support for targeted cells but also serve as templates that guide tissue regeneration and control the tissue structure. Over the past few years, owing to unique physicochemical properties and excellent biocompatibility, various types of two-dimensional (2D) nanomaterials have been developed as candidates for the construction of tissue engineering scaffolds, enabling remarkable achievements in bone repair, wound healing, neural regeneration, and cardiac tissue engineering. These efforts have significantly advanced the development of tissue engineering. In this review, we summarize the latest advancements in the application of 2D nanomaterials in tissue engineering. First, each typical 2D nanomaterial is introduced briefly, followed by a detailed description of its applications in tissue engineering. Finally, the existing challenges and prospects for the future of the application of 2D nanomaterials in tissue engineering are discussed. [ABSTRACT FROM AUTHOR]

Background: It is difficult to prospectively differentiate between benign (World Health Organization [WHO] I) and nonbenign (WHO II and III) meningiomas.Purpose: To evaluate the feasibility of preoperative differentiation between benign and nonbenign meningiomas by using texture analysis from multiparametric MR data.Study Type: Retrospective.Subjects: In all, 184 patients with meningioma (139 benign and 45 nonbenign) were included as the training cohort and 79 patients with meningioma (60 benign and 19 nonbenign) were included as the external validation cohort.Field Strength/sequence: T1 -weighted, T2 -weighted, and contrast-enhanced T1 -weighted imaging were performed on 1.5 or 3.0T MR systems from two centers.Assessment: Tumor segmentation and radiological characteristic (RC) evaluation were performed by experienced radiologists. The texture features were extracted from preprocessed images and combined with RCs, and then the combined features were reduced by using a two-step feature selection. Three single-sequence models and a multiparametric MRI (the combination of single sequences) model were constructed and then evaluated with the external validation cohort.Statistical Tests: Area under receiver operating characteristic curve (AUC), accuracy (Acc), f1-score (F1), sensitivity (Sen), and specificity (Spec), were calculated to quantify the performance of the models.Results: Among the four texture models, the multiparametric MRI model demonstrated the best performance for differentiating between benign and nonbenign meningiomas in both the training and external validation cohorts (AUC 0.91, Acc 89%, F1 0.88, Sen 0.93, and Spec 0.87 in the training cohort; AUC 0.83, Acc 80%, F1 0.77, Sen 0.84, and Spec 0.78 in the validation cohort).Data Conclusion: Nonbenign meningiomas might be preoperatively differentiated from benign meningiomas by using texture analysis from multiparametric MR data.Level Of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1810-1820. [ABSTRACT FROM AUTHOR]

Background: Cholesterol import into the mitochondria of steroid‐producing cells is the rate‐determining step in steroidogenesis. Numerous studies have provided evidence that the cholesterol‐binding translocator protein (18 kDa TSPO) plays an important role in cholesterol translocation into mitochondria and that it also might act on cholesterol homeostasis. Several TSPO‐specific ligands have been shown to increase steroid production in vitro and in vivo. Objectives: The present study assessed the effects of the TSPO drug ligand FGIN‐1‐27 on cholesterol accumulation and lipid droplet formation in relationship to steroid formation. Materials and Methods: Using MA‐10 and primary Leydig cells, immunocytochemical and molecular methods were used to examine cholesterol accumulation, the formation of lipid droplets, and steroid formation in response to LH and FGIN‐1‐27. Additionally, we determined the effects of Tspo knockout by CRISPR/Cas9, and of siRNA knockdowns of Tspo and Plin2 (Perilipin 2; also known as adipose differentiation‐related protein, ADFP) on LH‐ and FGIN‐1‐27‐induced steroidogenesis. Results: In response to LH and FGIN‐1‐27, cultured MA‐10 cells and primary Leydig cells increased steroid formation, cholesterol accumulation, and lipid droplet formation. Cholesterol accumulation in the lipid droplets also was increased in Tspo knockout cells. Knockout of Tspo or its knockdown in MA‐10 cells resulted in reduced progesterone formation in response to both LH and FGIN‐1‐27, as did knockdown of Plin2. Steroid production also was inhibited by the cholesteryl ester hydrolase inhibitor diethylumbelliferyl phosphate. Discussion and Conclusion: These results support the conclusion that FGIN‐1‐27 stimulates steroid formation by increasing TSPO‐mediated cholesterol translocation into the inner mitochondria for steroidogenesis, as well as into the cytosol for lipid droplet formation. FGIN‐1‐27 also increased steroid formation at least in part by inducing the conversion of cholesteryl ester located in lipid droplets to cholesterol, thus making available more substrate for steroid formation. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate an MRI-based radiomics strategy for the preoperative estimation of pathological grade in bladder cancer (BCa) tumors.Methods: A primary cohort of 70 patients (31 high-grade BCa and 39 low-grade BCa) with BCa were retrospectively enrolled. Three sets of radiomics features were separately extracted from tumor volumes on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. Two sets of multimodal features were separately generated by the maxout and concatenation of the above mentioned single-modality features. Each feature set was subjected to a two-sample t test and the least absolute shrinkage and selection operator (LASSO) algorithm for feature selection. Multivariable logistic regression (LR) analysis was used to obtain five corresponding radiomics models. The diagnostic abilities of the radiomics models were evaluated using receiver operating characteristic (ROC) curve analysis and compared using the DeLong test. Validation was performed on a time-independent cohort containing 30 consecutive patients.Results: The areas under the ROC curves (AUCs) of single-modality T2WI, DWI, and ADC models in the training cohort were 0.7933 (95% confidence interval [CI] 0.7471-0.8396), 0.8083 (95% CI 0.7565-0.8601), and 0.8350 (95% CI 0.7924-0.8776), respectively. Both multimodality models achieved higher AUCs (maxout 0.9233, 95% CI 0.9001-0.9466; concatenation 0.9233, 95% CI 0.9001-0.9466) than single-modality models. The AUCs of the maxout and concatenation models in the validation cohort were 0.9186 and 0.9276, respectively.Conclusions: The MRI-based multiparametric radiomics approach has the potential to be used as a noninvasive imaging tool for preoperative grading of BCa tumors. Multicenter validation is needed to acquire high-level evidence for its clinical application.Key Points: • Multiparametric MRI may help in the preoperative grading of BCa tumors. • The Joint_Model established from T2WI, DWI, and ADC feature subsets demonstrated a high diagnostic accuracy for preoperative prediction of pathological grade in BCa tumors. • The radiomics approach has the potential to preoperatively assess tumor grades in BCa and avoid subjectivity. [ABSTRACT FROM AUTHOR]

The lack of blood compatibility and antifouling ability is still one of the challenges of bare metallic implants and devices for biomedical applications. Here, based on the strong binding affinity of the phosphonic group on metallic substrates and excellent antifouling ability of zwitterionic materials, we reported the rational design of zwitterionic–phosphonic copolymers for efficient antifouling surface modification of diverse biomedical metals. Firstly, nine copolymers with a wide range of mole ratios between the zwitterionic and phosphonic components (from 10 : 90 to 99 : 1) were precisely prepared via conventional radical copolymerization. The XPS result revealed that the copolymers, even if only 1% of the phosphonic component was present, were able to bind onto the titanium alloy substrates. Water contact angle measurement showed that the more zwitterionic component in the coating copolymer, the better the surface wettability of the titanium alloy substrates. Systematic antifouling evaluation (protein adsorption, platelet adhesion, bacterial adhesion, and cell adhesion tests) results consistently indicated that the copolymers bearing the zwitterionic components, ranging from 20 to 95%, can efficiently confer perfect antifouling ability to the titanium alloy substrates, establishing a robust relationship between the composition of the copolymer and the surface antifouling property conferred to the titanium alloy substrates. In addition, the ability of the zwitterionic–phosphonic copolymers to improve the antifouling ability of other biomedical metals (pure Ti and stainless steel) and devices (scalpels) was clearly demonstrated, indicating that the zwitterionic–phosphonic copolymers could serve as general antifouling coating materials for biomedical metals. [ABSTRACT FROM AUTHOR]

The favorable biocompatibility, biodegradability and broadband absorption in the ultraviolet to near-infrared (NIR) region have made black phosphorus (BP) a new generation two-dimensional nanomaterial with great potential for photothermal therapy (PTT). However, an appropriate but not low dosage of nanoagent is required to achieve the satisfactory therapeutic effect in BP-based NIR PTT, due to the decreasing light absorption of BP in the NIR region. In this work, nanohybrids composed of BP nanosheets and several polypyrrole (PPy) nanoparticles attached to them (BP/PPy NSs) are fabricated for high-performance NIR PTT, benefiting from the superimposed NIR absorption characteristics of the two components. The nanocomposites exhibit irregular, speckled and flake-like morphologies with good biocompatibility and superior NIR photothermal transduction efficiency compared with that of the bare nanosheets. The utilization of BP/PPy NSs as novel nanotherapeutic agent for enhanced NIR photothermal cancer therapy is accomplished in vitro and in vivo. [ABSTRACT FROM AUTHOR]