Nanobody-Induced Aggregation of Gold Nanoparticles: A Mix-and-Read Strategy for the Rapid Detection of Cronobacter sakazakii.

Protein-nanoparticle interactions play a crucial role in both biomedical applications and the biosafety assessment of nanomaterials. Here, we found that nanobodies can induce citrate-capped gold nanoparticles (AuNPs) to aggregate into large clusters. Subsequently, we explored the mechanism behind this aggregation and proposed the "gold nucleation mechanism" to explain this phenomenon. Building on this observation, we developed a one-step label-free colorimetric method based on nanobody-induced AuNP aggregation. When nanobodies bind to target bacteria, spatial hindrance occurs, preventing further AuNPs aggregation. This alteration in surface plasmon resonance properties results in visible color changes. As an example, we present a simple and sensitive "mix-and-read" chromogenic immunosensor for Cronobacter sakazakii (C. sakazakii). The experiment can be completed within 20 min, with a visual detection limit of 103 CFU/mL and a quantitative detection limit of 136 CFU/mL. Importantly, our method exhibits no cross-reactivity with other bacterial species. This strategy harnesses the excellent properties of nanobodies and the optical characteristics of AuNPs for direct and rapid detection of foodborne pathogen.

Curcumin inhibits propofol-induced autophagy of MN9D cells via Akt/mTOR/p70S6K signaling pathway.

The rapid rise in propofol dependency and abuse has highlighted limited resources for addressing substance abuse-related cognitive impairment, prompting the development of novel therapies. Dysregulated autophagy flow accelerates neuronal cell death, and interventions countering this dysregulation offer an appealing strategy for neuronal protection. Curcumin, a potent natural polyphenol derived from turmeric rhizomes, is renowned for its robust antineurotoxic properties and enhanced cognitive function. Utilizing CCK-8 and Ki67 fluorescent staining, our study revealed that curcumin treatment increased cell viability and proliferative potential in MN9D cells exposed to propofol-induced neurotoxicity. Furthermore, enzyme-linked immunosorbent assay and western blot analysis demonstrated the partial restoration of dopamine synthesis, secretion levels, and TH expression in damaged MN9D cells treated with curcumin. Scanning electrode microscope images displayed reduced autolysosomes and phagosomes in curcumin-treated cells compared to the propofol group. Immunoblotting revealed that curcumin mitigated the degradation of LC3I to LC3II and p62 induced by propofol stimulation, with green fluorescence expression of LC3 postcurcumin treatment resembling that following autophagy inhibitor HCQ treatment, indicating that modulating autophagy flow can alleviate propofol's toxic effects. Moreover, curcumin treatment upregulated the Akt/mTOR/p70S6K signaling pathway, suggesting that curcumin potentially curtails autophagy dysregulation in nerve cells by activating Akt/mTOR/p70S6K. In conclusion, our findings suggest that curcumin can ameliorate propofol abuse-induced neurotoxicity, partially through autophagy regulation and Akt/mTOR/p70S6K signaling activation.

Evolving indications and surgical techniques for corneal transplantation at a tertiary eye care center in southern China.

BACKGROUND: This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021. METHODS: The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty. RESULTS: The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002). CONCLUSIONS: The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.

Efficacy of esketamine for the treatment of postpartum depression and pain control following cesarean section: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postpartum depression (PPD) following a cesarean delivery is a frequently seen complication. Despite the prophylactic effects of ketamine, the impact of esketamine on PPD in women undergoing cesarean section remains uncertain. This study aimed to assess the effectiveness of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) in preventing PPD in women undergoing caesarean section. METHODS: A total of 275 parturients undergoing caesarean section and subsequent patient-controlled intravenous analgesia (PCIA) were randomly assigned to receive either the control treatment (sufentanil 2 µg/kg + tropisetron 10 mg) or the experimental treatment with additional esketamine (1.5 mg/kg). The primary outcome measured was the incidence of postpartum depression (PPD), classified by Edinburgh Postnatal Depression Scale (EPDS) scores equal to or greater than 13 indicating PPD. Secondary outcomes included cumulative sufentanil consumption during specific time periods (0-24 h, 24-48 h, and 0-48 h) after the surgical procedure and numerical rating scale (NRS) scores at rest and during movements. RESULTS: The final analysis included a total of 246 postpartum women who had undergone caesarean delivery. On postoperative day 42, the incidence of depression among the control group was 17.6%, which was significantly higher compared to the esketamine group with a rate of 8.2% (P = 0.02). The EPDS scores also showed a significant difference between the two groups, with a mean score of 9.02 ± 2.21 in the control group and 6.87 ± 2.14 in the esketamine group (p < 0.0001). In terms of pain management, the esketamine group showed lower sufentanil consumption in the 0-24 h (42.5 ± 4.58 µg vs. 50.15 ± 5.47 µg, P = 0.04) and 0-48 h (87.40 ± 9.51 µg vs. 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Differences in movement were also observed between the two groups at 24 and 48 h after the cesarean Sect. (3.39 ± 1.57 vs. 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs. 3.56 ± 0.76, P = 0.02). It is worth noting that the frequency of side effects observed in both groups was comparable. CONCLUSIONS: Esketamine at a dose of 1.5 mg/kg, when used as a supplement in PCIA, has been shown to significantly reduce the occurrence of PPD within 42 days. Additionally, it has been found to decrease cumulative consumption of sufentanil over a 48-hour period following cesarean operation, all without increasing the rate of adverse effects. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.

Effect of different anesthesia depths on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia.

BACKGROUND: To analyze the effects of different anesthesia depths on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, and to provide a basis for clinical application. METHODS: A total of 111 patients with gastric cancer who were treated with epidural anesthesia combined with general anesthesia were selected as the study subjects, and the patients were randomly divided into group A, group B and group C. The bispectral index (BIS) was maintained by adjusting the infusion speed of anesthetics, the BIS of group A was maintained at 50 ~ 59, the BIS of group B was maintained at 40 ~ 49, and the BIS of group C was maintained at 30 ~ 39. The high-frequency power (HFP), low-frequency power (LFP), total power (TP), mean arterial pressure (MAP), heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured before anesthesia induction (T1), immediately after intubation (T2), 3 min after intubation (T3), and 6 min after extubation (T4). The cognitive function of the patients was evaluated before and 48 h after surgery. RESULTS: The HFP, LFP/HFP, TP, HR, DBP and SBP between the three groups at T1 ~ T3 are significantly difference from each other (P < 0.05). There were significant differences in spontaneous breathing recovery time, eye opening time and extubation time among group A, B and C groups, and group B had the lowest spontaneous breathing recovery time, eye opening time and extubation time (P < 0.05). There was no significant difference in the incidence of adverse reactions during anesthesia between the three groups. The cognitive function score of group B was significantly higher than that of group A and group C (P < 0.05). CONCLUSIONS: BIS maintenance of 40 ~ 49 has little effect on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, which is helpful for postoperative recovery.

Comprehensive analysis of HHV-6 and HHV-7-related gene signature in prognosis and response to temozolomide of glioma.

Human herpesvirus (HHV)-6 and HHV-7 have been detected in central nervous system and glioma tissue, while their exact role in glioma remains uncertain. Omics profiles and clinical information were downloaded from public databases, including The Cancer Genome Atlas cohort for training set and the Chinese Glioma Genome Atlas cohorts for validation sets. Differentially expressed genes between HHV-6 and HHV-7 infected or noninfected glioma patients were screened for establishing the HHV-6 and HHV-7 infection (HI) model through Lasso regression analysis. Bioinformatics methods were used to analyze the correlation between HI scores and prognosis, metastasis in glioma patients. Predictable efficacy of HI in temozolomide-resistance and HI-related genetic signatures were also explored. The HI model was constructed as: Risk score = (0.014709*DIRAS3) + (0.029787*TEX26) + (0.223492*FBXO39) + (0.074951*MYBL1) + (0.060202*HILS1). The five gene signature showed good performance in predicting survival time for glioma patients, while higher HI score is correlated with malignant features. Moreover, DNA mismatch repair genes were augmented in glioma patients with higher HI score as well as nonresponse to temozolomide treatment, which was in parallel with the transcriptomic result of temozolomide-resistant glioma cell. Targeting the five gene signature is beneficial for prognosis of glioma patients, especially in glioma patients underwent temozolomide treatment.

Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.

OBJECTIVES: The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS: Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS: Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT: Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS: • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

A Polymer Network Layer Containing Dually Anchored Ionic Liquids for Stable Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries with high sulfur utilization, long-cycle life, and dendrite-free features hold great promise for the development of next-generation energy storage devices of high energy density. Considerable efforts have been committed to solving the polysulfide shuttle problem toward highly stable Li-S batteries. Here, a unique polymer network containing dually anchored ionic liquids (DA-PIL) is devolped to improve the cycling performance and coulombic efficiency of Li-S batteries. This DA-PIL electrolyte incorporates the amphiphilicity of both the polysulfides anion and lithium cation, creating an ionic function layer on polypropylene separator. Noteworthily, the DA-PIL network is "clean" in the sense that no free ionic specifies are introduced to the electrolyte system. The DA-PIL layer not only enables strong supression against polysulfide shuttling but simultaneously allows fast lithium transportation owing to cooperate electrostatic interaction among anchored cations and anions. The DA-PIL layer functionalized on a polypropylene separator can boost excellent stability of Li-S battery with >1600 h cycling test at 0.25 mA cm-2 . The Li-S cell with DA-PIL layer delivers a higher discharge capacity of 827.4 mAh g-1 at 1C. A discharge capacity of 630.6 mAh g-1 is retained after 1000 cycles.

Melatonin reduces myocardial cell damage in myocardial ischemia/reperfusion rats by inhibiting NLRP3 activation.

Melatonin (Mel) is an endogenous hormone with many pharmacological effects, such as sedation, hypnosis, antidepressant, blood pressure regulation, anti-inflammatory and anti-tumor. It is mainly synthesized by pineal gland in vivo. Mel can regulate the function of cardiovascular system and effectively reduce myocardial cell injury, thus playing a role in myocardial protection, but its specific mechanism is unclear. Ischemia-reperfusion injury (IRI) often leads to poor prognosis and complications in patients with cardiovascular diseases, and inflammatory reaction mediated by nod-like receptor thermoprotein domain-related protein 3(NLRP3) is an important reason for the further aggravation of subsequent injury after IRI. Rats were intervened with Mel or NLRP3 inhibitor MCC950 for 10 days, and then the IRI rat model was established. After that, rats were anesthetized and killed, and myocardial tissues were collected for experiments. The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Mel may improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibiting NLRP3.

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4 gene (PTGER4) DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers. Methods: We developed a multimodal prediction model with a training set of 257 individuals. The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects. In addition, we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal. Results: There were significant differences between the early-stage lung cancers and benign groups in the methylation levels. The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693, 0.497 and 0.864, respectively, while the AUCs of PTGER4 were 0.559, 0.739 and 0.619, respectively. With the highest AUC of 0.894, the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set. Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations. Conclusions: The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation.

INTRODUCTION: Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified. METHODS: ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay. RESULTS: 1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19. CONCLUSION: Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.

Saturated Nonsingular Fast Sliding Mode Control for the Crane-Form Pipeline System.

The crane-form pipeline (CFP) system is a kind of petrochemical mechanical equipment composed of multiple rotating joints and rigid pipelines. It is often used to transport chemical fluid products in the factory to tank trucks. In order to realize the automatic alignment of the CFP and the tank mouth, the trajectory tracking control problem of the CFP must be solved. Therefore, a saturated nonsingular fast terminal sliding mode (SNFTSM) algorithm is proposed in this paper. The new sliding mode manifold is constructed by the nonsingular fast terminal sliding mode (NFTSM) manifold, saturation functions and signum functions. Further, according to the sliding mode control algorithm and the dynamic model of the CFP system, the SNFTSM controller is designed. Owing to the existence of saturation functions in the controller, the stability analysis using the Lyapunov equation needs to be discussed in different cases. The results show that the system states can converge to the equilibrium point in finite time no matter where they are on the state's phase plane. However, due to the existence of signum functions, the control signal will produce chattering. In order to eliminate the chattering problem, the form of the controller is improved by using the boundary layer function. Finally, the control effect of the algorithm is verified by simulation and compared with the NTSM, NFTSM and SNTSM algorithms. From the comparison results, it is obvious that the controller based on the SNFTSM algorithm can effectively reduce the amplitude of the control torque while guaranteeing the fast convergence of the CFP system state error. Specifically, compared with the NFTSM algorithm, the maximum input torque can even be reduced by more than half.

Zebrafish Minichromosome Maintenance Protein 5 Gene Regulates the Development and Migration of Facial Motor Neurons via Fibroblast Growth Factor Signaling.

Minichromosome maintenance protein 5 (MCM5), a member of the microchromosomal maintenance protein family, plays an important role in the initiation and extension of DNA replication. However, its role in neural development in zebrafish remains unclear. Here, we used morpholino (MO) and CRISPR/Cas9 to knock down mcm5 and investigated the developmental features of facial motor neurons (FMNs) in the hindbrain of zebrafish. We found that knockdown of mcm5 using mcm5 MO resulted in a small head, small eyes, and a blurred midbrain-hindbrain boundary, while MO injection of mcm5 led to decrease in FMNs and their migration disorder. However, the mutant of mcm5 only resulted in the migration defect of FMNs rather than quantity change. We further investigated the underlying mechanism of mcm5 in the development of hindbrain using in situ hybridization (ISH) and fgfr1a mRNA co-injected with mcm5 MO. Results from ISH showed that the fibroblast growth factor (FGF) signaling pathway was changed when the MCM5 function was lost, with the decrease in fgfr1a and the increase in fgf8, while that of pea3 had opposite trend. FMN development defects were rescued by fgfr1a mRNA co-injected with mcm5 MO. Our results demonstrated that FGF signaling pathway is required for FMN development in zebrafish. Specifically, mcm5 regulates FMN development during zebrafish growing.

Encapsulating Copper Nanocrystals into Metal-Organic Frameworks for Cascade Reactions by Photothermal Catalysis.

Composite materials with multifunctional properties usually possess synergetic effects in catalysis toward cascade reactions. In this work, a facile strategy to the encapsulation of octahedral Cu2 O nanocrystals (NCs) by metal-organic frameworks (MOFs) is reported, and an oriented growth of MOF enclosures (namely, HKUST-1) around Cu2 O NCs with desired feedstock ratio is achieved. The strategy defines the parameter range that precisely controls the etching rate of metal oxide and the MOF crystallization rate. Finally, the Cu@HKUST-1 composites with uniform morphology and controlled MOF thickness have been successfully fabricated after the reduction of Cu2 O to Cu NCs in HKUST-1. The integration of Cu NCs properties with MOF advantages helps to create a multifunctional catalyst, which exhibits cooperative catalytic activity and improved recyclability toward the one-pot cascade reactions under mild conditions involving visible-light irradiation. The superior performance can be attributed to the plasmonic photothermal effect of Cu NCs, while HKUST-1 shell provides Lewis acid sites, substrates and H2 enrichment, and stabilizes the Cu cores.

Protective Strategy to Boost the Stability of Aminated Graphene in Fenton-like Reactions.

Improving the stability of aminated metal-free catalysts is a big challenge in Fenton-like reactions. Herein, trinuclear iron cluster (Fe3 cluster)-protected aminated graphene (Fe3-NH2-GR) is designed by a protective strategy. By protecting with the Fe3 cluster, the lone pair electrons of amino groups are protected and the N content of Fe3-NH2-GR can be fixed steadily. In peroxymonosulfate (PMS)-based Fenton-like reactions with a fixed-bed reactor, the lifetime of Fe3-NH2-GR is two times longer than that of aminated graphene (NH2-GR) under the same conditions. The deactivation kinetics shows that both Fe3-NH2-GR and NH2-GR follow zero-order kinetics and the deactivation rate constants of Fe3-NH2-GR are lower than that of NH2-GR at every period. Moreover, Fe3-NH2-GR still maintains 50% phenol degradation after 40 h rather than being constantly deactivated as NH2-GR. This stable activity is attributed to the formation of -O-NO2, while the N content will be lost in NH2-GR. This protective strategy by the Fe3 cluster provides a reliable method to enhance the efficiency and stability of carbon catalysts in Fenton-like reactions.

CircPDE4B inhibits retinal pathological angiogenesis via promoting degradation of HIF-1α though targeting miR-181c.

Retinopathy of prematurity is a major cause of childhood blindness worldwide. Hence, exploring the proper treatment methods is a must in tacking this disease. qRT-PCR and western blot were used to detect the expression of genes and proteins, respectively. The proliferation of human retinal vascular endothelial cells (HRECs) was ensured by MTT assay. The luciferase activity was measured through luciferase assay. The inverted phase-contrast light microscope was used to observe the formation of a vascular tube. In the present study, our data demonstrated that circPDE4B was downregulated, while hypoxia-inducible factor-1α (HIF-1α) and VEGFA were upregulated in the retinopathy of prematurity model in vitro and in vivo. CircPDE4B increasing remarkably inhibited the expression of HIF-1α and VEGFA in hypoxia-induced HRECs and subsequent repressed cell proliferation and pathological angiogenesis. We further found that miR-181c suppressed the expression of von Hippel-Lindau (VHL), while circPDE4B could promote VHL expression via binding to miR-181c. Finally, our results revealed that circPDE4B inhibited the expression of VEGFA and pathological angiogenesis via facilitating VHL-mediated ubiquitin degradation of HIF-1α. In conclusion, circPDE4B suppressed the expression of VEGFA and pathological angiogenesis via promoting VHL-mediated ubiquitin degradation of HIF-1α through binding to miR-181c. Our study indicated that circPDE4B might be an effective therapeutic target of retinopathy of prematurity.

Elaboration of a multisequence MRI-based radiomics signature for the preoperative prediction of the muscle-invasive status of bladder cancer: a double-center study.

OBJECTIVES: To develop a multisequence MRI-based radiomics signature for the preoperative prediction of the muscle-invasive status of bladder cancer (BCa). METHODS: This retrospective study involved 106 eligible patients from two independent clinical centers. All patients underwent a preoperative 3.0 T MRI scan with T2-weighted image (T2WI) and multi-b-value diffusion-weighted image (DWI) sequences. In total, 1404 radiomics features were extracted from the largest region of the reported tumor locations on the T2WI, DWI, and corresponding apparent diffusion coefficient map (ADC) of each patient. A radiomics signature, namely the Radscore, was then generated using the recursive feature elimination approach and a logistic regression algorithm in a training cohort (n = 64). Its performance was then validated in an independent validation cohort (n = 42). The primary imaging and clinical factors in conjunction with the Radscore were used to determine whether the performance could be further improved. RESULTS: The Radscore, generated by 36 selected radiomics features, demonstrated a favorable ability to predict muscle-invasive BCa status in both the training (AUC 0.880) and validation (AUC 0.813) cohorts. Subsequently, integrating the two independent predictors (including the Radscore and MRI-determined tumor stalk) into a nomogram exhibited more favorable discriminatory performance, with the AUC improved to 0.924 and 0.877 in both cohorts, respectively. CONCLUSIONS: The proposed multisequence MRI-based radiomics signature alone could be an effective tool for quantitative prediction of muscle-invasive status of BCa. Integrating the Radscore with MRI-determined tumor stalk could further improve the discriminatory power, realizing more accurate prediction of nonmuscle-invasive and muscle-invasive BCa. KEY POINTS: • DWI is superior to T2WI sequence in reflecting the heterogeneous differences between NMIBC and MIBC, and multisequence MRI helps in the preoperative prediction of muscle-invasive status of BCa. • Co-occurrence (CM), run-length matrix (RLM), and gray-level size zone matrix (GLSZM) features were the favorable feature categories for the prediction of muscle-invasive status of BCa. • The Radscore (proposed multisequence MRI-based radiomics signature) helps predict preoperatively muscle invasion. Combination with the MRI-determined tumor stalk further improves prediction.

GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells.

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.

Multiparametric MRI for Bladder Cancer: Validation of VI-RADS for the Detection of Detrusor Muscle Invasion.

Background The Vesical Imaging-Reporting and Data System (VI-RADS) scoring system was created in 2018 to standardize imaging and reporting of bladder cancer staging with multiparametric MRI. The system provides a five-point VI-RADS score, which suggests the likelihood of detrusor muscle invasion. Muscle-invasive disease carries a worse prognosis and requires radical surgery. Purpose To determine the performance of the VI-RADS score in detecting muscle-invasive bladder cancer in a cohort of patients undergoing multiparametric MRI before surgery. Materials and Methods In this retrospective study, a total of 340 patients with bladder cancer were identified from a database of consecutive patients undergoing multiparametric MRI from November 2011 to August 2018. The tumor with the largest burden was selected in those patients with multifocal tumors. Bladder tumors were retrospectively categorized according to the VI-RADS five-point scoring system by two readers, independently and in consensus, who were blinded to histologic findings. The VI-RADS score was compared with postoperative pathology for each tumor, and the performance of VI-RADS for determining detrusor muscle invasion was analyzed by using the Cochran-Armitage test. Results Among the 340 patients, there were 296 men and 44 women; the median age was 64.0 years (interquartile range [IQR], 57.0-87.0 years). Of 340 tumors, 255 (75.0%) were verified as non-muscle-invasive and 85 (25.0%) as muscle-invasive bladder cancer. Both the VI-RADS score and its components were associated with muscle-invasive condition (P < .001). The area under the receiver operating characteristic curve for VI-RADS for muscle invasion was 0.94 (95% confidence interval [CI]: 0.90, 0.98). The sensitivity and specificity of a VI-RADS score of 3 or greater were 87.1% (95% CI: 78%, 93%) and 96.5% (95% CI: 93%, 98%), respectively. Conclusion The Vesical Imaging-Reporting and Data System score effectively defines the likelihood of detrusor muscle invasion in bladder cancer and should be considered for evaluation of tumors prior to surgery. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Margolis and Hu in this issue.

A predictive nomogram for individualized recurrence stratification of bladder cancer using multiparametric MRI and clinical risk factors.

BACKGROUND: Preoperative prediction of bladder cancer (BCa) recurrence risk is critical for individualized clinical management of BCa patients. PURPOSE: To develop and validate a nomogram based on radiomics and clinical predictors for personalized prediction of the first 2 years (TFTY) recurrence risk. STUDY TYPE: Retrospective. POPULATION: Preoperative MRI datasets of 71 BCa patients (34 recurrent) were collected, and divided into training (n = 50) and validation cohorts (n = 21). FIELD STRENGTH/SEQUENCE: 3.0T MRI/T2 -weighted (T2 W), multi-b-value diffusion-weighted (DW), and dynamic contrast-enhanced (DCE) sequences. ASSESSMENT: Radiomics features were extracted from the T2 W, DW, apparent diffusion coefficient, and DCE images. A Rad_Score model was constructed using the support vector machine-based recursive feature elimination approach and a logistic regression model. Combined with the important clinical factors, including age, gender, grade, and muscle-invasive status (MIS) of the archived lesion, tumor size and number, surgery, and image signs like stalk and submucosal linear enhancement, a radiomics-clinical nomogram was developed, and its performance was evaluated in the training and the validation cohorts. The potential clinical usefulness was analyzed by the decision curve. STATISTICAL TESTS: Univariate and multivariate analyses were performed to explore the independent predictors for BCa recurrence prediction. RESULTS: Of the 1872 features, the 32 with the highest area under the curve (AUC) of receiver operating characteristic were selected for the Rad_Score calculation. The nomogram developed by two independent predictors, MIS and Rad_Score, showed good performance in the training (accuracy 88%, AUC 0.915, P << 0.01) and validation cohorts (accuracy 80.95%, AUC 0.838, P = 0.009). The decision curve exhibited when the risk threshold was larger than 0.3, more benefit was observed by using the radiomics-clinical nomogram than using the radiomics or clinical model alone. DATA CONCLUSION: The proposed radiomics-clinical nomogram has potential in the preoperative prediction of TFTY BCa recurrence. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1893-1904.