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Background. MRI is an important tool for accurate detection and targeted biopsy of prostate lesions. However, the imaging appearances of some prostate cancers are similar to those of the surrounding normal tissue on MRI, which are referred to as MRI-invisible prostate cancers (MIPCas). The detection of MIPCas remains challenging and requires extensive systematic biopsy for identification. In this study, we developed a weakly supervised UNet (WSUNet) to detect MIPCas. Methods. The study included 777 patients (training set: 600; testing set: 177), all of them underwent comprehensive prostate biopsies using an MRI-ultrasound fusion system. MIPCas were identified in MRI based on the Gleason grade (≥7) from known systematic biopsy results. Results. The WSUNet model underwent validation through systematic biopsy in the testing set with an AUC of 0.764 (95% CI: 0.728-0.798). Furthermore, WSUNet exhibited a statistically significant precision improvement of 91.3% (p < 0.01) over conventional systematic biopsy methods in the testing set. This improvement resulted in a substantial 47.6% (p < 0.01) decrease in unnecessary biopsy needles, while maintaining the same number of positively identified cores as in the original systematic biopsy. Conclusions. In conclusion, the proposed WSUNet could effectively detect MIPCas, thereby reducing unnecessary biopsies. [ABSTRACT FROM AUTHOR]

• Laboratory experiments were conducted on dike stability under various configurations. • The submerged breakwater induced inconspicuous improvement in dike stability. • Wave impact primarily induced dike failure at high water elevation. • The superposition of structures in mitigating storm surges was not entirely positive. Four tests were conducted to investigate the wave attenuation and dike stability effectiveness of a basic dike, a dike that combined with the submerged breakwater, with mangrove, and with both submerged breakwater and mangrove. Wave variation, hydrodynamic responses (wave scour, wave pressure, pore pressure), and dike stability were investigated. It was found that the submerged breakwater effectively reduced wave height and wave pressure in small wave conditions. However, the dike stability was not improved due to the balance between the positive effect of wave attenuation and the negative effect of water elevation increase in large wave conditions. The mangrove's wave attenuation effects were remarkable at both small and large wave conditions, leading to smaller hydrodynamic responses and ultimately contributing to a significant improvement in the dike stability. The combination of submerged breakwater and mangrove induced the best wave attenuation effect in shallow water with the smallest hydrodynamic responses. However, the presence of submerged breakwater amplified water elevation and significant wave height in deep water conditions, inducing stronger wave impact and more intense wave scour, ultimately resulting in the weaker stability of the dike. [ABSTRACT FROM AUTHOR]

Human organoids stand at the forefront of basic and translational research, providing experimentally tractable systems to study human development and disease. These stem cell-derived, in vitro cultures can generate a multitude of tissue and organ types, including distinct brain regions and sensory systems. Neural organoid systems have provided fundamental insights into molecular mechanisms governing cell fate specification and neural circuit assembly and serve as promising tools for drug discovery and understanding disease pathogenesis. In this review, we discuss several human neural organoid systems, how they are generated, advances in 3D imaging and bioengineering, and the impact of organoid studies on our understanding of the human nervous system. • Human stem cell-derived neural organoids stand at the forefront of basic and translational research, providing experimentally tractable systems to study human development and disease. • Neural organoid systems have provided fundamental insights into molecular mechanisms governing cell fate specification and neural circuit assembly. • Neural organoids serve as promising tools for drug discovery and understanding disease pathogenesis. • This review describes the generation of several human neural organoid systems, advances in 3D imaging and bioengineering, and the impact of organoid studies on our understanding of the human nervous system. [ABSTRACT FROM AUTHOR]

Large‐scale genetic studies revealed SCN2A as one of the most frequently mutated genes in patients with neurodevelopmental disorders. SCN2A encodes for the voltage‐gated sodium channel isoform 1.2 (Nav1.2) expressed in the neurons of the central nervous system. Homozygous knockout (null) of Scn2a in mice is perinatal lethal, whereas heterozygous knockout of Scn2a (Scn2a+/−) results in mild behavior abnormalities. The Nav1.2 expression level in Scn2a+/− mice is reported to be around 50–60% of the wild‐type (WT) level, which indicates that a close to 50% reduction of Nav1.2 expression may not be sufficient to lead to major behavioral phenotypes in mice. To overcome this barrier, we characterized a novel mouse model of severe Scn2a deficiency using a targeted gene‐trap knockout (gtKO) strategy. This approach produces viable homozygous mice (Scn2agtKO/gtKO) that can survive to adulthood, with about a quarter of Nav1.2 expression compared to WT mice. Innate behaviors like nesting and mating were profoundly disrupted in Scn2agtKO/gtKO mice. Notably, Scn2agtKO/gtKO mice have a significantly decreased center duration compared to WT in the open field test, suggesting anxiety‐like behaviors in a novel, open space. These mice also have decreased thermal and cold tolerance. Additionally, Scn2agtKO/gtKO mice have increased fix‐pattern exploration in the novel object exploration test and a slight increase in grooming, indicating a detectable level of repetitive behaviors. They bury little to no marbles and have decreased interaction with novel objects. These Scn2a gene‐trap knockout mice thus provide a unique model to study pathophysiology associated with severe Scn2a deficiency. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE. Jingliang Zhang et al. examine how dysfunctional PKA signaling impacts neuronal activity and seizure susceptibility in a mouse model of temporal lobe epilepsy. Their data suggest that autophosphorylation of the RIIβ subunit regulates neuronal excitability, and may act as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Cancer is a public health problem and the main cause of human mortality and morbidity worldwide. Complete removal of tumors and metastatic lymph nodes in surgery is significantly beneficial for the prognosis of patients. Tumor-targeted, near-infrared fluorescent (NIRF) imaging is an emerging field of real-time intraoperative cancer imaging based on tumor-targeted NIRF dyes. Targeted NIRF dyes contain NIRF fluorophores and specific binding ligands such as antibodies, peptides and small molecules. The present article reviews recently updated tumor-targeted NIRF dyes for the molecular imaging of malignant tumors in the preclinical stage and clinical trials. The strengths and challenges of NIRF agents with tumor-targeting ability are also summarized. Smaller ligands, near infrared II dyes, dual-modality dyes and activatable dyes may contribute to quicker, deeper, stronger imaging in the nearest future. In this review, we highlighted tumor-targeted NIRF dyes for fluorescence-guided surgery and their potential clinical translation. [ABSTRACT FROM AUTHOR]

This article discusses the development and validation of a prognostic model for predicting flares in generalized pustular psoriasis (GPP). GPP is a rare auto-inflammatory skin disease characterized by recurrent flares of neutrophil-filled sterile pustules. These flares can have a significant impact on the daily activities and overall well-being of patients and can lead to life-threatening complications if left untreated. The study aimed to identify risk factors for GPP flare and construct a predictive model based on clinical characteristics to forecast the occurrence of flares. The model incorporates four features: history of psoriasis vulgaris, risky alcohol use, temperature at fever, and albumin levels. The model achieved promising results in internal and external validation processes and may provide critical insights into GPP flare patterns and help prevent such episodes. [Extracted from the article]

Objective Our study aimed to evaluate the association between the multidrug resistance 1 (MDR 1 )/cytochrome P450 3A4 (CYP3A4)/μ-opioid receptor (OPRM 1 ) gene polymorphisms and the post-caesarean analgesic effect of fentanyl on Chinese women. Methods We recruited 240 patients who received lower segment caesarean section surgeries. Sanger sequencing was used to analyze the MDR 1 1236C > T/CYP3A4*1G/OPRM 1 A118G polymorphisms. We evaluated post-operative fentanyl consumption and the effect of intravenous analgesia in patients with different genotypes. Results 1. Subjects with the TT genotype at the 1236C > T polymorphism in the MDR 1 gene consumed significantly more fentanyl than that consumed by subjects with the CC and CT genotypes in the first post-operative 24 h and 48 h ( P  < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually increased immediately after surgery and in the first post-operative 24 h. 2. Subjects with the CYP3A4*1G/*1G genotype needed less fentanyl to achieve pain control than that needed by subjects carrying the CYP3A4*1/*1 and CYP3A4*1/*1G genotypes in the first post-operative 24 h and 48 h ( P  < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually decreased immediately after surgery and in the first post-operative 24 h. 3. Subjects with the GG genotype at the A118G polymorphism in the OPRM 1 gene consumed significantly more fentanyl than that consumed by subjects with the AA and AG genotypes in the first post-operative 24 h and 48 h ( P  < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually increased immediately after surgery and in the first post-operative 24 h. 4. There were no significant differences in the adverse reactions to fentanyl in patients with different genotypes ( P   >   0.05 ). Conclusion These results indicated that the MDR 1 /CYP3A4/OPRM 1 gene polymorphisms influenced the fentanyl consumption and the physiological effects of intravenous analgesia in the Chinese women who received lower segment caesarean section surgeries. Moreover, the present study provides an important foundation and theoretical evidence for the gene-directed rationalization and individualization of medication before caesarean section surgeries. [ABSTRACT FROM AUTHOR]

An extracellular chondroitinase ABC (ChSase ABC, EC 4.2.2.4) produced by cultivating Acinetobacter sp. C26, was purified to homogeneity from the supernatant by ammonium sulfate fractionation, Q-Sepharose Fast Flow and Sephadex G-100 chromatography. The 76 kDa enzyme was purified 48.09-fold to homogeneity with specific activity of 348.64 U/mg, Using the chondroitin sulfate A (CS-A) as substrate, the maximal reaction rate (Vmax) and Michaelis-Menten constant (Km) of ChSase ABC were found to be 10.471 μmol/min/ml and 0.105 mg/ml, respectively. The enzyme showed the highest activity at the optimal conditions of pH 6.0 and 42 ∘C, respectively. This enzyme was stable at pH 5–10, 5–9 and 5–7 at 4 °C, 37 °C and 42 °C, respectively. Investigation about thermal stability of ChSase ABC displayed that it was stable at 37 °C. ChSase ABC activity was increased in presence of Na + , K + , Mn 2+ , 1,10-phenanthrolin and strongly inhibited by Cu 2+ , Hg 2+ , Al 3+ and SDS. These properties suggested that ChSase ABC from Acinetobacter sp. C26 bring promising prospects in medical and industry applications. [ABSTRACT FROM AUTHOR]

Objectives: Our purpose was to compare the performance of prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) traditional fixed threshold (FT) and newly established Prostate Imaging Reporting and Data System (PI-RADS)-based segmented threshold (ST) for diagnosing clinically significant prostate cancer (csPCa). Methods: The study retrospectively included 218 patients who underwent multiparametric magnetic resonance imaging (mpMRI) and PSMA-PET examination for suspected prostate cancer (PCa) from January 2018 to November 2021. Lesions with Gleason score ≥ 3 + 4 were diagnosed as csPCa. In PSMA-PET maximum standardized uptake value (SUVmax), the FT for all the lesions and STs for lesions with different PI-RADS score for diagnosing csPCa were determined by receiver operating characteristic (ROC) curves analysis and compared with Z test. The McNemar test was used to compare sensitivity and specificity. Results: Among the 218 patients, there were 113 csPCa and 105 non-csPCa. The PSMA-PET FT was SUVmax > 5.3 (area under the curve, AUC = 0.842) and STs for PI-RADS 3/4/5 were SUVmax > 4.2/5.7/6.0 (AUCs = 0.870/0.867/0.882), respectively. The AUC of PSMA-PET ST was higher than that of PSMA-PET FT (0.872 vs. 0.842), especially for PI-RADS 3 (0.870 vs. 0.653). Multimodality diagnostic criteria combining PSMA-PET ST and PI-RADS scores of mpMRI was established and its AUC was higher than that of PSMA-PET ST (0.893 vs. 0.872) and significantly higher than that of PSMA-PET FT (0.893 vs. 0.842) with an improvement in sensitivity (93% vs. 78%, p < 0.05) without significantly sacrificing specificity (86% vs. 91%, p > 0.05). Conclusions: For diagnosing csPCa, PI-RADS-based PSMA-PET segmented threshold achieved better performance than traditional fixed threshold, especially for PI-RADS 3 lesions. Multimodality diagnostic criteria demonstrated higher diagnostic performance than segmented threshold and significantly better than PSMA-PET fixed threshold for detecting csPCa. [ABSTRACT FROM AUTHOR]

Prostate specific membrane antigen positron emission tomography (PSMA PET) is an excellent molecular imaging technique for prostate cancer. Currently, PSMA PET for patients with primary prostate cancer is supplementary to conventional imaging techniques, according to guidelines. This supplementary function of PSMA PET is due to a lack of systematic review of its strengths, limitations, and potential development direction. Thus, we review PSMA ligands, detection, T, N, and M staging, treatment management, and false results of PSMA PET in clinical studies. We also discuss the strengths and challenges of PSMA PET. PSMA PET can greatly increase the detection rate of prostate cancer and accuracy of T/N/M staging, which facilitates more appropriate treatment for primary prostate cancer. Lastly, we propose that PSMA PET could become the first-line imaging modality for primary prostate cancer, and we describe its potential expanded application. [ABSTRACT FROM AUTHOR]

Abstract: The functionality and reliability of Li-ion batteries as major energy storage devices have received more and more attention from a wide spectrum of stakeholders, including federal/state policymakers, business leaders, technical researchers, environmental groups and the general public. Failures of Li-ion battery not only result in serious inconvenience and enormous replacement/repair costs, but also risk catastrophic consequences such as explosion due to overheating and short circuiting. In order to prevent severe failures from occurring, and to optimize Li-ion battery maintenance schedules, breakthroughs in prognostics and health monitoring of Li-ion batteries, with an emphasis on fault detection, correction and remaining-useful-life prediction, must be achieved. This paper reviews various aspects of recent research and developments in Li-ion battery prognostics and health monitoring, and summarizes the techniques, algorithms and models used for state-of-charge (SOC) estimation, current/voltage estimation, capacity estimation and remaining-useful-life (RUL) prediction. [Copyright &y& Elsevier]

• Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. • Bi-parameter MRI could detect the zonal Heterogeneity of PCa by ADC value. • Zonal location diagnosed by bpMRI could bring added value in predicting PCa patients of ISUP ≥ 3 grades. Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. This passage aims to preliminarily evaluate the relationship between the zonal heterogeneity of PCa quantitatively assessed by bpMRI and pathological risk stratification of the primary lesion. This prospective study was conducted from January 2019 to February 2023. A total of 113 PCa patients whose bpMRI data indicated that the lesions located in only 1 single zone of the prostate were selected. A transrectal ultrasound and MRI-targeted biopsy were performed to verify the bpMRI results, and then radical prostatectomy (RP) was performed in 3 weeks after the biopsy. The high-risk (HR) group was defined as ISUP grades ≥ 3. Binary regression was performed to evaluate if the zonal heterogeneity could be an independent predictor of the HR group. The receiver operator characteristic (ROC) curve was performed to analyze the added value of zonal location in predicting the HR group. PSA, T staging, and ISUP grades, incidence of positive surgical margins were significantly lower in the TZ PCa, and the ADCmin, and ADCmean values in the TZ PCa were significantly higher (all P <.01). The zonal heterogeneity could independently predict the HR group patients (OR: 5.170 [1.663-16.067], P =.005) and improve the predicting efficiency of HR patients (AUC 0.824, 95% CI, 0.741-0.889). BpMRI could quantitively assess the zonal heterogeneity of PCa precisely and increase the predicting efficacy of HR patients , which can provide better help for clinical individualized treatment. It has not been discussed that whether bi-parameter MRI (bpMRI) could be a detector of prostate cancer (PCa) zonal heterogeneity. The prospective-multicenter study recruited 113 peripheral zone (PZ)-only or transitional zone (TZ)-only PCa patients diagnosed by bpMRI. PZ-located patients showed a malignant clinical-pathological character. PZ-located lesion diagnosed by bpMRI could help predict the ISUP ≥ 3 patients. BpMRI could precisely detect PCa zonal heterogeneity quantitively. [ABSTRACT FROM AUTHOR]

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration‐resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron‐dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane‐coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M‐gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA‐specific, CRPC‐targeting platform for ferroptosis induction with increased efficacy and safety. [ABSTRACT FROM AUTHOR]

Purpose: Pharmaceutical buffer systems, especially for injectable biologics such as monoclonal antibodies, are an important component of successful FDA-approved medications. Clinical studies indicate that buffer components may be contributing factors for increased injection site pain. Methods: To determine the potential nociceptive effects of clinically relevant buffer systems, we developed an in vitro multi-electrode array (MEA) based recording system of rodent dorsal root ganglia (DRG) sensory neuron cell culture. This system monitors sensory neuron activity/firing as a surrogate of nociception when challenged with buffer components used in formulating monoclonal antibodies and other injectable biologics. Results: We show that citrate salt and citrate mannitol buffer systems cause an increase in mean firing rate, burst frequency, and burst duration in DRG sensory neurons, unlike histidine or saline buffer systems at the same pH value. Lowering the concentration of citrate leads to a lower firing intensity of DRG sensory neurons. Conclusion: Increased activity/firing of DRG sensory neurons has been suggested as a key feature underlying nociception. Our results support the utility of an in vitro MEA assay with cultured DRG sensory neurons to probe the nociceptive potential of clinically relevant buffer components used in injectable biologics. [ABSTRACT FROM AUTHOR]

Endothelial cell inflammation and oxidative stress are critical to developing diabetic vascular complications. GRP78 translocation to the cell surface has been observed in different types of endothelial cells, but the potential role of cell surface GRP78 in modulating endothelial inflammation and oxidative stress remains uncertain. In this study, we investigated whether inhibiting cell surface GRP78 function using a novel anti-GRP78 monoclonal antibody (MAb159) could suppress high glucose (HG)-induced endothelial inflammation and oxidative stress. Our findings demonstrated that the expression of cell surface GRP78 was increased in HG-treated HUVECs. Inhibition of cell surface GRP78 using MAb159 attenuated HG-induced endothelial injury, inflammation and oxidative stress, while activation of GRP78 by recombinant GRP78 further amplified HG-induced endothelial damage, inflammation and oxidative stress. Additionally, we discovered that cell surface GRP78 promoted HG-induced inflammation and oxidative stress by activating the TLR4/NF-κB signalling pathway. Moreover, HG-induced GRP78 translocation to the cell surface is dependent on ER stress. Our data demonstrate that targeting cell surface GRP78 could be a promising therapeutic strategy for mitigating endothelial injury, inflammation and oxidative stress. • Expression of cell surface GRP78 was increased in high glucose-treated HUVECs. • Inhibition of cell surface GRP78 using MAb159 attenuated HG-induced endothelial injury, inflammation and oxidative stress. • Cell surface GRP78 promoted HG-induced inflammation and oxidative stress by activating the TLR4/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Recently traffic induced geotechnical problems have been receiving increasing attention. Yet the silty clay from the third layer of Shanghai, which is within the main influence depth of traffic loading and overconsolidated, had not been sufficiently studied. A series of monotonic and cyclic undrained triaxial tests were thus carried out on reconstituted Shanghai silty clay with various overconsolidation ratios (OCRs). The silty clay specimens showed phase transformation behavior, which was characterized by stages of initial contraction, temporary phase transformation and later dilation. Such behavior could be termed as a transitional mode between the behavior seen for typical clays and that for sands. The dilation behavior in the later stage was shown more significant for overconsolidated specimens. Six different failure criteria were employed to study the friction angle. There was no observable effect of OCR on the friction angle for this silty clay as if it was a granular material. The undrained shear strength could be normalized with only a small deviation. The normalized shear strength increased with OCR and it behaved more as typical silts than clays at high OCRs. The development of permanent strain under cyclic loading was shown to depend significantly on the cyclic stress ratio and OCR. A higher OCR resulted in smaller permanent and resilient strains, and the decrease of the permanent strain with OCR was remarkable for lightly overconsolidated specimens. Such effect of OCR would be more significant in real soil condition where the soil is at least partially drained. Highlights • The mechanical behavior of Shanghai silty clay is first extensively studied. • The silty clay shows phase transformation behavior, differently from typical clays. • No observable effect of OCR is found on the friction angle of this silty clay. • For undrained shear strength, it behaves more like a typical silt at high OCRs. • A higher OCR results in smaller permanent and resilient strains under cyclic loading. [ABSTRACT FROM AUTHOR]

Extracellular polysaccharide (EPS) produced by Bacillus megaterium GJT321 was isolated from fermentation broth and further purified by gel filtration chromatography. The molecular weight of EPS was estimated as 1946 kDa by gel permeation chromatography (GPC), so this EPS was determined as macromolecular polysaccharide. Fourier transform infrared spectrometry (FT-IR) showed that the kind of heterocyclic compound composing EPS was furanose. The structural characteristics of EPS were investigated by means of enzymatic method, electrospray ionization mass spectrometry (ESI–MS) and NMR spectra analysis. The structure elucidation of the EPS was accomplished, and it was β − (2, 6) −D− fructofuranose, namely levan. [ABSTRACT FROM AUTHOR]

Purpose: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies.A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies.The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873–0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0–40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5–40% for csPCa in both the development and validation cohorts.The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.Methods: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies.A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies.The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873–0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0–40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5–40% for csPCa in both the development and validation cohorts.The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.Results: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies.A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies.The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873–0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0–40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5–40% for csPCa in both the development and validation cohorts.The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.Conclusion: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies.A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies.The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873–0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0–40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5–40% for csPCa in both the development and validation cohorts.The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa. [ABSTRACT FROM AUTHOR]

Understanding the dissipation effect of mangroves is essential for assessing the performance of mangrove forests in mitigating damages from storm surges. In this study, a novel local-drag-force-based approach is proposed for simulating wave propagation through mangrove forests using a 3D-SPH numerical model. In the proposed model, the mangrove forest is represented as emergent rigid cylinders. The dissipation effect of each individual mangrove is defined by the local drag force, which is smoothly distributed around each individual mangrove based on SPH kernel function. The proposed model allows for the consideration of mangrove distribution without the need to simulate flow around each mangrove individually. The proposed model is validated using laboratory wave flume experiment results. The wave-damping coefficient β exhibits a linear relationship with the mangrove total longitudinal cross-sectional area A total. The presence of an open channel within mangrove patch weakens the wave-attenuation ability due to the decrease in A total. The wave-driven flow field shows that the horizontal flow velocity is greater along the open channel, signifying that the effect of mangrove distribution is considered in the proposed model, e.g. the effect of the open channel is simulated. The obtained numerical results show promising potential of the proposed model to investigate the wave dissipation by mangrove forests and corresponding 3D flow field. • A novel local-drag-force-based approach is proposed for simulating wave dissipation by mangrove forests. • Riemann-SPH combined with weighted kernel gradient correction (WKGC) is implemented to simulate 3D stable regular waves. • A linear relationship between wave-damping coefficient and total longitudinal cross-sectional area of the mangrove patch is observed. • The open channel within a mangrove patch tends to weaken the wave-attenuation ability and increase the horizontal wave-driven flow velocity. [ABSTRACT FROM AUTHOR]

The oblique interactions between internal solitary waves frequently occur in the ocean owing to their different propagation directions after originated from more than one potential generation sites, which can further be modulated and reshaped by the varying topography and the Earth's rotation. Here a variable-coefficient rotational Kadomtsev–Petviashvili (KP) equation is devoted to investigate the interaction of initial X-shaped waves in presence of the respective one-dimensional (1D) and two-dimensional (2D) slope-shelf topography and rotations at different latitudes. Based on the analytical solutions, the long-time results can be classified as three types depending on the initial amplitudes and oblique angles. Then, numerical results suggest that the sufficiently shallow 1D shoaling topography can render polarity change, which reshapes the waveform of oblique interactions to resemble webs composed of straight wave crest lines. If the rotation were also taken into account, then the nonlinear interactions are inhibited resulting in less waves in the eventual long-time wave packets and more junction points in the webs of waveform. More importantly, the combined effect of rotation and localized small and narrow canyons and plateaus resting on 1D shoaling topography can significantly modulate the waveforms induced by oblique interactions to make them more like rank-ordered wavetrains. • The topography and Earth's rotation jointly render web structures on oblique ISW interactions. • The 2D shoaling topography distorts the wave crestlines leading to interactions with peripheric waves. • The shoaling topography can lead to the generation of dispersive shock waves. [ABSTRACT FROM AUTHOR]

This paper considers intelligent diagnosis of structural cracks emanating from rows of rivet holes in thin metallic plates using active sensing network. Lamb waves are generated using actuators and propagate across the plates and received by sensors. We extract an effective feature called energy ratio change from time domain signals using wavelet transform. Then we develop neural networks using this feature to diagnose health condition. The sensing network is optimized by developing a mixed integer programming model. The results show that our method can effectively detect cracks and determine their locations, and the number of sensors of the sensing network can be significantly reduced while keeping high diagnostic accuracy. Important insights are also obtained such as in which area the sensing network has the weakest diagnostic capability. [ABSTRACT FROM AUTHOR]

Abstract: Two novel compensation schemes based on accelerometer measurements to attenuate the effect of external vibrations on mechanical systems are proposed in this paper. The first compensation algorithm exploits the neural network as the feedback-feedforward compensator whereas the second is the neural network feedforward compensator. Each compensation strategy includes a feedback controller and a neural network compensator with the help of a sensor to detect external vibrations. The feedback controller is employed to guarantee the stability of the mechanical systems, while the neural network is used to provide the required compensation input for trajectory tracking. Dynamics knowledge of the plant, disturbances and the sensor is not required. The stability of the proposed schemes is analyzed by the Lyapunov criterion. Simulation results show that the proposed controllers perform well for a hard disk drive system and a two-link manipulator. [Copyright &y& Elsevier]

Bladder cancer (BLCA) is the most common malignancy whose early diagnosis can ensure a better prognosis. However, the predictive accuracy of commonly used predictors, including patients' general condition, histological grade, and pathological stage, is insufficient to identify the patients who need invasive treatment. Autophagy is regarded as a vital factor in maintaining mitochondrial function and energy homeostasis in cancer cells. Whether autophagy-related genes (ARGs) can predict the prognosis of BLCA patients deserves to be investigated. Based on BLCA data retrieved from the Cancer Genome Atlas and ARGs list obtained from the Human Autophagy Database website, we identified prognosis-related differentially expressed ARGs (PDEARGs) through Wilcox text and constructed a PDEARGs-based prognostic model through multivariate Cox regression analysis. The predictive accuracy, independent forecasting capability, and the correlation between present model and clinical variables or tumor microenvironment were evaluated through R software. Enrichment analysis of PDEARGs was performed to explore the underlying mechanism, and a systematic prognostic signature with nomogram was constructed by integrating clinical variables and the aforementioned PDEARGs-based model. We found that the risk score generated by PDEARGs-based model could effectively reflect deteriorated clinical variables and tumor-promoting microenvironment. Additionally, several immune-related gene ontology terms were significantly enriched by PDEARGs, which might provide insights for present model and propose potential therapeutic targets for BLCA patients. Finally, a systematic prognostic signature with promoted clinical utility and predictive accuracy was constructed to assist clinician decision. PDEARGs are valuable prognostic predictors and potential therapeutic targets for BLCA patients. [ABSTRACT FROM AUTHOR]

Purpose: Although visual deficits can be observed at any stage of schizophrenia, few studies have focused on visual cortex alterations in individuals at high risk of schizophrenia. This study aimed to investigate the pathological changes of the primary visual cortex in a prenatal mouse model of MK801-induced high-risk schizophrenia. Methods: The high-risk schizophrenia model was generated by MK801 injection into pregnant mice. The male offspring without schizophrenia-like behaviors in early adulthood were defined as the high-risk mouse model of schizophrenia (HRMMS) and divided into two groups. One HRMMS group received the antipsychotic agent risperidone beginning at postnatal week 4 and another group did not receive any treatment. After treatment for 4 weeks, in vivo two-photon calcium imaging was performed to characterize the primary visual cortex activity. The novel object recognition test and the prepulse inhibition apparatus test were also implemented to assess the cognitive and behavioral performance, respectively. Results: Both groups of HRMMS mice, with or without antipsychotic treatment, had decreased neuronal calcium activity, demonstrating primary visual cortex impairment. More notably, antipsychotic treatment did not normalize the impaired neuronal activities in the primary visual cortex. Correspondingly, the treatment did not improve the cognitive or behavioral impairment. Conclusion: Visual cortex impairment might be a prominent feature of individuals at high risk of schizophrenia that cannot be normalized by early treatment with antipsychotic medication, indicating the presence of independent regulatory pathways for visual perception disturbance in schizophrenia. Thus, visual system impairment in schizophrenic patients must be further studied. [ABSTRACT FROM AUTHOR]

The study was aimed at assessing the diagnostic performance of 68Ga-PSMA-617 PET/CT in the detection of prostate cancer (PCa) in patients with a prostate-specific antigen (PSA) level of 4–20 ng/ml and to compare its efficacy with that of multiparametric MRI (mpMRI). We analyzed the data of 67 consecutive patients with PSA levels of 4–20 ng/ml who almost simultaneously underwent 68Ga-PSMA-617 PET/CT and mpMRI. 68Ga-PSMA-617 PET/CT and mpMRI diagnostic performances were compared via receiver operating characteristic (ROC) curve analysis. Of the 67 suspected PCa cases, 33 had pathologically confirmed PCa. 68Ga-PSMA-617 PET/CT showed a patient-based sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) of 87.88%, 88.24%, 87.88%, and 88.24%, respectively. The corresponding values for mpMRI were 84.85%, 52.94%, 63.64%, and 78.26%. The area under the curve values for 68Ga-PSMA-617 PET/CT and mpMRI were 0.881 and 0.689, respectively. 68Ga-PSMA-617 PET/CT showed a better diagnostic performance than mpMRI in the detection of PCa in patients with PSA levels of 4–20 ng/ml. [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorder is a prevalent and life-threatening illness in modern society. The susceptibility to major depressive disorder is profoundly influenced by environmental factors, such as stressful lifestyle or traumatic events, which could impose maladaptive transcriptional program through epigenetic regulation. However, the underlying molecular mechanisms remain elusive. Here, we examined the role of histone crotonylation, a novel type of histone modification, and chromodomain Y-like protein (CDYL), a crotonyl-coenzyme A hydratase and histone methyllysine reader, in this process. Methods We used chronic social defeat stress and microdefeat stress to examine the depressive behaviors. In addition, we combined procedures that diagnose behavioral strategy in male mice with histone extraction, viral-mediated CDYL manipulations, RNA sequencing, chromatin immunoprecipitation, Western blot, and messenger RNA quantification. Results The results indicate that stress-susceptible rodents exhibit lower levels of histone crotonylation in the medial prefrontal cortex concurrent with selective upregulation of CDYL. Overexpression of CDYL in the prelimbic cortex, a subregion of the medial prefrontal cortex, increases microdefeat-induced social avoidance behaviors and anhedonia in mice. Conversely, knockdown of CDYL in the prelimbic cortex prevents chronic social defeat stress–induced depression-like behaviors. Mechanistically, we show that CDYL inhibits structural synaptic plasticity mainly by transcriptional repression of neuropeptide VGF nerve growth factor inducible, and this activity is dependent on its dual effect on histone crotonylation and H3K27 trimethylation on the VGF promoter. Conclusions Our results demonstrate that CDYL-mediated histone crotonylation plays a critical role in regulating stress-induced depression, providing a potential therapeutic target for major depressive disorder. [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic performance of 68Ga-PSMA PET/CT for detecting suspected prostate cancer (PCa) and to compare it with that of two cancer-predicting nomograms. Methods: We performed a retrospective analysis of 146 consecutive patients with suspected PCa based on symptoms or elevated total prostate-specific antigen (tPSA) levels who underwent 68Ga-PSMA PET/CT and histopathologic examinations from April 2017 to April 2018 in a large tertiary care hospital in China. The 68Ga-PSMA PET/CT results (PCa or benignancy) were evaluated by two experienced nuclear medicine specialists. The risk of positive PCa was evaluated using ERSPC and PCPT nomograms. The diagnostic performances of 68Ga-PSMA PET/CT and that of the two nomograms were compared via receiver operating characteristic (ROC) curve analysis, decision curve analysis, and logistic regression. Results: A total of 58 patients with tPSA of 0.4–50 ng/ml were included in the final analysis; PCa diagnosis was confirmed in 37 patients and excluded in 21 patients. ROC analysis showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 68Ga-PSMA PET/CT were 91.67, 81.82, 89.19, and 85.71%, respectively, in per-patient analyses. 68Ga-PSMA PET/CT exhibited a higher AUC (0.867) than those of ERSPC-RC3 (0.855) and PCPT-RC (0.770). The net benefit of 68Ga-PSMA PET/CT was greatest for patients within threshold probabilities of 15–90%. Among the 58 patients, 11 (19%) biopsies suggested by ERSPC-RC3 were unnecessary and could have been avoided if judged by the 68Ga-PSMA PET/CT results. Multivariate analysis revealed that the maximum standardised uptake value (SUVmax) and prostate volume were significant predictive factors for positive PCa results. Conclusion: In suspected PCa patients with tPSA of 0.4–50 ng/ml, 68Ga-PSMA PET/CT outperformed the nomograms in predicting cancer and reducing unnecessary biopsies. In addition, the risk of PCa was positively correlated with a higher SUVmax and lower prostate volume, which could help clinicians in making preliminary estimates of individual cancer risk, monitoring 68Ga-PSMA PET/CT false-positive results and making biopsy decisions in daily medical practice. [ABSTRACT FROM AUTHOR]

Fibroblasts are critical pro-inflammatory regulators in chronic inflammatory and fibrotic skin diseases. However, fibroblast heterogeneity and the absence of a unified cross-disease taxonomy have hindered our understanding of the shared/distinct pathways in non-communicable skin inflammation. By integrating 10× single-cell data from 75 skin samples, we constructed a single-cell atlas across inflammatory and fibrotic skin diseases and identified 9 distinct subsets of skin fibroblasts. We found a shared subset of CCL19+ fibroblasts across these diseases, potentially attracting and educating immune cells. Moreover, COL6A5+ fibroblasts were a distinct subset implicated in the initiation and relapse of psoriasis, which tended to differentiate into CXCL1+ fibroblasts, inducing neutrophil chemotaxis and infiltration; while CXCL1+ fibroblasts exhibited a more heterogeneous response to certain inflammatory conditions. Differentiation trajectory and regulatory factors of these fibroblast subsets were also revealed. Therefore, our study presents a comprehensive atlas of skin fibroblasts and highlights pathogenic fibroblast subsets in skin disorders. • We developed a single-cell atlas of dermal fibroblasts and identified 9 distinct fibroblast subsets across chronic inflammatory (psoriasis, atopic dermatitis, lupus) and fibrotic skin disorders. • A shared subset of CCL19+ fibroblasts was found to mediate skin inflammation in all the diseases examined. • COL6A5+ fibroblasts were a distinct subset in psoriasis that had the ability to differentiate into CXCL1+ fibroblasts. • COL6A5+ fibroblasts were implicated in the recurrence of psoriasis based on the non-lesional and relapsing skin data. [ABSTRACT FROM AUTHOR]

Vascular endothelial dysfunction (VED) is the onset event of cardiovascular complications in type 2 diabetes mellitus. Ginsenoside Rg1 (Rg1) can improve the cardiovascular system, but its mechanism in diabetic vascular endothelial dysfunction has received little attention. Male calpain-1-knockout and wild-type C57BL/6 J mice were intraperitoneally injected with streptozotocin and treated with Rg1 (10 and 20 mg/kg) for 8 weeks. Human aortic endothelial cells (HAECs) were incubated with high glucose (HG) and were pretreated with Rg1 (10, 20 μM), MDL-28170 (calpain-1 inhibitor), LY-333531 (PKC-β inhibitor), NAC (ROS inhibitor) and calpain-1 overexpression. Then, factors related to mitochondrial dysfunction, oxidative stress and VED were measured. The administration of Rg1 and calpain-1 knockout ameliorated diabetic mitochondrial dysfunction, oxidative stress and VED and inhibited the calpain-1/ROS/PKC-β axis. LY-333531 and NAC treatment restored destructive endothelium-dependent vasodilation in mice with diabetes, while pyrogallol (ROS agonist), PMA (PKC-β agonist) or L-NAME (eNOS inhibitor) treatment abrogated the protective effect of Rg1 against diabetic endothelial dysfunction. The administration of Rg1, MDL-28170, LY-333531 and NAC improved mitochondrial dysfunction, oxidative stress and VED, whereas the overexpression of calpain-1 amplified mitochondrial dysfunction, oxidative stress and VED and further upregulated the expression of PKC-β in HAECs exposed to HG. Overexpression of calpain-1 abrogated the protective effect of Rg1 against HG-induced oxidative stress and VED. These findings reveal that Rg1 can protect against VED by suppressing the calpain-1/ROS/PKC-β axis and alleviating the development of mitochondrial dysfunction and oxidative stress. [ABSTRACT FROM AUTHOR]

Key points: ERG3 channels have a high expression level in the central nervous system. Knockdown of ERG3 channels enhances neuronal intrinsic excitability (caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials) in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. The expression of ERG3 protein is reduced in human and mouse hippocampal epileptogenic foci. Knockdown of ERG3 channels in hippocampus enhanced seizure susceptibility, while mice treated with the ERG channel activator NS‐1643 were less prone to epileptogenesis. The results provide strong evidence that ERG3 channels have a crucial role in the regulation of neuronal intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells and are critically involved in the onset and development of epilepsy. Abstract: The input–output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements. Profound changes in intrinsic properties have been observed in various physiological and pathological processes, such as learning, memory and epilepsy. However, the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully understood. Here, we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Knock‐down of ERG3 channels significantly increases neuronal intrinsic excitability, which is mainly caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials. Interestingly, the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe epilepsy. Moreover, ERG3 channel knockdown in hippocampus significantly enhanced seizure susceptibility, while mice treated with the ERG channel activator NS‐1643 were less prone to epileptogenesis. Taken together, our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of epilepsy. ERG3 channels may thus be a novel therapeutic target for the prevention of epilepsy. [ABSTRACT FROM AUTHOR]

Yield, physico-chemical and gelling properties of agar from Gracilaria tenuistipitata as affected by alkaline treatments conditions at various levels were investigated. Agar with alkaline treatment, especially at higher alkali concentration, showed better gelling property as evidenced by higher gel strength (624.4–1250.8 g cm −2 ), gelling (28.1–43.2 °C) and melting (96.4–99.6 °C) temperatures with coincidentally increased 3,6-anhydrogalactose content (38.93%–44.78%) and decreased sulphate content (7.79%–3.48%), but reducing yield (22.34%–15.61%). Treatment temperature or time has a positive influence on agar properties in appropriate range, while higher temperature or longer time might result in yield reducing. Alkaline treatment with 6% alkali at 80 °C for 1.5 h was the optimal pretreatment process, with the gel strength reached to 1068.15 g cm −2 and obtained high yield (23.14%), which are higher than the earlier reports. Meanwhile, the study of the correlation between physico-chemical and gelling properties of agar confirmed that the gel strength has negative correlation relationship with sulphate content (p < 0.05), while positive correlation with 3,6-anhydrogalactose content (p < 0.01) and gelling (p > 0.05) or melting temperatures (p > 0.05). Overall, this work suggested the feasibility of the exploitation of G . tenuistipitata for production of superior quality agar, which are mainly from Gelidium species. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) affects ~2% of the population in the US, and monogenic forms of ASD often result in the most severe manifestation of the disorder. Recently, SCN2A has emerged as a leading gene associated with ASD, of which abnormal sleep pattern is a common comorbidity. SCN2A encodes the voltage-gated sodium channel Na V 1.2. Predominantly expressed in the brain, Na V 1.2 mediates the action potential firing of neurons. Clinical studies found that a large portion of children with SCN2A deficiency have sleep disorders, which severely impact the quality of life of affected individuals and their caregivers. The underlying mechanism of sleep disturbances related to Na V 1.2 deficiency, however, is not known. Using a gene-trap Scn2a -deficient mouse model (Scn2a trap), we found that Scn2a deficiency results in increased wakefulness and reduced non-rapid-eye-movement (NREM) sleep. Brain region-specific Scn2a deficiency in the suprachiasmatic nucleus (SCN) containing region, which is involved in circadian rhythms, partially recapitulates the sleep disturbance phenotypes. At the cellular level, we found that Scn2a deficiency disrupted the firing pattern of spontaneously firing neurons in the SCN region. At the molecular level, RNA-sequencing analysis revealed differentially expressed genes in the circadian entrainment pathway including core clock genes Per1 and Per2. Performing a transcriptome-based compound discovery, we identified dexanabinol (HU-211), a putative glutamate receptor modulator, that can partially reverse the sleep disturbance in mice. Overall, our study reveals possible molecular and cellular mechanisms underlying Scn2a deficiency-related sleep disturbances, which may inform the development of potential pharmacogenetic interventions for the affected individuals. • Scn2a deficiency results in sleep disturbance in mice. • Scn2a deficiency-related sleep disturbance involves suprachiasmatic nucleus. • Scn2a deficiency disrupts neuronal firing in suprachiasmatic nucleus. • Scn2a deficiency results in a change of core clock gene expression. • Transcriptome-based molecule discovery identifies HU-211 to alleviate sleep disturbance. [ABSTRACT FROM AUTHOR]

Abstract: This paper proposes an approach to detecting and characterizing structural cracks emanating from rows of rivet holes in thin metallic plates using lamb wave, wavelet transform and neural networks. When lamb waves propagate through rows of holes, there exist strong wave interferences among different transmitted waves which make health diagnosis complicated. An active sensing network is mounted on the plate and wavelet transform is used to extract a robust and effective feature called energy ratio change from time domain signals. The relationship between energy ratio change and the crack characteristics is analyzed and the effective detection paths are found out. Neural networks are then developed using the feature to diagnose health condition in stages. One neural network is first used to diagnose plate integrity. If cracks are detected, then the second neural network is called to determine their locations. The method is first examined in simulation data, then the NNs trained by simulation data are used to diagnose real plates. The results shows that the method can effectively detect cracks and identify their locations in both simulation and experimental data, hence demonstrating the feasibility of using the method to develop built-in real time intelligent diagnosis systems. [Copyright &y& Elsevier]

Synchronous writing in BPMR has been recognized as a crucial yet challenging issue. It has been shown that position jitter and switching field distribution can lead to spatially uncorrelated random write failures. On top of that, the spindle speed variation and other mechanical vibration may lead to accumulative phase drift during writing which causes long streams of insertion/deletion write failures. However no experiments have been conducted to quantitatively testify the later concept, nor provide precise written-in error characteristics when both phenomena are present in BPMR systems. This gap of understanding is filled by this work through spinstand and hard disk measurements and analysis. It is shown that timing inaccuracy not only introduces insertion/deletion write failures but also given rise to substantial increase of substitution (random) write errors. It also reveals that instead of the commonly accused spindle motor speed variation, timing error in BPMR based HDD may well be the result of estimation error due to limited or improperly configured timing preambles. [ABSTRACT FROM AUTHOR]

The acidic polysaccharide ulvan extracted from the cell wall of the green algae Ulva is a good ligand for metal ions. Therefore, the adsorption properties of the U. clathrata derived ulvan toward Ca(II), Zn(II), Co(II), Cu(II), and Cr(III) were investigated in this study. The results demonstrate that ulvan exhibited good metal ion adsorption capacity at pH 7 and 50 °C. These adsorption processes can largely be explained by the Freundlich isotherm model and the pseudo-second-order kinetic model. The order of the adsorption capacity and affinity is as follows: Cr(III) > Cu(II) > Zn(II) ≈ Co(II) > Ca(II) and Cr(III) > Zn(II) > Co(II) ≈ Cu(II) > Ca(II). Furthermore, structural characterization revealed that the hydroxyl and carboxyl groups were the main functional groups involved in metal ion binding. Unlike the divalent metal ions, Cr(III) can trigger crosslinking of the ulvan chains, and its adsorption capacity was approximately 4.0 mmol/g. • Metal adsorption processes of ulvan were well described by Freundlich isotherm model. • The order of adsorption affinity was Cr(III) > Zn(II) > Co(II) ≈ Cu(II) > Ca(II). • Hydroxyl and carboxyl groups on the ulvan chains involved in metal ion binding. • Cr(III) can trigger cross-linking of the ulvan chains. [ABSTRACT FROM AUTHOR]