Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

The unreliable prediction of the low frequency components from inverted acoustic impedance causes uncertainty in quantitative seismic interpretation. To address this issue, we first calculate various seismic and geological attributes that contain low frequency information, such as relative geological age, interval velocity, and integrated instantaneous amplitude. Then, we develop a method to predict the low frequency content of seismic data using these attributes, their high frequency components, and recurrent neural networks. Next, we test how to predict the low frequency components using stacking velocity obtained from velocity analysis. Using all the attributes and seismic data, we propose a supervised deep learning method to predict the low frequency components of the inverted acoustic impedance. The results obtained in both synthetic and real data cases show that the proposed method can improve the prediction accuracy of the low frequency components of the inverted acoustic impedance, with the best improvement in a real data example of 57.7% compared with the impedance predicted using well log interpolation.

The three-phase separator was perforated after four years’ service. The perforation position is at the bottom of the vessel under the baffle plate in an oil transfer station. The cause of perforation was investigated by chemical analysis using a direct-reading spectrometer, microstructure examined by optical microscope(OM), and lab simulated corrosion experiments by electrochemical workstation, and the corrosion products examined with scanning electron microscopy(SEM), energy dispersive spectrometer(EDS) in this paper. The analyses indicated that the coating at the base of the pressure vessel failed and this led to the direct exposure of the carbon steel plate to the corrosive medium. The electrical contact between the carbon steel and the stainless steel, sets up a galvanic cell that accelerated the corrosion of the pressure vessel which eventually led leads to the perforation.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Hypoglossal nerve stimulator (HGNS) is a minimally invasive device used for treating obstructive sleep apnea (OSA). The conventional implantable HGNS is a device that consists of a stimuli generator, a breathing sensor, and electrodes connected to the hypoglossal nerve via leads. However, this implant is bulky and causes significant trauma. In this paper, we propose a minimally invasive HGNS based on an electrocardiogram (ECG) sensor and a wireless power transfer (WPT), consisting of a wearable breathing monitor and an implantable stimulator. The breathing external monitor utilizes an ECG sensor to identify abnormal breathing patterns associated with OSA with 88.68$\%$ accuracy, achieved through the utilization of a Convolutional Neural Network (CNN) algorithm. With a skin thickness of 5mm and a receiving coil diameter of 9mm, the power conversion efficiency was measured at 31.8$\%$. The implantable device, on the other hand, is composed of a front-end CMOS Power Management Module (PMM), a Binary Phase Shift Keying (BPSK)-based data demodulator, and a bipolar biphasic current stimuli generator. The PMM, with a silicon area of 0.06 $mm^2$ (excluding pads), demonstrates a power conversion efficiency of 77.5$\%$ when operating at a receiving frequency of 2 MHz. Furthermore, it offers three-voltage options (1.2V, 1.8V, and 3.1V). Within the data receiver component, a low-power BPSK demodulator has been ingeniously incorporated, consuming only 42 $\mu$W when supplied with a voltage of 0.7V. The performance is achieved through the implementation of the self-biased phase-locked loop (PLL) technique. The stimuli generator delivers biphasic constant currents, providing a 5-bit programmable range spanning from 0 to 2.4 mA. The functionality of proposed ECG and WPT-based HGNS was validated, representing a highly promising solution for the effective management of OSA, all while minimizing trauma and space requirements.