Redistribution of lamina-associated domains reshapes binding of pioneer factor FOXA2 in development of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus and the elderly, impacting 40% of individuals over 70. Regulation of heterochromatin at the nuclear lamina has been associated with aging and age-dependent metabolic changes. We previously showed that changes at the lamina in aged hepatocytes and laminopathy models lead to redistribution of lamina-associated domains (LADs), opening of repressed chromatin, and up-regulation of genes regulating lipid synthesis and storage, culminating in fatty liver. Here, we test the hypothesis that change in the expression of lamina-associated proteins and nuclear shape leads to redistribution of LADs, followed by altered binding of pioneer factor FOXA2 and by up-regulation of lipid synthesis and storage, culminating in steatosis in younger NAFLD patients (aged 21-51). Changes in nuclear morphology alter LAD partitioning and reduced lamin B1 signal correlate with increased FOXA2 binding before severe steatosis in young mice placed on a western diet. Nuclear shape is also changed in younger NAFLD patients. LADs are redistrubted and lamin B1 signal decreases similarly in mild and severe steatosis. In contrast, FOXA2 binding is similar in normal and NAFLD patients with moderate steatosis and is repositioned only in NAFLD patients with more severe lipid accumulation. Hence, changes at the nuclear lamina reshape FOXA2 binding with progression of the disease. Our results suggest a role for nuclear lamina in etiology of NAFLD, irrespective of aging, with potential for improved stratification of patients and novel treatments aimed at restoring nuclear lamina function.

KBMeasure: small sample in-situ damage automatic measurement method based on the combination of keypoints detection and binocular 3D reconstruction for aero-engine blades.

Size is one of the important bases for the level assessment of aero-engine blade damage and the disposal method selection for damaged blades. Therefore, research on in-situ damage measurement of aero-engine blades is conducted in this paper. We break the inherent pipeline of "3D reconstruction and manual annotation of keypoints" in traditional damage measurement methods, and propose an in-situ damage automatic measurement method (KBMeasure) based on the combination of damage keypoints intelligent detection and binocular 3D reconstruction. KBMeasure replaces the manual annotation of damage keypoints, improves the damage measurement efficiency, and reduces the dependence on professional inspectors. The proposed method also overcomes the problem of high computational cost and low efficiency caused by redundant 3D reconstruction of the entire damaged area. For the characteristics of large changes in damage scale, low image resolution, the requirement of high-precision keypoints positioning, limited annotated data, and lightweight deployment in aero-enginge blade damage measurement task, a novel blade damage keypoints detection model (DKeyDet) with top-down framework is designed by introducing coordinate classification, semi-supervised learning, and knowledge distillation. Then, intersecting optical axis binocular model is used to estimate the spatial coordinates of the detected keypoints and compute the size of damage. The keypoints detection average precision (AP) and average recall (AR) of our method are 87.6 and 91.3, and the damage measurement size error (SE) is 0.08, which is superior to existing methods. This research provides a new theoretical support for in-situ damage automatic measurement for aero-engine in service, and provides what we believe is a novel idea for damage measurement of industrial components in other fields.

Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat. Due to the asymptomatic nature of the disease and lack of curative treatment modalities, the 5-y survival rate of PDAC patients is one of the lowest of any cancer type. The recurrent genetic alterations in PDAC are yet to be targeted. Therefore, identification of effective drug combinations is desperately needed. Here, we performed an in vivo CRISPR screen in an orthotopic patient-derived xenograft (PDX) model to identify gene targets whose inhibition creates synergistic tumor growth inhibition with gemcitabine (Gem), a first- or second-line chemotherapeutic agent for PDAC treatment. The approach revealed protein arginine methyltransferase gene 5 (PRMT5) as an effective druggable candidate whose inhibition creates synergistic vulnerability of PDAC cells to Gem. Genetic depletion and pharmacological inhibition indicate that loss of PRMT5 activity synergistically enhances Gem cytotoxicity due to the accumulation of excessive DNA damage. At the molecular level, we show that inhibition of PRMT5 results in RPA depletion and impaired homology-directed DNA repair (HDR) activity. The combination (Gem + PRMT5 inhibition) creates conditional lethality and synergistic reduction of PDAC tumors in vivo. The findings demonstrate that unbiased genetic screenings combined with a clinically relevant model system is a practical approach in identifying synthetic lethal drug combinations for cancer treatment.

High-Precision DOA Estimation Based on Synthetic Aperture and Sparse Reconstruction.

The direction-of-arrival (DOA) estimation is predominantly influenced by the antenna's aperture size. However, space constraints on flight platforms often necessitate the use of antennas with smaller apertures and fewer array elements. This inevitably imposes limitations on the DOA estimation's resolution and degrees of freedom. To address these precision constraints, we introduce an accurate DOA estimation method based on spatial synthetic aperture model. This method adopts a two-stage strategy to ensure both efficiency and precision in DOA estimation. Initially, the orthogonal matching pursuit (OMP) reconstruction algorithm processes the original aperture data, providing a rough estimate of target angles that guides the aircraft's flight direction. Subsequently, the early estimations merge with the aircraft's motion space samples, forming equivalent spatially synthesized array samples. The refined angle estimation then employs the OMP-RELAX algorithm. Moreover, with the off-grid issue in mind, we devise an estimation method integrating Bayesian parameter estimation with dictionary sequence refinement. The proposed technique harnesses the spatial synthetic aperture for pinpoint estimation, effectively addressing the challenges of atomic orthogonality and angular off-grid on estimation accuracy. Importantly, the efficiency of deploying sparse reconstruction for angle estimation is bolstered by our phased strategy, eliminating the necessity for fine grid analysis across the entire observation scene. Moreover, the poor estimation accuracy caused by coherent source targets and angular-flickering targets is improved by sparse reconstruction. Through simulation and experiment, we affirm the proposed method's efficacy in angle estimation. The results indicate that target angle estimation errors are limited to within 1°. Furthermore, we assess the impact of variables such as target state, heading angle, spatial sampling points, and target distance on the estimation accuracy of our method, showcasing its resilience and adaptability.

Covalent Bonding and Coulomb Repulsion-Guided AuNP Array: A Tunable and Reusable Substrate for Metabolomic Characterization of Lung Cancer Patient Sera.

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has gained increased attention in the metabolic characterization of human biofluids. However, the stability and reproducibility of nanoparticle-based substrates remain two of the biggest challenges in high-salt environments. Here, by controlling the extent of Coulomb repulsion of 26 nm positively charged AuNPs, a homogeneous layer of covalently bonded AuNPs on a coverslip with tunable interparticle distances down to 16 nm has been successfully fabricated to analyze small biomolecules in human serum. Compared with the self-assembled AuNP array, the covalently bonded AuNP array showed superior performances on stability, reproducibility, and sensitivity in high-salt environments. The stable attachment of AuNPs maintained a detection reproducibility with a RSD less than 12% and enabled the reusability of the array for 10 experiments without significant signal deterioration (<15%) and carryover effects. Moreover, the closely positioned AuNPs allowed the coupling of photoinduced plasmons to generate an enhanced electric field, which promotes the generation of excited electrons to facilitate the desorption/ionization processes instead of the heat dissipation, thus enhancing the detection sensitivity with detection limits down to the femtomole level. Combined with machine learning methods, the AuNP array has been successfully applied to discover seven biomarkers for differentiating early-stage lung cancer patients from healthy controls. It is anticipated that this simple approach of developing robust AuNP arrays can also be extended to other types of NP arrays for wider applications of SALDI-MS technology.

RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA.

BACKGROUND: RNPC1 is reported to act as a tumor suppressor by binding and regulating the expression of target genes in various cancers. However, the role of RNPC1 in gastric cancer and the underlying mechanisms are still unclear. METHODS: Gastric cancer cells were stably transfected with lentivirus. Proliferation, migration, invasion, cell cycle in vitro and tumorigenesis in vivo were used to assess the role of RNPC1. Quantitative real-time PCR, western blotting and immunohistochemistry were used to detect the relationship between RNPC1 and aurora kinase B (AURKB). RNA immunoprecipitation (RIP), RNA electrophoretic mobility shift assays (REMSAs), and dual-luciferase reporter assays were used to identify the direct binding sites of RNPC1 with AURKB mRNA. A CCK-8 assay was conducted to confirm the function of AURKB in RNPC1-induced growth promotion. RESULTS: High RNPC1 expression was found in gastric cancer tissues and cell lines and was associated with high TNM stage. RNPC1 overexpression significantly promoted the proliferation, migration, and invasion of gastric cancer cells. Knockdown of RNPC1 could impede gastric cancer tumorigenesis in nude mice. AURKB expression was positively related to RNPC1. RNPC1 directly binds to the 3'-untranslated region (3'-UTR) of AURKB and enhances AURKB mRNA stability. AURKB reversed the proliferation induced by RNPC1 in gastric cancer cells. RNPC1 resulted in mitotic defects, aneuploidy and chromosomal instability in gastric cancer cells, similar to AURKB. CONCLUSION: RNPC1 acts as an oncogene in gastric cancer by influencing cell mitosis by increasing AURKB mRNA stability, which may provide a potential biomarker and a therapeutic target for gastric cancer.

Reverse "cheese wire" fenestration for abdominal aortic dissection repair: a case report and literature review.

BACKGROUND: Aortic dissection is one of the most common emergency condition leading to internal organs or lower limb ischemia and aortic rupture. Herein, we described a reverse "cheese wire" endovascular fenestration repair (CWFER) in a patient with complicated abdominal aortic dissection which had never been reported. CASE PRESENTATION: A 62-year-old male presented abdominal tear-like pain and acute ischemia of the right lower extremity during the endovascular treatment of celiac trunk aneurysms. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) showed abdominal aortic type B dissection with acute ischemia of the right lower extremity preoperatively. After a detailed preoperative examination, the patient then was performed a reverse CWFER. So far, the patient has been followed-up for 6 months, postoperative CTA demonstrated good stent-graft expansion and perfusion of bilateral common iliac arteries; also, no endoleak was detected. CONCLUSIONS: The right iliac artery in this patient supplied by false lumen, which lead to acute ischemia of the right lower extremity, needed to be treated as an emergency and dealt with promptly. CWFER is a very high-risk treatment that requires the rich experience of vascular surgeon and accurate assessment of aortic dissection. After interventional treatment, the patient recovered uneventfully after 6 months' follow-up.

A Novel Baseline-Free Damage Detection Method Based on Path Scanning of Lamb Waves Using Mobile Transducers.

The baseline-free damage detection method of Lamb waves has the potential to obtain damage information efficiently in plate structures through damage scattering signals. However, the missing detection of damage occurs occasionally due to the angular scattering characteristic of Lamb waves. To solve this problem, a novel baseline-free damage detection approach based on path scanning at the detection region edges using mobile piezoelectric transducers is proposed herein. Several sensing points carrying separated damage scattering signals were picked out from the scanning paths. By removing the direct and boundary reflected signals, the damage signals were extracted and exported to a delay-and-sum imaging method to locate the damage. Two experiments with and without mobile transducers were conducted to validate the proposed method on an aluminum plate with artificially fabricated crack-like damage. The results show that the proposed baseline-free approach can locate the crack-like damage with high accuracy and efficiency and avoid potential loss of damage information. The proposed baseline-free method provides a novel and practical damage detection approach when considering the angular-dependent scattering characteristic of Lamb waves and can enhance the credibility of results in damage detection.

VMFNet: visual-microwave dual-modality real-time target detection model for detecting damage to curved radar absorbing materials.

Damage to radar absorbing materials (RAMs) reduces the stealth capabilities and battlefield survivability of the equipment. Research on RAM damage detection technology is key to outfield equipment maintenance. In this paper, an intelligent RAM damage detection method based on visual and microwave modalities is proposed. A compressed sensing planar-scanning microwave imaging method based on a range migration algorithm (RMA) imaging operator and fast Gaussian gridding nonuniform fast Fourier transform (FGG-NUFFT) is proposed, achieving high imaging quality and speed. A dual-modality, curved RAM dataset (DCR dataset) is constructed, composed of visual images and microwave images showing two kinds of damage: round shedding and strip cracks. A new dual-modality target detection model, the visual-microwave fusion network (VMFNet), is designed to detect RAM damage. Its mean average precision (mAP) reaches 81.87%, and its inference speed reaches 35.91 fps. A visual network (VisNet) and microwave network (MicNet) are designed as the backbone of VMFNet for extracting the visual and microwave features of RAMs. A path aggregation network (PANet) unit is designed to fuse the multiscale features of the two modalities, resulting in good retention of shallow-level features and high detection accuracy. The head contains different receptive fields and outputs three scales of detection results, effectively detecting damage of different sizes.

Intelligent recognition of composite material damage based on deep learning and infrared testing.

Composite materials are commonly used in aircraft, and the integrity of these materials affects both flight and safety performance. Damage detection technology involving infrared nondestructive testing has played an important role in damage detection in aircraft composite materials. Traditional manual detection methods are inefficient, and the use of intelligent detection methods can effectively improve detection efficiency. Due to the diverse types of damage that can occur in composite materials, this damage is difficult to distinguish solely from infrared images. The introduction of infrared signals, which is temporal signals, provides the possibility of judging the type of damage. In this paper, a 1D-YOLOv4 network is established. The network is based on the YOLOv4 network and adds a changing neck and a 1D-CNN for improvement. Testing shows that the algorithm can identify infrared images and infrared signals in composite materials. Its recognition accuracy is 98.3%, with an AP of 91.9%, and a kappa of 0.997. Comparing the network in this paper with networks such as YOLOv3, YOLOv4 and YOLOv4+Neck, the results show that the proposed network is more effective. At the same time, the detection effects of the original data, the fitted data, the first derivative data and the second derivative data are studied, and the detection effect of the first derivative data has the best outcome.

Recognition and detection of aero-engine blade damage based on Improved Cascade Mask R-CNN.

Aero-engine blades are an integral part of the aero-engine, and the integrity of these blades affects the flight performance and safety performance of an aircraft. The traditional manual detection method is time-consuming, labor-intensive, and inefficient. Hence, it is particularly important to use intelligent detection methods to detect and identify damage. In order to quickly and accurately identify the damage of the aero-engine blades, the present study proposes a network based on the Improved Cascade Mask R-CNN network-to establish the damage related to the aero-engine blades and detection models. The model can identify the damage type and locate and segment the area of damage. Furthermore, the accuracy rate can reach up to 98.81%, the Bbox-mAP is 78.7%, and the Segm-mAP is 77.4%. In comparing the Improved Cascade Mask R-CNN network with the YOLOv4, Cascade R-CNN, Res2Net, and Cascade Mask R-CNN networks, the results revealed that the network used in the present is excellent and effective.

Infrared and ultrasonic intelligent damage recognition of composite materials based on deep learning.

With the large-scale application of composite materials in military aircraft, various composite material detection technologies with infrared nondestructive and ultrasonic nondestructive testing as the core have played an important role in detecting composite material component damage in military aircraft. At present, the damage of composite materials is mostly recognized manually, which is time-consuming, laborious, and inefficient. It can effectively improve detection efficiency and accuracy by using intelligent detection methods to detect and recognize damage. Moreover, the effect of infrared detection is significantly reduced with increasing detection depth, while ultrasonic detection has shallow-blind areas. A cascade fusion R-CNN network is proposed in order to comprehensively identify composite material damage. This network realizes the intelligent fusion recognition of infrared and ultrasonic damage images of composite materials. The network is based on a cascade R-CNN network, using fusion modules and BiFPN for improvement. For the infrared image and ultrasonic C-scan image data set established in this paper, the algorithm can identify the type and location of damage detected by infrared and ultrasonic testing. Its recognition accuracy is 99.3% and mean average precision (mAP) is 90.4%. In the detection process, the characteristics of infrared and ultrasonic images are used to realize the recognition of damage depth. Compared to SSD, YOLOv4, faster R-CNN and cascade R-CNN, the network proposed in this paper is better and more effective.

Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple-negative breast cancer cells.

Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.

TRPC1 inhibits the proliferation and migration of estrogen receptor-positive Breast cancer and gives a better prognosis by inhibiting the PI3K/AKT pathway.

PURPOSE: Previous studies have indicated that transient receptor potential (TRP) channels can influence cancer development. The TRPC subfamily consists of seven subtypes, TRPC1 - TRPC7. Interestingly, the expression levels of TRPC1 have been shown to be totally different in different breast cancer cell lines. Nevertheless, the underlying mechanism remains unknown. In this study, we explore the significance of TRPC1 expression in breast cancer. METHODS: Immunohistochemical TRPC1 staining was performed in 278 samples. TRPC1 expression in different breast tissues were examined. Then, the influence of TRPC1 on migration, invasion and proliferation was explored. We analyzed the protein of TRPC1 by Western blot to prove which pathway may be involved in. Finally, we use online database to predict the prognosis of TRPC1 in breast cancer. RESULTS: Through immunohistochemistry and in vitro experiments, we found that the expression level of TRPC1 was higher in breast cancer cells as compared with that in normal breast epithelial cells. Moreover, the expression level of TRPC1 was different between estrogen receptor-positive (ER +) and -negative (ER -) breast cancer. It was shown that TRPC1 inhibited MCF7 cell proliferation, migration, and invasion in vitro. Western blotting revealed that TRPC1 inhibited the PI3K/AKT pathway and epithelium-mesenchymal transformation, leading to subsequent inhibition of cell proliferation and metastasis. In luminal A and luminal B patients, those with high TRPC1 expression had a better prognosis. On the contrary, in basal-like and triple-negative breast cancer (TNBC) subtypes, patients with high-TRPC1 expression had a worse prognosis. CONCLUSIONS: We confirmed that TRPC1 was high expression in breast cancer. Overexpression of TRPC1 inhibits proliferation and migration of ER + breast cancer and gives a better prognosis by inhibiting PI3K/AKT pathway activation. TRPC1 may be an independent prognostic predictor in breast cancer patients.

CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations.

CRISPR-Cas9-induced DNA damage may have deleterious effects at high-copy-number genomic regions. Here, we use CRISPR base editors to knock out genes by changing single nucleotides to create stop codons. We show that the CRISPR-STOP method is an efficient and less deleterious alternative to wild-type Cas9 for gene-knockout studies. Early stop codons can be introduced in ∼17,000 human genes. CRISPR-STOP-mediated targeted screening demonstrates comparable efficiency to WT Cas9, which indicates the suitability of our approach for genome-wide functional screenings.

Surface optimization of gold nanoparticle mass tags for the sensitive detection of protein biomarkers via immuno-capture LI-MS.

HPV-induced cervical cancer is one of the most lethal cancers. Therefore, the development of a reliable and accurate method for the early diagnosis of HPV infections is highly important. Here, gold nanoparticles (AuNPs) were utilized as mass tags in an immuno-capture LI-MS assay for the detection of HPV marker proteins. Through the optimization of the amount of antibodies and surface charges on AuNPs, high antigen detection efficiency with minimal non-specific binding was achieved. With optimized antibody-conjugated AuNPs, low attomole amount of HPV proteins in HeLa cell lysate was quantified.

A Retrospective Study Comparing the Effectiveness and Safety of EXOSEAL Vascular Closure Device to Manual Compression in Patients Undergoing Percutaneous Transbrachial Procedures.

BACKGROUND: This study aimed to assess the safety and efficacy of EXOSEAL vascular closure device (EVCD) insertion by comparing its performance with manual compression (MC) in achieving hemostasis at the brachial artery puncture site. METHODS: A retrospective study of brachial artery access by using either MC or EVCD for achieving hemostasis from March 2016 to October 2017 was conducted. Patients with Stanford type B aortic dissection (TBAD) undergoing percutaneous transbrachial procedures were included. Time to hemostasis (TTH) was the primary efficacy end point. Seven-day incidence of major access site-related complications was the primary safety end point. TTH and major and minor complications associated with treatment of these 2 groups were also evaluated. RESULTS: A total of 157 patients with TBAD undergoing percutaneous transbrachial procedures entered the analysis. Of these, 107 patients underwent EVCD insertion and 50 patients underwent MC. The baseline characteristics of the 2 groups were similar. TTH was significantly shorter for EVCD over MC (P < 0.05). The TTH ≥10 min in the MC group was 100.0% (n = 50), but in the EVCD group, it was ≤2 min, 87.9% (n = 107); 2-5 min, 7.5% (n = 107); and ≥10 min, 4.7% (n = 107). The EVCD group had several major complications, while the MC group had none. Two patients (1.9%, n = 107) required vascular repair, one patient (0.6%, n = 107) required blood transfusion, and 1 patient (0.6%, n = 107) developed upper limb numbness and weakness after EVCD deployment. Minor complication such as the occurrence of hematoma (≤5 cm) in the MC group was 4 (8.0%) but was also 4 (3.7%) in the EVCD group, showing statistically significant difference (P = 0.030). The incidence of ecchymosis was 8 (7.5%) in the EVCD group when compared with 13 (26.0%) in the MC group, which showed statistically significant difference (P = 0.001). Other major and minor complications showed no significant differences between these 2 groups. CONCLUSIONS: After invasive procedures by 6F percutaneous access via the brachial artery in preprocedurally fully anticoagulated patients, TTH was significantly reduced in patients who underwent EVCD when compared with patients who underwent MC. MC is a safer and more convenient way to achieve hemostasis but has higher incidence of minor complications.

Outcome of Surgical Treatment for Carotid Body Tumors in Different Shambling Type Without Preoperative Embolization: A Single-Center Retrospective Study.

BACKGROUND: Carotid body tumor (CBT) is the most common head and neck paragangliomas. Surgical resection is the golden standard management for CBT. While preoperative embolization is still controversial, long-term outcomes and perioperative results are still deficient. We, here, presented the outcomes of surgical treatment for CBT without preoperative embolization at our institution. METHODS: In this retrospective study, we collected data from 101 patients who received surgical treatment for CBTs without preoperative embolization from 2011 to 2016. In addition, we attempted to conduct 2 years of follow-up under the guidance of both neurologist and vascular surgeon. Patients' demographics, clinical characteristics, complications, and follow-up results were all analyzed with descriptive statistics. RESULTS: Complete resection of the CBT was achieved in 101 cases (100%). Postoperative adverse events (AEs) mostly observed during hospitalization were as follows: tongue bias (I: 4, 36.4%; II: 8, 19.5%; III: 13, 26.5%), hoarseness (I: 1, 9.1%; II: 4, 9.8%; III: 7, 14.3%), dysphagia (I: 0; II: 2, 4.9%; III: 7, 14.3%), and hematoma (I: 0; II: 0; III: 1, 2.0%). No other serious AEs were observed. The total incidence of AEs in type I patients was 5 (45.5%), 14 (34.1%) in type II, and 28 (57.1%) in type III, and the type III group has significantly higher than the other two groups. At the end of 2 years of follow-up, there were no AEs in type I patients. The number of patients with AEs in type III was greater than that in type II, although there was no significant difference. Based on our findings, 3 most commonly injured cranial nerves (CNs) after surgical resection of CBT were CN XII (hypoglossal nerve, 21.9%), CN X (vagus nerve, 20.3%), and recurrent laryngeal nerve (18.8%). CONCLUSIONS: Surgical management without preoperative embolization for CBT patients is a safe and effective therapeutic approach.

Upregulation of miR-330-5p is associated with carotid plaque's stability by targeting Talin-1 in symptomatic carotid stenosis patients.

BACKGROUND: The aim of this study was to investigate the relationship between Talin-1 and stability of carotid atherosclerosis plaque and also find out the role of miRNA, as an upstream regulator, in regulating the expression level of Talin-1. METHODS: Human carotid plaques were obtained from 20 symptomatic carotid stenosis patients who underwent carotid endarterectomy (CEA) in our hospital between October 2014 and August 2017. Western blot analysis and immunohistochemistry was carried out to detect the distribution and expression level of Talin-1 in each plaque sample. The content of miRNAs in carotid plaque was decected by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the relative expression levels were calculated by 2-△△Ct method after the (cycle threshold) Ct value (power amplification knee point) was obtained. Dual-luciferase reporter assays were applied to verify the successful transfections. Finally, we compared all the groups with independent-samples t-test and one-way analysis of variance (ANOVA). RESULTS: Talin-1 was significantly downregulated in human unstable carotid plaque samples compared with stable carotid plaques (P < 0.05), and the distribution of Talin-1 was mainly found in the fibrous cap of carotid plaque. The overexpression of miRNA-330-5p was found in unstable carotid plaque, which significantly induced the inhibition of expression level of Talin-1. CONCLUSION: Upregulated miR-330-5p may lead to unstable carotid plaques by targeting Talin-1 in symptomatic carotid stenosis patients. This might be a new target for the treatment of atherosclerotic diseases through future studies.

Large-Scale in Vitro Transcription, RNA Purification and Chemical Probing Analysis.

BACKGROUND/AIMS: RNA elements such as catalytic RNA, riboswitch, microRNA, and long non coding RNA (lncRNA) play central roles in many cellular processes. Studying diverse RNA functions require large quantities of RNA for precise structure analysis. Current RNA structure and function studies can benefit from improved RNA quantity and quality, simpler separation procedure and enhanced accuracy of structural analysis. METHODS: Here we present an optimized protocol for analyzing the structure of any RNA, including in vitro transcription, size-exclusion chromatography (SEC) based denaturing purification and improved secondary structure analysis by chemical probing. RESULTS: We observed that higher Mg2+, nucleoside triphosphate (NTP) concentrations and longer reaction duration can improve the RNA yield from in vitro transcription, specifically for longer and more complicated constructs. Our improved SEC-based denaturing RNA purification effectively halved the experiment duration and labor without introducing any contaminant. Finally, this study increased the accuracy and signal-to-noise ratio (SNR) of selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemical probing for analyzing RNA structure. CONCLUSION: Part or all of our modified method can improve almost any RNA-related study from protein-RNA interaction analysis to crystallography.