Visual analysis of the research frontiers, hotspots and trends of exercise therapy intervention in tumor-related sleep-wake disorders.

Objective: To systematically understand the research frontiers, hotspots and development trends of exercise therapy in the intervention of tumor-related sleep-wake disorders, and to provide scientific basis for follow-up research. Methods: Downloaded the original research papers on February 26, 2024, from the Web of Science core collection database, on tumor-associated sleep-wake disorders. The data that met the inclusion criteria were imported into the Bibliometric Analysis Platform (http://biblimetric.com), CiteSpace 6.3.R1 and VOSviwer1.6.20 software for visual analysis, and imported into Excel2021. Scientometric analysis was performed with Oringin2021 and PyCharm Community Edition 2022.1.3. Results: A total of 512 original research papers on tumor-related sleep-wake disorders were obtained. The most influential countries in the subject area are the United States, Spain and German, the institutions are the University of California System, Sun Yat Sen University and Northwestern University, et al., the authors are Berger AM, Aaronson NK, Bower JE, et al., and the journals are Cancer, Brit J Cancer and Cancer Nurs. The co-cited references suggest that the current research frontier in the field mainly involves the level, place and program of exercise therapy, including the relationship between physical activity, sedentary behavior and cancer prevention and control. The results of co-occurrence keyword network analysis showed that quality of life, physical activity, breast cancer, exercise, fatigue, and survivors may be the research hotspots in this field, with breast cancer, health, aerobic exercise, adults, and chemotherapy being the most popular. Conclusions: The number of papers published and the research enthusiasm in this field show a steady upward trend. However, there is a lack of influential institutions and scholars, and there is relatively little research collaboration across countries/regions/institutions. The scientific research influence of institutions and scholars in most European and American countries/regions is significantly ahead of that of institutions and scholars in Asian and African countries/regions. But Sun Yat Sen University in China is a relatively active and influential scientific research institution in recent years, which is worthy of attention. In addition, the research frontier of this discipline is the level, place and program of exercise therapy auxiliary intervention, and the research hotspots involve breast cancer, health, aerobic exercise, adults, chemotherapy, et al. Their clinical efficacy needs to be further demonstrated in multi-center, large-sample and high-quality prospective studies.

Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a fearful disease that can cause a variety of immune events. Nevertheless, precise immune-related mechanisms have yet to be systematically elucidated. This study aimed to identify immune-related signatures using machine learning and to validate them with animal experiments and single cell analysis. METHODS: In this study, we screened 24 differentially expressed genes (DEGs) while identifying immune-related signatures that may play a key role in IS development through a comprehensive strategy between least absolute shrinkage and selection operation (LASSO) regression, support vector machine (SVM) and immune-related genes. In addition, we explored immune infiltration using the CIBERSORT algorithm. Finally, we performed validation in mouse brain tissue and single cell analysis. RESULTS: We identified 24 DEGs for follow-up analysis. ID3 and SLC22A4 were finally identified as the better immune-related signatures through a comprehensive strategy among DEGs, LASSO, SVM and immune-related genes. RT-qPCR, western blot, and immunofluorescence revealed a significant decrease in ID3 and a significant increase in SLC22A4 in the middle cerebral artery occlusion group. Single cell analysis revealed that ID3 was mainly concentrated in endothelial_2 cells and SLC22A4 in astrocytes in the MCAO group. A CIBERSORT finds significantly altered levels of immune infiltration in IS patients. CONCLUSIONS: This study focused on immune-related signatures after stroke and ID3 and SLC22A4 may be new therapeutic targets to promote functional recovery after stroke. Furthermore, the association of ID3 and SLC22A4 with immune cells may be a new direction for post-stroke immunotherapy.

DPAM-PSPNet: ultrasonic image segmentation of thyroid nodule based on dual-path attention mechanism.

Objective.Deep learning has demonstrated its versatility in the medical field, particularly in medical image segmentation, image classification, and other forms of automated diagnostics. The clinical diagnosis of thyroid nodules requires radiologists to locate nodules, diagnose conditions based on nodule boundaries, textures and their experience. This task is labor-intensive and tiring; therefore, an automated system for accurate thyroid nodule segmentation is essential. In this study, a model named DPAM-PSPNet was proposed, which automatically segments nodules in thyroid ultrasound images and enables to segment malignant nodules precisely.Approach.In this paper, accurate segmentation of nodule edges is achieved by introducing the dual path attention mechanism (DPAM) in PSPNet. In one channel, it captures global information with a lightweight cross-channel interaction mechanism. In other channel, it focus on nodal margins and surrounding information through the residual bridge network. We also updated the integrated loss function to accommodate the DPAM-PSPNet.Main results.The DPAM-PSPNet was tested against the classical segmentation model. Ablation experiments were designed for the two-path attention mechanism and the new loss function, and generalization experiments were designed on the public dataset. Our experimental results demonstrate that DPAM-PSPNet outperforms other existing methods in various evaluation metrics. In the model comparison experiments, it achieved performance with an mIOU of 0.8675, mPA of 0.9357, mPrecision of 0.9202, and Dice coefficient of 0.9213.Significance.The DPAM-PSPNet model can segment thyroid nodules in ultrasound images with little training data and generate accurate boundary regions for these nodules.

Compound organic acid could improve the growth performance, immunity and antioxidant properties, and intestinal health by altering the microbiota profile of weaned piglets.

This study aimed to investigate the impact of compound organic acid (COA) and chlortetracycline (CTC) on serum biochemical parameters, intestinal health, and growth performance of weaned piglets. Twenty-four piglets (24 d of age) were randomly allocated into three treatments with eight replicate pens (one piglet per pen). Feed the basal diet or a diet containing 3,000 mg/kg COA or 75 mg/kg CTC, respectively. Results showed that both COA and CTC significantly increased average daily gain and reduced diarrhea rates (P < 0.05). They also upregulated serum total antioxidant capacity and downregulated serum interleukin (IL-10) levels (P < 0.05), increased crude protein digestibility and propionic acid concentration in the colon, and decreased spermidine and putrescine contents (P < 0.05). Intestinal microbiota analysis revealed that both COA and CTC increased the Shannon and Chao1 index and decreased the relative abundance of Blautia and Roseburia, but increased the relative abundance of Clostridium-sensu-stricto-1. Correlation analysis indicated that Clostridium-sensu-stricto-1 may be closely related to inflammation levels and microbial metabolites in piglets. Based on the results, COA may be a potential substitute for CTC to reduce antibiotic use and biogenic amine emission while improving piglet growth and intestinal health.

Weaned piglets face challenges due to their underdeveloped digestive system, resulting in high gastrointestinal tract pH and insufficient enzyme secretion. To address this issue, we found supplementing piglet diets with 3,000 mg/kg of compound organic acid positively impacted the immune and antioxidant levels of piglets, promoted their intestinal health, improved nutrient digestibility, and enhanced their overall growth performance. These benefits were attributed to the regulation of intestinal microbiota by the compound organic acid. By improving piglet health and growth, this research offers a potential solution to the challenges of piglet weaning stress.

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice.

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear. METHODS: Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet-induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed. RESULTS: We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a ß-aminopropionitrile diet, Marfan mice with fibrillin-1 haploinsufficiency (Fbn1C1041G/+), and ApoE-/- mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in ß-aminopropionitrile-treated mice, Fbn1C1041G/+ mice, and Ang II-infused ApoE-/- mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that FcγR (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated FcγR-mediated ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or FcγR deficiency. CONCLUSIONS: This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid-lowering drug may represent a promising therapeutic approach for TAAD.

Bilateral Diffuse Uveal Melanocytic Proliferation Initially Presented as Glaucoma.

PURPOSE: To report a bilateral diffuse uveal melanocytic proliferation (BDUMP) patient whose initial presentation was glaucoma. METHODS: Clinical review of a BDUMP case. RESULTS: A 65-year-old woman presented with ocular pain of the left eye for 1 day and vision loss of the right eye for 1 week. An ophthalmological examination revealed increased intraocularr pressure in the left eye and shallow anterior chamber in both eyes. BDUMP was diagnosed following a series of auxiliary examinations. After 1.5 years of follow-up, progressive cataracts appeared, and the patient accepted cataract surgery in both eyes. Visual acuity improved from light perception to 20/100 in both eyes 1.5 years after cataract surgery, but declined to light perception again at the last follow-up. CONCLUSION: BDUMP can be initially presented as glaucoma, and cataract surgery can be considered in BDUMP patients in order to improve the patients' quality of life, even if exudative retinal detachment exists.

Neuroprotective effects of a new triterpenoid from edible mushroom on oxidative stress and apoptosis through the BDNF/TrkB/ERK/CREB and Nrf2 signaling pathway in vitro and in vivo.

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties. In this study, 10 secondary metabolites (1-10), including a new lanostane triterpenoid named 2α-hydroxy-inotodiol (2α-HI, 1), were identified from the edible mushroom I. obliquus through high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance spectroscopy (NMR) data analysis. The neuroprotective function of all steroidal metabolites in H2O2-induced SH-SY5Y cells was investigated. The results showed that 2α-HI exhibited the most remarkable neuroprotective activity. In the meantime, 2α-HI significantly ameliorated oxidative stress damage, reactive oxygen species (ROS) accumulation and mitochondrial damage induced by H2O2 in SH-SY5Y cells. The Nrf2 siRNA and inhibitors transfected the SH-SY5Y cells, indicating the Nrf2 and BDNF/TrkB/ERK/CREB pathway mediated the neuroprotective effects of 2α-HI against the H2O2-stimulated oxidative stress and apoptosis. Moreover, the neuroprotection of 2α-HI was preliminarily verified in zebrafish. In conclusion, this research was the first to confirm that 2α-HI could effectively protect SH-SY5Y cells against H2O2-induced oxidative stress and apoptosis via the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Hence, this mushroom could be a potential dietary supplement to ameliorate neurodegenerative diseases.

Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance.

How glucose metabolism remodels pro-tumor functions of tumor-associated macrophages (TAMs) needs further investigation. Here we show that M2-like TAMs bear the highest individual capacity to take up intratumoral glucose. Their increased glucose uptake fuels hexosamine biosynthetic pathway-dependent O-GlcNAcylation to promote cancer metastasis and chemoresistance. Glucose metabolism promotes O-GlcNAcylation of the lysosome-encapsulated protease Cathepsin B at serine 210, mediated by lysosome-localized O-GlcNAc transferase (OGT), elevating mature Cathepsin B in macrophages and its secretion in the tumor microenvironment (TME). Loss of OGT in macrophages reduces O-GlcNAcylation and mature Cathepsin B in the TME and disrupts cancer metastasis and chemoresistance. Human TAMs with high OGT are positively correlated with Cathepsin B expression, and both levels predict chemotherapy response and prognosis of individuals with cancer. Our study reports the biological and potential clinical significance of glucose metabolism in tumor-promoting TAMs and reveals insights into the underlying mechanisms.

Characterization of Choroidal Morphology and Vasculature in the Phenotype of Pachychoroid Diseases by Swept-Source OCT and OCTA.

The objective of this study was to characterize the choroidal morphology and vasculature in pachychoroid diseases (PCD). A total of 49 eyes with polypoidal choroidal vasculopathy (PCV), 43 eyes with neovascular age-related macular degeneration (nAMD), and 50 eyes with central serous chorioretinopathy (CSC), along with 80 healthy eyes, were enrolled in this nested case-control study. The swept-source optical coherent tomography (OCT), OCT angiography, and En face images were quantitatively analyzed. Multivariate logistic regression models showed that older age and increased vessel density (VD) in the choriocapillaris (CC) layer were independent risk factors for both PCV (page < 0.001, pVD = 0.004), and nAMD (page < 0.001, pVD = 0.005). Decreased VD in the Sattler's layer was an independent risk factor for PCV (p = 0.014). Increased VD in the Haller's layer was an independent risk factor for CSC (p = 0.001). The proportion of the diffuse type of collateral circulation in the Sattler' layer in CSC group was significantly higher than in the other three groups (p < 0.001). We concluded that the involvement of the blood flow in the CC, Haller's, and Sattler's layers are differently affected in CSC, nAMD, and PCV eyes, indicating the different pathological mechanism underlying the phenotype of PCD. The age-dependent establishment of collateral circulation in the Sattler's layer may play a compensatory role regarding ischemic injury in the development of PCD.

Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation.

Cerebral infarct penumbra due to hypoxia and toxin accumulation is not conducive to the transplantation of neural stem cells (NSCs), although mild hypothermia can improve the local microenvironment of the ischemic penumbra and exert neuroprotective effects. However, insufficient understanding of the molecular mechanism by which mild hypothermia protects the brain limits widespread clinical application. This study evaluated the molecular mechanism of mild hypothermia-induced brain protection from the perspective of global protein small ubiquitin-like modifier (SUMO) modification, with the aim of improving NSC transplant survival rates in the penumbra to enhance neurological function. NSCs from neonatal rats were extracted to detect the effects of hypoxia and mild hypothermia on SUMOylation modification levels, cell stemness, and hypoxia-induced injury. Overexpression and knockdown of UBC9 in NSCs were used to evaluate their ability to maintain stemness and withstand hypoxic injury. Finally, a rat middle cerebral artery occlusion (MCAO) model was used to verify the effect of mild hypothermia treatment and UBC9 overexpression on neural function of NSCs following penumbra transplantation in rats. Results showed that hypoxia and mild hypothermia promoted both the SUMOylation modification and maintenance of NSC stemness. Overexpression of UBC9 enhanced the abilities of NSCs to maintain stemness and resist hypoxic injury, while UBC9 knockdown had the opposite effect. Following transplantation into the ischemic penumbra of MCAO model rats, mild hypothermia and Ubc9-overexpressing NSCs significantly reduced cerebral infarct areas and improved neurological function. In conclusion, this study demonstrated that global protein SUMOylation is an important molecular mechanism for NSCs to tolerate hypoxia, and mild hypothermia can further increase the degree of global SUMOylation to enhance the hypoxia tolerance of NSCs, which increases their survival during transplantation in situ and ability to perform nerve repair in the penumbra of cerebral infarction.

A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the Effects of Cigarette Smokers' Serum on RPE Cells With AMD High-Risk Alleles.

PURPOSE: The aim of this study was to explore whether there are interactions between genetic (ARMS2/HTRA1) and environmental factors (cigarette smoking) in the pathogenesis of age-related macular degeneration (AMD). METHODS: Primary human retinal pigment epithelial (hRPE) cells were obtained from four donors' eyes with AMD high-risk ARMS2/HTRA1 alleles, and two donors' eyes with wild-type alleles were used as controls. The pooled serum from 32 smokers and 35 nonsmokers were collected and used separately to treat hRPE cells. The isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics was used to identify associated proteins and comparing the differences between AMD high-risk and low-risk HTRA1/ARMS2 alleles after exposure to smokers' serum. RESULTS: After stimulation with the smokers' serum, 400 differentially expressed proteins (DEPs) were detected in the high-risk allele cells. Several DEPs are involved in neuronal protein degeneration and oxidative stress pathways. The smokers' serum stimulation or HTRA1 overexpression can both upregulate caveolin-1, which was one of the DEPs. Besides, the smokers' serum enhanced the phagocytosis of cultured human RPE cells. CONCLUSIONS: The study confirmed the AMD high-risk alleles, HTRA1, and cigarette smoking can promote AMD development by regulating caveolin-1 expression. TRANSLATIONAL RELEVANCE: AMD high-risk alleles and environmental risk factors can promote the occurrence and development of AMD by regulating caveolin-1 expression, upregulation of which will induce apoptotic cell death in response to cellular stress in early AMD conditions.

SUMOylation of Translationally Regulated Tumor Protein Modulates Its Immune Function.

Translationally controlled tumor protein (TCTP) is a highly conserved protein possessing numerous biological functions and molecular interactions, ranging from cell growth to immune responses. However, the molecular mechanism by which TCTP regulates immune function is largely unknown. Here, we found that knockdown of Bombyx mori translationally controlled tumor protein (BmTCTP) led to the increased susceptibility of silkworm cells to virus infection, whereas overexpression of BmTCTP significantly decreased the virus replication. We further demonstrated that BmTCTP could be modified by SUMOylation molecular BmSMT3 at the lysine 164 via the conjugating enzyme BmUBC9, and the stable SUMOylation of BmTCTP by expressing BmTCTP-BmSMT3 fusion protein exhibited strong antiviral activity, which confirmed that the SUMOylation of BmTCTP would contribute to its immune responses. Further work indicated that BmTCTP is able to physically interact with interleukin enhancer binding factor (ILF), one immune molecular, involved in antivirus, and also induce the expression of BmILF in response to virus infection, which in turn enhanced antiviral activity of BmTCTP. Altogether, our present study has provided a novel insight into defending against virus via BmTCTP SUMOylation signaling pathway and interacting with key immune molecular in silkworm.

[Corrigendum] SNHG15 affects the growth of glioma microvascular endothelial cells by negatively regulating miR­153.

Following the publication of this article, the authors have realized that they had inadvertently used the same western blotting data to show the GAPDH control western blots in Figs. 1C and 4D. In examining their original data, the authors realized that the data for Fig. 1C had been placed incorrectly in the figure. The corrected version of Fig. 1, showing the correct GAPDH bands, is shown below. The authors sincerely apologize for the error made during the preparation of this Figure, thank the Editor for granting them the opportunity to publish this Corrigendum, and regret any inconvenience that this mistake may have caused. [the original article was published in Oncology Reports 38: 3265­3277, 2017; DOI: 10.3892/or.2017.5985].

Light irradiation maintains the sensory quality, health-promoting phytochemicals, and antioxidant capacity of post-harvest baby mustard.

The ability of white, red, and blue irradiation to maintain sensory quality, health-promoting compounds, and antioxidant capacity, and regulate glucosinolate metabolism-related gene expression in post-harvest baby mustard was studied. Irradiation with 80 µmol m-2 s-1 extended the shelf life of post-harvest baby mustard. Irradiation delayed the increase in weight loss and the decrease in sensory parameter scores and the levels of ascorbic acid, total phenolics, glucosinolate, and antioxidant capacity during storage of baby mustard. Irradiation induced the expression of glucosinolate biosynthesis genes and inhibited glucosinolate degradation gene expression. The glucosinolate content and glucosinolate metabolism-related gene expression in post-harvest baby mustard were higher under white and red light irradiation compared with blue light irradiation. These findings indicate that irradiation (80 µmol m-2 s-1 ), especially of white and red light, is an effective technique for maintaining the sensory and nutritional qualities in post-harvest baby mustard stored at 20°C. PRACTICAL APPLICATION: This study was to evaluate the effect of white, red, and blue irradiation on the sensory quality, health-promoting compounds, antioxidant capacity, and glucosinolate metabolism-related gene expression of baby mustard during post-harvest storage, providing an effective and sustainable post-harvest method to extend shelf life and maintain the post-harvest quality of baby mustard under ambient temperature storage. Irradiation (80 µmol m-2 s-1 ), especially of white and red light, is an effective technique for maintaining the sensory and nutritional qualities in post-harvest baby mustard stored at 20°C.

Unspliced XBP1 Counteracts ß-Catenin to Inhibit Vascular Calcification.

BACKGROUND: Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the XBP1u (unspliced XBP1) and XBP1s (spliced XBP1) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear. METHODS: We aim to investigate the role of XBP1u in vascular calcification. XBP1u protein levels were reduced in high phosphate-induced calcified vascular smooth muscle cells, calcified aortas from mice with adenine diet-induced chronic renal failure, and calcified radial arteries from patients with chronic renal failure. RESULTS: Inhibition of XBP1u rather than XBP1s upregulated in the expression of the osteogenic markers Runx2 (runt-related transcription factor 2) and Msx2 (msh homeobox 2), and exacerbated high phosphate-induced vascular smooth muscle cell calcification, as verified by calcium deposition and Alizarin red S staining. In contrast, XBP1u overexpression in high phosphate-induced vascular smooth muscle cells significantly inhibited osteogenic differentiation and calcification. Consistently, smooth muscle cell-specific XBP1 deficiency in mice markedly aggravated the adenine diet- and 5/6 nephrectomy-induced vascular calcification compared with that in the control littermates. Further interactome analysis revealed that XBP1u is bound directly to ß-catenin, a key regulator of vascular calcification, via amino acid (aa) 205-230 in its C-terminal degradation domain. XBP1u interacted with ß-catenin to promote its ubiquitin-proteasomal degradation and thus inhibited ß-catenin/TCF (T-cell factor)-mediated Runx2 and Msx2 transcription. Knockdown of ß-catenin abolished the effect of XBP1u deficiency on vascular smooth muscle cell calcification, suggesting a ß-catenin-mediated mechanism. Moreover, the degradation of ß-catenin promoted by XBP1u was independent of GSK-3ß (glycogen synthase kinase 3ß)-involved destruction complex. CONCLUSIONS: Our study identified XBP1u as a novel endogenous inhibitor of vascular calcification by counteracting ß-catenin and promoting its ubiquitin-proteasomal degradation, which represents a new regulatory pathway of ß-catenin and a promising target for vascular calcification treatment.

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

BACKGROUND: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME). METHODS: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline. RESULTS: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study. CONCLUSION: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept. TRIAL REGISTRATION NUMBER: NCT02194634.

Magnetic Resonance Imaging Image Feature Analysis Algorithm under Convolutional Neural Network in the Diagnosis and Risk Stratification of Prostate Cancer.

This work aimed to explore the accuracy of magnetic resonance imaging (MRI) images based on the convolutional neural network (CNN) algorithm in the diagnosis of prostate cancer patients and tumor risk grading. A total of 89 patients with prostate cancer and benign prostatic hyperplasia diagnosed by MRI examination and pathological examination in hospital were selected as the research objects in this study (they passed the exclusion criteria). The MRI images of these patients were collected in two groups and divided into two groups before and after treatment according to whether the CNN algorithm was used to process them. The number of diagnosed diseases and the number of cases of risk level inferred based on the tumor grading were compared to observe which group was closer to the diagnosis of pathological biopsy. Through comparative analysis, compared with the positive rate of pathological diagnosis (44%), the positive rate after the treatment of the CNN algorithm (42%) was more similar to that before the treatment (34%), and the comparison was statistically marked (P < 0.05). In terms of risk stratification, the grading results after treatment (37 cases) were closer to the results of pathological grading (39 cases) than those before treatment (30 cases), and the comparison was statistically obvious (P < 0.05). In addition, it was obvious that the MRT images would be clearer after treatment through the observation of the MRT images before and after treatment. In conclusion, MRI image segmentation algorithm based on CNN was more accurate in the diagnosis and risk stratification of prostate cancer than routine MRI. According to the evaluation of Dice similarity coefficient (DSC) and Hausdorff I distance (HD), the CNN segmentation method used in this study was more perfect than other segmentation methods.

IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation.

Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1's association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.

Downregulation of long non-coding RNA PVT1 enhances fracture healing via regulating microRNA-497-5p/HMGA2 axis.

Fragility fracture is a common and serious complication of osteoporosis. Abnormal expression of long non-coding RNAs is closely related to orthopedic diseases and bone metabolism. In the study, the role of lncRNA PVT1 during fracture healing, and the potential mechanism were explained. In the present study, 80 cases with fragility fracture were collected, serum samples were also collected at 7, 14, 21 days after standardized fixation therapy. qRT-PCR was applied for the measurement of mRNA levels. hFOB1.19 cells were recruited for the cell experiments, and the cell viability and apoptosis were detected. Luciferase reporter gene assay was performed for target gene confirmation. It was found that the level of PVT1 increased gradually, while miR-497-5p showed a downward trend over time in both intra-articular and hand fracture patients, and the changes reached a significant level at 21 day after treatment. In vitro experiments demonstrated that PVT1 knockdown promoted cell proliferation and inhibited cell apoptosis in HFOB1.19 cells. LncRNA PVT1 acts as a competing endogenous RNA (ceRNA) of miR-497-5p, and the influence of PVT1 knockdown on HFOB1.19 cell proliferation and apoptosis was reversed by miR-497-5p inhibition. HMGA2 is the target gene of miR-497-5p. It was concluded that LncRNA PVT1 silencing may enhance fracture healing via mediating miR-497-5p/HMGA2 axis.

AAV-Containing Exosomes as a Novel Vector for Improved Gene Delivery to Lung Cancer Cells.

Lung carcinoma is the most common type of cancer and the leading cause of cancer-related death worldwide. Among the numerous therapeutic strategies for the treatment of lung cancer, adeno-associated virus (AAV)-mediated gene transfer has been demonstrated to have the potential to effectively suppress tumor growth or reverse the progression of the disease in a number of preclinical studies. AAV vector has a safety profile; however, the relatively low delivery efficacy to particular subtypes of lung carcinoma has limited its prospective clinical translation. Exosomes are nanosized extracellular vesicles secreted from nearly all known cell types. Exosomes have a membrane-enclosed structure carrying a range of cargo molecules for efficient intercellular transfer of functional entities, thus are considered as a superior vector for drug delivery. In the present study, we developed a novel strategy to produce and purify AAV-containing exosomes (AAVExo) from AAV-packaging HEK 293T cells. The cellular uptake capacity of exosomes assisted and enhanced AAV entry into cells and protected AAV from antibody neutralization, which was a serious challenge for AAV in vivo application. We tested a list of lung cancer cell lines representing non-small-cell lung cancer and small-cell lung cancer and found that AAVExo apparently improved the gene transfer efficiency compared to conventional AAV vector. Our in vitro results were supported in vivo in a lung cancer xenograft rodent model. Additionally, we evaluated the gene delivery efficiency in the presence of neutralizing antibody on lung cancer cells. The results demonstrated that AAVExo-mediated gene transfer was not impacted, while the AAV vectors were significantly blocked by the neutralizing antibody. Taken together, we established an efficient methodology for AAVExo purification, and the purified AAVExo largely enhanced gene delivery to lung cancer cells with remarkable resistance to antibody neutralization.