o8G Site-Specifically Modified tRF-1-AspGTC: A Novel Therapeutic Target and Biomarker for Pulmonary Hypertension.

BACKGROUND: Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. We aimed to gain insight into the mechanistic contribution of oxidative stress-induced 8-oxoguanine in pulmonary vascular remodeling. METHODS: Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine -modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH. RESULTS: This modification occurs at the position 5 of the tRF-1-AspGTC (5o8G tRF). Inhibition of the 5o8G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o8G tRF retargeted mRNA of WNT5A (Wingless-type MMTV integration site family, member 5A) and CASP3 (Caspase3) and inhibited their expression. Ultimately, BMPR2 (Bone morphogenetic protein receptor 2) -reactive oxygen species/5o8G tRF/WNT5A signaling pathway exacerbated the progression of PH. CONCLUSIONS: Our study highlights the role of site-specific 8-oxoguanine-modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o8G tRF as a potential innovative marker for diagnosing this disease.

Focused ultrasound-mediated brain genome editing.

Gene editing in the brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches mainly rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.

CircNAP1L4 regulates pulmonary artery smooth muscle cell proliferation via the NAP1L4-mediated super-enhancer-driven glycolysis gene hexokinase II (HK II) in pulmonary hypertension.

Glycolysis is a major determinant of pulmonary artery smooth muscle cell (PASMC) proliferation in pulmonary hypertension (PH). Circular RNAs (circRNAs) are powerful regulators of glycolysis in multiple diseases; however, the role of circRNAs in glycolysis in PH has been poorly characterized. The aim of this study was to uncover the regulatory mechanism of a new circRNA, circNAP1L4, in human pulmonary artery smooth muscle cell (HPASMC) proliferation through the host protein NAP1L4 to regulate the super-enhancer-driven glycolysis gene hexokinase II (HK II). CircNAP1L4 was downregulated in hypoxic HPASMCs and plasma of PH patients. Functionally, circNAP1L4 overexpression inhibited glycolysis and proliferation in hypoxic HPASMCs. Mechanistically, circNAP1L4 directly bound to its host protein NAP1L4 and affected the ability of NAP1L4 to move into the nucleus to regulate the epigenomic signals of the super-enhancer of HK II. Intriguingly, circNAP1L4 overexpression inhibited the proliferation but not the migration of human pulmonary arterial endothelial cells (HPAECs) cocultured with HPASMCs. Furthermore, pre-mRNA-processing-splicing Factor 8 (PRP8) was found to regulate the production ratio of circNAP1L4 and linear NAP1L4. In vivo, targeting circNAP1L4 alleviates SU5416 combined with hypoxia (SuHx)-induced PH. Overall, these findings reveal a new circRNA that inhibits PASMC proliferation and serves as a therapeutic target for PH.

Integrative Proteomics and N-Glycoproteomics Analyses of Rheumatoid Arthritis Synovium Reveal Immune-Associated Glycopeptides.

Rheumatoid arthritis (RA) is a typical autoimmune disease characterized by synovial inflammation, synovial tissue hyperplasia, and destruction of bone and cartilage. Protein glycosylation plays key roles in the pathogenesis of RA but in-depth glycoproteomics analysis of synovial tissues is still lacking. Here, by using a strategy to quantify intact N-glycopeptides, we identified 1260 intact N-glycopeptides from 481 N-glycosites on 334 glycoproteins in RA synovium. Bioinformatics analysis revealed that the hyper-glycosylated proteins in RA were closely linked to immune responses. By using DNASTAR software, we identified 20 N-glycopeptides whose prototype peptides were highly immunogenic. We next calculated the enrichment scores of nine types of immune cells using specific gene sets from public single-cell transcriptomics data of RA and revealed that the N-glycosylation levels at some sites, such as IGSF10_N2147, MOXD2P_N404, and PTCH2_N812, were significantly correlated with the enrichment scores of certain immune cell types. Furthermore, we showed that aberrant N-glycosylation in the RA synovium was related to increased expression of glycosylation enzymes. Collectively, this work presents, for the first time, the N-glycoproteome of RA synovium and describes immune-associated glycosylation, providing novel insights into RA pathogenesis.

Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Super Enhancer-Associated Circular RNA-CircKrt4 Regulates Hypoxic Pulmonary Artery Endothelial Cell Dysfunction in Mice.

BACKGROUND: Circular RNAs (circRNAs) have been implicated in pulmonary hypertension progression through largely unknown mechanisms. Pulmonary artery endothelial cell (PAEC) dysfunction is a hallmark in the pathogenesis of pulmonary hypertension. However, the specific role of circular RNAs in PAEC injury caused by hypoxia remains unclear. METHODS: In this study, using the Western blotting, RNA pull down, Dual-luciferase reporter assay, immunohistochemistry, and immunofluorescence, we identified a novel circular RNA derived from alternative splicing of the keratin 4 gene (circKrt4). RESULTS: CircKrt4 was upregulated in lung tissues and plasma and specifically in PAECs under hypoxic conditions. In the nucleus, circKrt4 induces endothelial-to-mesenchymal transition by interacting with the Pura (transcriptional activator protein Pur-alpha) to promote N-cadherin gene activation. In the cytoplasm, increased circKrt4 leads to mitochondrial dysfunction by inhibiting cytoplasmic-mitochondrial shuttling of mitochondrial-bound Glpk (glycerol kinase). Intriguingly, circKrt4 was identified as a super enhancer-associated circular RNA that is transcriptionally activated by a transcription factor, CEBPA (CCAAT enhancer binding protein alpha). Furthermore, RBM25 (RNA-binding-motif protein 25) was found to regulate circKrt4 cyclization by increase the back-splicing of Krt4 gene. CONCLUSIONS: These findings demonstrate that a super enhancer-associated circular RNA-circKrt4 modulates PAEC injury to promote pulmonary hypertension by targeting Pura and Glpk.

A new strategy for the treatment of Parkinson's disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.

Risk factors for in-hospital mortality in recipients of allogeneic hematopoietic stem cell transplantation with acute respiratory distress syndrome: a retrospective study based on the 2023 new definition of acute respiratory distress syndrome.

INTRODUCTION: ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. METHODS: From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. RESULTS: Under the new definition, SOFA score (OR = 1.351, 95% CI: 1.146-1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972-0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164-3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961-0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313-40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072-1.265, P < 0.01) were independently associated with in-hospital mortality. CONCLUSION: These prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.

Self-Assembled Pure Covalent Tubes Exhibiting Circularly Polarized Luminescence.

Here, we successfully synthesized four structurally analogous, self-assembled chiral molecular tubes with relatively high yields. This achievement involved the condensation of six equivalents of enantiomerically pure trans-cyclohexane-1,2-diamine (trans-CHDA) and three equivalents of the corresponding tetraformyl precursor. Each precursor was equipped with a luminescent linker terminated by two m-phthalaldehyde units. Even though these tetraformyl precursors are barely soluble in almost all organic solvents, the molecular tubes are highly soluble in nonpolar solvents such as chloroform, allowing us to fully characterize them in solution. The stereo-chirality of the chiral bisamino building blocks endows the frameworks of molecular tubes with planar chirality. As a consequence, all of these molecular tubes exhibit circularly polarized luminescence (CPL) with relatively large dissymmetry values |glum| up to 7×10-3, providing an efficient method for synthesizing CPL-active materials.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design.

Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.

Psychometric Comparison of EQ-5D-Y, CHU-9D, and PedsQL 4.0 in Chinese Children and Adolescents With Functional Dyspepsia: A Multicenter Study.

OBJECTIVES: This study aimed to assess and compare psychometric properties of the 3 health-related quality of life (HRQOL) instruments EQ-5D Youth version (EQ-5D-Y), Child Health Utility 9D (CHU-9D), and Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) in children and adolescents with functional dyspepsia (FD) in China. METHODS: A consecutive sample of FD outpatients were recruited from 6 tertiary medical centers in Hangzhou. The patients self-completed the 3 instruments in random order. Their feasibility, acceptability, construct validity (convergent, divergent, and known-group validity), and sensitivity were assessed. Multiple linear regression was used for identifying HRQOL-associated factors. RESULTS: A total of 1100 patients (mean age, 9.2 years; girl, 56.8%) completed the survey with no missing responses. Ceiling effect was quite higher in EQ-5D-Y (60.9%) than CHU-9D (33.8%) and PedsQL 4.0 (1.0%). The EQ-5D-Y and CHU-9D utility scores and PedsQL 4.0 total score were highly correlated (|r| = 0.593-0.661), except for the EuroQol visual analog scale score (EQ-VAS). The intraclass correlation coefficient between the 2 utility scores was fair (0.542). Most conceptually similar dimensions among the 3 instruments showed moderate to high correlations (|r| > 0.3) as hypothesized. The difference was statistically significant for the 2 utility scores and PedsQL 4.0 total score in varied severity groups (P < .001), and PedsQL 4.0 total score had higher relative efficiency and effect size values. The child's age, severity of FD symptoms, and their guardian's education had significant impact on HRQOL (P < .001). CONCLUSIONS: EQ-5D-Y, CHU-9D, and PedsQL 4.0 demonstrated acceptable psychometric properties in Chinese children with FD. PedsQL 4.0 showed superior sensitivity and is recommended. EQ-5D-Y and CHU-9D utility scores were not interchangeable. The measurement properties of EQ-VAS need to be further explored.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

Heterojunction photocatalyst FeS2/g-C3N5 for activating sulfites to degrade tetracycline: A stable degradation system based on heterogeneous processes.

The UV/sulfite system is a promising source of •SO4- and/or •OH, but its application is largely limited by the use of UV light due to its high cost and high energy consumption. Graphite carbon nitride (g-C3N5), as a new photocatalytic material, has better visible light absorption capacity and narrower band gap than g-C3N4, which is expected to activate sulfite under visible light to solve this problem. Herein, a novel FeS2/CN heterojunction material based on g-C3N5 was constructed by hydrothermal in-situ synthesis method and successfully activated sulfite, which was confirmed by tetracycline degradation experiments in water. Under optimized conditions, the degradation rate of TC in 1 h reached 96%. The experimental results revealed that the FeS2/CN heterostructure enhances the absorption of visible light and inhibits the recombination of carriers, enabling more electrons and holes to be utilized. Holes play a major role in the degradation reaction, promote the sulfite chain reaction, and effectively regulate the cycle of Fe2+ and Fe3+ in the solution. Iron ion leaching is negligible and the degradation reaction remains stable at pH 5-9.

The Management and Antithrombotic Strategies of Patients with Coronary Artery Disease and High Bleeding Risk.

PURPOSE OF REVIEW: In this review, we aim to summarize the current understanding of high bleeding risk (HBR) patients in coronary artery disease (CAD) and provide a comprehensive evaluation of the available antithrombotic strategies for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures. RECENT FINDINGS: CAD is a major cause of mortality among cardiovascular diseases, resulting from insufficient blood flow in the coronary artery due to atherosclerosis. Antithrombotic therapy is a crucial component of drug therapy for CAD and multiple studies had been focusing on the optimal antithrombotic strategies of different CAD populations. However, there is no fully harmonized definition of the model of bleeding, and the optimal antithrombotic strategy for such patients at HBR is inconclusive. In this review, we summarize bleeding risk stratification models for CAD patients and discuss the de-escalation of antithrombotic strategies among HBR patients. Furthermore, we realize that for certain subgroups of CAD-HBR patients, more individualized and precise antithrombotic strategy development is needed. So, we highlight special populations, such as CAD patients combined with valvular diseases, with both high ischemia and bleeding risks, and those proceeding surgical treatment, which requires greater research attention. We note that de-escalating therapy for CAD-HBR patients is an emerging trend in managing this population, but the optimal antithrombotic strategies should be re-considered according to the patient's baseline characteristics.

[Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II].

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 µmol/L) with or without Ang II (0.4 µmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

LncRNA FENDRR with m6A RNA methylation regulates hypoxia-induced pulmonary artery endothelial cell pyroptosis by mediating DRP1 DNA methylation.

BACKGROUND: Pyroptosis is a form of programmed cell death involved in the pathophysiological progression of hypoxic pulmonary hypertension (HPH). Emerging evidence suggests that N6-methyladenosine (m6A)-modified transcripts of long noncoding RNAs (lncRNAs) are important regulators that participate in many diseases. However, whether m6A modified transcripts of lncRNAs can regulate pyroptosis in HPH progression remains unexplored. METHODS: The expression levels of FENDRR in hypoxic pulmonary artery endothelial cells (HPAECs) were detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). Western blot, Lactate dehydrogenase (LDH) release assay, Annexin V-FITC/PI double staining, Hoechst 33342/PI fluorescence staining and Caspase-1 activity assay were used to detect the role of FENDRR in HPAEC pyroptosis. The relationship between FENDRR and dynamin-related protein 1 (DRP1) was explored using bioinformatics analysis, Chromatin Isolation by RNA Purification (CHIRP), Electrophoretic mobility shift assay (EMSA) and Methylation-Specific PCR (MSP) assays. RNA immunoprecipitation (RIP) and m6A dot blot were used to detect the m6A modification levels of FENDRR. A hypoxia-induced mouse model of pulmonary hypertension (PH) was used to test preventive effect of conserved fragment TFO2 of FENDRR. RESULTS: We found that FENDRR was significantly downregulated in the nucleus of hypoxic HPAECs. FENDRR overexpression inhibited hypoxia-induced HPAEC pyroptosis. Additionally, DRP1 is a downstream target gene of FENDRR, and FENDRR formed an RNA-DNA triplex with the promoter of DRP1, which led to an increase in DRP1 promoter methylation that decreased the transcriptional level of DRP1. Notably, we illustrated that the m6A reader YTHDC1 plays an important role in m6A-modified FENDRR degradation. Additionally, conserved fragment TFO2 of FENDEE overexpression prevented HPH in vivo. CONCLUSION: In summary, our results demonstrated that m6A-induced decay of FENDRR promotes HPAEC pyroptosis by regulating DRP1 promoter methylation and thereby provides a novel potential target for HPH therapy.

Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.

Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.

Circular RNA Calm4 Regulates Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cells Pyroptosis via the Circ-Calm4/miR-124-3p/PDCD6 Axis.

[Figure: see text].

Learning to predict the cosmological structure formation.

Matter evolved under the influence of gravity from minuscule density fluctuations. Nonperturbative structure formed hierarchically over all scales and developed non-Gaussian features in the Universe, known as the cosmic web. To fully understand the structure formation of the Universe is one of the holy grails of modern astrophysics. Astrophysicists survey large volumes of the Universe and use a large ensemble of computer simulations to compare with the observed data to extract the full information of our own Universe. However, to evolve billions of particles over billions of years, even with the simplest physics, is a daunting task. We build a deep neural network, the Deep Density Displacement Model ([Formula: see text]), which learns from a set of prerun numerical simulations, to predict the nonlinear large-scale structure of the Universe with the Zel'dovich Approximation (ZA), an analytical approximation based on perturbation theory, as the input. Our extensive analysis demonstrates that [Formula: see text] outperforms the second-order perturbation theory (2LPT), the commonly used fast-approximate simulation method, in predicting cosmic structure in the nonlinear regime. We also show that [Formula: see text] is able to accurately extrapolate far beyond its training data and predict structure formation for significantly different cosmological parameters. Our study proves that deep learning is a practical and accurate alternative to approximate 3D simulations of the gravitational structure formation of the Universe.

Coarctation of aorta combined with multiple aneurysms.

We reported a case of a 53-year-old patient with coarctation of the aorta and multiple aneurysmatic changes on the aortic arch. Enhanced computed tomography and reconstruction revealed significant coarctation and multiple aneurysmatic dilatations. The patient underwent stent implantation and was discharged with symptoms relieved. Follow-up examination progression of aneurysms, however, without symptoms.