In-orbit background simulation of a type-B CATCH satellite

The Chasing All Transients Constellation Hunters (CATCH) space mission plans to launch three types of micro-satellites (A, B, and C). The type-B CATCH satellites are dedicated to locating transients and detecting their time-dependent energy spectra. A type-B satellite is equipped with lightweight Wolter-I X-ray optics and an array of position-sensitive multi-pixel Silicon Drift Detectors. To optimize the scientific payloads for operating properly in orbit and performing the observations with high sensitivities, this work performs an in-orbit background simulation of a type-B CATCH satellite using the Geant4 toolkit. It shows that the persistent background is dominated by the cosmic X-ray diffuse background and the cosmic-ray protons. The dynamic background is also estimated considering trapped charged particles in the radiation belts and low-energy charged particles near the geomagnetic equator, which is dominated by the incident electrons outside the aperture. The simulated persistent background within the focal spot is used to estimate the observation sensitivity, i.e. 4.22$\times$10$^{-13}$ erg cm$^{-2}$ s$^{-1}$ with an exposure of 10$^{4}$ s and a Crab-like source spectrum, which can be utilized further to optimize the shielding design. The simulated in-orbit background also suggests that the magnetic diverter just underneath the optics may be unnecessary in this kind of micro-satellites, because the dynamic background induced by charged particles outside the aperture is around 3 orders of magnitude larger than that inside the aperture.Comment: 24 pages, 13 figures, 7 tables, accepted for publication in Experimental Astronom

Twenty Novel Disease Group-Specific and 12 New Shared Macrophage Pathways in Eight Groups of 34 Diseases Including 24 Inflammatory Organ Diseases and 10 Types of Tumors.

The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ markers than lean adipose tissue Mφ (ATMφ) physiologically. (3) Pro-adipogenic TFs C/EBPα and PPARγ and proinflammatory adipokine leptin upregulate the expression of M1 Mφ markers. (4) Among 10 immune checkpoint receptors (ICRs), LLSI-Mφ and bone marrow (BM) Mφ express higher levels of CD274 (PDL-1) than ATMφ, presumably to counteract the M1 dominant status via its reverse signaling behavior. (5) Among 24 intercellular communication exosome mediators, LLSI- and BM- Mφ prefer to use RAB27A and STX3 than RAB31 and YKT6, suggesting new inflammatory exosome mediators for propagating inflammation. (6) Mφ in peritoneal tissue and LLSI-Mφ upregulate higher levels of immunometabolism enzymes than does ATMφ. (7) Mφ from peritoneum and LLSI-Mφ upregulate more trained immunity enzyme genes than does ATMφ. Our results suggest that multiple new mechanisms including the cell surface, intracellular immunometabolism, trained immunity, and TFs may be responsible for disease group-specific and shared pathways. Our findings have provided novel insights on the pathophysiological regulation of tissue Mφ, the disease group-specific and shared pathways of Mφ, and novel therapeutic targets for cancers and inflammations

29 m 6 A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation - 102 Transcriptomic Dataset Analyses

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m6A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers

Spatiotemporal Evolution and Influencing Factors of Carbon Emission Efficiency in the Yellow River Basin of China: Comparative Analysis of Resource and Non-Resource-Based Cities

Comparing the carbon emission efficiency (CEE) of resource and non-resource-based cities in the Yellow River Basin (YRB) can guide their synergistic development and low-carbon transition. This study used the super-efficiency slacks-based measure (super-SBM) model to measure the CEE of cities in the YRB. Kernel density estimation and Theil index decomposition methods were used to explore the spatiotemporal evolutionary patterns, and a panel regression model was established to analyze the influencing factors of CEE. The research results showed that the CEE of the two types of cities have an overall upward trend in time, with a widening regional gap. Resource-based cities mainly displayed the characteristics of decentralized regional agglomeration, while non-resource-based cities mainly showed the characteristics of convergent regional agglomeration. Panel regression results showed that the levels of economic development, indus-trial structure, and population density are significantly positively correlated with CEE in the YRB, while foreign direct investment and resource endowment are significantly negatively correlated with CEE. Except for economic development and industrial structure, there is some variability in the contribution of the remaining influencing factors to the CEE of the resource and non-resource-based cities. The research results suggest developing classification measures for low-carbon transition in the YRB

Clinical Significance of ROS1 Rearrangements in Non-small Cell Lung Cancer

Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in multiple malignancies, including non-small cell lung cancer (NSCLC). ROS1 rearrangement defines a new molecular subset of NSCLC with the prevalence of ROS1 rearrangements around 1%-2%. ROS1-positive NSCLCs arise in young never-smokers with adenocarcinoma that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib demonstrates in vitro activity and early clinical trial shows marked antitumor activity in ROS1-rearranged patients. The overall response rate is around 56% and the disease control rate at 8 weeks is about 76%. Further understanding the ROS1 fusions in the pathogenesis of NSCLC, methods to detect ROS1 rearrangements, and targeting ROS1-rearranged NSCLC patients with specific kinase inhibitors would lead to an era of personalized medicine

A Combination of Ilizarov Frame, Externalized Locking Plate and Tibia Bridging for an Adult with Large Tibial Defect and Severe Varus Deformity Due to Chronic Osteomyelitis in Childhood: A Case Report

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction–compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions

A Combination of Ilizarov Frame, Externalized Locking Plate and Tibia Bridging for an Adult with Large Tibial Defect and Severe Varus Deformity Due to Chronic Osteomyelitis in Childhood: A Case Report

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction–compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions

UiO-66 nanoparticles combat influenza A virus in mice by activating the RIG-I-like receptor signaling pathway

Abstract The Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 μg mL−1 and 60 mg kg−1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine. Graphical Abstrac

Dynamic Analysis and Experiment of a Space Mirror Based on a Linear State Space Expression

Dynamic analysis of the optical–mechanical structure based on the linear state space expression is performed for a three-point flexural mount lightweight space mirror with a diameter of ϕ740 mm. Using linear structure dynamics and linear state space theories, the state space model of the mirror assembly is established based on modal information. The DC gain method is used to reduce modes and a frequency response analysis of the reduced modes is performed to obtain the frequency domain transfer function between the excitation input and response output points and determine the contribution of each mode to the total frequency response. The frequency response curve is plotted. A mechanical vibration test is performed to verify the accuracy and rationality of simulation analysis. The dynamic analysis method based on state space theory provides a new method of investigating optical and mechanical structures, which can help efficiently and accurately analyze the frequency response characteristics of complex linear systems