Browse Articles

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE

Abstract Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE–CMD and SLE–non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE–CMD and SLE–non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.

A disproportionality analysis of FDA adverse event reporting system events for misoprostol

Abstract Misoprostol was originally used to treat gastric ulcers, and has been widely used in abortion, cervical maturation, induced labour and postpartum hemorrhage. But there are still many undetected adverse events (AEs). The purpose of this study was to provide a comprehensive overview of the safety of misoprostol. Adverse events related to misoprostol were collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2024. This study used proportional disequilibrium methods such as reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) to detect AEs. After analyzing 17,427,762 adverse event reports, a total of 2032 adverse events reports related to misoprostol were identified, involving 23 system organ classes and 30 preferred terms. The most common AEs were foetal exposure during delivery(n = 201), uterine tachysystole(n = 95), uterine rupture (n = 95), and heart rate decreased (n = 93). Although most AEs complied with the drug instruction, new AEs signals such as congenital aqueductal stenosis and congenital brain damage were also identified. Clinicians should make appropriate evaluation when using misoprostol, closely monitor the indicators of patients, and have appropriate countermeasures for possible adverse events.

Evaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses

Secure channel estimation model for cognitive radio network physical layer security using two-level shared key authentication

Abstract Physical Layer Security (PLS) in Cognitive Radio Networks (CRN) improves the confidentiality, availability, and integrity of the external communication between the devices/ users. The security models for sensing and beamforming reduce the impact of adversaries such as eavesdroppers in the signal processing layer. To such an extent, this article introduces a Secure Channel Estimation Model (SCEM) using Channel State Information (CSI) and Deep Learning (DL) to improve the PLS. In this proposed model, the CSI is exploited to evaluate the channel utilization and actual capacity availability throughout the allocation intervals. The change in channel capacity and utilization augments the need for security through 2-level key shared authentication. The deep learning algorithm verifies the authentication completeness for maximum channel capacity utilization irrespective of adversary interference. This verification follows mutual authentication between the primary and secondary users sharing the maximum capacity channel with high secrecy. The learning monitors the outage secrecy rates to verify failed allocations such that the replacement for allocation is pursued. Thus, the physical layer security between different user categories is administered through maximum CSI exploitation with high beamforming abilities. The proposed model leverages the secrecy rate by 10.77% and the probability of detection by 15.01% and reduces the interference rate by 11.07% for the varying transmit powers.

Identification of a binding site for small molecule inhibitors targeting human TRPM4

Abstract Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug development targeting TRPM4. We determine three cryo-EM structures of full-length human TRPM4 embedded in native lipid nanodiscs without inhibitor, bound to NBA, and an anthranilic acid derivative, IBA. We found that the small molecules NBA and IBA were bound in a pocket formed between the S3, S4, and TRP helices and the S4-S5 linker of TRPM4. Our structural data and results from patch clamp experiments enable validation of a binding site for small molecule inhibitors, paving the way for further drug development targeting TRPM4.

Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics

Abstract Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. Topoisomerase III-β (TOP3B), the only RNA topoisomerase in metazoans, promotes R-loop disassembly and translation of mRNAs. Defects in TOP3B lead to severe neurological diseases. We present a series of cryo-EM structures of human TOP3B with its cofactor TDRD3 during cleavage and rejoining of DNA or RNA, thus elucidating the roles of divalent metal ions and key enzyme residues in each step of the catalytic cycle. We also obtained the structure of an open-gate configuration that addresses the long-standing question of the strand-passage mechanism. Our studies reveal how TOP3B catalyzes both DNA and RNA relaxation, while TOP3A acts only on DNA.

New links between auxin and starch

Molecular ferroelectric self-assembled interlayer for efficient perovskite solar cells

Explicit relation between thin film chromatography and column chromatography conditions from statistics and machine learning

Optimizing the growth conditions of superconducting MoSi thin films for single photon detection

Abstract We investigate the growth of amorphous MoSi thin films using magnetron co-sputtering and optimize the growth conditions with respect to crystal structure and superconducting properties (e.g., critical temperature $$T_{\text {c}}$$ ). The deposition pressure, Mo:Si stoichiometry and substrate temperature are systematically varied to achieve a transition temperature of 8.4(3) K for films with a thickness of 17.7(8) nm and 6.2(9) K for a 4.3(4) nm thick film. For Mo concentrations above 81% the crystalline phase $$\hbox {Mo}_\text {3}$$ Mo 3 Si is observed in grazing incidence X-ray diffraction measurements. The same phase appears when the working pressure during deposition is reduced below 3. $$1 \times 10^{\text {-3}}\hspace{1.66656pt}$$ 1 × 10 -3 mbar and when the substrate temperature during deposition is increased above $$100\hspace{1.66656pt}^{\circ } $$ C. By choosing a sufficient Si concentration and optimum deposition pressure we identify deposition conditions that ensure a homogeneous amorphous growth of the superconducting thin film. We then fabricate superconducting nanowire single-photon detectors which exhibit an unitary internal efficiency to single photons at an operational temperature of 1.2 K while simultaneously having a dark count rate below 1 Hz. Our results establish the link between MoSi film deposition, morphology and the performance of SSPD.

Association of the triglyceride glucose index with obesity indicators and hypertension in American adults based on NHANES 2013 to 2018

Study on the constitutive model and thermal deformation behavior of Incoloy825/P110 bimetallic composite material

Driver identification in advanced transportation systems using osprey and salp swarm optimized random forest model

Design and analysis of electromagnetic and mechanical structure of ultra-high-speed slotted solid rotor induction motor

Age- and sex-adjusted CT-based reference values for temporal muscle thickness, cross-sectional area and radiodensity

The associations of physical activity patterns and the triglyceride-glucose index in US adults: a secondary data analysis of NHANES (2007–2018)

Improving mechanical properties and electrical conductivity of Al-Cu-Mg matrix composites by GNPs and sc additions

Abstract To enhance the mechanical properties and electrical conductivity of Al-Cu-Mg-based composites, aluminum matrix composites containing scandium (Sc) and graphene nanoplatelets (GNPs) were fabricated by means of stepwise ball milling, vacuum hot pressing sintering, and hot rolling techniques. When Sc and GNPs were incorporated at concentrations of 0.1 wt% and 0.2 wt% respectively, the resultant composites demonstrated a maximum tensile strength of 326.81 MPa, an elongation of 3.2%, an electrical conductivity of 46.95% IACS, and a hardness of 112.96 HV. In comparison with the 2024 aluminum alloy matrix, enhancements of 39%, 255%, 51% and 51.21% were witnessed in tensile strength, elongation, electrical conductivity, and hardness respectively. These improvements can be primarily ascribed to the addition of Sc, which facilitated the precipitation of solute atoms and enhanced the interfacial bonding between the GNPs and the matrix, as well as the remarkable heterogeneous layered microstructure induced by the incorporation of GNPs. This study presents a feasible approach to concurrently enhance the strength and electrical conductivity of composites through the combined addition of Sc and GNPs.

Changes in microbiome composition during ontogeny and dispersal of the coral boring sponge Thoosa mismalolli

PET imaging of 52Mn labeled DOTATATE and DOTAJR11

Insights into the diverse roles of the terminal oxidases in Burkholderia cenocepacia H111

Abstract Burkholderia cenocepacia H111 is an obligate aerobic bacterium which has been isolated from a cystic fibrosis (CF) patient. In CF lungs the environment is considered micro-oxic or even oxygen-depleted due to bacterial activities and limited oxygen diffusion in the mucus layer. To adapt to low oxygen concentrations, bacteria possess multiple terminal oxidases. In this study, we identified six terminal oxidases of B. cenocepacia H111 and constructed reporter strains to monitor their expression in different environments. While the heme-copper oxidase aa 3 (cta) was constitutively expressed, the bd-1 oxidase (cyd) was induced under oxygen-limited growth conditions. The cyanide-insensitive bd-type terminal oxidase (cio-1) was mainly expressed in cells grown on the surface of solid medium or in liquid cultures in presence of cyanide, which is known to be produced in the CF lung by the often co-residing CF pathogen Pseudomonas aeruginosa. Indeed, a cio-1 insertional mutant was not able to grow in the presence of cyanide confirming the important role of Cio-1 in cyanide resistance. The caa 3 oxidase (caa), was only expressed under nutrient limitation when cells were grown on the surface of solid medium. We also investigated the involvement of two regulatory systems, Anr and RoxS/RoxR, in the expression of cio-1 and cyd. Our data suggest, that, given that Cio-1 is only present in prokaryotes and plays an important role in the defense against cyanide-producing P. aeruginosa, it may be a valuable drug target for treatment of polymicrobial infections in CF patients.