Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1

Aminoacyl-tRNA synthetases possess unique domains. In this study the structure of the vertebrate IARS1 and EARS1 complex reveals that vertebrate IARS1 protects the DNA repair factor BRCA1 from proteolytic degradation via its UBX-fold domain. Aminoacyl-tRNA synthetases (ARSs) have evolved to acquire various additional domains. These domains allow ARSs to communicate with other cellular proteins in order to promote non-translational functions. Vertebrate cytoplasmic isoleucyl-tRNA synthetases (IARS1s) have an uncharacterized unique domain, UNE-I. Here, we present the crystal structure of the chicken IARS1 UNE-I complexed with glutamyl-tRNA synthetase 1 (EARS1). UNE-I consists of tandem ubiquitin regulatory X (UBX) domains that interact with a distinct hairpin loop on EARS1 and protect its neighboring proteins in the multi-synthetase complex from degradation. Phosphomimetic mutation of the two serine residues in the hairpin loop releases IARS1 from the complex. IARS1 interacts with BRCA1 in the nucleus, regulates its stability by inhibiting ubiquitylation via the UBX domains, and controls DNA repair function

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression

DILOF: Effective and Memory Efficient Local Outlier Detection in Data Streams

With precipitously growing demand to detect outliers in data streams, many studies have been conducted aiming to develop extensions of well-known outlier detection algorithm called Local Outlier Factor (LOF), for data streams. However, existing LOF-based algorithms for data streams still suffer from two inherent limitations: 1) Large amount of memory space is required. 2) A long sequence of outliers is not detected. In this paper, we propose a new outlier detection algorithm for data streams, called DILOF that effectively overcomes the limitations. To this end, we first develop a novel density-based sampling algorithm to summarize past data and then propose a new strategy for detecting a sequence of outliers. It is worth noting that our proposing algorithms do not require any prior knowledge or assumptions on data distribution. Moreover, we accelerate the execution time of DILOF about 15 times by developing a powerful distance approximation technique. Our comprehensive experiments on real-world datasets demonstrate that DILOF significantly outperforms the state-of-the-art competitors in terms of accuracy and execution time. The source code for the proposed algorithm is available at our website: http://di.postech.ac.kr/DILOF.1

A review of carbon mineralization mechanism during geological CO2 storage

The CO2 trap mechanisms during carbon capture and storage (CCS) are classified into structural, residual, solution, and mineral traps. The latter is considered as the most permanent and stable storage mechanism as the injected CO2 is stored in solid form by the carbon mineralization. In this study, the carbon mineralization process in geological CO2 storage in basalt, sandstone, carbonate, and shale are reviewed. In addition, relevant studies related to the carbon mineralization mechanisms, and suggestions for future research directions are proposed. The carbon mineralization is defined as the conversion of CO2 into stable carbon minerals by reacting with divalent cations such as Ca2+, Mg2+, or Fe2+. The process is mainly affected by rock types, temperature, fluid composition, injected CO2 phase, competing reaction, and nucleation. Rock properties such as permeability, porosity, and rock strength can be altered by the carbon mineralization. Since changes of the properties are directly related to injectivity, storage capacity, and stability during the geological CO2 storage, the carbon mineralization mechanism should be considered for an optimal CCS design

Catalytic persulfate activation for oxidation of organic pollutants: A critical review on mechanisms and controversies

Persulfate-based advanced oxidation processes (PS-AOPs) have received increasing attention as new approaches to oxidize refractory organic pollutants in contaminated water and soil. In particular, PS-AOPs using catalysts have been the most intensively studied because a broad spectrum of materials can catalyze the reaction without requiring external input of energy. Despite recent advances in catalytic PS-AOPs, their activation mechanisms are still challenged by uncertainties. Persulfate can be activated via a radical mechanism to generate sulfate radical and hydroxyl radical, as well as via a nonradical mechanism to mediate electron transfer or generate other nonradical reactive oxidants (e.g., single oxygen or high valent metal species). The mechanisms of catalytic persulfate activation and the identities of dominant reactive oxidants remain controversial for many reported catalysts. Herein, we endeavor to address radical and nonradical mechanisms and their identification methods in catalytic persulfate activation, focusing on controversies over widely investigated catalysts. This article will improve the mechanistic understanding of catalytic PS-AOPs and offer a theoretical foundation for exploring novel PS-AOPs with better specificity and performance.N

Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain

A skin-friendly soft strain sensor with direct skin adhesion enabled by using a non-toxic surfactant

Wearable electronics, particularly soft strain sensors with direct skin adhesion, play a crucial role in applications such as smart healthcare systems and human-machine interfaces. However, the existing approaches for developing dry-adhesive soft electronic materials often involve potential biotoxicity and vulnerability to humid environments. In this study, we present an eco-friendly and biocompatible surfactant-based composite for soft conductive composite, soft dry-adhesive film, and skin-adherable soft strain sensors. Utilizing polyoxyethylene sorbitan monooleate, also known as Tween 80, as a non-toxic surfactant, polydimethylsiloxane (PDMS) as an elastomeric matrix, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as a conductive pathway, the composite exhibits excellent stretchability and conductivity. The soft dry-adhesive film based on Tween 80-added PDMS features exceptional softness and adhesiveness. We demonstrate a soft strain sensor based on these composites that can be directly adhered to the skin and effectively detect various human motions involving large deformations without delamination. This approach offers a promising avenue for future wearable electronics that are safe for both humans and the environment

Efficacy of Transcutaneous 4.4 MHz Radiofrequency Diathermy versus Therapeutic Ultrasound for Pain Relief and Functional Recovery in Patients with Knee Osteoarthritis: A Randomized Controlled Study

Knee osteoarthritis (KOA) is a prevalent common cause of disability and pain among adults. Transcutaneous radiofrequency (RF) diathermy and therapeutic ultrasound (US) are commonly employed treatments for addressing musculoskeletal conditions. This study aims to evaluate and compare the clinical effectiveness of transcutaneous 4.4 MHz RF diathermy and therapeutic US therapy in individuals diagnosed with KOA. A total of 108 patients with KOA were randomly assigned to either the RF or US groups. Each participant underwent a series of 10 treatment sessions over four weeks and was evaluated at different time points. The assessments included physical evaluations, vital sign measurements, the Numeric Rating Scale (NRS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, the Lequesne index, gait analysis, the 36-Item Short Form Health Survey (SF-36), and analysis of adverse responses. Both groups showed significant differences in NRS, WOMAC scores, and Lequesne index compared to baseline values at both the 10th treatment session and the one-month follow-up assessment. However, no significant disparities were observed between the two groups at each assessment point. In the gait analysis, following the 10th treatment, the RF group showed significant changes in stride length and stride velocity compared to baseline. Four weeks after the completion of treatment, both groups exhibited significant alterations in stride length and stride velocity when compared to baseline measurements. However, regarding cadence, only the RF group exhibited a significant difference compared to baseline. The findings suggest that transcutaneous 4.4 MHz RF diathermy displays a comparable effectiveness to therapeutic US in reducing pain and enhancing functional capacity among individuals with KOA. Further research endeavors are warranted to advance the efficacy of noninvasive treatments for KOA