Distinct Class Research Articles

Unraveling the Work-Related Distress Profiles of Election Officers in Yogyakarta: Lessons Learned from the 2019 General Election

Drawing from the 2019 electoral incident, this study seeks to comprehend election officials’ working context, providing insights for the forthcoming 2024 general election (Pemilu). Specifically, this study investigates the working conditions of election officials during Indonesia's 2019 general election by examining their job demands, job resources, psychological and physical stress responses. Utilizing the job demands-resources (JD-R) model, the study evaluated the job demands, job resources, psychological and physical stress responses of 212 election officials in Yogyakarta Province using part of The New Brief Job Stress Questionnaire (NBJSQ). Latent Class Analysis revealed three distinct class profiles among the 2019 election officials based on their JD-R model scores, which included job demands, job resources, psychological and physical stress responses. The majority of participants fell into class 2, characterized by high job demands and job resources but low stress reactions. In contrast, class 1 had low job demands and job resources but a high level of stress, while class 3 exhibited high job demands, low job resources, and low stress. These results indicate that high job demand and job resources can potentially lead to work-related stress, although this relationship is influenced by the specific context and nature of job demands and job resources.

Redox-Mediated Enantioselective Interactions in Chiral Metallopolymers Possessing Supramolecular Chirality

Synthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox-mediated electrochemical processes. Redox metallopolymers represent a distinct class of versatile functional materials and have been extensively studied for a wide scope of applications such as membranes, self-assembly, hydrogels, and redox-mediated ion separation. However, many studies have focused on molecularly-selective binding and release of achiral molecules, with limited studies on chirality strategies for enantioselective interactions. Chiral organic anions comprise an important class of biologically-relevant molecules, and their separation and sensing have received intense attention. Here, we introduce new chiral redox-polymers with chiral ferrocene (Fc) building blocks, that can serve as an electro-responsive enantioselective platform for a variety of amino acids and pharmaceutical carboxylates, taking advantage of supramolecular chirality for enhancing electrochemical recognition. Two chiral redox-metallopolymers were designed and synthesized based on Ugi’s amine-inspired chiral monomers containing an amide (poly-1) or amine group (poly-2), and their enantioselective recognitions toward amino acids and pharmaceutical carboxylates were investigated by redox potential shifts using square wave voltammetry. The half potential shift of both poly-(S)-1 and poly-(S)-2 increased more with increasing D-tryptophan concentration than the other enantiomer, L-tryptophan, while the half potential of poly-(R)-1 and poly-(R)-2 shifted more with L-tryptophan than with D-tryptophan, proving the enantioselective interaction of both redox-metallopolymers. Nuclear Overhauser Effect spectroscopy (2D NOESY) and solid-state circular dichroism revealed the emergence of supramolecular chirality of the polymers resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone, and the steric hindrance of the ferrocene within the polymer. The half-peak potential shift demonstrated the remarkable enhancement of enantioselective recognition with tryptophan (Trp) and naproxen, provided by the chiral polymers possessing the supramolecular chirality over the single-site, chiral building block itself. For instance, the two (S) polymers showed the potential shift difference 2.4-2.8 times higher than the corresponding monomers upon the binding of Trp enantiomers. The enantioselective potential shift of the chiral metallopolymer electrodes could determine enantiomeric excess (%ee) of Trp over the range of 0–100%ee. Investigation on solvent polarity and pH effect revealed that the enantioselective mechanism of the chiral redox polymers was attributed to the subtle balance between hydrogen bonding and π-π interaction. We also identified the importance of aromatic groups on the analytes for increasing enantioselectivity of the chiral redox polymers. This work highlights the potential of chiral redox-metallopolymers as platforms for electrochemically-modulated enantioselective processes toward a variety of amino acids and pharmaceutical carboxylates. Figure 1

Electrode Reactions on Conducting Polymers

The electrocatalysis behind the direct chemical-to-electrical energy interconversion is one of key facets in the development of sustainable economy. This results in a technological demand for a variety of applications such as electrical transportation, electrified synthesis and the grid balancing. Here are three examples of problematized electrocatalytic processes. (A) The sluggish kinetics and multistep character of oxygen reduction reaction (ORR) are causing losses in electrical energy conversion and poor selectivity, which limit the wide implementation of oxygen-associated energy conversion technologies. (B) The water electrolysis yielding the hydrogen evolution reaction (HER), the key process in technologies of green hydrogen, provides only 4% of worldwide hydrogen production due to the high catalyst cost. (C) The control of the proton-coupled electron transfers on organic redox molecules such as benzenediols. These three illustrate the stimulus of the intensive research on noble-metal-free electrocatalysts. Conducting polymers, the organic materials synthesised from abundant element, constitute a distinct class of molecular electrocatalysts [1, 2] attributed with behaviour of mixed ion-electron conductors (MIEC). Firstly, the landscape of ORR phenomena happening on p- and n-type conducting polymers at the mechanistic and device levels are discussed [1-3]. Secondly, the effect of proton supply is rationalized at both mechanistic and device levels for HER on PEDOT-triflate [4]. Thirdly, the significant effect of ionic transport on the rate of the proton-coupled electron transfers was observed and conceptualized as a ion-selective electrocatalysis (ISEC) [5].[1] E. Mitraka, M. Gryszel, M. Vagin, M.J. Jafar, A. Singh, M. Warczak, M. Mitrakas, M. Berggren, T. Ederth, I. Zozoulenko, X. Crispin, E.D. Głowacki, Electrocatalytic Production of Hydrogen Peroxide with Poly(3,4‐ethylenedioxythiophene) Electrodes, Advanced Sustainable Systems, 3 (2019) 1800110.[2] Z.X. Wu, P.H. Ding, V. Gueskine, R. Boyd, E.D. Glowacki, M. Oden, X. Crispin, M. Berggren, E.M. Bjork, M. Vagin, Conducting Polymer-Based e-Refinery for Sustainable Hydrogen Peroxide Production, Energy & Environmental Materials.[3] M. Vagin, V. Gueskine, E. Mitraka, S.H. Wang, A. Singh, I. Zozoulenko, M. Berggren, S. Fabiano, X. Crispin, Negatively-Doped Conducting Polymers for Oxygen Reduction Reaction, Advanced Energy Materials, 11 (2021) 2002664.[4] R. Valiollahi, M. Vagin, V. Gueskine, A. Singh, S.A. Grigoriev, A.S. Pushkarev, I.V. Pushkareva, M. Fahlman, X.J. Liu, Z. Khan, M. Berggren, I. Zozoulenko, X. Crispin, Electrochemical hydrogen production on a metal-free polymer, Sustainable Energy & Fuels, 3 (2019) 3387-3398.[5] M. Vagin, C.Y. Che, V. Gueskine, M. Berggren, X. Crispin, Ion-Selective Electrocatalysis on Conducting Polymer Electrodes - Improving the Performance of Redox Flow Batteries, Advanced Functional Materials, 30 (2020) 2007009.

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration.

Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Current Perspectives onthe Management ofPatients Poisoned With Novichok: A Scoping Review.

Nerve agents have emerged as a global threat since their discovery in the 1930s, posing severe risks due to their inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine in nerve synapses. Despite the enforcement of the Chemical Weapon Convention to control chemical weapons, including nerve agents, recent events, such as the Novichok attacks on Sergei Skripal and Alexei Navalny, have highlighted the persistent threat. Novichok, a distinct class of nerve agents, raises specific concerns regarding its management due to limited understanding. This article aims to comprehensively analyze existing literature. A scoping review was employed to comprehensively assess the current state of knowledge on managing patients poisoned with Novichok. Following the PRISMA-ScR guidelines, relevant literature was identified in peer-reviewed journals covering symptoms, diagnosis, treatment, decontamination, and long-term effects. Searches were conducted on February 1, 2023, across four electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) using "Novichok" as a keyword. No restrictions were applied, and additional studies were sought from the references of identified papers. Eligible papers included discussions on Novichok or its specific properties impacting management, regardless of study type, language, or publication date, while those unrelated to the study's conceptual framework were excluded. A total of 170 records were identified from the initial database search, with 86 studies screened after removing duplicates. Among these, 28 publications met the eligibility criteria and were included in the analysis. An additional relevant study was identified from the citation lists of included studies, bringing the total to 29. The review encompasses studies published from 2018 onwards, indicating the growing interest in this topic. While most studies are reviews on Novichok or nerve agents in general, several theoretical and experimental investigations were also found. This review highlights the significant uncertainties and knowledge gaps surrounding the management of patients poisoned with Novichok. While some aspects align with other nerve agents, limited research likely due to safety and ethical challenges leads to assumptions and uncertainties in patient care. The review identifies areas with ongoing research, such as decontamination and biomarker recognition, while other aspects remain understudied. The possible inefficacy of current treatment options and the need for further research on oximes, bioscavengers, and long-term effects emphasize the necessity for increased research to optimize patient outcomes. More studies are essential to clarify the actual threat and toxicity of Novichok. Moreover, raising awareness among medical staff is crucial for early diagnosis, prompt treatment, and safety. This review offers valuable insights into managing Novichok-poisoned patients and calls for increased research and awareness in this critical area.

A research article on polymeric surfactant and its applications

Polymeric surfactants represent a distinctive class of amphiphilic compounds that combine the versatility of polymers with the surfactant properties crucial for interfacial phenomena. This research article will focus on the basis of polymeric surfactants and their applications in various domains. Characterisation techniques, including spectroscopy, microscopy, and rheology, are employed to elucidate polymeric surfactants' structural features and self-assembly behaviour. Understanding these characteristics is pivotal for optimising their performance in diverse applications. The applications of polymeric surfactants span a broad spectrum, focusing on their use in emulsion polymerisation, drug delivery, enhanced oil recovery, and environmental remediation. Their unique structure imparts advantages such as improved stability, controlled release, and enhanced efficiency in various processes.

Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma

Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment. Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs. Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

A T cell receptor β chain-directed antibody fusion molecule activates and expands subsets of T cells to promote antitumor activity.

Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we describe a first-in-class bifunctional therapeutic molecule, STAR0602, that comprises an antibody targeting germline Vβ6 and Vβ10 T cell receptors (TCRs) fused to human interleukin-2 (IL-2) and simultaneously engages a nonclonal mode of TCR activation with costimulation to promote activation and expansion of αβ T cell subsets expressing distinct variable β (Vβ) TCR chains. In solution, STAR0602 binds IL-2 receptors in cis with Vβ6/Vβ10 TCRs on the same T cell, promoting expansion of human Vβ6 and Vβ10 CD4+ and CD8+ T cells that acquire an atypical central memory phenotype. Monotherapy with a mouse surrogate molecule induced durable tumor regression across six murine solid tumor models, including several refractory to anti-PD-1. Analysis of murine tumor-infiltrating lymphocyte (TIL) transcriptomes revealed that expanded Vβ T cells acquired a distinct effector memory phenotype with suppression of genes associated with T cell exhaustion and TCR signaling repression. Sequencing of TIL TCRs also revealed an increased T cell repertoire diversity within targeted Vβ T cell subsets, suggesting clonal revival of tumor T cell responses. These immunological and antitumor effects in mice were recapitulated in studies of STAR0602 in nonhuman primates and human ex vivo models, wherein STAR0602 boosted human antigen-specific T cell responses and killing of tumor organoids. Thus, STAR0602 represents a distinct class of T cell-activating molecules with the potential to deliver enhanced antitumor activity in checkpoint inhibitor-refractory settings.

Evaluation of healthcare professionals' understanding of fluoroquinolones' safety profile, usage, and boxed warnings in Pakistan

IntroductionFluoroquinolones (FQs) is a distinct class of antibiotics which are prescribed and used quite frequently worldwide, despite the box warnings (BW) issued by Food and Drug Administration (FDA). Literature has shown in spite of BWs related to FQs there is minimal impact on health care professionals (HCPs) prescribing habits, potentially attributing towards limited and insufficient awareness. In Pakistan, FQs are mostly prescribed antibiotics for microbial treatments, therefore the purpose of this study was to determine the level of knowledge about the safety profile, use, and BW of FQs among HCPs working in Pakistan.MethodsA cross-sectional study was undertaken among the HCPs of Khyber Pakhtunkhwa province of Pakistan from October 2022 to December 2022. A validated questionnaire was used to assess the knowledge of HCPs regarding FQs, its safety profile and BW. A random convenient sample technique was used while recruiting HCPs in this study. As the HCPs comprised physicians, dentists, pharmacist and nurses, all were approached in person and the study objective was fully elaborated and explained to them. The statistic test like: one-way ANOVA, independent-t test, multivariate logistic regression were used keeping the p-value < 0.05 as statistically significant.ResultsA total of n = 250 HCPs were approached, of which n = 186 HCPs completed the questionnaire with a response rate of 74.4%. FQs prescribing pattern was only assessed among the prescribers, i.e., physicians and dentists (39/186). The mean knowledge score for indications was 5.29 ± 3.05, while for the adverse effects was 7.70 ± 2.61. The highest score for knowledge for indications and adverse effect score was achieved by physicians followed by dentist. The mean knowledge score for the BW was 3.46 ± 2.93 and among the HCPs for the BW of FQs, 20.4% of the HCPs had appropriate knowledge score (score ≥ 50%). The knowledge score was significantly higher in males (p = 0.039), dentists (p = 0.001), HCPs having master/specialization level of education (p = 0.003), HCPs working in government sector hospitals (p = 0.010) and secondary care hospitals (p = 0.001) while the multivariate logistic regression analysis showed that HCPs working in primary care hospital (OR: 6.2) and secondary care hospital (OR: 20.3) were associated with the tendency to achieve 50% or above knowledge score.Conclusion Findings of this study reveals the unsatisfactory knowledge of HCPs regarding the safety profile, use, and BW of FQs putting patients at heightened risks of FQs associated AEs. Therefore, it is crucial to implement a national antimicrobial stewardship program, seminars and lectures aimed at continuously updating the knowledge of HCPs, regardless of their specialties, and effectively restrict the misuse of antimicrobial and disseminate FDA BWs in clinical practice.

Quantile time-frequency connectedness among G7 stock markets and clean energy markets

The rapid growth of clean energy markets as a distinct asset class has attracted significant investor attention. This study examines the interdependence between G7 stock markets and clean energy indices, specifically Renewable Energy Generation (REG), Energy Efficiency (EE), Advanced Materials (AM), and Clean Fuels (CF). Using a state-of-the-art volatility connectedness network and Maximum Overlaps Discrete Wavelet Transform (MODWT), we investigate the quantile time-frequency connectedness among the markets. Our findings reveal strong volatility linkages among all markets, with the exception of Clean Fuels, which has the least connection. We also observe higher dynamic spillover effects under extreme market conditions than normal conditions, with the US market being the most important transmitter of spillovers under bullish markets. Additionally, we highlight the importance of considering the time-varying nature of connectedness, emphasizing the heterogeneity between short-run, medium-run, and long-run transmission. Our study's implications suggest that investors should consider the dynamic nature of spillovers and connectedness when constructing portfolios containing clean energy and G7 stock market assets. The results also imply that the US market's performance has a substantial impact on other markets under bullish conditions, and that Clean Fuels may present an attractive investment opportunity for diversification purposes due to its relative independence.

Natural Inhibitors of Mammalian α-Amylases as Promising Drugs for the Treatment of Metabolic Diseases.

α-Amylase is a generally acknowledged molecular target of a distinct class of antidiabetic drugs named α-glucosidase inhibitors. This class of medications is scarce and rather underutilized, and treatment with current commercial drugs is accompanied by unpleasant adverse effects. However, mammalian α-amylase inhibitors are abundant in nature and form an extensive pool of high-affinity ligands that are available for drug discovery. Individual compounds and natural extracts and preparations are promising therapeutic agents for conditions associated with impaired starch metabolism, e.g., diabetes mellitus, obesity, and other metabolic disorders. This review focuses on the structural diversity and action mechanisms of active natural products with inhibitory activity toward mammalian α-amylases, and emphasizes proteinaceous inhibitors as more effective compounds with significant potential for clinical use.

Victimization or self-inflicted hurt: Double narrative movements in Katherine Mansfield’s The Little Governess

The paper aims to study the double narrative movements in Katherine Mansfield’s short story “The Little Governess” which has received limited critical attention because of its seemingly simple plot. Most of the previous interpretations concentrate on the victimization of the little governess by patriarchal forces. But the study of Mansfield’s subtle stylistic choices, together with intertextual comparison and the connection with the author’s personal life, reveals that behind the ‘overt plot,’ there exists a ‘covert progression’ in which another countervailing theme springs out: the victimization of the little governess by her class prejudice. By laying bare the heroine as a girl who is victimized by her distinct class consciousness, this essay exposes Mansfield’s criticism of the deep-rooted class division.

Multiple E3 ligases control tankyrase stability and function

Tankyrase 1 and 2 are ADP-ribosyltransferases that catalyze formation of polyADP-Ribose (PAR) onto themselves and their binding partners. Tankyrase protein levels are regulated by the PAR-binding E3 ligase RNF146, which promotes K48-linked polyubiquitylation and proteasomal degradation of tankyrase and its partners. We identified a novel interaction between tankyrase and a distinct class of E3 ligases: the RING-UIM (Ubiquitin-Interacting Motif) family. We show that RNF114 and RNF166 bind and stabilize monoubiquitylated tankyrase and promote K11-linked diubiquitylation. This action competes with RNF146-mediated degradation, leading to stabilization of tankyrase and its binding partner, Angiomotin, a cancer cell signaling protein. Moreover, we identify multiple PAR-binding E3 ligases that promote ubiquitylation of tankyrase and induce stabilization or degradation. Discovery of K11 ubiquitylation that opposes degradation, along with identification of multiple PAR-binding E3 ligases that ubiquitylate tankyrase, provide insights into mechanisms of tankyrase regulation and may offer additional uses for tankyrase inhibitors in cancer therapy.

Abstract 14843: Unveiling the Phenotype of Smooth Muscle Foam Cells in Human Atherosclerotic Lesions: Insights From Bulk and Single Cell RNA Sequencing

Background and Aims: Our previous studies of human coronary atherosclerosis and ApoE-/- mice indicated that at least 50% and ~70% of foam cells are of smooth muscle cell (SMC) origin, respectively. We also found that SMCs generate a distinct class of foam cells, due to several gene expression and regulatory differences compared to macrophage foam cells. In the current investigation we utilized transcriptomic approaches to identify and characterize the phenotype of SMC foam cells of human coronary plaques and in SMCs treated with aggregated LDL (ag-LDL). Methods: Sections of fresh human coronary artery were subjected to gentle digestion and the isolated cells used for single-cell RNA Sequencing (scRNA-Seq) (n=3) using 10X Genomics Chromium Single Cell 3’ Reagent Kits v3 Technology. Human vascular SMCs were treated with 100 μg/mL ag-LDL for 24 h (n=3) and stained with the fluorescent lipid probe BODIPY493/503. BODIPY high SMCs were collected and subjected to bulk RNA sequencing along with non-treated SMCs as control. Results: Single cell RNA sequencing of cells isolated from human coronary arteries followed by unsupervised Seurat-based clustering (R version 4.2.0) identified 15 distinct clusters including 8 SMC clusters with varying degrees of differentiation and macrophage foam and non-foam cells. The top 70 upregulated genes in ag-LDL treated SMCs were used to identify clusters corresponding to SMC foam cells in the scRNA-seq dataset. We found that these genes are mostly enriched in 2 clusters of less differentiated SMCs. SMC and macrophage foam cell clusters display distinct characteristics. SMC foam cell clusters exhibit upregulation of complement and coagulation cascades, as well as ECM-receptor interaction genes. In contrast, the macrophage foam cell cluster shows enrichment of proinflammatory genes, genes involved in the response to unfolded protein, and both pro- and anti-apoptotic genes. Conclusion: Our studies provide novel tools to investigate the nature of SMC foam cells in human atherosclerosis and may provide unique markers for SMC foam cells. Gaining a comprehensive insight of the significance and characteristics of SMC foam cells is crucial in elucidating their ultimate role and potential as a therapeutic target in atherosclerosis.

Hsa_circ_0020134 promotes liver metastasis of colorectal cancer through the miR-183-5p-PFN2-TGF-β/Smad axis

Circular RNAs (circRNAs) are a distinct class of non-coding RNAs that play regulatory roles in the initiation and progression of tumors. With advancements in transcriptome sequencing technology, numerous circRNAs that play significant roles in tumor-related genes have been identified. In this study, we used transcriptome sequencing to analyze the expression levels of circRNAs in normal adjacent tissues, primary colorectal cancer (CRC) tissues, and CRC tissues with liver metastasis. We successfully identified the circRNA hsa_circ_0020134 (circ0020134), which exhibited significantly elevated expression specifically in CRC with liver metastasis. Importantly, high levels of circ0020134 were associated with a poor prognosis among patients. Functional experiments demonstrated that circ0020134 promotes the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, upregulation of circ0020134 was induced by the transcription factor, PAX5, while miR-183-5p acted as a sponge for circ0020134, leading to partial upregulation of PFN2 mRNA and protein levels, thereby further activating the downstream TGF-β/Smad pathway. Additionally, downregulation of circ0020134 inhibited epithelial-mesenchymal transition (EMT) in CRC cells, which could be reversed by miR-183-5p inhibitor treatment. Collectively, our findings confirm that the circ0020134-miR-183-5p-PFN2-TGF-β/Smad axis induces EMT transformation within tumor cells, promoting CRC proliferation and metastasis, thus highlighting its potential as a therapeutic target for patients with CRC liver metastasis.

Solar Wind‐Magnetosphere Coupling During High‐Intensity Long‐Duration Continuous AE Activity (HILDCAA)

AbstractHigh‐Intensity Long‐Duration Continuous AE Activity (HILDCAA) intervals are driven by High Speed solar wind Streams (HSSs) during which the rapidly‐varying interplanetary magnetic field (IMF) produces high but intermittent dayside reconnection rates. This results in several days of large, quasi‐periodic enhancements in the auroral electrojet (AE) index. There has been debate over whether the enhancements in AE are produced by substorms or whether HILDCAAs represent a distinct class of magnetospheric dynamics. We investigate 16 HILDCAA events using the expanding/contracting polar cap model as a framework to understand the magnetospheric dynamics occurring during HSSs. Each HILDCAA onset shows variations in open magnetic flux, dayside and nightside reconnection rates, the cross‐polar cap potential, and AL that are characteristic of substorms. The enhancements in AE are produced by activity in the pre‐midnight sector, which is the typical substorm onset region. The periodicities present in the intermittent IMF determine the exact nature of the activity, producing a range of behaviors from a sequence of isolated substorms, through substorms which merge into one‐another, to almost continuous geomagnetic activity. The magnitude of magnetic fluctuations, dB/dt, in the pre‐midnight sector during HSSs is sufficient to produce a significant risk of Geomagnetically Induced Currents.

Differential Requirement for Plexin-A3 and -A4 in Mediating Responses of Sensory and Sympathetic Neurons to Distinct Class 3 Semaphorins

Differential Requirement for Plexin-A3 and -A4 in Mediating Responses of Sensory and Sympathetic Neurons to Distinct Class 3 Semaphorins

Ethnic Conflict And The Vulnerability Of Women

It is widely accepted that ethnicity is a sort of affiliation to a group, a type of distinctiveness involving an array of characteristics or attributes such as a shared culture that may be seen in their shared history, and language that serve as the basis for this affiliation. Does it satisfy any vital need of individuals, given how fiercely people cling to their ethnic identities? Clinging to an ethnic identity is often seen to provide certain personal or societal benefits. Ethnicity is perceived by many scholars as an expression of individual or group agendas as well as political scheming. Therefore, it is not unlikely for other forms of allegiances such as that of class, to override ethnic allegiance. Owing to the worldwide gender inequality, women due to their shared experience of oppression and subordination, both economic and social, may be categorized as a distinct class in itself. It is difficult to fathom the extent to which women are subjected to atrocities during times of conflict, given how vulnerable their existence is during ordinary circumstances. This paper seeks to investigate how the patriarchal grasp on ethnicity is reinforced by designating women's bodies as symbols of ethnic purity and employing them as boundary markers. Abuse of women to portray a masculine display of power over a rival community becomes a method of warfare. As their quality of life and chances of survival seem to deteriorate during such conflicts, women tend to transcend ethnic allegiances and push for conflict resolution.

The HD-Zip I transcription factor MdHB-7 negatively regulates Valsa canker resistance in apple (Malus domestica)

Valsa canker caused by Valsa mali, one of the major fungal diseases affecting the development of the apple industry in recent years, has led to serious reductions in the yield and quality of apples. HD-Zip transcription factors are a distinct class of transcription factors in higher plants involved in the response to biotic stresses, and they play key roles in plant immunity; however, they are understudied in apples. In this study, the expression of MdHB-7 was induced by V. mali infection. Compared with wild-type (WT) apple plants, transgenic apple plants overexpressing MdHB-7 (MdHB-7-OE) showed reduced V. mali resistance, whereas plants with the expression of MdHB-7 knocked down (MdHB-7-RNAi) showed high V. mali resistance. Upon V. mali infection, the salicylic acid (SA) content and the expression levels of SA-related genes were lower in MdHB-7-OE plants than in WT plants. The content of polyphenols and the activities of chitinase and β-1, 3 glucanase were lower in MdHB-7-OE plants than in WT plants. In addition, H2O2 accumulation was higher in MdHB-7-OE plants than in WT plants following V. mali infection. The opposite patterns were observed in MdHB-7-RNAi plants. Overall, MdHB-7 plays a negative role in regulating the defense of apple against V. mali by altering the content of SA and polyphenols, the activities of defense-related enzymes, and the content of H2O2.