Broad Functions Research Articles

Insights into the multifaceted role of interleukin-37 on human immune cell regulation

Autoinflammatory diseases, while having a variety of underlying causes, are mediated by dysfunctional innate immune responses. Therefore, standard treatments target innate cytokines or block their receptors. Despite excellent responses in some patients, first-line treatments fail in others, for reasons which remain to be understood.We studied the effects of IL-37, an anti-inflammatory cytokine, on immune cells using multi-omics profiling of 325 healthy adults. Our findings show that IL-37 is associated with inflammation control and generally reduced immune cell activity. Further, genetic variants in IL37 are associated with impaired trained immunity, a memory phenotype of innate immune cells contributing to autoinflammation. To underpin the medical potential of IL-37, an explorative cohort of seven autoinflammatory disorders was built. In vitro stimulation experiments argue for recombinant IL-37 as a potential therapy in IL-6-, and IL-22-driven conditions.Concluding, IL-37 is highlighted as a cytokine with broad anti-inflammatory functions, implicating its potential as therapeutic intervention.

Photoredox-Catalyzed Three-Component Construction of Aryl Sulfonyl Fluoride Using KHF2: Late-Stage Drug Fluorosulfonylation.

Aryl sulfonyl fluorides are prominently featured in organic synthesis and medicinal chemistry. Herein, a metal-free photoredox-catalyzed three-component assembly of aryl sulfonyl fluoride via aryl sulfonyl ammonium salt intermediate has been reported. A variety of structurally diverse aryl sulfonyl fluorides were synthesized rapidly from dibenzothiophenium (DBT) salts under mild conditions by using KHF2 as the fluorine source. Notably, this methodology can be employed as an efficient and sustainable approach for late-stage drug fluorosulfonylation. Good yields and broad functionality tolerance were the features of this methodology. Moreover, the derivatization of aryl sulfonyl fluoride molecules was also demonstrated to showcase its synthetic utility.

Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity

Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

Nickel-Catalyzed Enantioselective Reductive N-Cyclization-Thiolation Reaction of Alkene-Tethered Oxime Esters and Disulfides.

Asymmetric aza-Heck cyclization and coupling reactions offer efficient access to enantioenriched N-heterocycles, yet the current studies focus primarily on sequential C-N and C-C bond formation. Herein, we report an enantioselective reductive aza-Heck cyclization followed by a C-S coupling sequence, ultimately yielding sulfide-containing enantioenriched pyrrolines. The reaction is conducted under mild conditions and tolerates broad functionalities including alkynes, phenols, anilines, amides, nitriles, and bromides.

B - 65 Adolescent Cortico-Limbic Connectivity Mediates Associations between Internalizing Symptomology and Subsequent Neurocognitive Performance

Abstract Objective During development, internalizing symptoms negatively impact broad neurocognitive functioning. Hypoconnectivity between the Cingulo-Opercular network (CON) and limbic regions has been implicated in various psychiatric disorders. Here we attempt to investigate whether CON-limbic connectivity longitudinally mediates associations between internalizing behaviors and cognitive outcomes during adolescence. Method Internalizing symptoms were measured in 2668 youth (47% female) enrolled in the Adolescent Brain Cognitive Development study using the Child Behavior Checklist. Zero-order correlations were tested between baseline (ages 9–11) internalizing symptoms (anxiety, depression, somatic complaints) and performance on NIH Toolbox® neurocognitive measures at 4-year follow-up (ages 13–15). Significantly predicted tasks were included in a structural equation model (SEM), which tested whether a latent factor representing 2-year follow-up resting-state fMRI connectivity between the CON and limbic regions (i.e., bilateral hippocampus and amygdala) mediated associations between baseline internalizing symptoms and 4-year cognitive outcomes. Results Four neurocognitive tasks (Flanker, Picture Sequence, List Sorting, Pattern Comparison) regressed significantly onto at least one internalizing symptom. An SEM which tested the mediatory effects of CON-limbic connectivity on these associations fit the data well (CFI = 0.997; SRMR = 0.007; RMSEA =0.015 [0,0.027]). Increased anxiety and somatic symptoms significantly predicted reduced CON-limbic connectivity, while depression did not. Associations between anxiety and somatic symptoms and List Sorting performance were suppressed, indicating full mediation by CON-limbic connectivity on working memory. Connectivity also partially mediated a negative association between anxiety and Flanker performance. Conclusions Our findings point to CON-limbic hypoconnectivity as a potential mechanism underlying associations between late childhood internalizing symptoms and poorer executive functioning (most notably working memory) during early adolescence.

The dual role of ribosomal protein SA in pathogen infection: the key role of structure and localization.

Ribosomal protein SA (RPSA) plays multiple roles in cells, including ribosomal biogenesis and translation, cellular migration, and cytoskeleton reorganization. RPSA is crucial in the process of pathogen infection. Extensive research has examined RPSA's role in pathogen adhesion and invasion, but its broader functions, particularly its anti-infective capabilities, have garnered increasing attention in recent years. This dual role is closely related to its structural domains, which influence its localization and function. This review summarizes key research findings concerning the functional domains of RPSA and analyzes the relationship between its membrane localization and structural domains. Additionally, the functional implications of RPSA are categorized based on its different localizations during pathogen infection. Specifically, when RPSA is located on the cell surface, it promotes pathogen adhesion and invasion of host cells; conversely, when RPSA is located intracellularly, it exhibits anti-infective properties. Overall, RPSA shows a dual nature, both in facilitating pathogen invasion of the host and in possessing the ability to resist pathogen infection. This review comprehensively examines the dual role of RPSA in pathogen infection by analyzing its structural domains, localization, and interactions with cellular and pathogen molecules. Our aim is to update and deepen researchers' understanding of the various functions of RPSA during pathogen infection.

DUS4L suppresses invasion and metastasis in LUAD via modulation of PI3K/AKT and ERK/MAPK signaling through GRB2

ObjectiveLimited research has focused on the role of dihydrouridine synthases (DUS) family members in human tumors. Our previous findings indicated an impact of dihydrouridine synthase 4 like (DUS4L) on cell proliferation and apoptosis in lung adenocarcinoma (LUAD) A549 cell, yet its broader functions and regulatory mechanisms in LUAD remain elusive. MethodsUsing a LUAD tissue microarray and immunohistochemical (IHC) staining, we validated variations in DUS4L protein expression levels among LUAD patients and assessed its clinical significance. Additional experiments using short hairpin RNA (shRNA) against DUS4L (sh-DUS4L-2), LUAD cell lines, cell function assays (including wound healing, transwell migration and invasion, colony formation, and apoptosis assays), and mouse tumor xenografts were performed to examine the biological roles of DUS4L in LUAD progression. RNA sequencing, proteomic analyses, mass spectrometry, and co-immunoprecipitation experiments were conducted to identify and validate DUS4L-regulated downstream target genes and signaling pathways. ResultsWe identified a consistent upregulation of DUS4L in LUAD tissues. In vitro and in vivo experiments underscored the inhibitory effect of DUS4L downregulation on LUAD progression, including migration, invasion, and proliferation. Mechanistically, DUS4L was found to interact with the signaling molecule GRB2, promoting LUAD progression and metastasis by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK/MAPK pathways. ConclusionOur results establish the functional role of DUS4L in driving the progression and metastasis of LUAD, implicating its potential as a candidate therapeutic target for LUAD.

Poration of mitochondrial membranes by amyloidogenic peptides and other biological toxins.

Mitochondria are essential organelles known to serve broad functions, including in cellular metabolism, calcium buffering, signaling pathways and the regulation of apoptotic cell death. Maintaining the integrity of the outer (OMM) and inner mitochondrial membranes (IMM) is vital for mitochondrial health. Cardiolipin (CL), a unique dimeric glycerophospholipid, is the signature lipid of energy-converting membranes. It plays a significant role in maintaining mitochondrial architecture and function, stabilizing protein complexes and facilitating efficient oxidative phosphorylation (OXPHOS) whilst regulating cytochrome c release from mitochondria. CL is especially enriched in the IMM and at sites of contact between the OMM and IMM. Disorders of protein misfolding, such as Alzheimer's and Parkinson's diseases, involve amyloidogenic peptides like amyloid-β, tau and α-synuclein, which form metastable toxic oligomeric species that interact with biological membranes. Electrophysiological studies have shown that these oligomers form ion-conducting nanopores in membranes mimicking the IMM's phospholipid composition. Poration of mitochondrial membranes disrupts the ionic balance, causing osmotic swelling, loss of the voltage potential across the IMM, release of pro-apoptogenic factors, and leads to cell death. The interaction between CL and amyloid oligomers appears to favour their membrane insertion and pore formation, directly implicating CL in amyloid toxicity. Additionally, pore formation in mitochondrial membranes is not limited to amyloid proteins and peptides; other biological peptides, as diverse as the pro-apoptotic Bcl-2 family members, gasdermin proteins, cobra venom cardiotoxins and bacterial pathogenic toxins, have all been described to punch holes in mitochondria, contributing to cell death processes. Collectively, these findings underscore the vulnerability of mitochondria and the involvement of CL in various pathogenic mechanisms, emphasizing the need for further research on targeting CL-amyloid interactions to mitigate mitochondrial dysfunction.

Nickel-Catalyzed Reductive Amidation of Aryl Fluorosulfates with Isocyanates: Synthesis of Amides via C-O Bond Cleavage.

With the assistance of nickel as catalyst, 2,2'-bipyridine (bpy) as ligand, and manganese as reducing metal, the reductive amidation of isocyanates with readily accessible aryl fluorosulfates could be successfully accomplished. The reactions proceeded effectively via C-O bond activation in DMF at room temperature, enabling the facile synthesis of a range of structurally diverse amides in moderate to high yields with broad functionality compatibility. In addition, the synthetic usefulness of the method was further demonstrated by applying the reaction in scale-up synthesis and the late-stage functionalization of complex molecules with biological activities.

Primary SARS-CoV-2 variant of concern infections elicit broad antibody Fc-mediated effector functions and memory B cell responses.

Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by human sera is a strong correlate of protection against symptomatic and severe Coronavirus Disease 2019 (COVID-19). The emergence of antigenically distinct SARS-CoV-2 variants of concern (VOCs) and the relatively rapid waning of serum antibody titers, however, raises questions about the sustainability of serum protection. In addition to serum neutralization, other antibody functionalities and the memory B cell (MBC) response are suggested to help maintaining this protection. In this study, we investigate the breadth of spike (S) protein-specific serum antibodies that mediate effector functions by interacting with Fc-gamma receptor IIa (FcγRIIa) and FcγRIIIa, and of the receptor binding domain (RBD)-specific MBCs, following a primary SARS-CoV-2 infection with the D614G, Alpha, Beta, Gamma, Delta, Omicron BA.1 or BA.2 variant. Irrespectively of the variant causing the infection, the breadth of S protein-specific serum antibodies that interact with FcγRIIa and FcγRIIIa and the RBD-specific MBC responses exceeded the breadth of serum neutralization, although the Alpha-induced B cell response seemed more strain-specific. Between VOC groups, both quantitative and qualitative differences in the immune responses were observed, suggesting differences in immunogenicity. Overall, this study contributes to the understanding of protective humoral and B cell responses in the light of emerging antigenically distinct VOCs, and highlights the need to study the immune system beyond serum neutralization to gain a better understanding of the protection against emerging variants.

EWS-FLI1 and Activator Protein-1 (AP-1) Reciprocally Regulate Extracellular-Matrix Proteins in Ewing sarcoma Cells.

Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the synthesis of deoxyribonucleotides and the target of multiple chemotherapy drugs, including gemcitabine. We previously identified that inhibition of RNR in Ewing sarcoma tumors upregulates the expression levels of multiple members of the activator protein-1 (AP-1) transcription factor family, including c-Jun and c-Fos, and downregulates the expression of c-Myc. However, the broader functions and downstream targets of AP-1, which are highly context- and cell-dependent, are unknown in Ewing sarcoma tumors. Consequently, in this work, we used genetically defined models, transcriptome profiling, and gene-set -enrichment analysis to identify that AP-1 and EWS-FLI1, the driver oncogene in most Ewing sarcoma tumors, reciprocally regulate the expression of multiple extracellular-matrix proteins, including fibronectins, integrins, and collagens. AP-1 expression in Ewing sarcoma cells also drives, concurrent with these perturbations in gene and protein expression, changes in cell morphology and phenotype. We also identified that EWS-FLI1 dysregulates the expression of multiple AP-1 proteins, aligning with previous reports demonstrating genetic and physical interactions between EWS-FLI1 and AP-1. Overall, these results provide novel insights into the distinct, EWS-FLI1-dependent features of Ewing sarcoma tumors and identify a novel, reciprocal regulation of extracellular-matrix components by EWS-FLI1 and AP-1.

Multifractal analysis of heart rate variability in pregnancy during sleep.

Understanding the complex dynamics of heart rate variability (HRV) during pregnancy is crucial for monitoring both maternal well-being and fetal health. In this study, we use the Multifractal Detrended Fluctuations Analysis approach to investigate HRV patterns in pregnant individuals during sleep based on RR interval maxima (MM fluctuations). In addition, we study the type of multifractality within MM fluctuations, that is, if it arises from a broad probability density function or from varying long-range correlations. Furthermore, to provide a comprehensive view of HRV changes during sleep in pregnancy, classical temporal and spectral HRV indices were calculated at quarterly intervals during sleep. Our study population consists of 21 recordings from nonpregnant women, 18 from the first trimester (early-pregnancy) and 18 from the second trimester (middle-pregnancy) of pregnancy. Results. There are statistically significant differences ( -value < 0.05) in mean heart rate, rms heart rate, mean MM fluctuations, and standard deviation of MM fluctuations, particularly in the third and fourth quarter of sleep between pregnant and non-pregnant states. In addition, the early-pregnancy group shows significant differences ( -value < 0.05) in spectral indices during the first and fourth quarter of sleep compared to the non-pregnancy group. Furthermore, the results of our research show striking similarities in the average multifractal structure of MM fluctuations between pregnant and non-pregnant states during normal sleep. These results highlight the influence of different long-range correlations within the MM fluctuations, which could be primarily associated with the emergence of sleep cycles on multifractality during sleep. Finally, we performed a separability analysis between groups using temporal and spectral HRV indices as features per sleep quarter. Employing only three features after Principal Component Analysis (PCA) to the original feature set, achieving complete separability among all groups appears feasible. Using multifractal analysis, our study provides a comprehensive understanding of the complex HRV patterns during pregnancy, which holds promise for maternal and fetal health monitoring. The separability analysis also provides valuable insights into the potential for group differentiation using simple measures such as mean heart rate, rms heart rate, and mean MM fluctuations or in the transformed feature space based on PCA.

Systemic Factors Effecting Human Beta-Defensins in Oral Cavity.

Human beta-defensins are host defense peptides with broad antimicrobial and inflammatory functions. In the oral cavity, these peptides are produced mainly by the keratinocytes of the epithelium; however, fibroblasts, monocytes, and macrophages also contribute to oral human beta-defensin expressions. The resident and immune cells of the oral cavity come into contact with various microbe-associated molecular patterns continuously and simultaneously. The overall antimicrobial cellular response is highly influenced by local and environmental factors. Recent studies have produced evidence showing that not only systemic chronic diseases but also systemic factors like hyperglycemia, pregnancy, the long-term use of certain vitamins, and aging can modulate oral cellular antimicrobial responses against microbial challenges. Therefore, the aim of this narrative review is to discuss the role of systemic factors on oral human beta-defensin expressions.

Genome characterization of Leuconostoc pseudomesenteroides UTNElla29 isolated from Morus nigra (L.) fruits: A promising exopolysaccharides producing strain

Lactic acid bacteria produce various natural polysaccharides that are secreted into the cellular matrix and bonded to the cell surface or released into the surrounding environment. Due to their broad applications in the food industry, the search for novel polysaccharide producer strains remains of interest. In this study, we report the genome sequencing and characterization of Leuconostoc pseudomesenteroides strain UTNElla29 isolated from Morus nigra (L.) fruits. Using in silico different “genome mining” tools we prospect their genetic potential. The genome size was estimated at 2,272,560 bp and a GC content of 39.26%. Of the total proteins, 2170 matched in the EggNOG database. The key genes related to amino acid biosynthesis, carbohydrate metabolism, exopolysaccharide (EPS) production, were annotated. The genome harbors one intact prophage, one CRISPR array, and two putative gene sequences associated with CAS3 Type I, and no plasmids indicating its stability. Moreover, no acquired resistance genes, virulence and pathogenic factors, nor biogenic amines were predicted, suggesting its safety. In vitro preliminary studies showed that EPS yield from 0.4 to 10.2 (g/L) dry biomass and the production varied with the inoculum size and sugar type MRS containing medium. Furthermore, several polyketides and terpenes were predicted, indicating the possibility of generating a wide range of naturally compounds with broad biological functions. However, these promising results suggest that Ella29 is a beneficial strain to be further exploited in vitro for various technological use.

Selective Tyrosine Kinase 2 (TYK2) Inhibition in Plaque Psoriasis.

Members of the Janus kinase (JAK) superfamily, comprising tyrosine kinase 2 (TYK2) and JAK1, JAK2, and JAK3, mediate signaling by cytokines (eg, interleukin [IL]-23) involved in psoriasis pathogenesis. Binding of IL-23 to its receptor activates TYK2 and JAK2, which trigger signal transducer and activator of transcription (STAT) translocation to the nucleus to regulate target gene transcription, including genes of proinflammatory mediators such as IL-17. Physiologically, TYK2 solely mediates immune function, whereas JAK1,2,3 mediate broad systemic and immune functions. Inhibition of individual JAK family members is being evaluated in many dermatologic indications, including psoriasis. Selective TYK2 inhibition is therefore expected to be associated with few adverse effects in patients with psoriasis. People with genetic mutations leading to loss of function of TYK2 are protected from the development of psoriasis without an increased risk of infections or malignancies. In contrast, treatments with JAK1,2,3 inhibitors are associated with various systemic effects. We review the unique allosteric mechanism of action of the selective TYK2 inhibitor, deucravacitinib, which binds to the TYK2 regulatory (pseudokinase) domain, and the mechanisms of action of JAK1,2,3 inhibitors, which bind to the adenosine 5'-triphosphate-binding active (catalytic) site in the kinase domains of JAK1,2,3. Deucravacitinib, which is approved for the treatment of moderate to severe plaque psoriasis in adults in the United States and several other countries, represents a novel, targeted systemic treatment approach with a favorable safety profile. J Drugs Dermatol. 2024;23(8):645-652.&nbsp; doi:10.36849/JDD.8293.

A modular toolkit for environmental Rhodococcus, Gordonia, and Nocardia enables complex metabolic manipulation.

Soil-dwelling Actinomycetes are a diverse and ubiquitous component of the global microbiome but largely lack genetic tools comparable to those available in model species such as Escherichia coli or Pseudomonas putida, posing a fundamental barrier to their characterization and utilization as hosts for biotechnology. To address this, we have developed a modular plasmid assembly framework, along with a series of genetic control elements for the previously genetically intractable Gram-positive environmental isolate Rhodococcus ruber C208, and demonstrate conserved functionality in 11 additional environmental isolates of Rhodococcus, Nocardia, and Gordonia. This toolkit encompasses five Mycobacteriale origins of replication, five broad-host-range antibiotic resistance markers, transcriptional and translational control elements, fluorescent reporters, a tetracycline-inducible system, and a counter-selectable marker. We use this toolkit to interrogate the carotenoid biosynthesis pathway in Rhodococcus erythropolis N9T-4, a weakly carotenogenic environmental isolate and engineer higher pathway flux toward the keto-carotenoid canthaxanthin. This work establishes several new genetic tools for environmental Mycobacteriales and provides a synthetic biology framework to support the design of complex genetic circuits in these species.IMPORTANCESoil-dwelling Actinomycetes, particularly the Mycobacteriales, include both diverse new hosts for sustainable biomanufacturing and emerging opportunistic pathogens. Rhodococcus, Gordonia, and Nocardia are three abundant genera with particularly flexible metabolisms and untapped potential for natural product discovery. Among these, Rhodococcus ruber C208 was shown to degrade polyethylene; Gordonia paraffinivorans can assimilate carbon from solid hydrocarbons; and Nocardia neocaledoniensis (and many other Nocardia spp.) possesses dual isoprenoid biosynthesis pathways. Many species accumulate high levels of carotenoid pigments, indicative of highly active isoprenoid biosynthesis pathways which may be harnessed for fermentation of terpenes and other commodity isoprenoids. Modular genetic toolkits have proven valuable for both fundamental and applied research in model organisms, but such tools are lacking for most Actinomycetes. Our suite of genetic tools and DNA assembly framework were developed for broad functionality and to facilitate rapid prototyping of genetic constructs in these organisms.

How can networks address barriers to nature-based solutions? The case of agriculture and construction in the Netherlands

Nature-based solutions (NBS) can play a critical role in sustainability transitions in both urban and rural areas, but their uptake is hindered by a wide variety of barriers. While networks have been identified as a support structure for mainstreaming NBS, it is unclear what specific roles networks play in addressing the multiple barriers that NBS mainstreaming faces. Through qualitative research using focus group meetings and semi-structured interviews within two sectors in the Netherlands where attempts towards a nature-based transition are observed – i.e., agriculture and construction – we identify seven different functions through which networks address six specific barrier categories. We find broad network functions (e.g., knowledge sharing) that address multiple types of barriers simultaneously and targeted network functions (e.g., lobbying towards policy makers) aimed at alleviating one specific type of barrier. We also document that networks leave certain barriers unaddressed, such as technological and political barriers in the construction sector and social barriers in both sectors. Our results contribute to a more in-depth understanding of network function – barrier combinations for nature-based sustainability transitions, both in an urban and a rural context, which can help networks to further strategize and allocate their resources.

Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection.

Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.

Exploring EAP English text readability and reader ability of Chinese university students through Lexile measures and metaphorical conceptualizations

This study aimed to ascertain and then close gaps between the readability demanded by degree-level textbooks in English and the reading abilities of Chinese students in a foundation programme of an English-medium university in China. A quasi-experimental research design shows Lexile-based reading interventions conducted both outside and inside class over one year within an English for Academic Purposes (EAP) class which might close the reading gap. Participants' English reading experiences were explored through Metaphor Analysis of their constructed metaphors regarding reading, academic reading and EAP reading strategies. The quantitative results show a significant reading ability growth in the experimental group after engaging in Lexile-based reading activities. This suggests that the Lexile-based reading intervention tends to raise students' reading ability towards a desired standard. Students completing inside-class reading journals made greater reading improvements than those joining outside-class reading tutorials. The metaphor analysis showed conceptualisations within five broad functions of reading evident in the participants’ metaphors: cognitive, affective, socio-cultural, moral-spiritual, and aesthetic. The cognitive and emotional aspects emerge saliently in both positive and negative student comments in metaphors on reading. Pedagogic implications and applications are suggested.

Characterizing the gut phageome and phage-borne antimicrobial resistance genes in pigs

BackgroundMammalian intestine harbors a mass of phages that play important roles in maintaining gut microbial ecosystem and host health. Pig has become a common model for biomedical research and provides a large amount of meat for human consumption. However, the knowledge of gut phages in pigs is still limited.ResultsHere, we investigated the gut phageome in 112 pigs from seven pig breeds using PhaBOX strategy based on the metagenomic data. A total of 174,897 non-redundant gut phage genomes were assembled from 112 metagenomes. A total of 33,487 gut phage genomes were classified and these phages mainly belonged to phage families such as Ackermannviridae, Straboviridae, Peduoviridae, Zierdtviridae, Drexlerviridae, and Herelleviridae. The gut phages in seven pig breeds exhibited distinct communities and the gut phage communities changed with the age of pig. These gut phages were predicted to infect a broad range of 212 genera of prokaryotes, such as Candidatus Hamiltonella, Mycoplasma, Colwellia, and Lactobacillus. The data indicated that broad KEGG and CAZy functions were also enriched in gut phages of pigs. The gut phages also carried the antimicrobial resistance genes (ARGs) and the most abundant antimicrobial resistance genotype was diaminopyrimidine resistance.ConclusionsOur research delineates a landscape for gut phages in seven pig breeds and reveals that gut phages serve as a key reservoir of ARGs in pigs.53TvwP5ops6wwG1EthsGXZVideo