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A tungsten oxide load at submonolayer coverage of alumina renders highly dispersed dimeric polytungstate (octahedral and distorted octahedral coordination) and isolated monotungstate (tetrahedral) species. The polytungstate/monotungstate proportion increases when approaching monolayer. Crystalline WO3 nanoparticles emerge at higher loads. All components display hexavalent oxidation; yet, tungsten-oxide (W-O-W) and tungsten-oxide-alumina (W-O-Al) interactions were discerned by X-ray photoelectron spectroscopy of the WOx/Al2O3 materials herein prepared with 1, 3, and 5 weight percentages. The 5 wt % sample displayed the highest intensity percentage of W-O-Al species correlated to the highest methanol conversion (45 %), ascribed to the appearance of the weak acidity disclosed by temperature-programmed desorption of ammonia. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease (PD) is a chronic inflammatory disease of multifactorial origin that affects the supporting tissues of the tooth. According to WHO in 2022, severe periodontal disease will affect around 19% of the adult population worldwide. Its risk factors include the presence of periodontopathogenic bacteria in biofilm and the susceptibility of the host's immune system, among others. Preterm birth is defined as birth occurring before 37 weeks of gestational age. It also has a multifactorial origin and it's associated with risk factors such as intrauterine and extrauterine infections. There is a possibility that periodontal disease in pregnant women increases the risk of preterm birth through hematogenous pathways or the presence and intervention of inflammatory mediators., Material and Methods: Through a systematic review of existing scientific articles from 2014 to 2024, five randomized clinical trials were selected, including a total of 1984 pregnant patients diagnosed with periodontal disease. Half of these patients received non-surgical treatment, while the other half did not, aiming to evaluate a possible association between periodontal disease and/or its treatment and the occurrence of preterm birth. The risk of bias was assessed using the Cochrane "RoB 2" tool, and finally, a meta-analysis was conducted to compare the results obtained in the selected studies., Results: Four articles showed a trend favoring non-surgical periodontal treatment as a preventive measure for preterm birth. These articles accounted for 92.2% of the total weight, while the remaining 7.85% corresponded to the single article that did not favor the treatment. However, none of the articles showed statistically significant results., Conclusions: There is no demonstrated association between periodontal disease in pregnant women and the incidence of preterm birth. On the other hand, there is a slightly favorable trend towards non-surgical periodontal treatment during pregnancy as a measure to reduce the incidence of preterm birth, but it's not statistically significant. To obtain a definitive answer, more randomized clinical trials following similar study and design parameters are needed.

Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue., Competing Interests: MM, FF, CQ, FA, RR, MR, SB, YP, MC, IB, CK, RA, JG, MB No competing interests declared, (© 2024, Medina et al.)

Background: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC., Methods: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches., Results: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment., Conclusions: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction., (© 2024. The Author(s).)

Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the bla NDM-1 and tet (Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile during the COVID-19 pandemic. Methods : Antibiotic susceptibility testing was conducted on UCO-553 and UCO-554. Both isolates underwent whole-genome sequencing to ascertain their sequence type (ST), core genome multilocus sequence-typing (cgMLST) profile, antibiotic resistance genes, plasmids, and mobile genetic elements. Conjugation experiments were performed for both isolates. Results : Both isolates exhibited broad resistance, including resistance to carbapenems, third-generation cephalosporins, fluoroquinolones, tetracycline, cotrimoxazole, and aminoglycosides. Both isolates belong to sequence type ST PAS 1761, with a difference of 17 out of 2984 alleles. Each isolate carried a 47,274 bp plasmid with bla NDM-1 and aph(3')-VI genes and two highly similar plasmids: a 35,184 bp plasmid with tet (Y), sul2 , aph(6)-Id , and aph(3″)-Ib genes, and a 6078 bp plasmid containing the ant(2″)-Ia gene. Quinolone-resistance mutations were identified in the gyrA and parC genes of both isolates. Importantly, bla NDM-1 was located within a Tn 125 transposon, and tet (Y) was embedded in a Tn 5393 transposon. Conjugation experiments successfully transferred bla NDM-1 and tet (Y) into the A. baumannii ATCC 19606 strain, indicating the potential for horizontal gene transfer. Conclusions : This study highlights the critical role of plasmids in disseminating resistance genes in A. bereziniae and underscores the need for the continued genomic surveillance of this emerging pathogen. The findings emphasize the importance of monitoring A. bereziniae for its potential to cause difficult-to-treat infections and its capacity to spread resistance determinants against clinically significant antibiotics.

While understanding the genetic underpinnings of osteogenesis has far-reaching implications for skeletal diseases and evolution, a comprehensive characterization of the osteoblastic regulatory landscape in non-mammalian vertebrates is still lacking. Here, we compared the ATAC-Seq profile of Xenopus tropicalis (Xt) osteoblasts to a variety of non mineralizing control tissues, and identified osteoblast-specific nucleosome free regions (NFRs) at 527 promoters and 6747 distal regions. Sequence analyses, Gene Ontology, RNA-Seq and ChIP-Seq against four key histone marks confirmed that the distal regions correspond to bona fide osteogenic transcriptional enhancers exhibiting a shared regulatory logic with mammals. We report 425 regulatory regions conserved with human and globally associated to skeletogenic genes. Of these, 35 regions have been shown to impact human skeletal phenotypes by GWAS, including one trps1 enhancer and the runx2 promoter, two genes which are respectively involved in trichorhinophalangeal syndrome type I and cleidocranial dysplasia. Intriguingly, 60 osteoblastic NFRs also align to the genome of the elephant shark, a species lacking osteoblasts and bone tissue. To tackle this paradox, we chose to focus on dlx5 because its conserved promoter, known to integrate regulatory inputs during mammalian osteogenesis, harbours an osteoblast-specific NFR in both frog and human. Hence, we show that dlx5 is expressed in Xt and elephant shark odontoblasts, supporting a common cellular and genetic origin of bone and dentine. Taken together, our work (i) unravels the Xt osteogenic regulatory landscape, (ii) illustrates how cross-species comparisons harvest data relevant to human biology and (iii) reveals that a set of genes including bnc2, dlx5, ebf3, mir199a, nfia, runx2 and zfhx4 drove the development of a primitive form of mineralized skeletal tissue deep in the vertebrate lineage., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Terebriporidae is one of the four extant endolithic ctenostome bryozoan families, with colonies immersed into carbonate substrates like molluscan shells. This monogeneric family comprises 17 species, with 11 extant and 6 fossil species. It is currently considered closely related to vesicularioid ctenostomes, a group characterized by colonies interconnected by polymorphic stolons and a distinct gizzard as part of their digestive systems. However, confusion persists regarding the correct species identities and affiliations of many terebriporid species, and even the description of the entire family is based solely on a few external features of their boring traces, rendering the family an ichnotaxon (trace fossil). Our molecular analysis does not support a vesicularioid affinity, but corroborate a close relationship to Immergentia, another genus of boring bryozoans. Consequently, this study aims to untangle the systematic confusion surrounding Terebriporidae by examining the tracemaker of the type species of the family, Terebripora ramosa from Chile, and investigating its morphology and histology using modern techniques. The current analysis could not confirm typical vesicularioid characters such as a gizzard or true polymorphic stolons. Instead, all characters point towards a closer relationship to Immergentiidae as suggested by a recent molecular phylogeny. In fact, these two taxa share several characters such as cystid appendages and duplicature bands, and appear closely related, with the only difference being a characteristic vane with tubulets present in the tracemaker of T. ramosa. The sister-group relationship of the tracemaker and the genus Immergentia infers that these borers share a common boring ancestor, but also emphasizes that additional species from the ichnogenus Terebripora need to be studied for more clarity., (© 2024 The Author(s). Journal of Morphology published by Wiley Periodicals LLC.)

Background: Traffic accidents (TA) remain a significant global public health concern, impacting low-and middle-income countries. This study aimed to describe the trend in TA mortality and inequalities in Ecuador for 2011-2022, distributed by year, gender, age group, geographical location, type of accident, and social inequalities., Methods: An ecological study was conducted using INEC national-level data on TA fatalities in Ecuador. Mortality rates were calculated per 100,000 population and analyzed by year, gender, age group, geographic region, and accident type. Annual percentage variation (APV) was determined using linear regression models. Inequality analyses examined associations between TA mortality and socioeconomic factors like per capita income and literacy rates. Complex measures such as the Slope Inequality Index (SII) were calculated to assess the magnitude of inequalities., Results: There were 38,355 TA fatalities in Ecuador from 2011 to 2022, with an overall mortality rate of 19.4 per 100,000 inhabitants. The rate showed a non-significant decreasing trend (APV - 0.4%, p = 0.280). Males had significantly higher mortality rates than females (31.99 vs. 7.19 per 100,000), with the gender gap widening over time (APV 0.85%, p = 0.003). The Amazon region had the highest rate (24.4 per 100,000), followed by the Coast (20.4 per 100,000). Adults aged ≥ 60 years had the highest mortality (31.0 per 100,000), followed by those aged 25-40 years (28.6 per 100,000). The ≥ 60 age group showed the most significant rate decrease over time (APV - 2.25%, p < 0.001). Pedestrians were the most affected group after excluding unspecified accidents, with a notable decreasing trend (APV - 5.68%, p < 0.001). Motorcyclist fatalities showed an increasing trend, ranking third in TA-related deaths. Lower literacy rates and per capita income were associated with higher TA mortality risks. Inequality in TA mortality between provinces with the highest and lowest per capita income increased by 247.7% from 2011 to 2019, as measured by the SII., Conclusion: While overall TA mortality slightly decreased in Ecuador, significant disparities persist across demographic groups and geographic regions. Older adults, males, pedestrians, and economically disadvantaged populations face disproportionately higher risks. The increasing trend in motorcycle-related fatalities and widening socioeconomic inequalities are particularly concerning., (© 2024. The Author(s).)

Ctenostomes are a group of gymnolaemate bryozoans with an uncalcified chitinous body wall having few external, skeletal characters. Hence, species identification is challenging and their systematics remain poorly understood, even more so when they exhibit an endolithic (boring) lifestyle. Currently, there are four Recent families of endolithic bryozoans that live inside mineralized substrates like mollusk shells. In particular, Penetrantiidae Silén, 1946 has received considerable attention and its systematic affinity to either cheilostomes or ctenostomes has been debated. Species delimitation of penetrantiids remains difficult, owing to a high degree of colonial and zooidal plasticity. Consequently, an additional molecular approach is essential to unravel the systematics of penetrantiids, their phylogenetic placement and their species diversity. We therefore sequenced the mitochondrial (mt) genomes and two nuclear markers of 27 ctenostome species including nine penetrantiids. Our phylogeny supports the Penetrantiidae as a monophyletic group placed as sister taxon to the remaining ctenostomes alongside paludicellids, arachnidioids and terebriporids. The boring family Terebriporidae d'Orbigny, 1847 were previously considered to be among vesicularioids, but our results suggest an arachnidioid affinity instead. Ctenostome paraphyly is supported by our data, as the cheilostomes nest within them. A Multiporata clade is also well supported, including the former victorelloid genus Sundanella . Altogether, this study provides new insights into ctenostome systematics, assists with species delimitation and contributes to our understanding of the bryozoan tree of life., Competing Interests: All authors declare no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b-CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b-CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101-preNeus, and Lin-CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b-CD38+CD64dimCD115-, CD34+, and CD34dim/- cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/- neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34+CD45RA-/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/-CD45RA+/NCP3s, and CD34dim/-CD45RA-/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or "early neutrophil-committed progenitors," would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16- monocytes. Hence, presuming that neutrophil progenitors/"early neutrophil-committed progenitors" correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers' article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1+CD14+CD16- monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/"early neutrophil-committed progenitors" are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16- monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/"early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b + CD10 + CD16 + CD11b + PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

We report a novel case of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) mutation successfully treated with hematopoietic stem cell transplantation. The female patient presented delayed cord separation, chronic diarrhea, skin abscesses, skeletal dysmorphisms, and neutropenia with specific granule deficiency. Analysis of the transcriptomic profile of peripheral blood sorted mature and immature SMARCD2 neutrophils showed defective maturation process that associated with altered expression of genes related to specific, azurophilic, and gelatinase granules, such as LTF, CRISP3, PTX3, and CHI3L1. These abnormalities account for the prevalence of immature neutrophils in the peripheral blood, impaired function, and deregulated inflammatory responses., (© 2023 Wiley Periodicals LLC.)

The quantity and accuracy of satellite-geodetic measurements have increased over time, revolutionizing the monitoring of tectonic processes. Global Navigation Satellite System (GNSS) and satellite radar signals provide observations beyond ground deformation, including how earthquake and tsunami processes affect variations in the ionosphere. Here, we study the Hunga Tonga Hunga Ha'apai (HTHH) volcanic eruption 2022 and its associated tsunami propagation with the analysis GNSS derived Total Electron Content (TEC), Synthetic Aperture Radar (SAR) Sentinel-1 data, complemented with tide gauge observations. We utilize GNSS sites data within a ~ 5000 km radius from the volcanic eruption for estimating the ionospheric perturbation as Vertical TEC. We give evidence on the detection of acoustic gravity, internal gravity, and atmospheric Lamb waves signatures in the TEC perturbation. In particular, the internal gravity waves that concentrated in the southwest of Tonga, directly correlates with the observed tsunami propagation direction as accounted by the tide gauge measurements. However, the acoustic gravity wave signature in the TEC is dominant in the north direction suggesting a surface deformation, which could be verified using Sentinel-1A SAR amplitude data. The analysis presented herein shows that within 5 h of the volcanic eruption, the central part of the HTHH island landscape disappeared with the biggest explosion. The unprecedented detail resolved by integrating satellite data yields previously unknown details of the deformation of the 2022 HTHH volcano eruption., (© 2023. The Author(s).)

Introduction: Peripheral monocytes in humans are conventionally divided into classical (CL, CD14 ++ CD16 - ), intermediate (INT, CD14 ++ CD16 + ) and non-classical (NC, CD14 dim/- CD16 ++ ) cells, based on their expression levels of CD14 and CD16. A major fraction of the NC-monocytes has been shown to express the 6-sulfo LacNAc (slan) antigen, but whether these slan + /NC-monocytes represent the prototypical non-classical monocytes or whether they are simply a sub-fraction with identical features as the remainder of NC monocytes is still unclear., Methods: We analyzed transcriptome (by bulk and single cell RNA-seq), proteome, cell surface markers and production of discrete cytokines by peripheral slan + /NC- and slan - /NC-monocytes, in comparison to total NC-, CL- and INT- monocytes., Results: By bulk RNA-seq and proteomic analysis, we found that slan + /NC-monocytes express higher levels of genes and proteins specific of NC-monocytes than slan - /NC-monocytes do. Unsupervised clustering of scRNA-seq data generated one cluster of NC- and one of INT-monocytes, where all slan + /NC-monocytes were allocated to the NC-monocyte cluster, while slan - /NC-monocytes were found, in part (13.4%), within the INT-monocyte cluster. In addition, total NC- and slan - /NC-monocytes, but not slan + /NC-monocytes, were found by both bulk RNA-seq and scRNA-seq to contain a small percentage of natural killer cells., Conclusion: In addition to comparatively characterize total NC-, slan - /NC- and slan + /NC-monocyte transcriptomes and proteomes, our data prove that slan + /NC-, but not slan - /NC-, monocytes are more representative of prototypical NC-monocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LZ-H declared a shared committee with one of the authors MAC to the handling editor., (Copyright © 2023 Tamassia, Bianchetto-Aguilera, Gasperini, Grimaldi, Montaldo, Calzetti, Gardiman, Signoretto, Castellucci, Barnaba, Tripodi and Cassatella.)

The aim of this study was to investigate the genomic features of a carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolate (K-2157) collected in Chile. Antibiotic susceptibility was determined using the disk diffusion and broth microdilution methods. Whole-genome sequencing (WGS) and hybrid assembly were performed, using data generated on the Illumina and Nanopore platforms. The mucoid phenotype was analyzed using both the string test and sedimentation profile. The genomic features of K-2157 (e.g., sequence type, K locus, and mobile genetic elements) were retrieved using different bioinformatic tools. Strain K-2157 exhibited resistance to carbapenems and was identified as a high-risk virulent clone belonging to capsular serotype K1 and sequence type 23 (ST23). Strikingly, K-2157 displayed a resistome composed of β-lactam resistance genes ( bla SHV-190 , bla TEM-1 , bla OXA-9 , and bla KPC-2 ), the fosfomycin resistance gene fosA , and the fluoroquinolones resistance genes oqxA and oqxB . Moreover, several genes involved in siderophore biosynthesis ( ybt , iro , and iuc ), bacteriocins ( clb ), and capsule hyperproduction (plasmid-borne rmpA [ p rmpA ] and p rmpA2 ) were found, which is congruent with the positive string test displayed by K-2157. In addition, K-2157 harbored two plasmids: one of 113,644 bp (KPC+) and another of 230,602 bp, containing virulence genes, in addition to an integrative and conjugative element (ICE) embedded on its chromosome, revealing that the presence of these mobile genetic elements mediates the convergence between virulence and antibiotic resistance. Our report is the first genomic characterization of a hypervirulent and highly resistant K. pneumoniae isolate in Chile, which was collected during the coronavirus disease 2019 (COVID-19) pandemic. Due to their global dissemination and public health impact, genomic surveillance of the spread of convergent high-risk K1-ST23 K. pneumoniae clones should be highly prioritized. IMPORTANCE Klebsiella pneumoniae is a resistant pathogen involved primarily in hospital-acquired infections. This pathogen is characterized by its notorious resistance to last-line antibiotics, such as carbapenems. Moreover, hypervirulent K. pneumoniae (hvKp) isolates, first identified in Southeast Asia, have emerged globally and are able to cause infections in healthy people. Alarmingly, isolates displaying a convergence phenotype of carbapenem resistance and hypervirulence have been detected in several countries, representing a serious threat to public health. In this work, we analyzed the genomic characteristics of a carbapenem-resistant hvKp isolate recovered in 2022 from a patient with COVID-19 in Chile, representing the first analysis of this type in the country. Our results will provide a baseline for the study of these isolates in Chile, which will support the adoption of local measures aimed at controlling their dissemination., Competing Interests: The authors declare no conflict of interest.

COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease.

Subcutaneous undermining for brow lifting is not a new technique, but the gliding brow lift is evolutionary in the sense that it can be done through 1 or 2 tiny incisions and the brow shape maintained with transcutaneous running sutures (the hemostatic net). Undermining over the frontalis muscle and galea is performed using blunt dissectors and the lifting is done with superior traction, holding the brow in the desired shape with the hemostatic net., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Here we report the identification of human CD66b - CD64 dim CD115 - neutrophil-committed progenitor cells (NCPs) within the SSC lo CD45 dim CD34 + and CD34 dim/- subsets in the bone marrow. NCPs were either CD45RA + or CD45RA - , and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b + neutrophils in both in vitro differentiation and in vivo adoptive transfer experiments. Single-cell RNA-sequencing analysis indicated NCPs fell into four clusters, characterized by different maturation stages and distributed along two differentiation routes. One of the clusters was characterized by an interferon-stimulated gene signature, consistent with the reported expansion of peripheral mature neutrophil subsets that express interferon-stimulated genes in diseased individuals. Finally, comparison of transcriptomic and phenotypic profiles indicated NCPs represented earlier neutrophil precursors than the previously described early neutrophil progenitors (eNePs), proNeus and COVID-19 proNeus. Altogether, our data shed light on the very early phases of neutrophil ontogeny., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Echinoids are key components of modern marine ecosystems. Despite a remarkable fossil record, the emergence of their crown group is documented by few specimens of unclear affinities, rendering their early history uncertain. The origin of sand dollars, one of its most distinctive clades, is also unclear due to an unstable phylogenetic context. We employ 18 novel genomes and transcriptomes to build a phylogenomic dataset with a near-complete sampling of major lineages. With it, we revise the phylogeny and divergence times of echinoids, and place their history within the broader context of echinoderm evolution. We also introduce the concept of a chronospace - a multidimensional representation of node ages - and use it to explore methodological decisions involved in time calibrating phylogenies. We find the choice of clock model to have the strongest impact on divergence times, while the use of site-heterogeneous models and alternative node prior distributions show minimal effects. The choice of loci has an intermediate impact, affecting mostly deep Paleozoic nodes, for which clock-like genes recover dates more congruent with fossil evidence. Our results reveal that crown group echinoids originated in the Permian and diversified rapidly in the Triassic, despite the relative lack of fossil evidence for this early diversification. We also clarify the relationships between sand dollars and their close relatives and confidently date their origins to the Cretaceous, implying ghost ranges spanning approximately 50 million years, a remarkable discrepancy with their rich fossil record., Competing Interests: NM, JT, AH, MM, AA, SC, FA, OB, AK, RM, GR No competing interests declared, (© 2022, Mongiardino Koch et al.)

The vertebral column, or spine, provides mechanical support and determines body axis posture and motion. The most common malformation altering spine morphology and function is adolescent idiopathic scoliosis (AIS), a three-dimensional spinal deformity that affects approximately 4% of the population worldwide. Due to AIS genetic heterogenicity and the lack of suitable animal models for its study, the etiology of this condition remains unclear, thus limiting treatment options. We here review current advances in zebrafish phenogenetics concerning AIS-like models and highlight the recently discovered biological processes leading to spine malformations. First, we focus on gene functions and phenotypes controlling critical aspects of postembryonic aspects that prime in spine architecture development and straightening. Second, we summarize how primary cilia assembly and biomechanical stimulus transduction, cerebrospinal fluid components and flow driven by motile cilia have been implicated in the pathogenesis of AIS-like phenotypes. Third, we highlight the inflammatory responses associated with scoliosis. We finally discuss recent innovations and methodologies for morphometrically characterize and analyze the zebrafish spine. Ongoing phenotyping projects are expected to identify novel and unprecedented postembryonic gene functions controlling spine morphology and mutant models of AIS. Importantly, imaging and gene editing technologies are allowing deep phenotyping studies in the zebrafish, opening new experimental paradigms in the morphometric and three-dimensional assessment of spinal malformations. In the future, fully elucidating the phenogenetic underpinnings of AIS etiology in zebrafish and humans will undoubtedly lead to innovative pharmacological treatments against spinal deformities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muñoz-Montecinos, Romero, Sepúlveda, Vira, Fehrmann-Cartes, Marcellini, Aguilera, Caprile and Fuentes.)

Importance: Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels., Objective: To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia., Design, Setting, and Participants: This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials. TRILOGY 1 (Study of CaPre in Lowering Very High Triglycerides) enrolled participants at 71 US centers from January 23, 2018, to November 20, 2019; TRILOGY 2 enrolled participants at 93 US, Canadian, and Mexican centers from April 6, 2018, to January 9, 2020. Patients with fasting TG levels from 500 to 1500 mg/dL, with or without stable treatment with statins, fibrates, or other agents to lower cholesterol levels, were eligible to participate., Interventions: Randomization (2.5:1.0) to ω-3-PL/FFA, 4 g/d, vs placebo (cornstarch) for 26 weeks., Main Outcomes and Measures: The primary outcome was the mean percentage of change in TG levels at 12 weeks; persistence at 26 weeks was the key secondary outcome. Other prespecified secondary outcomes were effects on levels of non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), HDL-C, and low-density lipoprotein cholesterol (LDL-C); safety and tolerability; and TG level changes in prespecified subgroups., Results: A total of 520 patients were randomized, with a mean (SD) age of 54.9 (11.2) years (339 men [65.2%]), mean (SD) body mass index of 31.5 (5.1), and baseline mean (SD) TG level of 701 (222) mg/dL. Two hundred fifty-six patients (49.2%) were of Hispanic or Latino ethnicity; 275 (52.9%) had diabetes; and 248 (47.7%) were receiving statins. In the intention-to-treat analysis, TG levels were reduced by 26.0% (95% CI, 20.5%-31.5%) in the ω-3-PL/FFA group and 15.1% (95% CI, 6.6%-23.5%) in the placebo group at 12 weeks (mean treatment difference, -10.9% [95% CI, -20.4% to -1.5%]; P = .02), with reductions persisting at 26 weeks (mean treatment difference, -12.7% [95% CI, -23.1% to -2.4%]; P = .02). Compared with placebo, ω-3-PL/FFA had no significant effect at 12 weeks on mean treatment differences for non-HDL-C (-3.2% [95% CI, -8.0% to 1.6%]; P = .18), VLDL-C (-3.8% [95% CI, -12.2% to 4.7%]; P = .38), HDL-C (0.7% [95% CI, -3.7% to 5.1%]; P = .77), or LDL-C (4.5% [95% CI, -5.9% to 14.8%]; P = .40) levels; corresponding differences at 26 weeks were -5.8% (95% CI, -11.3% to -0.3%; P = .04) for non-HDL-C levels, -9.1% (95% CI, -21.5% to 3.2%; P = .15) for VLDL-C levels, 1.9% (95% CI, -4.8% to 8.6%; P = .57) for HDL-C levels, and 6.3% (95% CI, -12.4% to 25.0%; P = .51) for LDL-C levels. Effects on the primary end point did not vary significantly by age, sex, race and ethnicity, country, qualifying TG level, diabetes, or fibrate use but tended to be larger among patients taking statins or cholesterol absorption inhibitors at baseline (mean treatment difference, -19.5% [95% CI, -34.5% to -4.6%]; P = .08 for interaction) and with lower (less than median) baseline blood eicosapentaenoic acid plus docosahexaenoic acid levels (-19.5% [95% CI, -33.8% to -5.3%]; P = .08 for interaction). ω-3-PL/FFA was well tolerated, with a safety profile similar to that of placebo., Conclusions and Relevance: This study found that ω-3 -PL/FFA, a novel krill oil-derived ω-3 formulation, reduced TG levels and was safe and well tolerated in patients with severe hypertriglyceridemia., Trial Registration: ClinicalTrials.gov Identifiers: NCT03398005 and NCT03361501.

Understanding at microscopic level the generation of contents in an online social network (OSN) is highly desirable for an improved management of the OSN and the prevention of undesirable phenomena, such as online harassment. Content generation, i.e., the decision to post a contributed content in the OSN, can be modeled by neurophysiological approaches on the basis of unbiased semantic analysis of the contents already published in the OSN. This paper proposes a neuro-semantic model composed of (1) an extended leaky competing accumulator (ELCA) as the neural architecture implementing the user concurrent decision process to generate content in a conversation thread of a virtual community of practice, and (2) a semantic modeling based on the topic analysis carried out by a latent Dirichlet allocation (LDA) of both users and conversation threads. We use the similarity between the user and thread semantic representations to built up the model of the interest of the user in the thread contents as the stimulus to contribute content in the thread. The semantic interest of users in discussion threads are the external inputs for the ELCA, i.e., the external value assigned to each choice.. We demonstrate the approach on a dataset extracted from a real life web forum devoted to fans of tinkering with musical instruments and related devices. The neuro-semantic model achieves high performance predicting the content posting decisions (average F score 0.61) improving greatly over well known machine learning approaches, namely random forest and support vector machines (average F scores 0.19 and 0.21)., Competing Interests: Conflict of interestAuthors declare that they do not have conflict of interests., (© The Author(s) 2022.)