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Horizontal gene transfer (HGT) is an important evolutionary force shaping prokaryotic and eukaryotic genomes. HGT-acquired genes have been sporadically reported in insects, a lineage containing >50% of animals. We systematically examined HGT in 218 high-quality genomes of diverse insects and found that they acquired 1,410 genes exhibiting diverse functions, including many not previously reported, via 741 distinct transfers from non-metazoan donors. Lepidopterans had the highest average number of HGT-acquired genes. HGT-acquired genes containing introns exhibited substantially higher expression levels than genes lacking introns, suggesting that intron gains were likely involved in HGT adaptation. Lastly, we used the CRISPR-Cas9 system to edit the prevalent unreported gene LOC105383139, which was transferred into the last common ancestor of moths and butterflies. In diamondback moths, males lacking LOC105383139 courted females significantly less. We conclude that HGT has been a major contributor to insect adaptation.
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Mariposas Diurnas , Transferencia de Gen Horizontal , Animales , Mariposas Diurnas/genética , Cortejo , Evolución Molecular , Masculino , FilogeniaRESUMEN
Operons are a hallmark of bacterial genomes, where they allow concerted expression of functionally related genes as single polycistronic transcripts. They are rare in eukaryotes, where each gene usually drives expression of its own independent messenger RNAs. Here, we report the horizontal operon transfer of a siderophore biosynthesis pathway from relatives of Escherichia coli into a group of budding yeast taxa. We further show that the co-linearly arranged secondary metabolism genes are expressed, exhibit eukaryotic transcriptional features, and enable the sequestration and uptake of iron. After transfer, several genetic changes occurred during subsequent evolution, including the gain of new transcription start sites that were sometimes within protein-coding sequences, acquisition of polyadenylation sites, structural rearrangements, and integration of eukaryotic genes into the cluster. We conclude that the genes were likely acquired as a unit, modified for eukaryotic gene expression, and maintained by selection to adapt to the highly competitive, iron-limited environment.
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Eucariontes/genética , Transferencia de Gen Horizontal/genética , Operón/genética , Bacterias/genética , Escherichia coli/genética , Células Eucariotas , Evolución Molecular , Regulación Bacteriana de la Expresión Génica/genética , Genes Bacterianos/genética , Genoma Bacteriano/genética , Genoma Fúngico/genética , Saccharomycetales/genética , Sideróforos/genéticaRESUMEN
Budding yeasts (subphylum Saccharomycotina) are found in every biome and are as genetically diverse as plants or animals. To understand budding yeast evolution, we analyzed the genomes of 332 yeast species, including 220 newly sequenced ones, which represent nearly one-third of all known budding yeast diversity. Here, we establish a robust genus-level phylogeny comprising 12 major clades, infer the timescale of diversification from the Devonian period to the present, quantify horizontal gene transfer (HGT), and reconstruct the evolution of 45 metabolic traits and the metabolic toolkit of the budding yeast common ancestor (BYCA). We infer that BYCA was metabolically complex and chronicle the tempo and mode of genomic and phenotypic evolution across the subphylum, which is characterized by very low HGT levels and widespread losses of traits and the genes that control them. More generally, our results argue that reductive evolution is a major mode of evolutionary diversification.
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Evolución Molecular , Transferencia de Gen Horizontal , Genoma Fúngico , Filogenia , Saccharomycetales/clasificación , Saccharomycetales/genéticaRESUMEN
Genome-scale data and the development of novel statistical phylogenetic approaches have greatly aided the reconstruction of a broad sketch of the tree of life and resolved many of its branches. However, incongruence - the inference of conflicting evolutionary histories - remains pervasive in phylogenomic data, hampering our ability to reconstruct and interpret the tree of life. Biological factors, such as incomplete lineage sorting, horizontal gene transfer, hybridization, introgression, recombination and convergent molecular evolution, can lead to gene phylogenies that differ from the species tree. In addition, analytical factors, including stochastic, systematic and treatment errors, can drive incongruence. Here, we review these factors, discuss methodological advances to identify and handle incongruence, and highlight avenues for future research.
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Evolución Biológica , Genoma , Filogenia , Evolución Molecular , Hibridación GenéticaRESUMEN
MicroRNAs (miRNAs) are a class of nonprotein-coding short transcripts that provide a layer of post-transcriptional regulation essential to many plant biological processes. MiR858, which targets the transcripts of MYB transcription factors, can affect a range of secondary metabolic processes. Although miR858 and its 187-nt precursor have been well studied in Arabidopsis (Arabidopsis thaliana), a systematic investigation of miR858 precursors and their functions across plant species is lacking due to a problem in identifying the transcripts that generate this subclass. By re-evaluating the transcript of miR858 and relaxing the length cut-off for identifying hairpins, we found in kiwifruit (Actinidia chinensis) that miR858 has long-loop hairpins (1,100 to 2,100 nt), whose intervening sequences between miRNA generating complementary sites were longer than all previously reported miRNA hairpins. Importantly, these precursors of miR858 containing long-loop hairpins (termed MIR858L) are widespread in seed plants including Arabidopsis, varying between 350 and 5,500 nt. Moreover, we showed that MIR858L has a greater impact on proanthocyanidin and flavonol levels in both Arabidopsis and kiwifruit. We suggest that an active MIR858L-MYB regulatory module appeared in the transition of early land plants to large upright flowering plants, making a key contribution to plant secondary metabolism.
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Actinidia , Arabidopsis , Regulación de la Expresión Génica de las Plantas , MicroARNs , ARN de Planta , MicroARNs/genética , MicroARNs/metabolismo , Actinidia/genética , Actinidia/metabolismo , Arabidopsis/genética , ARN de Planta/genética , ARN de Planta/metabolismo , Semillas/genética , Semillas/metabolismo , Secuencia de BasesRESUMEN
How genomic differences contribute to phenotypic differences is a major question in biology. The recently characterized genomes, isolation environments, and qualitative patterns of growth on 122 sources and conditions of 1,154 strains from 1,049 fungal species (nearly all known) in the yeast subphylum Saccharomycotina provide a powerful, yet complex, dataset for addressing this question. We used a random forest algorithm trained on these genomic, metabolic, and environmental data to predict growth on several carbon sources with high accuracy. Known structural genes involved in assimilation of these sources and presence/absence patterns of growth in other sources were important features contributing to prediction accuracy. By further examining growth on galactose, we found that it can be predicted with high accuracy from either genomic (92.2%) or growth data (82.6%) but not from isolation environment data (65.6%). Prediction accuracy was even higher (93.3%) when we combined genomic and growth data. After the GALactose utilization genes, the most important feature for predicting growth on galactose was growth on galactitol, raising the hypothesis that several species in two orders, Serinales and Pichiales (containing the emerging pathogen Candida auris and the genus Ogataea, respectively), have an alternative galactose utilization pathway because they lack the GAL genes. Growth and biochemical assays confirmed that several of these species utilize galactose through an alternative oxidoreductive D-galactose pathway, rather than the canonical GAL pathway. Machine learning approaches are powerful for investigating the evolution of the yeast genotype-phenotype map, and their application will uncover novel biology, even in well-studied traits.
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Galactosa , Aprendizaje Automático , Galactosa/metabolismo , Genoma Fúngico , Redes y Vías Metabólicas/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genéticaRESUMEN
The Saccharomycotina yeasts ("yeasts" hereafter) are a fungal clade of scientific, economic, and medical significance. Yeasts are highly ecologically diverse, found across a broad range of environments in every biome and continent on earth; however, little is known about what rules govern the macroecology of yeast species and their range limits in the wild. Here, we trained machine learning models on 12,816 terrestrial occurrence records and 96 environmental variables to infer global distribution maps at ~1 km2 resolution for 186 yeast species (~15% of described species from 75% of orders) and to test environmental drivers of yeast biogeography and macroecology. We found that predicted yeast diversity hotspots occur in mixed montane forests in temperate climates. Diversity in vegetation type and topography were some of the greatest predictors of yeast species richness, suggesting that microhabitats and environmental clines are key to yeast diversity. We further found that range limits in yeasts are significantly influenced by carbon niche breadth and range overlap with other yeast species, with carbon specialists and species in high-diversity environments exhibiting reduced geographic ranges. Finally, yeasts contravene many long-standing macroecological principles, including the latitudinal diversity gradient, temperature-dependent species richness, and a positive relationship between latitude and range size (Rapoport's rule). These results unveil how the environment governs the global diversity and distribution of species in the yeast subphylum. These high-resolution models of yeast species distributions will facilitate the prediction of economically relevant and emerging pathogenic species under current and future climate scenarios.
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Biodiversidad , Ecosistema , Clima , Bosques , Carbono , LevadurasRESUMEN
Siderophores are crucial for iron-scavenging in microorganisms. While many yeasts can uptake siderophores produced by other organisms, they are typically unable to synthesize siderophores themselves. In contrast, Wickerhamiella/Starmerella (W/S) clade yeasts gained the capacity to make the siderophore enterobactin following the remarkable horizontal acquisition of a bacterial operon enabling enterobactin synthesis. Yet, how these yeasts absorb the iron bound by enterobactin remains unresolved. Here, we demonstrate that Enb1 is the key enterobactin importer in the W/S-clade species Starmerella bombicola. Through phylogenomic analyses, we show that ENB1 is present in all W/S clade yeast species that retained the enterobactin biosynthetic genes. Conversely, it is absent in species that lost the ent genes, except for Starmerella stellata, making this species the only cheater in the W/S clade that can utilize enterobactin without producing it. Through phylogenetic analyses, we infer that ENB1 is a fungal gene that likely existed in the W/S clade prior to the acquisition of the ent genes and subsequently experienced multiple gene losses and duplications. Through phylogenetic topology tests, we show that ENB1 likely underwent horizontal gene transfer from an ancient W/S clade yeast to the order Saccharomycetales, which includes the model yeast Saccharomyces cerevisiae, followed by extensive secondary losses. Taken together, these results suggest that the fungal ENB1 and bacterial ent genes were cooperatively integrated into a functional unit within the W/S clade that enabled adaptation to iron-limited environments. This integrated fungal-bacterial circuit and its dynamic evolution determine the extant distribution of yeast enterobactin producers and cheaters.
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Enterobactina , Evolución Molecular , Operón , Filogenia , Enterobactina/metabolismo , Enterobactina/genética , Sideróforos/metabolismo , Sideróforos/genética , Genes Fúngicos , Saccharomycetales/genética , Saccharomycetales/metabolismo , Transferencia de Gen HorizontalRESUMEN
Maximum likelihood (ML) phylogenetic inference is widely used in phylogenomics. As heuristic searches most likely find suboptimal trees, it is recommended to conduct multiple (e.g., ten) tree searches in phylogenetic analyses. However, beyond its positive role, how and to what extent multiple tree searches aid ML phylogenetic inference remains poorly explored. Here, we found that a random starting tree was not as effective as the BioNJ and parsimony starting trees in inferring ML gene tree and that RAxML-NG and PhyML were less sensitive to different starting trees than IQ-TREE. We then examined the effect of the number of tree searches on ML tree inference with IQ-TREE and RAxML-NG, by running 100 tree searches on 19,414 gene alignments from 15 animal, plant, and fungal phylogenomic datasets. We found that the number of tree searches substantially impacted the recovery of the best-of-100 ML gene tree topology among 100 searches for a given ML program. In addition, all of the concatenation-based trees were topologically identical if the number of tree searches was ≥ 10. Quartet-based ASTRAL trees inferred from 1 to 80 tree searches differed topologically from those inferred from 100 tree searches for 6 /15 phylogenomic datasets. Lastly, our simulations showed that gene alignments with lower difficulty scores had a higher chance of finding the best-of-100 gene tree topology and were more likely to yield the correct trees.
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Molecular evolution studies, such as phylogenomic studies and genome-wide surveys of selection, often rely on gene families of single-copy orthologs (SC-OGs). Large gene families with multiple homologs in 1 or more species-a phenomenon observed among several important families of genes such as transporters and transcription factors-are often ignored because identifying and retrieving SC-OGs nested within them is challenging. To address this issue and increase the number of markers used in molecular evolution studies, we developed OrthoSNAP, a software that uses a phylogenetic framework to simultaneously split gene families into SC-OGs and prune species-specific inparalogs. We term SC-OGs identified by OrthoSNAP as SNAP-OGs because they are identified using a splitting and pruning procedure analogous to snapping branches on a tree. From 415,129 orthologous groups of genes inferred across 7 eukaryotic phylogenomic datasets, we identified 9,821 SC-OGs; using OrthoSNAP on the remaining 405,308 orthologous groups of genes, we identified an additional 10,704 SNAP-OGs. Comparison of SNAP-OGs and SC-OGs revealed that their phylogenetic information content was similar, even in complex datasets that contain a whole-genome duplication, complex patterns of duplication and loss, transcriptome data where each gene typically has multiple transcripts, and contentious branches in the tree of life. OrthoSNAP is useful for increasing the number of markers used in molecular evolution data matrices, a critical step for robustly inferring and exploring the tree of life.
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Algoritmos , Evolución Molecular , Filogenia , Linaje , Factores de TranscripciónRESUMEN
Dual-labeled single fluorescent probes are powerful tools for studying autophagy on the molecular scale, yet their development has been hampered by design complexity and a lack of valid strategies. Herein, for the first time, we introduce a combinatorial regulation strategy to fabricate dual-labeled probes for studying autophagy by integrating the specific organelle-targeting group and the functional fluorescence switch into a pentacyclic pyrylium scaffold (latent dual-target scaffold). For proof of concept, we prepared a range of dual-labeled probes (TMOs) that display different emission colors in duple organelles. In these probes, TMO1 and TMO2 enabled the simultaneous two-color visualization of the lysosomes and mitochondria. The other probes (TMO3 and TMO4) discriminatively targeted lysosomes/nucleolus and lysosomes/lipid droplets (LDs) with dual-color emission characteristics, respectively. Intriguingly, by simply connecting the endoplasmic reticulum (ER) targeting group to the pentacyclic pyrylium scaffold, we created the first dual-labeled probe TMO5 for simultaneously labeling lysosomes/ER in distinctive fluorescent colors. Subsequently, using the dual-labeled probe TMO2, drug-induced mitophagy was successfully recorded by evaluating the alterations of multiple mitophagy-related parameters, and the mitophagy defects in a cellular model of Parkinson's disease (PD) were also revealed by simultaneous dual-color/dual-organelle imaging. Further, the probe TMO4 can track the movement of lysosomes and LDs in real time and monitor the dynamic process of lipophagy. Therefore, this work not only presents attractive dual-labeled probes to promote the study of organelle interactions during autophagy but also provides a promising combinatorial regulation strategy that may be generalized for designing other dual-labeled probes with multiple organelle combinations.
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Colorantes Fluorescentes , Orgánulos , Colorantes Fluorescentes/metabolismo , Orgánulos/metabolismo , Lisosomas/metabolismo , Mitocondrias , Retículo Endoplásmico , AutofagiaRESUMEN
Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1O2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1O2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy.
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Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.
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Photoacoustic (PA) tomography is an emerging biomedical imaging technology for precision cancer medicine. Conventional small-molecule PA probes usually exhibit a single PA signal and poor tumor targeting that lack the imaging reliability. Here, we introduce a series of cyanine/hemicyanine interconversion dyes (denoted Cy-HCy) for PA/fluorescent dual-mode probe development that features optimized ratiometric PA imaging and tunable tumor-targeting ability for precise diagnosis and resection of colorectal cancer (CRC). Importantly, Cy-HCy can be presented in cyanine (inherent tumor targeting and long NIR PA wavelength) and hemicyanine (poor tumor targeting and short NIR PA wavelength) by fine-tuning torsion angle and the ingenious transformation between cyanine and hemicyanine through regulation optically tunable group endows the NIR ratiometric PA and tunable tumor-targeting properties. To demonstrate the applicability of Cy-HCy dyes, we designed the first small-molecule tumor-targeting and NIR ratiometric PA probe Cy-HCy-H2S for precise CRC liver metastasis diagnosis, activated by H2S (a CRC biomarker). Using this probe, we not only visualized the subcutaneous tumor and liver metastatic cancers in CRC mouse models but also realized PA and fluorescence image-guided tumor excision. We expect that Cy-HCy will be generalized for creating a wide variety of inherently tumor-targeting NIR ratiometric PA probes in oncological research and practice.
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Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions inâ situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 inâ situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15â nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.
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Phylogenomic analyses of hundreds of protein-coding genes aimed at resolving phylogenetic relationships is now a common practice. However, no software currently exists that includes tools for dataset construction and subsequent analysis with diverse validation strategies to assess robustness. Furthermore, there are no publicly available high-quality curated databases designed to assess deep (>100 million years) relationships in the tree of eukaryotes. To address these issues, we developed an easy-to-use software package, PhyloFisher (https://github.com/TheBrownLab/PhyloFisher), written in Python 3. PhyloFisher includes a manually curated database of 240 protein-coding genes from 304 eukaryotic taxa covering known eukaryotic diversity, a novel tool for ortholog selection, and utilities that will perform diverse analyses required by state-of-the-art phylogenomic investigations. Through phylogenetic reconstructions of the tree of eukaryotes and of the Saccharomycetaceae clade of budding yeasts, we demonstrate the utility of the PhyloFisher workflow and the provided starting database to address phylogenetic questions across a large range of evolutionary time points for diverse groups of organisms. We also demonstrate that undetected paralogy can remain in phylogenomic "single-copy orthogroup" datasets constructed using widely accepted methods such as all vs. all BLAST searches followed by Markov Cluster Algorithm (MCL) clustering and application of automated tree pruning algorithms. Finally, we show how the PhyloFisher workflow helps detect inadvertent paralog inclusions, allowing the user to make more informed decisions regarding orthology assignments, leading to a more accurate final dataset.
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Eucariontes/genética , Filogenia , Programas InformáticosRESUMEN
BACKGROUND: This study aims to compare the clinical outcomes and safety of a novel hand-held retractor system-assisted Wiltse TLIF with that P-TLIF and assess whether this hand-held retractor system assisted Wiltse TLIF can yield less paraspinal muscle injury. METHODS: 56 patients (P-TLIF: 26, Wiltse TLIF: 30) were included in this one year prospective controlled study. The operation time, intraoperative blood loss, postoperative drainage, mobilization time, and discharge time were recorded. The clinical outcomes were evaluated by ODI, VAS, JOA, and SF-36 scores (7 days, 3, 6, and 12 months after surgery). Paraspinal muscle injury was assessed by postoperative MRI (6 months after surgery). CK and C-reaction protein were measured pre and postoperatively, and CT or X-ray (one year postoperatively) was used to assess bony union/non-union. RESULTS: The Wiltse (study) group was associated with significantly less estimated blood loss (79.67 ± 28.59 ml vs 192.31 ± 59.48 ml, P = 0.000*), postoperative drainage (43.33 ± 27.89 ml vs 285.57 ± 123.05 ml, P = 0.000*), and shorter mobilization (4.1 ± 1.2 d vs. 3.0 ± 0.9 d, P < 0.05) and discharge times (7.7 ± 1.9 d vs. 6.1 ± 1.2 d, P = 0.002*) than the P-TLIF (control) group. Serum CK activity at 24 h postoperatively in the study group was significantly lower than in the control group (384.10 ± 141.99 U/L vs 532.76 ± 225.76 U/L, P = 0.018*). At 7 days after surgery, VAS (2.3 ± 0.6 vs 3.2 ± 0.7, P = 0.000*)and ODI scores (43.9 ± 11.9 vs 55.2 ± 12.9, P = 0.001*) were lower, while the JOA scores (18.4 ± 3.4 vs 16.3 ± 4.2, P = 0.041*) was higher in the control group than in the study group. Results observed at 3 months of follow-up were consistent with those at 7 days. After six months postoperatively, paraspinal muscle degeneration in the control group was more significant than in the study group (P = 0.008*). CONCLUSION: Our study showed that this novel hand-held retractor system assisted Wiltse approach TLIF can significantly reduce paraspinal muscle injury, postoperative drainage, and intraoperative blood loss, mobilization and discharge time, as well as yield better short-term outcomes compared to P-TLIF. TRIAL REGISTRATION: 25/09/2023 NCT06052579.
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Vértebras Lumbares , Fusión Vertebral , Humanos , Resultado del Tratamiento , Estudios Prospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Pérdida de Sangre Quirúrgica , Estudios RetrospectivosRESUMEN
Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.
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Proteínas Reguladoras de la Apoptosis , Células Madre Hematopoyéticas , Pirimidinas , Ratones , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Acrilatos/farmacología , Apoptosis , Irradiación Corporal Total , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.
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Interleucina-17 , MicroARNs , Linfocitos T Reguladores , Células Th17 , Humanos , MicroARNs/sangre , Células Th17/inmunología , Niño , Masculino , Femenino , Linfocitos T Reguladores/inmunología , Interleucina-17/sangre , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/genética , Enfermedad de Hashimoto/sangre , Preescolar , Enfermedad de Graves/inmunología , Enfermedad de Graves/genética , Adolescente , Autoanticuerpos/sangreRESUMEN
As the most diverse group of animals on Earth, insects are key organisms in ecosystems. Horizontal gene transfer (HGT) refers to the transfer of genetic material between species by non-reproductive means. HGT is a major evolutionary force in prokaryotic genome evolution, but its importance in different eukaryotic groups, such as insects, has only recently begun to be understood. Genomic data from hundreds of insect species have enabled the detection of large numbers of HGT events and the elucidation of the functions of some of these foreign genes. Although quantification of the extent of HGT in insects broadens our understanding of its role in insect evolution, the scope of its influence and underlying mechanism(s) of its occurrence remain open questions for the field.