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The confinement of transgenic fish is essential to prevent their escape and reproduction in natural ecosystems. Reversible transgenic sterilization is a promising approach to control the reproduction of transgenic fish. Therefore, the present study was conducted to develop a reversibly sterile channel catfish (Ictalurus punctatus) via the transgenic overexpression of the goldfish (Carassius auratus) glutamic acid decarboxylase (GAD) gene driven by the common carp (Cyprinus carpio) ß-actin promoter to disrupt normal gamma-aminobutyric acid (GABA) regulation. Three generations of GAD-transgenic fish were produced. All studied generations showed repressed reproductive performance; however, this was not always statistically significant. In F1, 5.4% of the transgenic fish showed a sexual maturity score ≥ 4 (maximum = 5) at five years of age, which was lower (p = 0.07) than that of the control group (16.8%). In the spawning experiments conducted on F1 transgenic fish at six and nine years of age, 45.5% and 20.0% of fish spawned naturally, representing lower values (p = 0.09 and 0.12, respectively) than the percentages in the sibling control fish of the same age (83.3% and 66.7%, respectively). Four of six pairs of the putative infertile six-year-old fish spawned successfully after luteinizing hormone-releasing hormone analog (LHRHa) therapy. Similar outcomes were noted in the three-year-old F2 fish, with a lower spawning percentage in transgenic fish (20.0%) than in the control (66.7%). In one-year-old F2-generation transgenic fish, the observed mean serum gonadotropin-releasing hormone (GnRH) levels were 9.23 ± 2.49 and 8.14 ± 2.21 ng/mL for the females and males, respectively. In the control fish, the mean levels of GnRH were 11.04 ± 4.06 and 9.03 ± 2.36 ng/mL for the females and males, respectively, which did not differ significantly from the control (p = 0.15 and 0.27 for females and males, respectively). There was no significant difference in the estradiol levels of the female transgenic and non-transgenic fish in the one- and four-year-old F2-generation fish. The four-year-old F2-generation male transgenic fish exhibited significantly (p < 0.05) lower levels of GnRH and testosterone than the control fish. In conclusion, while overexpressing GAD repressed the reproductive abilities of channel catfish, it did not completely sterilize transgenic fish. The sterilization rate might be improved through selection in future generations.
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Reclaimed water irrigation has emerged as a critical alternative in agricultural regions facing water scarcity. However, soil pollution with microplastics (MPs) greatly increases the exposure risk and toxic effects of reclaimed water contaminations, such as phthalate esters (PAEs). A field experiment consisting of soil column pots evaluated the feasibility of using PAEs-contaminated water to irrigate oats (Avena sativa L.) in drought seasons. Three irrigation regimens based on soil matric potential thresholds (-10 kPa, -30 kPa, -50 kPa) explored the impact of PAE-contaminated water on oat physiology and environmental pollution in soil with and without MPs contamination. The results showed that treating oats at the SMP of -30 kPa boosted shoot biomass by 3.1%-14.0% compared to the drought condition at -50 kPa, and the root biomass of oats was significantly increased. The physiological metrics of oats indicated that irrigation at -50 kPa induced drought stress and oxidative damage in oats, particularly during the milk stage. Different irrigation treatments influenced the accumulation of PAEs in plants, soil, and leachate. The ratios of leachate to irrigation water in -10 kPa treatment with and without MPs addition were 1.18% and 4.48%, respectively, which aggravated the accumulation of pollutants in deep soil layers and may cause groundwater pollution. MPs pollution in soil increased the content of PAEs in the harvested oats and reduced the transport and accumulation of PAEs in deep soil layers (20-50 cm) and leachate. The coupling of PAEs in irrigation water with soil MPs pollution may exacerbate plant damage. However, the damage can be minimized under the scheduled irrigation at -30 kPa which could balance crop yield and potential risks.
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Riego Agrícola , Avena , Sequías , Microplásticos , Contaminantes del Suelo , Suelo , Avena/efectos de los fármacos , Avena/crecimiento & desarrollo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Suelo/química , Microplásticos/toxicidadAsunto(s)
Proteínas de Unión al ADN , Leiomiosarcoma , Neoplasias Uterinas , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/genética , Femenino , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/diagnóstico , Proteínas de Unión al ADN/genética , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genéticaRESUMEN
Dormancy release pattern, sprout growth and later reproduction were studied among various tuber sizes of Cyperus esculentus to determine effective methods to release dormancy and further to select suitable tuber size of this species in production. The results showed that medium tubers performed better during sprouting than large and small tubers under all pre-sprouting treatments. Pre-sprouting treatments at 25°C, 35°C, RT (room temperature) and -2°C were effective in relieving dormancy in medium tubers. Tiller number from medium tubers were significantly higher under 25°C, RT and 45°C than under 35°C and -2°C. Shoot and root mass from medium tubers were significantly higher under the 25°C, 35°C and RT than under other treatments. Tiller and tuber numbers both decreased with decreasing tuber size, as did tuber yield after three months of growth. Furthermore, leftover mass decreased with decreasing tuber mass and remained unchanged at sprouting and maturity periods. A significantly negative allometric correlation was found between plant mass and tuber mass from small tubers. However, a significantly positive allometric correlation was found between tuber size and tuber number from large tubers. In conclusion, medium tubers had a competitive advantage in sprouting, growth and reproduction.
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A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC.
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Fibroblastos Asociados al Cáncer , Neoplasias Ováricas , Humanos , Femenino , Línea Celular Tumoral , Análisis de Expresión Génica de una Sola Célula , Fibroblastos/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Neoplasias Ováricas/patología , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Extrachromosomal circular DNA (eccDNA) has emerged as a promising biomarker for disease diagnosis and prognosis prediction. However, its role in type 2 diabetes remains unexplored. OBJECTIVE: To investigate the characteristics and dynamics of circulating eccDNAs in newly diagnosed type 2 diabetes mellitus (T2DM) patients undergoing short-term intensive insulin therapy (SIIT), a highly effective treatment for inducing long-term glycemic remission. METHODS: We conducted Circle-Seq analysis on plasma samples from 35 T2DM patients at three time points: pre-SIIT, post-SIIT, and 1-year post-SIIT. Our analysis encompassed the characterization of eccDNA features, including GC content, eccDNA length distribution, genomic distribution, and the genes in eccDNAs. RESULTS: Following SIIT, we observed an increase in plasma eccDNA load, suggesting metabolic alterations during therapy. Notably, a correlation was identified between eccDNA profiles and glycemia in T2DM, both quantitatively and genetically. Our analysis also revealed the frequent presence of metabolism-related genes within T2DM plasma eccDNAs, some of which spanned gene exons and/or fractions. CONCLUSION: This study represents the first report of cell-free eccDNA in T2DM and underscores a compelling association between cell-free eccDNA and profound glycemic changes. These findings highlight the potential of eccDNAs as crucial players in the context of T2DM and glycemic control.
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Diabetes Mellitus Tipo 2 , Insulina , Humanos , Insulina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , ADN Circular/genética , Genoma , BiomarcadoresRESUMEN
Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.
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Ambystoma mexicanum , Encéfalo , Cromatina , Animales , Ambystoma mexicanum/genética , Ascomicetos , Aprendizaje , Mesencéfalo , Análisis de Expresión Génica de una Sola CélulaRESUMEN
Microplastic (MP) pollution is lately receiving increasing attention owing to its harmful impact on terrestrial ecosystems. In this microcosm study, we assessed the uptake and transfer of MPs in Solanum nigrum seedlings exposed to 50 mg L-1 of 0.2-µm polystyrene (PS) beads for 30 d. Confocal laser scanning micrographs helped detect highly intense red fluorescence signals from PS-MP beads in S. nigrum root compared with the controls. Confocal images revealed that the PS beads were primarily distributed in the epidermis and xylem of roots and vascular systems of stems and leaves. Scanning electron microscopy showed that PS beads were scattered on the cell walls of the root xylem and leaf vascular system. Few PS beads were transferred from roots to stems and leaves via the vascular system following the transpiration stream. In conclusion, our findings showed that PS beads accumulated in S. nigrum roots and were transferred from the roots to the aerial parts.
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Ecosistema , Solanum nigrum , Microplásticos , Plásticos , Poliestirenos , Plantones , Microscopía Electrónica de RastreoRESUMEN
Rapid on-site detection of copper(II) ions (Cu2+) with high sensitivity and selectivity is of great significance in the safety monitoring of drinking water and food. Colorimetric detection is a robust fast determination method with the main drawback of low sensitivity. Herein, we developed a colorimetric chemosensor based on a colored polymer product. Via a Cu-Fenton mechanism, 1-naphthylamine (α-NA) was oxidized by H2O2 and brownish-red poly(1-naphthylamine) (PNA) was produced. The obtained Cu2+ sensor showed a linear response from 0.05 µM to 7 µM, with a detection limit of 62 nM. Our findings expanded chromogenic reaction types for colorimetric detection.
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Recently, in combination with seed-mediated growth, thiolated chiral molecule-guided growth has shown great promise in obtaining chiral plasmonic nanostructures. Previously, with the assistance of chiral cysteines (Cys), we realized helical growth of plasmonic shells on gold nanorod (AuNR) seeds dispersed in cetyltrimethylammonium bromide (CTAB) solution. Herein, we further studied the roles of non-chiral cationic surfactants in tuning the helical growth. Both the counter anion and the hydrocarbon chain length of the surfactants were found to affect the formation of helical shells greatly. In particular, we exhibited surfactant-modulated conversion of the chiral shell deposition mode between layer growth and island growth. By optimizing growth conditions, an obvious plasmonic circular dichroism (PCD) response could be achieved for the island helical shell. Our findings demonstrated promising potential of nanochemical synthesis in fabricating chiral plasmonic nanostructures with small structural sizes.
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Nanoestructuras , Nanotubos , Oro/química , Tensoactivos , ADN/química , Nanotubos/química , Nanoestructuras/químicaRESUMEN
Mono-lactate glyceride (LG) is a short-chain fatty acid ester. It has been shown that short-chain fatty acid esters play an important role in maintaining intestinal structure and function. The aim of this study is to investigate the effects of mono-lactate glyceride on growth performance and intestinal morphology and function in weaned piglets. Sixteen 21-day-old weaned piglets of similar weight were distributed arbitrarily to two treatments: The control group (basal diet) and the LG group (basal diet + 0.6% mono-lactate glyceride). The experiment lasted for 21 days. On day 21 of the trial, piglets were weighed, and blood and intestinal samples were collected for further analysis. Results showed that dietary supplementation with 0.6% mono-lactate glyceride decreased (p < 0.05) the diarrhea rate and the contents of malondialdehyde and hydrogen peroxide in the ileum and jejunum and increased (p < 0.05) the expression of intestinal tight junction protein (Occludin) and the activities of superoxide dismutase and catalase in the ileum and colon. In addition, mono-lactate glyceride supplementation could enhance intestinal mucosal growth by increasing (p < 0.05) the mRNA levels of extracellular regulated protein kinases, promote intestinal mucosal water and nutrient transport and lipid metabolism by increasing (p < 0.05) the mRNA levels of b0,+ amino acid transporter, aquaporin 3, aquaporin 10, gap junction protein alpha 1, intestinal fatty acid-binding protein, and lipoprotein lipase, enhance antiviral and immune function by increasing (p < 0.05) the mRNA levels of nuclear factor kappa-B, interferon-ß, mucovirus resistance protein II, 2'-5'-oligoadenylate synthetase-like, interferon-γ, C-C motif chemokine ligand 2, and toll-like receptor 4, and enhance antioxidant capacity by increasing (p < 0.05) the mRNA levels of NF-E2-related factor 2 and glutathione S-transferase omega 2 and decreasing (p < 0.05) the mRNA level of NADPH oxidase 2. These results suggested that dietary supplementation with mono-lactate glyceride could decrease the diarrhea rate by improving intestinal antioxidant capacity, intestinal mucosal barrier, intestinal immune defense function, and intestinal mucosal water and nutrient transport. Collectively, dietary supplementation with 0.6% mono-lactate glyceride improved the intestinal function of weaned piglets.
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BACKGROUND: Bivalves have independently evolved a variety of symbiotic relationships with chemosynthetic bacteria. These relationships range from endo- to extracellular interactions, making them ideal for studies on symbiosis-related evolution. It is still unclear whether there are universal patterns to symbiosis across bivalves. Here, we investigate the hologenome of an extracellular symbiotic thyasirid clam that represents the early stages of symbiosis evolution. RESULTS: We present a hologenome of Conchocele bisecta (Bivalvia: Thyasiridae) collected from deep-sea hydrothermal vents with extracellular symbionts, along with related ultrastructural evidence and expression data. Based on ultrastructural and sequencing evidence, only one dominant Thioglobaceae bacteria was densely aggregated in the large bacterial chambers of C. bisecta, and the bacterial genome shows nutritional complementarity and immune interactions with the host. Overall, gene family expansions may contribute to the symbiosis-related phenotypic variations in different bivalves. For instance, convergent expansions of gaseous substrate transport families in the endosymbiotic bivalves are absent in C. bisecta. Compared to endosymbiotic relatives, the thyasirid genome exhibits large-scale expansion in phagocytosis, which may facilitate symbiont digestion and account for extracellular symbiotic phenotypes. We also reveal that distinct immune system evolution, including expansion in lipopolysaccharide scavenging and contraction of IAP (inhibitor of apoptosis protein), may contribute to the different manners of bacterial virulence resistance in C. bisecta. CONCLUSIONS: Thus, bivalves employ different pathways to adapt to the long-term co-existence with their bacterial symbionts, further highlighting the contribution of stochastic evolution to the independent gain of a symbiotic lifestyle in the lineage.
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Bivalvos , Animales , Bivalvos/genética , Transporte Biológico , Genoma Bacteriano , Proteínas Inhibidoras de la Apoptosis , LipopolisacáridosRESUMEN
Homologs of Autophagy-related (Atg) protein 4 are reported to cleave LC3 protein and facilitate autophagy occurrence differently in mammals, whereas their functions have not been investigated in insects. Three homologs, including BmAtg4a and its short form BmAtg4c as well as BmAtg4b, exist in Bombyx mori. Herein, the autophagic functions of BmAtg4a and BmAtg4b were investigated. qPCR detection found that BmAtg4a and BmAtg4b both peaked during larval-pupal metamorphosis when autophagy occurs robustly. Immunofluorescent staining showed that BmAtg4a was predominantly localized at the cytoplasm, while BmAtg4b had notable nuclear localization. Overexpression of BmAtg4a and BmAtg4b both slightly promoted basal autophagy but inhibited the autophagy induced by the infection of B. mori nucleopolyhedrovirus (BmNPV) and, thereby, its proliferation. In comparison, knockout of BmAtg4a or BmAtg4b significantly upregulated BmNPV-induced autophagy and its replication in BmN cells. Results of Co-immunoprecipitation associated with mass spectrum showed that the cytoskeleton protein B. mori actin A2 (BmACT2) and B. mori actin A1 (BmACT1) bound with BmAtg4a and BmAtg4b especially. Knockout of BmACT1 and BmACT2 inhibited BmAtg4b- and BmAtg4a-induced autophagy, respectively; moreover, knockout of BmACT1 reduced the ratio of cells with nuclear BmAtg4b. Of note, BmAtg4a and BmAtg4b had physical interaction, and they had an inhibitory effect on mutual autophagic function. In this work, we provide new insights into the autophagy machinery in insects as well as its function in the proliferation of BmNPV.
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Bombyx , Animales , Bombyx/metabolismo , Actinas/metabolismo , Línea Celular , Autofagia , Citoesqueleto , MamíferosRESUMEN
Cetaceans (dolphins, whales, and porpoises) have large and anatomically sophisticated brains. To expand our understanding of the cellular makeup of cetacean brains and the similarities and divergence between the brains of cetaceans and terrestrial mammals, we report a short-finned pilot whale (Globicephala macrorhynchus) single-nucleus transcriptome atlas. To achieve this goal, we assembled a chromosome-scale reference genome spanning 2.25 Gb on 22 chromosomes and profiled the gene expression of five major anatomical cortical regions of the short-finned pilot whale by single-nucleus RNA-sequencing (snRNA-seq). We identified six major cell lineages in the cerebral cortex (excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, astrocytes, and endothelial cells), eight molecularly distinct subclusters of excitatory neurons, and four subclusters of inhibitory neurons. Finally, a comparison of snRNA-seq data from the short-finned pilot whale, human, and rhesus macaque revealed a broadly conserved cellular makeup of brain cell types. Our study provides genomic resources and molecular insights into cetacean brain evolution.
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Delfines , Ballena de Aleta , Calderón , Animales , Humanos , Calderón/genética , Células Endoteliales , Macaca mulatta , Transcriptoma , Ballenas/genética , Ballenas/metabolismo , Delfines/genética , Corteza CerebralRESUMEN
Radish seed (RS), the dried ripe seed of Raphanus sativus L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; P adj < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, P < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension.
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Microplastics (MPs) pollution may be harmful to terrestrial ecosystems and is receiving increasing attention. A microcosm study on the uptake of MPs in maize (Zea mays) seedling roots exposed to small polystyrene (PS) beads (0.2, 0.5 and 1.0 µm) and large PS beads (2.0 and 5.0 µm) at 50 mg L-1 for 7 d was performed. Additionally, the absorption ability of different parts of the roots was also investigated after 10 d of exposure with 0.2 µm PS beads. The results showed that root and shoot biomass remained unchanged under different particle sizes of PS beads. The small PS beads markedly increased the accumulation and distribution of PS beads in roots more than large ones. Confocal laser scanning micrographs confirmed that strong fluorescence signals from small PS beads (0.2 µm) were seen in all tissues, as compared with the control. Large PS beads (2.0 µm) were mainly distributed in the xylem, and no PS beads were detected in any root tissues when treated with 5.0 µm PS beads. More PS beads were absorbed by the root maturation zone than by the root tip zone. Fluorescence intensity values of PS bead accumulations measured across the tissues further confirmed these results. As seen in scanning electron microscopy images, small PS beads assembled on the cell wall of the xylem, while large PS beads (2.0 µm) were scattered on the cell walls of root xylem. The present study revealed the effects of different PS bead sizes on accumulation and distribution in maize roots, as well as the absorption ability of different positions of the roots. Moreover, fluorescence intensity could be a useful method to evaluate the uptake and distribution of MPs accurately.
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Microplásticos , Plásticos , Zea mays , Plantones/química , Tamaño de la Partícula , Ecosistema , Poliestirenos/análisisRESUMEN
BACKGROUND: Cryptotia is a common congenital auricular malformation seen in Asian people. To date, multiple surgical procedures have been described for correcting cryptotia. However, the deformity often recurs, presenting as an unclear auriculotemporal sulcus and a malformed helix. The present study aimed to introduce a novel surgical approach to obtain a stable and aesthetic auricular correction in cryptotia patients and to acquire an understanding toward improved surgical management of cryptotia. METHODS: Twenty-four cryptotia patients (28 ears), who were operated between April 2018 and November 2021, were included in this study. All patients underwent surgical correction for cryptotia using a modified V-Y advancement flap with helix rounding technique, performed by a senior surgeon. RESULTS: Patients were followed for an average period of 9.4 months (6 to 18 months). Twenty-one patients (87.5%) were satisfied, three (12.5%) were partially satisfied, and none were unsatisfied. Most patients experienced temporary edema as a postsurgical complication, which resulted in a swollen auricle appearance lasting for three to four weeks postoperatively. One patient experienced skin necrosis in one ear on the anterior portion of the upper helix and this was solved by skin grafting. CONCLUSIONS: The method of surgical correction utilizing a modified V-Y advancement flap with helix rounding technique proved to be a reliable option in cryptotia patients. It can provide stable aesthetic results after cryptotia correction in clinical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Pabellón Auricular , Procedimientos de Cirugía Plástica , Humanos , Colgajos Quirúrgicos/cirugía , Oído Externo/cirugía , Trasplante de Piel/métodos , Pabellón Auricular/cirugía , Pabellón Auricular/anomalíasRESUMEN
Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs. GII.6 NoV is one of the predominant genotypes in humans, which recognizes the type ABO secretor of HBGAs. However, the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive. In this study, we investigated the binding features of the GII.6 strain to HBGAs using saliva- and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide. We showed that the GII.6 âP domain recognized some A and O secretor's saliva samples, most B secretor's saliva samples, and H disaccharide antigen, but did not bind non-secretors' saliva. Further, we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7 âÅ, revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs. Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs, demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity. Finally, structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup. Taken together, our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs, and shed light on NoV evolution, epidemiology, and anti-viral drug development.
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Antígenos de Grupos Sanguíneos , Infecciones por Caliciviridae , Norovirus , Humanos , Antígenos de Grupos Sanguíneos/metabolismo , Norovirus/genética , Acoplamiento Viral , Unión Proteica , Polisacáridos/metabolismo , Disacáridos/metabolismo , GenotipoRESUMEN
HYPOTHESIS: Treatment of congenital microtia in adults remains challenging due to the unique physiological characteristics of the costal cartilages and retroauricular skin, which interfere with obtaining a satisfactory aesthetic result; thus, different perspectives and technical modifications during treatment are warranted. This article aims to present complementary new information and essential tips to refine the surgical technique in adult microtia reconstruction. METHODS: A total of 346 adult microtia patients underwent surgical intervention at the Auricular Reconstruction Center of Plastic Surgery Hospital (Beijing, China) between 2006 and 2021. Each patient underwent a rigorous preoperative evaluation and stages one and two surgeries. RESULTS: Patients were followed in our clinic for 6 months to 10 years (average: 15.3 months). The postoperative complication rate was 8.1%, which included cartilage exposure, broken helix, local hematoma, infection, poor skin graft survival, and scar hypertrophy. CONCLUSIONS: Our results showed that the two-stage treatment strategy for adults is versatile, reliable, and effective for the treatment of congenital microtia. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2148-2153, 2023.
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Microtia Congénita , Cartílago Costal , Procedimientos de Cirugía Plástica , Adulto , Humanos , Microtia Congénita/cirugía , Cartílago Costal/trasplante , Trasplante de Piel/métodos , Cartílago/trasplanteRESUMEN
SCOPE: This study investigates the potential effects of N-acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)-infected porcine model. METHODS AND RESULTS: Thirty-two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)-1 day-1 ) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty-acid binding protein, as well as IL-1ß, IL-8, and TNF-α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down-regulates the expression of interferon-related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. CONCLUSION: NAC administration alleviates PEDV-induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.