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A key question in plant biology is how oriented cell divisions are integrated with patterning mechanisms to generate organs with adequate cell type allocation. In the root vasculature, a gradient of miRNA165/6 controls the abundance of HD-ZIP III transcription factors, which in turn control cell fate and spatially restrict vascular cell proliferation to specific cells. Here, we show that vascular development requires the presence of ARGONAUTE10, which is thought to sequester miRNA165/6 and protect HD-ZIP III transcripts from degradation. Our results suggest that the miR165/6-AGO10-HDZIP III module acts by buffering cytokinin responses and restricting xylem differentiation. Mutants of AGO10 show faster growth rates and strongly enhanced survival under severe drought conditions. However, this superior performance is offset by markedly increased variation and phenotypic plasticity in sub-optimal carbon supply conditions. Thus, AGO10 is required for the control of formative cell division and coordination of robust cell fate specification of the vasculature, while altering its expression provides a means to adjust phenotypic plasticity.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas Argonautas , Divisão Celular , Regulação da Expressão Gênica de Plantas , MicroRNAs , Raízes de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/citologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Divisão Celular/genética , Raízes de Plantas/citologia , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Xilema/citologia , Xilema/metabolismo , Xilema/crescimento & desenvolvimento , Xilema/genéticaRESUMO
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.
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Estudo de Associação Genômica Ampla , Esquizofrenia , Alelos , Predisposição Genética para Doença/genética , Genômica , Humanos , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genéticaRESUMO
Root development is tightly controlled by light, and the response is thought to depend on signal transmission from the shoot. Here, we show that the root apical meristem perceives light independently from aboveground organs to activate the light-regulated transcription factor ELONGATED HYPOCOTYL5 (HY5). The ROS balance between H2O2 and superoxide anion in the root is disturbed under darkness with increased H2O2. We demonstrate that root-derived HY5 directly activates PER6 expression to eliminate H2O2. Moreover, HY5 directly represses UPBEAT1, a known inhibitor of peroxidases, to release the expression of PERs, partially contributing to the light control of ROS balance in the root. Our results reveal an unexpected ability in roots with specific photoreception and provide a mechanistic framework for the HY5-mediated interaction between light and ROS signaling in early root development.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Peróxido de Hidrogênio/metabolismo , Luz , Regulação da Expressão Gênica de PlantasRESUMO
Gene-based association tests aggregate multiple SNP-trait associations into sets defined by gene boundaries and are widely used in post-GWAS analysis. A common approach for gene-based tests is to combine SNPs associations by computing the sum of χ2 statistics. However, this strategy ignores the directions of SNP effects, which could result in a loss of power for SNPs with masking effects, e.g., when the product of two SNP effects and the linkage disequilibrium (LD) correlation is negative. Here, we introduce "mBAT-combo," a set-based test that is better powered than other methods to detect multi-SNP associations in the context of masking effects. We validate the method through simulations and applications to real data. We find that of 35 blood and urine biomarker traits in the UK Biobank, 34 traits show evidence for masking effects in a total of 4,273 gene-trait pairs, indicating that masking effects is common in complex traits. We further validate the improved power of our method in height, body mass index, and schizophrenia with different GWAS sample sizes and show that on average 95.7% of the genes detected only by mBAT-combo with smaller sample sizes can be identified by the single-SNP approach with a 1.7-fold increase in sample sizes. Eleven genes significant only in mBAT-combo for schizophrenia are confirmed by functionally informed fine-mapping or Mendelian randomization integrating gene expression data. The framework of mBAT-combo can be applied to any set of SNPs to refine trait-association signals hidden in genomic regions with complex LD structures.
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Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Desequilíbrio de Ligação , Genômica , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Wheat (Triticum aestivum L.) is one of the most important crops worldwide and a major source of human Cd intake. Limiting grain Cd concentration (Gr_Cd_Conc) in wheat is necessary to ensure food safety. However, the genetic factors associated with Cd uptake, translocation, distribution, and Gr_Cd_Conc in wheat are poorly understood. Here, we mapped quantitative trait loci (QTL) for Gr_Cd_Conc and its related transport pathway using a recombinant inbred line (RIL_DT) population derived from two Polish wheat varieties (dwarf Polish wheat [DPW] and tall Polish wheat [TPW]). We identified 29 novel major QTLs for grain and tissue Cd concentration; 14 novel major QTLs for Cd uptake, translocation, and distribution; and 27 major QTLs for agronomic traits. We also analyzed the pleiotropy of these QTLs. Six novel QTLs (QGr_Cd_Conc-1A, QGr_Cd_Conc-3A, QGr_Cd_Conc-4B, QGr_Cd_Conc-5B, QGr_Cd_Conc-6A and QGr_Cd_Conc-7A) for Gr_Cd_Conc explained 8.16-17.02% of the phenotypic variation. QGr_Cd_Conc-3A, QGr_Cd_Conc-6A and QGr_Cd_Conc-7A pleiotropically regulated Cd transport; three other QTLs were organ-specific for Gr_Cd_Conc. We fine-mapped the locus of QGr_Cd_Conc-4B and identified the candidate gene as Cation/Ca exchanger 2 (TpCCX2-4B), which was differentially expressed in DPW and TPW. It encodes an endoplasmic reticulum membrane/plasma membrane-localized Cd efflux transporter in yeast. Overexpression of TpCCX2-4B reduced Gr_Cd_Conc in rice. The average Gr_Cd_Conc was significantly lower in TpCCX2-4BDPW genotypes than in TpCCX2-4BTPWgenotypes of the RIL_DT population and two other natural populations, based on a KASP marker derived from the different promoter sequences between TpCCX2-4BDPW and TpCCX2-4BTPW. Our study reveals the genetic mechanism of Cd accumulation in wheat and provides valuable resources for genetic improvement of low-Cd-accumulating wheat cultivars.
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Singlet oxygen (1O2) has a very short half-life of 10-5 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of 1O2 and shows drastic changes in nuclear gene expression. Only two plastid proteins, EX1 (executer 1) and EX2 (executer 2), have been identified in the singlet oxygen signaling. Here, we found that the transcription factor abscisic acid insensitive 4 (ABI4) binds the promoters of genes responsive to 1O2-signals. Inactivation of the ABI4 protein in the flu/abi4 double mutant was sufficient to compromise the changes of almost all 1O2-responsive-genes and rescued the lethal phenotype of flu grown under light/dark cycles, similar to the flu/ex1/ex2 triple mutant. In addition to cell death, we reported for the first time that 1O2 also induces cell wall thickening and stomatal development defect. Contrastingly, no apparent growth arrest was observed for the flu mutant under normal light/dim light cycles, but the cell wall thickening (doubled) and stomatal density reduction (by two-thirds) still occurred. These results offer a new idea for breeding stress tolerant plants.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Luz , Oxigênio Singlete/metabolismo , Transcriptoma , Estômatos de Plantas/metabolismoRESUMO
BACKGROUND: Dendrobium officinale Kimura et Migo, a renowned traditional Chinese orchid herb esteemed for its significant horticultural and medicinal value, thrives in adverse habitats and contends with various abiotic or biotic stresses. Acid invertases (AINV) are widely considered enzymes involved in regulating sucrose metabolism and have been revealed to participate in plant responses to environmental stress. Although members of AINV gene family have been identified and characterized in multiple plant genomes, detailed information regarding this gene family and its expression patterns remains unknown in D. officinale, despite their significance in polysaccharide biosynthesis. RESULTS: This study systematically analyzed the D. officinale genome and identified four DoAINV genes, which were classified into two subfamilies based on subcellular prediction and phylogenetic analysis. Comparison of gene structures and conserved motifs in DoAINV genes indicated a high-level conservation during their evolution history. The conserved amino acids and domains of DoAINV proteins were identified as pivotal for their functional roles. Additionally, cis-elements associated with responses to abiotic and biotic stress were found to be the most prevalent motif in all DoAINV genes, indicating their responsiveness to stress. Furthermore, bioinformatics analysis of transcriptome data, validated by quantitative real-time reverse transcription PCR (qRT-PCR), revealed distinct organ-specific expression patterns of DoAINV genes across various tissues and in response to abiotic stress. Examination of soluble sugar content and interaction networks provided insights into stress release and sucrose metabolism. CONCLUSIONS: DoAINV genes are implicated in various activities including growth and development, stress response, and polysaccharide biosynthesis. These findings provide valuable insights into the AINV gene amily of D. officinale and will aid in further elucidating the functions of DoAINV genes.
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Dendrobium , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , beta-Frutofuranosidase , Dendrobium/genética , Dendrobium/enzimologia , beta-Frutofuranosidase/genética , beta-Frutofuranosidase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Genoma de Planta , Estresse Fisiológico/genética , Genes de PlantasRESUMO
INTRODUCTION: Parthenogenetic chimera is an extremely rare condition in human. Very few patients with parthenogenetic chimerism with XX/XY cells have been identified. CASE PRESENTATION: We report the clinical findings and molecular analysis of chimerism with a 46,XX/46,XY karyotype in a patient presenting idiopathic oligoasthenoteratozoospermia (OAT). To clarify the mechanism of chimera formation, short tandem repeat analysis using 21 loci was carried out. Quantitation of alleles in D6S1043, D12S391, fibrinogen alpha chain, and amelogenin revealed double paternal and one maternal genetic contribution to the patient, which is consistent with a parthenogenetic chimerism. The likely mechanism of chimerism formation was also discussed, followed by a literature review. CONCLUSION: This is the first documented case of parthenogenetic chimerism in an adult male with XX/XY cells presenting OAT. Improved cell sampling and more sensitive and specific detection methods are necessary to identify more patients with XX/XY chimerism for systematic studies on this condition in the future.
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Quimerismo , Humanos , Masculino , Adulto , Oligospermia/genética , Partenogênese/genética , Repetições de Microssatélites/genética , Cromossomos Humanos Y/genética , Cromossomos Humanos X/genética , Azoospermia/genética , CariotipagemRESUMO
DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Metilação de DNA , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Imunomodulação , Microambiente Tumoral/genéticaRESUMO
Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.
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KEY MESSAGE: The new stripe rust resistance gene Yr4EL in tetraploid Th. elongatum was identified and transferred into common wheat via 4EL translocation lines. Tetraploid Thinopyrum elongatum is a valuable genetic resource for improving the resistance of wheat to diseases such as stripe rust, powdery mildew, and Fusarium head blight. We previously reported that chromosome 4E of the 4E (4D) substitution line carries all-stage stripe rust resistance genes. To optimize the utility of these genes in wheat breeding programs, we developed translocation lines by inducing chromosomal structural changes through 60Co-γ irradiation and developing monosomic substitution lines. In total, 53 plants with different 4E chromosomal structural changes were identified. Three homozygous translocation lines (T4DS·4EL, T5AL·4EL, and T3BL·4EL) and an addition translocation line (T5DS·4EL) were confirmed by the genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), FISH-painting, and wheat 55 K SNP array analyses. These four translocation lines, which contained chromosome arm 4EL, exhibited high stripe rust resistance. Thus, a resistance gene (tentatively named Yr4EL) was localized to the chromosome arm 4EL of tetraploid Th. elongatum. For the application of marker-assisted selection (MAS), 32 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome arm 4EL and co-segregation with Yr4EL. Furthermore, the 4DS·4EL line could be selected as a good pre-breeding line that better agronomic traits than other translocation lines. We transferred Yr4EL into three wheat cultivars SM482, CM42, and SM51, and their progenies were all resistant to stripe rust, which can be used in future wheat resistance breeding programs.
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Basidiomycota , Triticum , Triticum/genética , Hibridização in Situ Fluorescente , Melhoramento Vegetal , Tetraploidia , Poaceae/genéticaRESUMO
KEY MESSAGE: An adult plant gene for resistance to stripe rust was narrowed down to the proximal one-third of the 2NvS segment translocated from Aegilops ventricosa to wheat chromosome arm 2AS, and based on the gene expression analysis, two candidate genes were identified showing a stronger response at the adult plant stage compared to the seedling stage. The 2NvS translocation from Aegilops ventricosa, known for its resistance to various diseases, has been pivotal in global wheat breeding for more than three decades. Here, we identified an adult plant resistance (APR) gene in the 2NvS segment in wheat line K13-868. Through fine mapping in a segregating near-isogenic line (NIL) derived population of 6389 plants, the candidate region for the APR gene was narrowed down to between 19.36 Mb and 33 Mb in the Jagger reference genome. Transcriptome analysis in NILs strongly suggested that this APR gene conferred resistance to stripe rust by triggering plant innate immune responses. Based on the gene expression analysis, two disease resistance-associated genes within the candidate region, TraesJAG2A03G00588940 and TraesJAG2A03G00590140, exhibited a stronger response to Puccinia striiformis f. sp. tritici (Pst) infection at the adult plant stage than at the seedling stage, indicating that they could be potential candidates for the resistance gene. Additionally, we developed a co-dominant InDel marker, InDel_31.05, for detecting this APR gene. Applying this marker showed that over one-half of the wheat varieties approved in 2021 and 2022 in Sichuan province, China, carry this gene. Agronomic trait evaluation of NILs indicated that the 2NvS segment effectively mitigated the negative effects of stripe rust on yield without affecting other important agronomic traits. This study provided valuable insights for cloning and breeding through the utilization of the APR gene present in the 2NvS segment.
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Aegilops , Basidiomycota , Mapeamento Cromossômico , Resistência à Doença , Perfilação da Expressão Gênica , Genes de Plantas , Doenças das Plantas , Triticum , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Basidiomycota/patogenicidade , Basidiomycota/fisiologia , Aegilops/genética , Aegilops/microbiologia , Melhoramento Vegetal , Transcriptoma , Cromossomos de Plantas/genética , Puccinia/patogenicidade , Puccinia/fisiologia , Regulação da Expressão Gênica de PlantasRESUMO
Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.
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RATIONALE: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology. RESULTS: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. CONCLUSIONS: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.
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Lignanas , Farmacologia em Rede , Osteoporose , Ratos Sprague-Dawley , Animais , Lignanas/farmacologia , Lignanas/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/química , Metabolômica/métodos , Glucosídeos/farmacologia , Metaboloma/efeitos dos fármacos , Espectrometria de Massas/métodosRESUMO
Preventing the widespread occurrence of stripe rust in wheat largely depends on the identification of new stripe rust resistance genes and the breeding of cultivars with durable resistance. In previous study, we reported 6E of wheat-tetraploid Thinopyrum elongatum 6E (6D) substitution line contains adult-stage stripe rust resistance genes. In this study, three novel wheat-tetraploid Th. elongatum translocation lines were generated from the offspring of a cross between common wheat and the 6E (6D) substitution line. Genomic in situ hybridization (GISH), fluorescence in situ hybridization chromosome painting (FISH painting), repetitive sequential FISH, and 55 K SNP analyses indicated that K227-48, K242-82, and K246-6 contained 42 chromosomes and were 6DL·6ES, 2DL·6EL, and 6DS·6EL translocation lines, respectively. The assessment of stripe rust resistance revealed that K227-48 was susceptible to a mixture of Pst races, whereas the 6EL lines K242-82 and K246-6 were highly resistance to stripe rust at the adult stage. Thus, this resistance was due to the chromosome arm 6EL of tetraploid Th. elongatum. The improved agronomic performance of 6DS·6EL translocation line may be a useful novel germplasm resource for wheat breeding programs. For the application of marker-assisted selection (MAS), 47 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome 6E using the whole-genome sequence of diploid Th. elongatum. The 6DS·6EL translocation line and SSR markers have the potential to be deploy for future stripe rust resistance wheat breeding program. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01493-6.
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BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.
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Hepatectomia , Humanos , Hepatectomia/métodos , Masculino , Feminino , Resultado do Tratamento , Estudos Retrospectivos , Dilatação Patológica/cirurgia , Lactente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pré-EscolarRESUMO
BACKGROUND Arthroscopic knee surgery (AKS) is minimally invasive, reducing hospital stay compared to traditional surgery, but postoperative pain remains a significant issue. This study compared the analgesic and functional outcomes following AKS following anesthesia using adductor canal block (ACB) with and without anesthesia using the interspace between the popliteal artery and posterior capsule of the knee (IPACK) block under spinal anesthesia (SA). MATERIAL AND METHODS We randomly allocated 120 patients into 3 groups: IPACK+ACB+SA for Group A (n=40), ACB+SA for Group B (n=40), and SA for Group C (n=40). The outcome was the visual analog scale (VAS) score evaluated at rest and during activity at 3 h, 6 h, 12 h, 24 h, and 48 h postoperatively, the frequency of administration of postoperative rescue analgesic, and the maximal walking distance at 24 h and 48 h postoperatively. RESULTS Compared with Group C, the VAS scores in Group A were significantly lower at 48 h postoperatively (P<0.05). There was a significant difference in the frequency of postoperative rescue analgesia use among the 3 groups (P=0.001). In a subgroup analysis of meniscus shaping under arthroscopy, the resting VAS score in Group A was lower than that in Group B and Group C at 48 h postoperatively (P<0.05). The maximum walking distance of Group A was longer than that of Group B and Group C at 24 h and 48 h postoperatively (P<0.01). CONCLUSIONS The effect of postoperative analgesia in the group receiving IPACK combined with ACB after AKS was obviously superior. In arthroscopic meniscus repair surgery, the duration of analgesia was longer, and the maximum walking distance at 48 h postoperatively was longer.
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Artroscopia , Articulação do Joelho , Bloqueio Nervoso , Manejo da Dor , Medição da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Artroscopia/métodos , Artroscopia/efeitos adversos , Feminino , Masculino , Bloqueio Nervoso/métodos , Pessoa de Meia-Idade , Adulto , Manejo da Dor/métodos , Articulação do Joelho/cirurgia , Medição da Dor/métodos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. METHODS: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). RESULTS: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). CONCLUSIONS: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.
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BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.
Assuntos
Aldo-Ceto Redutases , Curcumina , Hepatopatia Gordurosa não Alcoólica , Triglicerídeos , Curcumina/farmacologia , Curcumina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Humanos , Células Hep G2 , Aldo-Ceto Redutases/metabolismo , Ratos , Masculino , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/metabolismo , Aldeído Redutase/metabolismo , Aldeído Redutase/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Simulação de Acoplamento Molecular , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metformina/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Rodanina/análogos & derivados , TiazolidinasRESUMO
Objectives To compare the gender differences in isolated mitral regurgitation (MR) repair. Methods Of 381 adults aged 54.8±12.3 years undergoing mitral valve repair (MVP) for isolated MR from 01/2019-12/2022, the baseline and operative data, and outcomes were compared between 161 women (42.3%) and 220 men (57.7%). Results Women tended to be non-smoker (98.1% vs 45%, P<0.001), and have more cerebrovascular accidents (38.5% vs 24.1%, P=0.004), lower creatinine (70.0±19.5 vs 86.3±19.9 µmol/dL, P<0.001), smaller LVEDD (54.4±6.7 vs 57.8±6.6 mm, P<0.001) and isolated annular dilatation (19.3% vs 9.1%, P=0.010). One female died of stroke at 2 days (0.3%). Another female (0.3%) underwent MV replacement for failed repair. Stroke occurred in 4 (1.0%). Two underwent re-exploration for bleeding (0.5%). Women were more likely to have less 24-hour drainage (290±143 vs 385±196 mL, P<0.001). Over a mean follow-up of 2.1±1.1 years (100% complete), one woman died, one man underwent a reoperation; 28 had moderate MR, and 9 had severe MR. Neither did early and late mortality and reoperation, nor freedom from late moderate/severe MR (71.6% vs 71.4% at 5 years; P=0.992) differ significantly between two genders. Predictors for late moderate/severe MR were anterior leaflet prolapse (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.18-16.72; P=0.027) and isolated annular dilation (HR 5.47, 95% CI 1.29-23.25; P=0.021). Conclusions Despite significant differences in smoking, cerebrovascular accidents, creatinine, LVEDD, and isolated annular dilatation at baseline, and 24-hour drainage, women and men did not show significant difference in early and late survival, reoperation and freedom from late moderate/severe MR.