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Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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Organogênese , Transcriptoma , Animais , DNA/genética , Embrião de Mamíferos , Feminino , Perfilação da Expressão Gênica/métodos , Mamíferos/genética , Camundongos , Organogênese/genética , Gravidez , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Transcriptoma/genéticaRESUMO
Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a key component of complexes of DSB-promoting proteins that assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution because of reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers, leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects co-occur with a genome-wide delay in assembling DSB-promoting proteins on autosome axes and loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins in wild type. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated DSB-promoting proteins.
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Proteínas de Transporte/genética , Quebras de DNA de Cadeia Dupla , Recombinação Homóloga/genética , Meiose/genética , Animais , Proteínas de Transporte/química , Segregação de Cromossomos/genética , Masculino , Camundongos , Regiões Pseudoautossômicas/genética , Espermatócitos/crescimento & desenvolvimento , Espermatócitos/metabolismo , Cromossomo X/genética , Cromossomo Y/genéticaRESUMO
BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.
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In CRISPR/Cas9 genome editing, the tight and persistent target binding of Cas9 provides an opportunity for efficient genetic and epigenetic modification on genome. In particular, technologies based on catalytically dead Cas9 (dCas9) have been developed to enable genomic regulation and live imaging in a site-specific manner. While post-cleavage target residence of CRISPR/Cas9 could alter the pathway choice in repair of Cas9-induced DNA double strand breaks (DSBs), it is possible that dCas9 residing adjacent to a break may also determine the repair pathway for this DSB, providing an opportunity to control genome editing. Here, we found that loading dCas9 onto a DSB-adjacent site stimulated homology-directed repair (HDR) of this DSB by locally blocking recruitment of classical non-homologous end-joining (c-NHEJ) factors and suppressing c-NHEJ in mammalian cells. We further repurposed dCas9 proximal binding to increase HDR-mediated CRISPR genome editing by up to 4-fold while avoiding exacerbation of off-target effects. This dCas9-based local inhibitor provided a novel strategy of c-NHEJ inhibition in CRISPR genome editing in place of small molecule c-NHEJ inhibitors, which are often used to increase HDR-mediated genome editing but undesirably exacerbate off-target effects.
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Sistemas CRISPR-Cas , Quebras de DNA de Cadeia Dupla , Animais , Reparo do DNA por Junção de Extremidades , Reparo de DNA por Recombinação , Edição de Genes/métodos , DNA/genética , Reparo do DNA , Mamíferos/genéticaRESUMO
BACKGROUND: KIAA1429, a regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms. METHODS: The expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, m6A dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC. RESULTS: Both the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the m6A level of RASD1 mRNA and enhanced its stability in an m6A-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of prooncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues. CONCLUSIONS: KIAA1429 plays a prooncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.
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Adenosina , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Estabilidade de RNA , RNA Mensageiro , Proteínas de Ligação a RNA , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proliferação de Células/genética , Animais , Estabilidade de RNA/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Masculino , Camundongos Nus , Feminino , Pessoa de Meia-Idade , Movimento Celular/genética , Camundongos , Prognóstico , Camundongos Endogâmicos BALB CRESUMO
Optical camera communication (OCC) has attracted increased attention for its inherent security advantage. However, there still exists the risk of eavesdropping on the broadcasting channel of OCC. To achieve confidential communication, we propose the confidentiality-interference dual light-emitting diode (LED) communication (CIDLC) scheme at the transmitter (TX) and elimination of interference (EI) scheme at the receiver (RX). Meanwhile, interference signals refer to the bit shift of confidential signals. Further, we propose the two-dimensional pilot-aided channel estimation (2D-PACE) scheme to enhance the reliability of multiple-input multiple-output (MIMO) OCC. Experiment results validate the effectiveness of our schemes, which guarantee confidentiality while performing well at a 2 m non-line-of-sight (NLOS) distance. Finally, the communication-illumination integration OCC is constructed via the energy equalization coding (EEC) scheme.
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BACKGROUND: Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. METHODS: Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. RESULTS: YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. CONCLUSIONS: This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.
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In the originally published version of this Article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'D/D' rather than 'd/d' in Fig. 1a and the accompanying legend, the main text and the Methods section. The original Article has been corrected online.
RESUMO
Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (Ambystoma mexicanum) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene Pax3. However, mutation of the axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.
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Ambystoma mexicanum/genética , Evolução Molecular , Genoma/genética , Genômica , Animais , DNA Intergênico/genética , Genes Essenciais/genética , Proteínas de Homeodomínio/genética , Íntrons/genética , Masculino , Camundongos , Fator de Transcrição PAX3/genética , Fator de Transcrição PAX7/genética , Picea/genética , Pinus/genética , Regeneração/genética , Retroelementos/genética , Sequências Repetidas Terminais/genéticaRESUMO
The leftward asymmetry of the visual field and posterior brain regions, a feature of the normal attention process, can be strengthened by brain stimulation, e.g. administering alpha frequency stimulation to the left posterior cortex. However, whether it can be strengthened by cognitive training, especially with nonlateralized tasks, is unknown. We used a dataset from a 2-month-long randomized controlled trial and compared the control group with 2 training groups trained with backward or forward memory span tasks. A lateralized change detection task with varied memory loads was administered as the pre-, mid-, and post-tests with simultaneous electroencephalographic recording. Intrasubject response variability (IRV) and the alpha modulation index (MI) were calculated. Analysis of IRV showed more enhanced leftward attentional bias in the backward group than in the other groups. Consistently, analysis of MI found that its enhancements in the left hemisphere (but not the right hemisphere) of the backward group were significantly higher than those of the other groups. Further analysis revealed that left MI changes predicted left IRV improvement. All of these results indicated that backward memory span training enhanced leftward attentional asymmetry at both the behavioral and neural levels.
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Viés de Atenção , Memória de Curto Prazo , Memória de Curto Prazo/fisiologia , Atenção/fisiologia , Encéfalo/fisiologia , Campos VisuaisRESUMO
BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.
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Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteômica/métodos , Fibrinogênio/uso terapêuticoRESUMO
Screen use while eating has been recently identified as a highly common and potentially important specific setting of screen use in relation to eating disorder symptomatology. However, given this area of research is still in its infancy, how screen use while eating may be related to eating disorder symptomatology remains largely unexplored. To fill this gap, the present study probed the potential roles of mindfulness and intuitive eating in the association between screen use while eating and eating disorder symptomatology. A large sample of Chinese adults (N = 800, aged 18-67 years old) recruited through a Chinese survey platform, Credamo, completed questionnaires assessing screen use while eating, eating disorder symptomatology, mindfulness, and intuitive eating. Structural equation modeling was used to test the proposed model. Results confirmed our hypotheses that the association between screen use while eating and eating disorder symptomatology was partially explained by mindfulness and intuitive eating, after adjusting for covariates (e.g., gender, age, body mass index, total screen time, and social media use). That said, higher screen use while eating was associated first with lower mindfulness and then with lower intuitive eating, which in turn were related to higher eating disorder symptomatology. The findings underline the importance of including eating-specific screen use for future research on eating disorder symptomatology and also have implications for an integrative intervention of mindfulness-based approaches and intuitive eating for mitigating the adverse effects of excessive screen use on eating behaviors.
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Transtornos da Alimentação e da Ingestão de Alimentos , Atenção Plena , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Índice de Massa Corporal , Comportamento Alimentar , Inquéritos e Questionários , Ingestão de AlimentosRESUMO
BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.
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Hemorragia Gastrointestinal , Hemostase Endoscópica , Adulto , Humanos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hemostase Endoscópica/efeitos adversos , Hemostase Endoscópica/métodos , Resultado do Tratamento , Austrália , China , Endoscopia Gastrointestinal/efeitos adversosRESUMO
AIM: Blunted niacin response (BNR) was an endophenotype of schizophrenia, but the underlying mechanism remains unclarified. The objective of this study was to verify whether genes associated with BNR pathway constitute the genetic basis and the pathological mechanism of BNR phenotypic psychiatric patients. METHODS: Two independent sample sets consisting of 971 subjects were enrolled in this study. A total of 62 variants were genotyped in the discovery set, then the related variants were verified in the verification set. The published PGC GWAS data were used to validate the associations between the variants and psychiatry disorders. RT-PCR analysis, eQTL data, and Dual-Luciferase Reporter experiment were used to investigate the potential molecular mechanisms of the variants underlying BNR. RESULTS: The results showed that two SNPs, rs56959712 in HCAR2 and rs2454721 in HCAR3 were significantly associated with niacin response. The risk allele T of rs2454721 could affect the niacin responses of psychiatric patients through elevated HCAR3 gene expression. These two genes, especially HCAR3, were significantly associated with the risk of schizophrenia, as identified in this study and verified using the published GWAS data. CONCLUSION: HCAR3 is a novel schizophrenia susceptibility gene which is significantly associated with blunted niacin response in schizophrenia. In-depth investigation of HCAR3 is of great significance for uncovering the pathogenesis and propose new therapeutic targets for psychiatric disorders, especially for the BNR subgroup patients.
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Niacina , Receptores Nicotínicos , Esquizofrenia , Humanos , Niacina/farmacologia , Niacina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Endofenótipos , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Receptores Nicotínicos/genética , Receptores Nicotínicos/uso terapêutico , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/uso terapêuticoRESUMO
Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35â µM. Proprotogracillin selectively inhibited A549 (IC50=0.58â µM) and A549/Taxol (IC50=0.74â µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40â µM.
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Antineoplásicos Fitogênicos , Ensaios de Seleção de Medicamentos Antitumorais , Melanthiaceae , Rizoma , Saponinas , Espirostanos , Humanos , Saponinas/isolamento & purificação , Saponinas/farmacologia , Saponinas/química , Rizoma/química , Melanthiaceae/química , Espirostanos/química , Espirostanos/isolamento & purificação , Espirostanos/farmacologia , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Conformação Molecular , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: This study explored the optimal time interval between staged bilateral total knee arthroplasty (BTKA) to minimize early complications of the second TKA and maximise the long-term function of the first and second knees. METHODS: We retrospectively reviewed 266 patients who underwent staged BTKA between 2013 and 2018. Groups 1-4 had time intervals between BTKAs of 1-6, 6-12, 12-18, and 18-24 months, respectively. Demographics, postoperative complications within 90 days of the second TKA, Knee Society Score (KSS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were compared among the groups. RESULTS: In total, 54, 96, 75, and 41 patients were assigned to groups 1-4, respectively. Although group 1 had the highest overall complication rate (11.11%), there was no significant difference in the complication rate among the four groups. Also, no significant differences were found among the four groups in functional and patient-reported outcomes, in either the first or second knee at 5 years postoperatively, including KSS-knee, KSS-function, WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function. The interval between BTKA did not influence complications or the function of the second knee. The TKA type (posterior-stabilised vs. medial-pivot) and age did not correlate significantly with any scores. CONCLUSIONS: There was no group difference in early complications of the second TKA, and postoperative function was equivalent between the two knees and did not vary by the interval between surgeries. The results of this study give surgeons and patients more choices. If patients cannot tolerate severe symptoms in the contralateral knee after the first TKA, the second TKA should be performed as early as possible. If knee joint function is not well recovered after the first TKA, and patients are anxious to undergo the second TKA, surgeons can advise patients to postpone the operation based on these results.
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Artroplastia do Joelho , Complicações Pós-Operatórias , Humanos , Artroplastia do Joelho/métodos , Artroplastia do Joelho/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Fatores de Tempo , Osteoartrite do Joelho/cirurgia , Recuperação de Função FisiológicaRESUMO
With clustered data, such as where students are nested within schools or employees are nested within organizations, it is often of interest to estimate and compare associations among variables separately for each level. While researchers routinely estimate between-cluster effects using the sample cluster means of a predictor, previous research has shown that such practice leads to biased estimates of coefficients at the between level, and recent research has recommended the use of latent cluster means with the multilevel structural equation modeling framework. However, the latent cluster mean approach may not always be the best choice as it (a) relies on the assumption that the population cluster sizes are close to infinite, (b) requires a relatively large number of clusters, and (c) is currently only implemented in specialized software such as Mplus. In this paper, we show how using empirical Bayes estimates of the cluster means can also lead to consistent estimates of between-level coefficients, and illustrate how the empirical Bayes estimate can incorporate finite population corrections when information on population cluster sizes is available. Through a series of Monte Carlo simulation studies, we show that the empirical Bayes cluster-mean approach performs similarly to the latent cluster mean approach for estimating the between-cluster coefficients in most conditions when the infinite-population assumption holds, and applying the finite population correction provides reasonable point and interval estimates when the population is finite. The performance of EBM can be further improved with restricted maximum likelihood estimation and likelihood-based confidence intervals. We also provide an R function that implements the empirical Bayes cluster-mean approach, and illustrate it using data from the classic High School and Beyond Study.
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Teorema de Bayes , Método de Monte Carlo , Humanos , Análise por Conglomerados , Simulação por Computador/estatística & dados numéricos , Viés de Seleção , Interpretação Estatística de Dados , Funções Verossimilhança , Modelos EstatísticosRESUMO
Many researchers consider gut microbiota (trillions of microorganisms) an endogenous organ of its animal host, which confers a vast genetic diversity in providing the host with essential biological functions. Particularly, the gut microbiota regulates not only gut tissue structure but also gut health and gut functionality. This paper first summarized those common bacterial species (dominated by the Firmicutes, Bacteroidota, and Proteobacteria phyla) in swine gut and then briefly discussed their roles in swine nutrition and health, which include roles in nutrient metabolism, pathogen exclusion, and immunity modulation. Secondly, the current knowledge on how dietary nutrients and feed additives affect the gut bacterial composition and nutrient metabolism in pigs was discussed. Finally, how dietary amino acids affect the relative abundances and metabolism of bacteria in the swine gut was reviewed. Tryptophan supplementation promotes the growth of beneficial bacteria and suppresses pathogens, while arginine metabolism affects nitrogen recycling, impacting gut immune response and health. Glutamate and glutamine supplementations elevate the levels of beneficial bacteria and mitigate pathogenic ones. It was concluded that nutritional strategies to manipulate gut microbial ecosystems are useful measures to optimize gut health and gut functions. For example, providing pigs with nutrients that promote the growth of Lactobacillus and Bifidobacterium can lead to better gut health and growth performance, especially when dietary protein is limited. Further research to establish the mechanistic cause-and-effect relationships between amino acids and the dynamics of gut microbiota will allow swine producers to reap the greatest return on their feed investment.
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Microbioma Gastrointestinal , Suínos , Animais , Microbioma Gastrointestinal/fisiologia , Ecossistema , Dieta , Bactérias , Aminoácidos , Ração Animal/análise , Suplementos NutricionaisRESUMO
The Intuitive Eating Scale-2 (IES-2) is a measure of intuitive eating behaviors that has been extensively validated, with traditional latent variable modeling approaches, in youth and adults from many different populations, including college students in China. However, there is still a lack of research on the psychometric properties of the IES-2 in adults from the Chinese general population. Moreover, psychometric network analysis, as a complement to traditional latent variable modeling approaches, has not been used for examining the psychometric properties of the IES-2. Thus, the present study used a psychometric network approach to evaluate the psychometric properties of the IES-2 in Chinese adults from the general population. A sample of 700 Chinese general adults (50% women; Mage = 31.13 years, SD = 9.19) recruited online were included in the present study. Psychometric network analysis was performed. Exploratory graph analysis (EGA) identified four dimensions, which were well separated in the estimated network. The network structure showed excellent stability and metric measurement invariance (i.e., network loadings) across men and women. Furthermore, several items on the IES-2 were identified as key nodes in the network of the IES-2 that may be important for the development and maintenance of intuitive eating. For example, two items (i.e., "I trust my body to tell me when to eat," and "I trust my body to tell me when to stop eating") related to reliance on body cues were the most impactful nodes in the complete network. The findings of our study provide a greater understanding of the IES-2 from the perspective of network analysis and have implications for applications of intuitive eating interventions for general populations.
Assuntos
Comportamento Alimentar , Intuição , Psicometria , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , População do Leste Asiático , Adulto JovemRESUMO
The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.