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1.
Proc Natl Acad Sci U S A ; 121(16): e2319119121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38588435

RESUMO

The advancement of atomically precise dinuclear heterogeneous catalysts holds great potential in achieving efficient catalytic ozonation performance and contributes to the understanding of synergy mechanisms during reaction conditions. Herein, we demonstrate a "ship-in-a-bottle and pyrolysis" strategy that utilizes Fe2(CO)9 dinuclear-cluster to precisely construct Fe2 site, consisting of two Fe1-N3 units connected by Fe-Fe bonds and firmly bonded to N-doped carbon. Systematic characterizations and theoretical modeling reveal that the Fe-Fe coordination motif markedly reduced the devotion of the antibonding state in the Fe-O bond because of the strong orbital coupling interaction of dual Fe d-d orbitals. This facilitates O-O covalent bond cleavage of O3 and enhances binding strength with reaction intermediates (atomic oxygen species; *O and *OO), thus boosting catalytic ozonation performance. As a result, Fe dinuclear site catalyst exhibits 100% ozonation efficiency for CH3SH elimination, outperforming commercial MnO2 catalysts by 1,200-fold. This research provides insights into the atomic-level structure-activity relationship of ozonation catalysts and extends the use of dinuclear catalysts in catalytic ozonation and beyond.

2.
Proc Natl Acad Sci U S A ; 120(1): e2209062120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36577070

RESUMO

Hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous group of cells with expansion, differentiation, and repopulation capacities. How HSPCs orchestrate the stemness state with diverse lineage differentiation at steady condition or acute stress remains largely unknown. Here, we show that zebrafish mutants that are deficient in an epigenetic regulator Atf7ip or Setdb1 methyltransferase undergo excessive myeloid differentiation with impaired HSPC expansion, manifesting a decline in T cells and erythroid lineage. We find that Atf7ip regulates hematopoiesis through Setdb1-mediated H3K9me3 modification and chromatin remodeling. During hematopoiesis, the interaction of Atf7ip and Setdb1 triggers H3K9me3 depositions in hematopoietic regulatory genes including cebpß and cdkn1a, preventing HSPCs from loss of expansion and premature differentiation into myeloid lineage. Concomitantly, loss of Atf7ip or Setdb1 derepresses retrotransposons that instigate the viral sensor Mda5/Rig-I like receptor (RLR) signaling, leading to stress-driven myelopoiesis and inflammation. We find that ATF7IP or SETDB1 depletion represses human leukemic cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation. These findings establish that Atf7ip/Setdb1-mediated H3K9me3 deposition constitutes a genome-wide checkpoint that impedes the myeloid potential and maintains HSPC stemness for diverse blood cell production, providing unique insights into potential intervention in hematological malignancy.


Assuntos
Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase , Peixe-Zebra , Animais , Humanos , Diferenciação Celular , Linhagem da Célula , Hematopoese , Células-Tronco Hematopoéticas/patologia , Histona-Lisina N-Metiltransferase/genética , Inflamação/patologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
3.
J Infect Dis ; 229(6): 1866-1877, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38262678

RESUMO

BACKGROUND: Active case finding (ACF) is a potentially promising approach for the early identification and treatment of tuberculosis patients. However, evidence on its cost-effectiveness, particularly in low- and middle-income countries, remains limited. This study evaluates the cost-effectiveness of a community-based ACF practice in Shenzhen, China. METHODS: We employed a Markov model-based decision analytic method to assess the costs and effectiveness of 3 tuberculosis detection strategies: passive case finding (PCF), basic ACF, and advanced ACF. The analysis was conducted from a societal perspective on a dynamic cohort over a 20-year horizon, focusing on active tuberculosis (ATB) prevalence and the incremental cost-effectiveness ratio (ICER). RESULTS: Compared to the PCF strategy, the basic and advanced ACF strategies effectively reduced ATB cases by 6.8 and 10.2 per 100 000 population, respectively, by the final year of this 20-year period. The ICER for the basic and advanced ACF strategies were ¥14 757 and ¥8217 per quality-adjusted life-year, respectively. Both values fell below the cost-effectiveness threshold. CONCLUSIONS: Our findings indicate that the community-based ACF screening strategy, which targets individuals exhibiting tuberculosis symptoms, is cost-effective. This underscores the potential benefits of adopting similar community-based ACF strategies for symptomatic populations in tuberculosis-endemic areas.


Assuntos
Análise Custo-Benefício , Cadeias de Markov , Tuberculose , Humanos , China/epidemiologia , Tuberculose/diagnóstico , Tuberculose/economia , Tuberculose/epidemiologia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Prevalência
4.
BMC Genomics ; 25(1): 480, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750582

RESUMO

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (FST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, FST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.


Assuntos
Tamanho da Ninhada de Vivíparos , Sequenciamento Completo do Genoma , Animais , Tamanho da Ninhada de Vivíparos/genética , Ovinos/genética , Seleção Genética , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Cruzamento , Feminino , Fertilidade/genética , Reprodução/genética
5.
Neuroimage ; 290: 120560, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431181

RESUMO

Brain extraction and image quality assessment are two fundamental steps in fetal brain magnetic resonance imaging (MRI) 3D reconstruction and quantification. However, the randomness of fetal position and orientation, the variability of fetal brain morphology, maternal organs around the fetus, and the scarcity of data samples, all add excessive noise and impose a great challenge to automated brain extraction and quality assessment of fetal MRI slices. Conventionally, brain extraction and quality assessment are typically performed independently. However, both of them focus on the brain image representation, so they can be jointly optimized to ensure the network learns more effective features and avoid overfitting. To this end, we propose a novel two-stage dual-task deep learning framework with a brain localization stage and a dual-task stage for joint brain extraction and quality assessment of fetal MRI slices. Specifically, the dual-task module compactly contains a feature extraction module, a quality assessment head and a segmentation head with feature fusion for simultaneous brain extraction and quality assessment. Besides, a transformer architecture is introduced into the feature extraction module and the segmentation head. We utilize a multi-step training strategy to guarantee a stable and successful training of all modules. Finally, we validate our method by a 5-fold cross-validation and ablation study on a dataset with fetal brain MRI slices in different qualities, and perform a cross-dataset validation in addition. Experiments show that the proposed framework achieves very promising performance.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Gravidez , Feminino , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cabeça , Feto/diagnóstico por imagem
6.
Neuroimage ; 295: 120652, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38797384

RESUMO

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.


Assuntos
Encéfalo , Aprendizado Profundo , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Macaca mulatta , Neuroimagem/métodos , Pan troglodytes/anatomia & histologia , Envelhecimento/fisiologia
7.
BMC Plant Biol ; 24(1): 114, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365570

RESUMO

BACKGROUND: The small YABBY plant-specific transcription factor has a prominent role in regulating plant growth progress and responding to abiotic stress. RESULTS: Here, a total of 16 PvYABBYs from switchgrass (Panicum virgatum L.) were identified and classified into four distinct subgroups. Proteins within the same subgroup exhibited similar conserved motifs and gene structures. Synteny analyses indicated that segmental duplication contributed to the expansion of the YABBY gene family in switchgrass and that complex duplication events occurred in rice, maize, soybean, and sorghum. Promoter regions of PvYABBY genes contained numerous cis-elements related to stress responsiveness and plant hormones. Expression profile analysis indicated higher expression levels of many PvYABBY genes during inflorescence development and seed maturation, with lower expression levels during root growth. Real-time quantitative PCR analysis demonstrated the sensitivity of multiple YABBY genes to PEG, NaCl, ABA, and GA treatments. The overexpression of PvYABBY14 in Arabidopsis resulted in increased root length after treatment with GA and ABA compared to wild-type plants. CONCLUSIONS: Taken together, our study provides the first genome-wide overview of the YABBY transcription factor family, laying the groundwork for understanding the molecular basis and regulatory mechanisms of PvYABBY14 in response to ABA and GA responses in switchgrass.


Assuntos
Arabidopsis , Panicum , Panicum/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas , Genes de Plantas , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo
8.
Small ; : e2400551, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516940

RESUMO

Electrocatalytic nitrogen reduction technology seamlessly aligns with the principles of environmentally friendly chemical production. In this paper, a comprehensive review of recent advancements in electrocatalytic NH3 synthesis utilizing single-atom catalysts (SACs) is offered. Into the research and applications of three categories of SACs: noble metals (Ru, Au, Rh, Ag), transition metals (Fe, Mo, Cr, Co, Sn, Y, Nb), and nonmetallic catalysts (B) in the context of electrocatalytic ammonia synthesis is delved. In-depth insights into the material preparation methods, single-atom coordination patterns, and the characteristics of the nitrogen reduction reaction (NRR) are provided. The systematic comparison of the nitrogen reduction capabilities of various SAC types offers a comprehensive research framework for their integration into electrocatalytic NRR. Additionally, the challenges, potential solutions, and future prospects of incorporating SACs into electrocatalytic nitrogen reduction endeavors are discussed.

9.
EMBO Rep ; 23(5): e54090, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35301795

RESUMO

Despite the importance of cilia in cell signaling and motility, the molecular mechanisms regulating cilium formation remain incompletely understood. Herein, we characterize enkurin domain-containing protein 1 (ENKD1) as a novel centrosomal protein that mediates the removal of centriolar coiled-coil protein 110 (CP110) from the mother centriole to promote ciliogenesis. We show that Enkd1 knockout mice possess ciliogenesis defects in multiple organs. Super-resolution microscopy reveals that ENKD1 is a stable component of the centrosome throughout the ciliogenesis process. Simultaneous knockdown of ENKD1 and CP110 significantly reverses the ciliogenesis defects induced by ENKD1 depletion. Protein interaction analysis shows that ENKD1 competes with centrosomal protein 97 (CEP97) in binding to CP110. Depletion of ENKD1 enhances the CP110-CEP97 interaction and detains CP110 at the mother centriole. These findings thus identify ENKD1 as a centrosomal protein and uncover a novel mechanism controlling CP110 removal from the mother centriole for the initiation of ciliogenesis.


Assuntos
Centríolos , Proteínas Associadas aos Microtúbulos , Animais , Camundongos , Proteínas de Ligação a Calmodulina/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Centríolos/genética , Centríolos/metabolismo , Centrossomo/metabolismo , Cílios/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Plasma Seminal/metabolismo
10.
Acta Haematol ; 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342094

RESUMO

INTRODUCTION: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors in AML remained unclear. This study aimed to investigate the prevalence, risk factors, and prognostic value of anxiety and depression in AML patients. METHODS: Totally, 132 de novo AML patients, 60 non-malignant hematological disease patients (as disease controls) and 60 healthy controls were enrolled. Anxiety and depression status were evaluated by Hospital Anxiety and Depression Scale (HADS) in all participants. RESULTS: HADS-anxiety score (8.2±3.2 vs. 6.1±2.9 vs. 4.7±2.8), anxiety rate (48.5% vs. 25.0% vs. 10.0%), HADS-depression score (7.8±3.0 vs. 5.8±3.0 vs. 4.0±2.8) and depression rate (43.2% vs. 23.3% vs. 8.3%) were highest in AML patients, followed by disease controls, and the lowest in healthy controls (all P<0.001). Multivariate logistic regression analysis identified that factors independently associated with anxiety included male (P=0.002, odds ratio (OR)=0.240), smoking (P=0.043, OR=2.474), education duration (P=0.024, OR=0.889) and NCCN high-risk stratification (P=0.008, OR=2.347); while those independently associated with depression were age (P=0.005, OR=1.055), single/divorced/widowed status (P=0.014, OR=3.149), NCCN high-risk stratification (P=0.002, OR=3.077) and WBC (P<0.001, OR=1.062). Additionally, depression was correlated with shorter accumulating event-free survival (P=0.012) and overall survival (P=0.041) in AML patients, whereas anxiety was not. CONCLUSIONS: Anxiety and depression are prevalent, among which depression is associated with poor survival profile, but anxiety is not; moreover, age, male, education, single/divorced/widowed status, smoking, NCCN high-risk stratification and WBC were independent related factors of anxiety and depression in AML patients.

11.
Nucleic Acids Res ; 50(13): 7560-7569, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35819229

RESUMO

5'-Adenylated oligonucleotides (AppOligos) are widely used for single-stranded DNA/RNA ligation in next-generation sequencing (NGS) applications such as microRNA (miRNA) profiling. The ligation between an AppOligo adapter and target molecules (such as miRNA) no longer requires ATP, thereby minimizing potential self-ligations and simplifying library preparation procedures. AppOligos can be produced by chemical synthesis or enzymatic modification. However, adenylation via chemical synthesis is inefficient and expensive, while enzymatic modification requires pre-phosphorylated substrate and additional purification. Here we cloned and characterized the Pfu RNA ligase encoded by the PF0353 gene in the hyperthermophilic archaea Pyrococcus furiosus. We further engineered fusion enzymes containing both Pfu RNA ligase and T4 polynucleotide kinase. One fusion enzyme, 8H-AP, was thermostable and can directly catalyze 5'-OH-terminated DNA substrates to adenylated products. The newly discovered Pfu RNA ligase and the engineered fusion enzyme may be useful tools for applications using AppOligos.


Assuntos
Monofosfato de Adenosina/química , Técnicas Genéticas , MicroRNAs , Oligonucleotídeos/química , Polinucleotídeo 5'-Hidroxiquinase , DNA/química , DNA Ligases/metabolismo , DNA de Cadeia Simples , Polinucleotídeo 5'-Hidroxiquinase/genética , Pyrococcus furiosus/enzimologia , RNA Ligase (ATP)/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-38904633

RESUMO

Objective: To study the clinical effectiveness of the 4P nursing model combined with Amisulpride and Clozapine in the management of psychiatric patients. Method: 100 patients with refractory schizophrenia treated in the Psychiatry department of Ganzhou People's Hospital from January 3, 2021, to January 4, 2022, were selected as the study subjects. They were randomly divided into observation and control groups, with 50 patients in each group. The clinical efficacy in the two groups was then assessed and compared using such parameters as the PANSS score, body mass index (BMI), blood lipid levels, incidence of side effects, and nursing satisfaction scores. Results: The difference in total treatment efficacy was statistically significant (χ2=11.724, 9.458, P ≤ .001, RR0.24, 95%CI (0.117-0.363)). The post-treatment PANSS score, positive symptom score, negative symptom score, and general pathological score treatment were all lower than the pre-treatment scores in both groups. The difference was statistically significant (RR0.12, 95%CI (0.098-0.203)). There was a reduction in the BMI of patients in the observation group after treatment, while there was an increase in that of patients in the control group. However, after treatment, there were significant reductions in the concentrations of T-CHO, LDL-C, and HDL-C in both groups (all P < .05, RR0.26, 95%CI (0.156-0.371)), with more significant reductions seen in the observation group than in the control group. The patients in the observation group recorded a much lower incidence of such side effects as drowsiness, nausea and vomiting, constipation, and weight gain and were more satisfied with the nursing they received as compared to their counterparts in the control group (all P < .05, RR0.28, 95%CI (0.171-0.351)). Conclusion: The 4P nursing model combined with Amisulpride and Clozapine can improve adherence to treatment, as well as the overall effectiveness of treatment. This nursing method has a high safety profile, improves the quality of life, and its use deserves more widespread promotion.

13.
BMC Biol ; 21(1): 303, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129834

RESUMO

BACKGROUND: Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood. RESULTS: We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment. CONCLUSIONS: This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.


Assuntos
Domesticação , Patos , Animais , Patos/genética , Patos/metabolismo , Herança Multifatorial , Regiões Promotoras Genéticas , Ácidos Graxos/metabolismo
14.
J Anim Physiol Anim Nutr (Berl) ; 108(3): 816-838, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324000

RESUMO

Eucommia ulmoides has been used as a food and medicine homologue for a long time in China. We hypothesize that Eucommia ulmoides achieves its health-promoting effects via altering gut microbiota. Here, we investigated the effects of water extract of Eucommia ulmoides bark on caecal microbiota and growth performance, antioxidant activity, and immunity in white-feathered broilers treated for 42 days. A total of 108 one-day-old Cobb white-feathered broilers were randomly assigned to three treatment groups: control diet, 0.75% Eucommia ulmoides diet (EU Ⅰ) and 1.5% Eucommia ulmoides diet (EU Ⅱ). The results showed that EU Ⅱ treatment improved average body weight (ABW), thigh muscle quality and total length of intestines, and decreased the serum total triglycerides and total cholesterol (TC) (p < 0.05). Eucommia ulmoides supplementation increased serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant activities and content of immunoglobulins, and reduced levels of malondialdehyde and tumour necrosis factor-α (TNF-α) (p < 0.05). Moreover, the supplementation increased the diversity of caecal microbiota and reduced the pathogenic genera Escherichia Shigella and Helicobacter. The genera Ochrobactrum, Odoribater, Klebsiella, Enterobacter, Georgenia and Bifidobacterium were positively associated with the ABW, total intestinal length, serum levels of GSH-Px, SOD and immunoglobulins (p < 0.001) and negatively associated with the TC and TNF-α (p < 0.01), suggesting an association of the changes of gut microbiota and improvement of broiler health. Meanwhile, Eucommia ulmoides supplementation enriched the Kyoto Encyclopedia of Genes and Genomes pathway of exocrine secretion from the pancreas, circadian entrainment and inhibited lipopolysaccharide biosynthesis. In conclusion, Eucommia ulmoides water extract can be used as a feed additive to improve poultry industry production.


Assuntos
Ração Animal , Ceco , Galinhas , Dieta , Suplementos Nutricionais , Eucommiaceae , Casca de Planta , Extratos Vegetais , Animais , Eucommiaceae/química , Ração Animal/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ceco/microbiologia , Dieta/veterinária , Casca de Planta/química , Fenômenos Fisiológicos da Nutrição Animal , Microbioma Gastrointestinal/efeitos dos fármacos
15.
Angew Chem Int Ed Engl ; 63(11): e202319647, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38198183

RESUMO

Here we present a modular, chemo-, regio-, and stereoselective synthesis of fully-substituted and configuration-defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive approach involves the chemo- and regioselective functionalization of the CF2 unit in gem-difluorinated cyclopropanes with O-H and C-H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring-opening process to produce fully-substituted and configuration-defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual-functional copper catalysis, which is involved in both the functionalization of the CF2 unit and the subsequent ring-opening process.

16.
Angew Chem Int Ed Engl ; 63(22): e202403602, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38515395

RESUMO

The use of gem-difluorinated cyclopropanes (gem-DFCPs) as fluoroallyl surrogates under transition-metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono-fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem-DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem-DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

17.
Development ; 147(18)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988975

RESUMO

Teleost zebrafish and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through dedifferentiation and proliferation of pre-existing cardiomyocytes (CMs). Although many mitogenic signals that stimulate zebrafish heart regeneration have been identified, transcriptional programs that restrain injury-induced CM renewal are incompletely understood. Here, we report that mutations in gridlock (grl; also known as hey2), encoding a Hairy-related basic helix-loop-helix transcriptional repressor, enhance CM proliferation and reduce fibrosis following damage. In contrast, myocardial grl induction blunts CM dedifferentiation and regenerative responses to heart injury. RNA sequencing analyses uncover Smyd2 lysine methyltransferase (KMT) as a key transcriptional target repressed by Grl. Reduction in Grl protein levels triggered by injury induces smyd2 expression at the wound myocardium, enhancing CM proliferation. We show that Smyd2 functions as a methyltransferase and modulates the Stat3 methylation and phosphorylation activity. Inhibition of the KMT activity of Smyd2 reduces phosphorylated Stat3 at cardiac wounds, suppressing the elevated CM proliferation in injured grl mutant hearts. Our findings establish an injury-specific transcriptional repression program in governing CM renewal during heart regeneration, providing a potential strategy whereby silencing Grl repression at local regions might empower regeneration capacity to the injured mammalian heart.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Coração/fisiologia , Lisina/genética , Metiltransferases/genética , Regeneração/genética , Transcrição Gênica/genética , Vertebrados/genética , Proteínas de Peixe-Zebra/genética , Animais , Animais Recém-Nascidos , Diferenciação Celular/genética , Proliferação de Células/genética , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fosforilação/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Peixe-Zebra/genética
18.
FASEB J ; 36(8): e22461, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35838582

RESUMO

Brown adipose tissue (BAT) is an important component of energy expenditure and necessary to maintain body temperature for newborn mammals. In the previous study, we found that L-carnitine was enriched in BAT and promoted BAT adipogenesis and thermogenesis in goat brown adipocytes. However, whether dietary L-carnitine regulates BAT heat production and energy expenditure in lambs remains unclear. In this study, maternal L-carnitine supplementation elevated the rectal temperature, as well as the expression of UCP1 and mitochondrial DNA content to promote BAT thermogenesis in newborn goats. Moreover, maternal L-carnitine supplementation increased the levels of triglycerides (TG), non-esterified fatty acids (NEFA), and lactate in plasma, as well as the content of lipid droplet and glycogen in BAT of newborn goats. Lipidomic analysis showed that maternal L-carnitine supplementation remodeled the lipid composition of BAT in newborn goats. L-carnitine significantly increased the levels of TG and diglyceride (DG) and decreased the levels of glycerophospholipids and sphingolipids in BAT. Further studies showed that L-carnitine promoted TG and glycogen deposition in brown adipocytes through AMPKα. Our results indicate that maternal L-carnitine supplementation promotes BAT development and thermogenesis in newborn goats and provides new evidence for newborn goats to maintain body temperature in response to cold exposure.


Assuntos
Tecido Adiposo Marrom , Carnitina , Tecido Adiposo Marrom/metabolismo , Animais , Animais Recém-Nascidos , Carnitina/metabolismo , Carnitina/farmacologia , Temperatura Baixa , Suplementos Nutricionais , Metabolismo Energético , Glicogênio/metabolismo , Cabras/metabolismo , Ovinos , Termogênese/fisiologia , Triglicerídeos/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
19.
Environ Sci Technol ; 57(35): 13205-13216, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37487235

RESUMO

The design of a micro-/nanoreactor is of great significance for catalytic ozonation, which can achieve effective mass transfer and expose powerful reaction species. Herein, the mesoporous carbon with atomic Fe-N4 sites embedded in the ordered carbon nanochannels (Fe-N4/CMK-3) was synthesized by the hard-template method. Fe-N4/CMK-3 can be employed as nanoreactors with preferred electronic and geometric catalytic microenvironments for the internal catalytic ozonation of CH3SH. During the CH3SH oxidation process, the mass transfer coefficient of the Fe-N4/CMK-3 confined system with sufficient O3 transfer featured a level of at least 1.87 × 10-5, which is 34.6 times that of the Fe-N4/C-Si unconfined system. Detailed experimental studies and theoretical calculations demonstrated that the anchored atomic Fe-N4 sites and nanoconfinement effects regulated the local electronic structure of the catalyst and promoted the activation of O3 molecules to produce atomic oxygen species (AOS) and reactive oxygen species (ROS), eventually achieving efficient oxidation of CH3SH into CO2/SO42-. Benefiting from the high diffusion rate and the augmentation of AOS/ROS, Fe-N4/CMK-3 exhibited an excellent poisoning tolerance, along with high catalytic durability. This contribution provides the proof-of-concept strategy for accelerating catalytic ozonation of sulfur-containing volatile organic compounds (VOCs) by combining confined catalysis and atomic catalysts and can be extended to the purification of other gaseous pollutants.


Assuntos
Carbono , Ozônio , Espécies Reativas de Oxigênio , Catálise , Nanotecnologia
20.
Surg Endosc ; 37(10): 7591-7599, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460818

RESUMO

BACKGROUND: In order to explore the surgical safety and the reliability of axillary staging of single-port endoscopic-sentinel lymph node biopsy, we combined it with indocyanine green that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles as a tracer and compared this method to conventional open sentinel lymph node biopsy. METHODS: This is a retrospective and observational study, there were 20 patients in each group and the total sample size was 60: Group 1, single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles; Group 2, single-port endoscopic-sentinel lymph node biopsy with carbon nanoparticles only; Group 3, conventional sentinel lymph node biopsy with indocyanine green and carbon nanoparticles. Sentinel lymph node detection and upper extremity function were determined to measure the safety and efficacy of the novel single-port endoscopic-sentinel lymph node biopsy (SPE-SLNB) technique to the standard conventional sentinel lymph node biopsy technique. RESULTS: The detection rate of sentinel lymph nodes was 100% in Group 1, 100% in Group 2, and 95% in Group 3. There were no significant differences in upper arm function and pain scores between the three groups. CONCLUSION: The novel technique of combining indocyanine green and carbon nanoparticles with single-port endoscopic-sentinel lymph node biopsy achieved a similar detection rate and mean number of sentinel lymph nodes as conventional sentinel lymph node biopsy. Traditional open surgery requires two different incisions for breast surgery and SLNB. While the most important advantage of SPE-SLNB is that two procedures can be effectively performed through a single-port in the axilla Therefore, for patients who meet the indications, single-port endoscopic-sentinel lymph node biopsy is as safe and reliable as conventional sentinel lymph node biopsy but has the aesthetic advantage of only one incision.


Assuntos
Neoplasias da Mama , Nanopartículas , Linfonodo Sentinela , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Verde de Indocianina , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Endoscopia , Carbono , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Corantes
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