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1.
Sci China Life Sci ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38679670

RESUMO

Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.

2.
J Org Chem ; 89(3): 1967-1979, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241611

RESUMO

Herein, we describe an effective method for the synthesis of 2-alkoxyamides and 1,2-diamines through visible-light-mediated difunctionalization of alkenes. N-Aminopyridinium salts were employed as appropriate precursors to generate key amidyl radical intermediates via a photoinduced single-electron transfer (SET) process. The amidyl radicals would react with alkenes, followed by oxidation and nucleophilic addition. Excellent functional group tolerance and good yields demonstrate the synthetic potential of this transformation.

3.
Front Microbiol ; 14: 1234817, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808322

RESUMO

Introduction: After COVID-19, there was an outbreak of a new infectious disease caused by monkeypox virus. So far, no specific drug has been found to treat it. Xuanbai Chengqi decoction (XBCQD) has shown effects against a variety of viruses in China. Methods: We searched for the active compounds and potential targets for XBCQD from multiple open databases and literature. Monkeypox related targets were searched out from the OMIM and GeneCards databases. After determining the assumed targets of XBCQD for monkeypox treatment, we built the PPI network and used R for GO enrichment and KEGG pathway analysis. The interactions between the active compounds and the hub targets were investigated by molecular docking and molecular dynamics (MD) simulations. Results: In total, 5 active compounds and 10 hub targets of XBCQD were screened out. GO enrichment and KEGG analysis demonstrated that XBCQD plays a therapeutic role in monkeypox mainly by regulating signaling pathways related to viral infection and inflammatory response. The main active compound estrone binding to target AR was confirmed to be the best therapy choice for monkeypox. Discussion: This study systematically explored the interactions between the bioactive compounds of XBCQD and the monkeypox-specific XBCQD targets using network pharmacological methods, bioinformatics analyses and molecular simulations, suggesting that XBCQD could have a beneficial therapeutic effect on monkeypox by reducing the inflammatory damage and viral replication via multiple pathways. The use of XBCQD on monkeypox disease was confirmed to be best worked through the estrone-target AR interaction. Our work could provide evidence and guidance for further research on the treatment of monkeypox disease.

4.
Org Lett ; 25(42): 7661-7666, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37844134

RESUMO

A catalyst-free approach for the multicomponent aminoheteroarylation reaction of alkenes with N-aminopyridinium salts and heteroarenes is herein described. The reaction shows good functional group tolerance and allows the generation of valuable ß-heteroarylethylamines in satisfying yields. In this transformation, N-aminopyridinium salts and heteroarenes are utilized to generate electron donor-acceptor complexes, which undergo a single-electron transfer process upon light irradiation to form key amidyl radicals and heteroaryl radical cations. The amidyl radical is subsequently captured by alkenes, followed by a Minisci-type reaction to yield the desired ß-heteroarylamines as products.

5.
Pestic Biochem Physiol ; 195: 105558, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37666594

RESUMO

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an extremely destructive notifiable quarantine pest. Over the last two decades, neonicotinoid insecticides, particularly thiamethoxam and imidacloprid, have been used to control it in Xinjiang, and local field populations have developed different levels of resistance in consequence. However, the contributions of nicotinic acetylcholine receptors (nAChRs) to neonicotinoid resistance are currently poorly understood in CPB. Previous studies have shown that nAChRα1, α3, α8 and ß1 are major target subunits for neonicotinoids in some model and important agricultural insects including nAChRα1 subunit of L. decemlineata (Ldα1). In this study, the expression levels of Ldα3, Ldα8 and Ldß1 following 72 h of treatments with median lethal doses of thiamethoxam and imidacloprid were compared using real-time quantitative PCR. These genes were then individually and simultaneously knocked down with Ldα1 by RNA interference (RNAi) using a double-stranded RNA (dsRNA) feeding method for six days to explore their roles in CPB susceptibility to imidacloprid and thiamethoxam. The results showed that the expressions of Ldα3, Ldα8 and Ldß1 were significantly decreased by 36.99-74.89% after thiamethoxam and imidacloprid treatments, compared with the control. The significant downregulation of the target genes resulting from RNAi significantly reduced the mortality of adults exposed to thiamethoxam and imidacloprid by 34.53% -56.44% and 28.78%-43.93%, respectively. Furthermore, the adult survival rates were not affected by every dsRNA-feeding treatment, while the body weight of the test adults significantly deceased after four and six days of individual gene RNAi. This study showed that Ldα3, Ldα8 and Ldß1 are down-regulated by thiamethoxam and imidacloprid and play important roles in the tolerance of CPB to neonicotinoids.


Assuntos
Besouros , Solanum tuberosum , Animais , Besouros/genética , Tiametoxam , Neonicotinoides/farmacologia
6.
RSC Adv ; 13(15): 9800-9810, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36998522

RESUMO

SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings. The spike aspartic acid-614 to glycine (D614G) substitution in the spike represents a "more transmissible form of SARS-CoV-2" and occurs in all SARS-CoV-2 mutants. However, the underlying mechanism of the D614G substitution in virus infectivity has remained unclear. In this paper, we adopt molecular simulations to study the contact processes of the D614G mutant and wild-type (WT) spikes with hACE2. The interaction areas with hACE2 for the two spikes are completely different by visualizing the whole binding processes. The D614G mutant spike moves towards the hACE2 faster than the WT spike. We have also found that the receptor-binding domain (RBD) and N-terminal domain (NTD) of the D614G mutant extend more outwards than those of the WT spike. By analyzing the distances between the spikes and hACE2, the changes of number of hydrogen bonds and interaction energy, we suggest that the increased infectivity of the D614G mutant is not possibly related to the binding strength, but to the binding velocity and conformational change of the mutant spike. This work reveals the impact of D614G substitution on the infectivity of the SARS-CoV-2, and hopefully could provide a rational explanation of interaction mechanisms for all the SARS-CoV-2 mutants.

7.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36835006

RESUMO

Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE-RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine-AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol-AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Neoplasias , Scutellaria baicalensis , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Farmacologia em Rede , Estigmasterol/química , Estigmasterol/farmacologia , Neoplasias da Mama/tratamento farmacológico
8.
Oncol Lett ; 25(1): 22, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36466996

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-ß pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-ß pathway. Previous studies have shown that FXR1 promotes the proliferation, invasion, and migration of colorectal cancer cells. The aim of the present study was to explore the effects of FXR1 on HCC via the TGF-ß/SMAD signaling pathway. Immunohistochemical analysis was used to detect the expression of FXR1 in HCC and normal tissues. Western blotting was used to detect protein expression levels in the HCC cell lines, cell migration and invasion were assessed using Transwell assays, and cell proliferation was assessed using a colony formation assay. The ability of the liver cancer cells to grow in vivo was investigated using a nude mouse tumor-bearing model. The results showed that FXR1 expression was upregulated in HCC tissues compared with normal tissues. Knockdown of FXR1 resulted in reduced expression of SMAD2/3 and EMT-related proteins in HCC cells. In addition, FXR1 knockdown inhibited the proliferation, migration, and invasion of HCC cells. FXR1 knockdown also reversed the promoting effect of TGF-ß on the invasive ability of HCC cells. Knockdown of SMAD2/3 reversed the increase in HCC cell invasion induced by FXR1 overexpression. Finally, upregulated FXR1 expression was associated with a poorer prognosis in patients with HCC. In conclusion, FXR1 promoted HCC proliferation, migration, and invasion through the regulation of SMAD2/3.

9.
J Biomater Sci Polym Ed ; 34(8): 1090-1100, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36476323

RESUMO

Bleeding complications are associated with substantial tissue morbidities and mortalities. Biomimetic composite materials that possess the ability to sufficiently stimulate and augment different physiological mechanisms of hemostasis are highly desirable to reduce bleeding-related casualties, which, however, are still largely under-explored. This study aims to develop a composite hemostatic system by combining collagen hydrogel with tissue factor (TF)-integrated liposome and silica nanoparticle, which could integrate the platelet plug-promoting capacity of collagen with the abilities of the latter two components to activate the extrinsic and intrinsic pathways of coagulation respectively. Several hydrogel compositions were synthesized and characterized. We show that lipidated TF and silica were evenly distributed in the collagen-based hydrogels, while exhibiting tunable release kinetics in simulated body fluid. Time-to-coagulation test revealed that each component in the TF-liposome/silica/collagen ternary hydrogels was hemostasis-active, and their combination showed enhanced and potent procoagulant performance, without detectable cytotoxicity against NIH/3T3 model cells. These results suggest that collagen hydrogels with embedded TF-liposome and silica nanoparticle may serve as a platform for an effective hemostatic composite that incorporates all the basic known pathways of coagulation.


Assuntos
Hemostáticos , Nanopartículas , Hidrogéis , Tromboplastina , Lipossomos , Dióxido de Silício , Hemostasia , Colágeno
10.
J Adv Res ; 42: 315-329, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36513421

RESUMO

INTRODUCTION: Legume crops are an important source of protein and oil for human health and in fixing atmospheric N2 for soil enrichment. With an objective to accelerate much-needed genetic analyses and breeding applications, draft genome assemblies were generated in several legume crops; many of them are not high quality because they are mainly based on short reads. However, the superior quality of genome assembly is crucial for a detailed understanding of genomic architecture, genome evolution, and crop improvement. OBJECTIVES: Present study was undertaken with an objective of developing improved chromosome-length genome assemblies in six different legumes followed by their systematic investigation to unravel different aspects of genome organization and legume evolution. METHODS: We employed in situ Hi-C data to improve the existing draft genomes and performed different evolutionary and comparative analyses using improved genome assemblies. RESULTS: We have developed chromosome-length genome assemblies in chickpea, pigeonpea, soybean, subterranean clover, and two wild progenitor species of cultivated groundnut (A. duranensis and A. ipaensis). A comprehensive comparative analysis of these genome assemblies offered improved insights into various evolutionary events that shaped the present-day legume species. We highlighted the expansion of gene families contributing to unique traits such as nodulation in legumes, gravitropism in groundnut, and oil biosynthesis in oilseed legume crops such as groundnut and soybean. As examples, we have demonstrated the utility of improved genome assemblies for enhancing the resolution of "QTL-hotspot" identification for drought tolerance in chickpea and marker-trait associations for agronomic traits in pigeonpea through genome-wide association study. Genomic resources developed in this study are publicly available through an online repository, 'Legumepedia'. CONCLUSION: This study reports chromosome-length genome assemblies of six legume species and demonstrates the utility of these assemblies in crop improvement. The genomic resources developed here will have significant role in accelerating genetic improvement applications of legume crops.


Assuntos
Cicer , Fabaceae , Humanos , Fabaceae/genética , Mapeamento Cromossômico , Genoma de Planta , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Cicer/genética , Produtos Agrícolas/genética , Glycine max/genética , Cromossomos
11.
Org Lett ; 24(36): 6560-6565, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36069753

RESUMO

We report a vinyl radical-mediated 1,5-hydrogen atom transfer (1,5-HAT) strategy for the remote C(sp3)-H functionalization reaction, which includes cyanation, oxidation, and etherification under visible-light-induced photochemical conditions. This reaction is achieved using readily available alkyl N-hydroxyphthalimide esters as radical precursors, which can efficiently react with diverse alkynes to form key vinyl radical intermediates followed by a 1,5-HAT process. A series of structurally diverse γ-cyano, γ-carbonyl, and γ-oxygenated alkenes with excellent stereoselectivity can be efficiently constructed by this synthetic protocol.


Assuntos
Alcenos , Hidrogênio , Alcinos , Catálise , Ésteres
12.
Biomed Pharmacother ; 155: 113635, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36095957

RESUMO

Non-SMC Condensin I complex subunit G (NCAPG), a mitosis-associated chromosomal condensation protein, is related to sister chromatid appropriate separation during the condensation and fusion of chromosomes and responsible for the condensation and stabilization of chromosomes during meiosis and mitosis. Studies have shown that NCAPG is highly adjusted in a variety of cancers, and its related molecular mechanism affects tumor cell proliferation, invasion, metastasis, and apoptosis including hepatocellular carcinoma, prostate cancer, breast cancer, gastric cancer, gliomas, lung adenocarcinoma, colorectal cancer, ovarian cancer, and endometrial cancer. Clinically, the expression of NCAPG is strongly correlated with N-classification, M-classification, and clinical stage, and NCAPG is valuable for the prognosis of patients with lung adenocarcinoma. In addition, NCAPG can also reduce the sensitivity of tumor cells such as breast cancer to reduce the reaction of the original chemotherapy, so that tumor cells are drug-resistance. In summary, NCAPG can serve as a new diagnosis and treatment target for a variety of cancers, and is also a very promising prognostic marker. Therefore, this review summarizes the critical role of NCAPG in the diagnosis, treatment, and prognosis for various cancers, and the mechanism by which NCAPG plays its pivotal roles.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Proteínas de Ciclo Celular/metabolismo , Carcinoma Hepatocelular/patologia , Meiose , Neoplasias Hepáticas/patologia
13.
Comput Struct Biotechnol J ; 20: 5014-5027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091720

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has led to a global pandemic. Deep learning (DL) technology and molecular dynamics (MD) simulation are two mainstream computational approaches to investigate the geometric, chemical and structural features of protein and guide the relevant drug design. Despite a large amount of research papers focusing on drug design for SARS-COV-2 using DL architectures, it remains unclear how the binding energy of the protein-protein/ligand complex dynamically evolves which is also vital for drug development. In addition, traditional deep neural networks usually have obvious deficiencies in predicting the interaction sites as protein conformation changes. In this review, we introduce the latest progresses of the DL and DL-based MD simulation approaches in structure-based drug design (SBDD) for SARS-CoV-2 which could address the problems of protein structure and binding prediction, drug virtual screening, molecular docking and complex evolution. Furthermore, the current challenges and future directions of DL-based MD simulation for SBDD are also discussed.

14.
Front Immunol ; 13: 970117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967375

RESUMO

Introduction: Necroptosis is a novel pattern of immunogenic cell death and has triggered an emerging wave in antitumor therapy. More evidence has suggested the potential associations between necroptosis and intra-tumoral heterogeneity. Currently, the underlying role of necroptosis remains elusive in hepatocellular carcinoma (HCC) at antitumor immunity and inter-tumoral heterogeneity. Methods: This study enrolled a total of 728 HCC patients and 139 immunotherapy patients from eight public datasets. The consensus clustering approach was employed to depict tumor heterogeneity of cancer necroptosis. Subsequently, our study further decoded the heterogeneous clinical outcomes, genomic landscape, biological behaviors, and immune characteristics in necroptosis subtypes. For each patient, providing curative clinical recommendations and developing potential therapeutic drugs were used to promote precise medicine. Results: With the use of the weighted gene coexpression network analysis (WGCNA) algorithm, necroptosis-associated long non-coding RNAs (lncRNAs) (NALRs) were identified in HCC. Based on the NALR expression, two heterogeneous subtypes were decoded with distinct clinical outcomes. Compared to patients in C1, patients in C2 harbored superior pathological stage and presented more unfavorable overall survival and recurrence-free survival. Then, the robustness and reproducibility of necroptosis subtypes were further validated via the nearest template prediction (NTP) approach and classical immune phenotypes. Through comprehensive explorations, C1 was characterized by enriched immune-inflammatory and abundant immune infiltration, while C2 possessed elevated proliferative and metabolic activities and highly genomic instability. Moreover, our results indicated that C1 was more prone to obtain desirable benefits from immunotherapy. For patients in C2, numerous underlying therapeutic agents were developed, which might produce significant efficacy. Conclusion: This study identified two necroptosis subtypes with distinct characteristics, decoding the tumor heterogeneity. For an individualized patient, our work tailored corresponding treatment strategies to improve clinical management.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Humanos , Imunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Necroptose , Reprodutibilidade dos Testes
15.
DNA Res ; 29(5)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35980175

RESUMO

Mucuna pruriens, commonly called velvet bean, is the main natural source of levodopa (L-DOPA), which has been marketed as a psychoactive drug for the clinical management of Parkinson's disease and dopamine-responsive dystonia. Although velvet bean is a very important plant species for food and pharmaceutical manufacturing, the lack of genetic and genomic information about this species severely hinders further molecular research thereon and biotechnological development. Here, we reported the first velvet bean genome, with a size of 500.49 Mb and 11 chromosomes encoding 28,010 proteins. Genomic comparison among legume species indicated that velvet bean speciated ∼29 Ma from soybean clade, without specific genome duplication. Importantly, we identified 21 polyphenol oxidase coding genes that catalyse l-tyrosine to L-DOPA in velvet bean, and two subfamilies showing tandem expansion on Chr3 and Chr7 after speciation. Interestingly, disease-resistant and anti-pathogen gene families were found contracted in velvet bean, which might be related to the expansion of polyphenol oxidase. Our study generated a high-quality genomic reference for velvet bean, an economically important agricultural and medicinal plant, and the newly reported L-DOPA biosynthetic genes could provide indispensable information for the biotechnological and sustainable development of an environment-friendly L-DOPA biosynthesis processing method.


Assuntos
Mucuna , Catecol Oxidase/genética , Catecol Oxidase/metabolismo , Cromossomos/metabolismo , Dopamina/metabolismo , Levodopa/genética , Levodopa/metabolismo , Mucuna/genética , Mucuna/metabolismo , Preparações Farmacêuticas/metabolismo , Pesquisa , Tirosina/genética , Tirosina/metabolismo
16.
J Clin Neurosci ; 103: 14-19, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35797769

RESUMO

It is well-established that complete expansion and proper apposition to the vessel wall of flow-diverter stents are critical for optimizing endovascular aneurysm outcomes by using flow diversion techniques. We aimed to evaluate the clinical value of high-resolution cone-beam CT (HR-CBCT) upon flow-diverter stent implantation in intracranial aneurysms. In this study, we retrospectively analyzed the clinical data of eighty-one patients (101 intracranial aneurysms) who underwent flow-diverter stent implantation (Pipeline™ or Tubridge™). Images were reconstructed using conventional cone-beam CT (CBCT)(voxel size 0.43 mm isotropic) and HR-CBCT(voxel size 0.15 mm isotropic). Immediately after stent deployment, dual volume 3D fusion images were obtained from 3D-digital subtraction angiography (DSA) and HR-CBCT. The image quality for stent visualization was graded from 0 to 2 (0:not able to assess, 1:limited, but able to assess; 2:clear visualization), and the stent expansion status (full, under-expanded or poor apposition) was also recorded. Finally, patients were treated using flow-diverter stents (n = 92: 17 Pipeline and 75 Tubridge). Compared to CBCT, HR-CBCT led to improved visualization of the structures of the stents and significantly improved the image quality (mean score: 0.59 ± 0.67 vs. 1.6 ± 0.63, P < 0.001). For 28 stents (seven Pipeline and 21 Tubridge), partially incomplete apposition was observed by HR-CBCT but not by conventional CBCT and resolved by microguidewire looping dilation or balloon dilation. High-resolution cone-beam CT could better display flow-diverter stent details and yielded an improved image quality, which facilitated the assessment of stent deployment, potentially reducing the incidence of complications.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Angiografia Cerebral , Tomografia Computadorizada de Feixe Cônico , Humanos , Estudos Retrospectivos , Stents , Resultado do Tratamento
17.
Org Lett ; 24(24): 4365-4370, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35686872

RESUMO

The photoinitiated deaminative [3 + 2] annulation reaction of N-aminopyridinium salts with alkenes for the synthesis of functionalized γ-lactams is described. This transformation shows good functional group tolerance as well as excellent diastereoselectivity. Preliminary studies suggest that the employed N-aminopyridinium salts generate the key amidyl radical intermediates through N-N bond cleavage via a photoinduced single-electron transfer (SET) process. The amidyl radical species would add to the double bond of alkenes, followed by a radical-mediated annulation process, to afford the desired γ-lactams.


Assuntos
Lactamas , Sais , Alcenos/química , Transporte de Elétrons , Lactamas/química
18.
Planta ; 256(1): 16, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35737139

RESUMO

MAIN CONCLUSION: Extensive histology of pistillate flowers revealed two pollen tube arresting sites (the style-joining and micropyle) within the pistil of Quercus acutissima during the postpollination-prezygotic stage, which reflects a unique female and male gametophyte recognition/selection mechanism. Sexual reproduction is among the most delicate and essential stages in plant life cycles and involves a series of precise interactions between pistils and male gametophytes. Quercus is a woody genus that dominates Northern Hemisphere forests and is notorious for interspecific hybridization, but its sexual reproduction is poorly understood, especially its pollen tube (PT) growth dynamics within pistils. This study used microtome techniques and scanning electron microscopy to observe the postpollination-prezygotic process in the biennially fruiting oak Quercus acutissima. Many pollen grains germinated at anthesis instantly, and PTs penetrated stigmatic surfaces and elongated through the stylar transmitting tissue, then arrested at style-joining for about 12-13 months. Few PTs resumed growth along the compitum in the upper ovarian locule wall in the subsequent April, concurrent with the rapid growth of rudimentary ovules. PTs arrived in the micropyle, and upper septum during megaspore mother cell meiosis, then arrested again for 7-10 days waiting for the embryo sac maturation. Fertilization occurred one week later. Our study shows a clear female dominant crosstalk growth pattern between PT and the ovule. The intermittent PT growth might reflect a unique male gametophyte recognition/selection mechanism to avoid self-pollination and enhance PT competition while increasing interspecific hybridization.


Assuntos
Tubo Polínico , Quercus , Flores , Polinização , Reprodução
19.
Neurol India ; 70(2): 694-698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35532641

RESUMO

Background: In recent years, among patients with chronic cerebral artery occlusion, recanalization can be achieved by an endovascular operation. However, complications and restenosis rates remain high. Objective: To evaluate the utility of high-resolution C-arm CT (Dyna micro-CT) for stent placement in patients with chronic cerebral artery occlusion. Methods and Materials: We retrospectively reviewed the clinical data of 27 patients with chronic cerebral artery occlusion who underwent mechanical recanalization and stent implantation. Images were reconstructed using conventional C-arm CT (Dyna CT) and Dyna micro-CT. Whether the stent was fully expanded and image quality was evaluated. Follow-up assessments included clinical and angiographic outcomes and complications. Results: Twenty-two patients successfully underwent stenting (22 stents; 14 cases: Neuroform EZ; eight cases: Enterprise); stenting failed in five patients. Compared to Dyna CT, Dyna micro-CT afforded improved visualization of the stent structure, providing significantly improved image quality (P < 0.05). In seven patients, the stent under-expanded and dilatation was performed; thereafter, stent malapposition improved. One patient experienced sudden headache 22 hours after the procedure; CT showed intraparenchymal hemorrhage. The remaining 21 patients did not have acute thrombosis or bleeding complications and were followed up by imaging for 3-6 months. In three patients, digital subtraction angiography showed mild in-stent stenosis. Conclusions: High-resolution C-arm CT can improve visualization of stent structures in chronic cerebral artery occlusion, making it easy to determine the extent of stent deployment and potentially reduce complications and stent restenosis.


Assuntos
Arteriopatias Oclusivas , Stents , Angiografia Cerebral/métodos , Artérias Cerebrais , Constrição Patológica , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Nat Ecol Evol ; 6(6): 738-749, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35484219

RESUMO

Genomic studies are now poised to explore whole communities of species. The ~70 species of woody plants that anchor the coastal ecosystems of the tropics, collectively referred to as mangroves, are particularly suited to this exploration. In this study, we de novo sequenced the whole genomes of 32 mangroves, which we combined with other sequences of 30 additional species, comprising almost all mangroves globally. These community-wide genomic data will be valuable for ecology, evolution and biodiversity research. While the data revealed 27 independent origins of mangroves, the total phylogeny shows only modest increases in species number, even in coastal areas of active speciation, suggesting that mangrove extinction is common. A possible explanation for common extinction is the frequent sea-level rises and falls (SLRs and SLFs) documented in the geological record. Indeed, near-extinctions of species with extremely small population size (N) often happened during periods of rapid SLR, as revealed by the genome-wide heterozygosity of almost all mangroves. Reduction in N has possibly been further compounded by population fragmentation and the subsequent accumulation of deleterious mutations, thus pushing mangroves even closer to extinction. Crucially, the impact of the next SLR will be exacerbated by human encroachment into these mangrove habitats, potentially altering the ecosystems of tropical coasts irreversibly.


Assuntos
Ecossistema , Florestas , Genoma , Humanos , Filogenia , Plantas
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