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The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (â¼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to â¼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.
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A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.
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BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.
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Fibrilação Atrial , Ablação por Cateter , Fístula Esofágica , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Complexo Antígeno L1 Leucocitário , Átrios do Coração , Fístula Esofágica/etiologia , Ablação por Cateter/efeitos adversosRESUMO
Antiferroelectrics characterized by voltage-driven reversible transitions between antiparallel and parallel polarity are promising for cutting-edge electronic and electrical power applications. Wide-ranging explorations revealing the macroscopic performances and microstructural characteristics of typical antiferroelectric systems have been conducted. However, the underlying mechanism has not yet been fully unraveled, which depends largely on the atomistic processes. Herein, based on atomic-resolution transmission electron microscopy, the deterministic phase transition pathway along with the underlying lattice-by-lattice details in lead zirconate thin films was elucidated. Specifically, we identified a new type of ferrielectric-like dipole configuration with both angular and amplitude modulations, which plays the role of a precursor for a subsequent antiferroelectric to ferroelectric transformation. With the participation of the ferrielectric-like phase, the phase transition pathways driven by the phase boundary have been revealed. We provide new insights into the consecutive phase transformation in low-dimensional lead zirconate, which thus would promote potential antiferroelectric-based multifunctional devices.
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Drug impurities are important factors that affect drug safety and efficacy. The aim of this study is to separate and confirm the structure of two degradation impurities of esomeprazole sodium, designated X and Y. The impurities X and Y were successfully isolated using preparative HPLC by developing separation methods with the help of ACD/Labs AutoChrom software. There was a steady increase in X and Y impurities in forced esomeprazole sodium degradation. Impurity X was confirmed as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-amino-3,5-dimethylpyridinecarboxylate and impurity Y as 6-methoxy-1h-benzo[d]imidazole-2-yl-4-hydroxy-3,5-dimethylpyridinecarboxylate using nuclear magnetic resonance spectrometry, infrared spectroscopy, and high-resolution mass spectrometry. These findings provide a comprehensive understanding of the impurity profile of esomeprazole sodium because these impurities are reported for the first time. Based on our results, active pharmaceutical ingredient manufacturers can further control process parameters to reduce impurity generation, and drug production manufacturers can optimize the packaging and storage conditions of esomeprazole sodium.
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Esomeprazol , Imidazóis , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de MedicamentosRESUMO
Root-knot nematodes of the genus Meloidogyne parasitize the roots of thousands of plants and can cause severe damage and yield loss. Here, we report a new root-knot nematode, Meloidogyne limonae n. sp., parasitizing "lemon" (Citrus limon) in Hainan Province, South China. Lemon trees infected by the root-knot nematode showed poor-quality lemons, chlorosis of foliage, weak growth, and numerous root galls with white females and egg masses protruding outside. Phylogenetic trees of sequences within the ribosomal and mitochondria DNA demonstrated that this species differs clearly from other previously described root-knot nematodes. Morphologically, the new species is characterized by an oval-shaped perineal pattern and the lateral field marked by a ridge of cuticle on one or both sides, the dorsal arch is low with fine to coarse, smooth cuticle striae, vulva slit centrally located at the unstriated area; spicules of males are arcuate, curved ventrally; gubernaculum is distinct and curved; labial disc of second-stage juveniles is prominent and dumbbell-shaped; stylet knobs oval and sloping backwardly; pharyngeal glands not filling the body cavity, overlapping intestine ventrally; conical tail gradually tapering. Phylogenetic trees based on ITS1-5.8S-ITS2, D2-D3 of the 28S rDNA, and the COI and COII-16S rRNA genes of the mtDNA showed that Meloidogyne limonae n. sp. belongs to an undescribed root-knot nematode lineage that is separated from other species with the resemblance in morphology, such as M. floridensis M. hispanica, M. acronea, and M. paranaenis.
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On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.
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Nematoides , Solanum tuberosum , Animais , China , SoloRESUMO
The present study demonstrated for the first time that SNORA70E, which belongs to box H/ACA small nucleolar noncoding RNAs (snoRNAs) who could bind and induce pseudouridylation of RNAs, was significantly elevated in ovarian cancer tissues and was an unfavourable prognostic factor of ovarian cancer. The over-expression of SNORA70E showed increased cell proliferation, invasion and migration in vitro and induced tumour growth in vivo. Further research found that SNORA70E regulates RAS-Related Protein 1B (RAP1B) mRNA through pseudouracil modification by combing with the pyrimidine synthase Dyskerin Pseudouridine Synthase 1 (DKC1) and increase RAP1B protein level. What's more, the silencing of DKC1/RAP1B in SNORA70E overexpression cells both inhibited cell proliferation, migration and invasion through reducing ß-catenin, PI3K, AKT1, mTOR, and MMP9 protein levels. Besides, RNA-Seq results revealed that SNORA70E regulates the alternative splicing of PARP-1 binding protein (PARPBP), leading to the 4th exon-skipping in PARPBP-88, forming a new transcript PARPBP-15, which promoted cell invasion, migration and proliferation. Finally, ASO-mediated silencing of SNORA70E could inhibit ovarian cancer cell proliferation, invasion, migration ability in vitro and inhibit tumorigenicity in vivo. In conclusion, SNORA70E promotes the occurrence and development of ovarian cancer through pseudouridylation modification of RAP1B and alternative splicing of PARPBP. Our results demonstrated that SNORA70E may be a new diagnostic and therapeutic target for ovarian cancer.
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Proteínas de Ligação a DNA , Neoplasias Ovarianas , RNA Nucleolar Pequeno , Proteínas rap de Ligação ao GTP , Processamento Alternativo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Metaloproteinase 9 da Matriz/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/genética , Inibidores de Poli(ADP-Ribose) Polimerases , RNA Mensageiro , RNA Nucleolar Pequeno/genética , Serina-Treonina Quinases TOR/genética , beta Catenina/genética , Proteínas rap de Ligação ao GTP/genéticaRESUMO
The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 µM to 10.36 µM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 µM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.
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Antineoplásicos/farmacologia , Descoberta de Drogas , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/químicaRESUMO
Proteolysis-targeting chimeras (PROTACs), bifunctional molecules consisting of a ligand of protein of interest (POI), an E3 ligase ligand and a linker, have been developed to hijack the ubiquitin-proteasome system (UPS) to induce different POIs degradation. Currently, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging efficacy in clinical trials of prostate and breast cancer treatment, which turns a new avenue for the development of PROTAC research. In this review, we focus on a detailed summary of the latest progress of PROTACs and elucidate the advantages of PROTACs technology. In addition, potential challenges and perspectives of PRTOACs are discussed.
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Descoberta de Drogas , Proteólise , Ubiquitina-Proteína Ligases , LigantesRESUMO
BACKGROUND: The aim was to investigate the distribution of antibiotic resistance determinants and virulence factors in a group of carbapenem non-susceptible Pseudomonas aeruginosa (P. aeruginosa). METHODS: From March 2018 to May 2019, a total of 98 P. aeruginosa samples were collected from 6 hospitals in Ningbo and Hangzhou, Zhejiang Province, China. Drug susceptibility tests to 13 antimicrobial agents were conducted. The presence of antibiotic resistance determinants and virulence factors were investigated by PCR, including 39 ß-lactamase genes, 14 aminoglycoside modifying enzyme genes, 10 16SrRNA methylase genes, and 11 virulence genes. Phylogenetics of 98 P. aeruginosa was analyzed by sample cluster analysis (UPGMA). RESULTS: PCR revealed the presence of 7 ß-lactamase genes, 5 aminoglycoside modifying enzymes, 1 16S rRNA methylase gene, and 8 virulence genes in total, at least 2 ß-lactamase genes and 4 virulence genes were positive in every isolate. In addition, regional differences in distributions of resistance and virulence genes remained between 2 cities. Sample cluster analysis showed that the strains had obvious aggregation and were divided into several clusters, strains in the same cluster were isolated from different hospitals, even from different cities. CONCLUSIONS: Carrying resistance genes blaPDC and blaOXA-50 group and virulence genes plcH, aprA, and algD were the important epidemiological characteristics of this group of P. aeruginosa. The present findings provide insights into the mechanisms of hypervirulence as well as resistance to ß-lactams and aminoglycosides. To the best of our knowledge, this is the first report of blaPDC, blaOXA-50, and aph(3')-XV in P. aeruginosa in China.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/genética , RNA Ribossômico 16S , Fatores de Virulência/genética , beta-Lactamases/genéticaRESUMO
The potato cyst nematodes (PCN) Globodera rostochiensis and Globodera pallida are the very important quarantine nematode pests of potato [Stone 1973]. Both species cause serious potato tuber yield losses. These species are subjected to strict quarantine regulations in many countries (EPPO 2017). G. rostochiensis was detected in Sichuan and Yunnan province, China in 2022 (Jiang et al. 2022). A survey for cyst nematodes in potato fields was conducted in Guizhou Province from 2018 to 2020. A total of 200 samples, including roots and soil, were collected from 40 potato fields in Hezhang (N27 06.145, E104 39.153) and Weining (N26 50.541, E104 09.885) counties in Guizhou Province, China. The Cobb decanting and sieving method was used to isolate cysts and J2s from the soil samples (Southey 1986). The potato roots were stained with acid fusion to observe cyst development. Morphological and molecular analyses indicated that 27 (13.5%) of the samples contained G. rostochiensis. The cyst density ranged between 1-85 cysts per 100 cm3 of soil and a mean density was 15 cysts per 100 cm3 soil. The smoothly rounded cysts were in brown and golden color, and the terminal cone was absent and circumfenestrate. The key morphometrics of cysts (n=20) were 695 ± 26 (685-757) µm in length excluding neck and 690 ± 30 (668 to769) µm in width; the number of cuticular ridges between anus and vulval fenestra was 16.3 ±2.1 (14 to 18); fenestral length was 15.1 ± 2.1 µm (13.18 to 19.27); distance from anus to the edge of fenestra was 61.12 ± 8.9 (49.22 to76.27) µm; and Granek's ratio was 4.54 ± 0.8 (3.97-5.26). The key morphometrics of J2 (n = 20): 468.0 ± 20.1 (427 to - 521) µm in body length, 20.58 ± 0.7 (20.2 to 21.8) µm in stylet length, 43.9 ± 5.6 (40.3 to 53.9) µm in tail length, and 23.1 ± 1.8 (21.77 to 25.32) µm in hyaline region length. The cyst and J2 morphologies were consistent with those of G. rostochiensis (Subbotin et al. 2010, EPPO 2017). Genomic DNA was isolated from cysts (n=20). DNA extraction was performed in a volume of 20 µl containing 3 µl 10× PCR buffer, 3 µl Proteinase K (600 µg µl-1), 14 µl distilled water and a single cyst was added and ground in an ice bath as described by Ou et al. (2008). The internal transcribed spacer (ITS) regions were amplified using the universal primers: rDNA1 (5'-TTGATTACGTCCCTGCCCTTT-3') and rDNA2 (5'-TTTCACTCGCCGTTACTAAGG-3') (Fleming 1998 ), and the 28S rDNA-D2/D3 regions were amplified using the primers: D2A (5´-ACAAGTACCGTGAGGGAAAGTTG-3´) and D3B (5´-TCGGAAGGAACCAGCTACTA-3´) (Subbotin et al. 2006). After the brackets at the beginning and end of the sequences were closed-up, the ITS rDNA sequences (GenBank Accession No. MZ042367 and MZ042368) showed 99.66% - 99.92% identity to G. rostochiensis sequences available in GenBank (FJ212166.1, GQ294513, FJ212164.1 and KJ409617.1). Sequences from the 28S region (GenBank Accession No. MZ057597 and MZ057598) were 99.23% - 99.74% similar to those of G. rostochiensis isolate from Slovakia (KJ409625.1), Italy (KJ409631.1) and United Kingdom (KJ409633.1). We used species specific primers ITS5ï¼5'-GGAAGTAAAAGTCGTAACAAGG-3'ï¼and PITSr3 (5'AGCGCAGACATGCCGCAA-3') to amplify the product (Bulman & Marshall 1997; EPPO 2017). A single 434bp fragment was obtained from Hezhang and Weining populations. A host test for the Hezhang and Weining populations were performed by inoculating 1,000 eggs per plant of varieties Qingshu 9, Huize 2 and Hezuo 88 grown in the pots containing 800 cm3 of sterilized soil (soil: sand ratio was 3:1), and four replications were tested in greenhouse under 16 h light, 22°C in the day and 8 h dark in the night. At 90 days post inoculation, 32.6 ± 7, 31.2 ± 8, and 29.5 ± 8 females and cysts were extracted from the infected roots and soils of the varieties Qingshu 9, Huize 2 and Hezuo 88, respectively. No females and cysts were observed on the control plants. The trial indicated that potato cultivars Qingshu 9, Huize 2 and Hezuo 88 are hosts for the Hezhang and Weining populations of Globodera rostochiensis. To the best of our knowledge, this is the first detection of potato cyst nematode Globodera rostochiensis in Guizhou Province, China.
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All-purpose electrode materials (APEMs), which can be effectively available on not only alkali-ion batteries but also emerging Li metal batteries, are urgently pursued to open up cost-efficient tactics for practical application of energy storage systems (ESSs), but still remain challenging. Herein, the hierarchical porous carbon nanotubes network (NOPCT) with well-tailored nanoarchitecture and high N/O-co-doping content (20.6 at%) is developed to present large-span application on ESSs. As for Li/Na-ion batteries, the NOPCT delivered excellent cycle stability and robust rate performance in a conventional ester-based electrolyte. Moreover, NOPCT also serving as a metal Li host can effectively guide smooth and uniform Li nucleation/growth to enhance the cycle stability of hybrid Li metal anodes. In addition, the NOPCT played an important role in the sustainability of sulfur electrodes, promising the feasibility of shared NOPCT for practical Li-S batteries. First-principle calculations demonstrate that graphitic-N and CO function groups favor for improving electron conductivity while the pyridinic-N and CO function group make sense for improved Li/Na adsorption and affinity through Lewis acid-base interaction, enlightening the interplay between various doped categories on improved electrochemical performance of NOPCT. This work provides profound theoretical and experimental insight into the design and development of APEMs for advanced ESSs.
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Lithium metal anodes (LMAs) with high energy density have recently captured increasing attention for development of next-generation batteries. However, practical viability of LMAs is hindered by the uncontrolled Li dendrite growth and infinite dimension change. Even though constructing 3D conductive skeleton has been regarded as a reliable strategy to prepare stable and low volume stress LMAs, engineering the renewable and lithiophilic conductive scaffold is still a challenge. Herein, a robust conductive scaffold derived from renewable cellulose paper, which is coated with reduced graphene oxide and decorated with lithiophilic Au nanoparticles, is engineered for LMAs. The graphene cellulose fibres with high surface area can reduce the local current density, while the well-dispersed Au nanoparticles can serve as lithiophilic nanoseeds to lower the nucleation overpotential of Li plating. The coupled relationship can guarantee uniform Li nucleation and unique spherical Li growth into 3D carbon matrix. Moreover, the natural cellulose paper possesses outstanding mechanical strength to tolerate the volume stress. In virtue of the modulated deposition behaviour and near-zero volume change, the hybrid LMAs can achieve reversible Li plating/stripping even at an ultrahigh current density of 10â mA cm-2 as evidenced by high Coulombic efficiency (97.2 % after 60â cycles) and ultralong lifespan (1000â cycles) together with ultralow overpotential (25â mV). Therefore, this strategy sheds light on a scalable approach to multiscale design versatile Li host, promising highly stable Li metal batteries to be feasible and practical.
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Voltage-gated sodium channels are currently recognized as one of the targets of analgesics. Magnolol (Mag), an active component isolated from Magnolia officinalis, has been reported to exhibit analgesic effects. The objective of this study was to investigate whether the analgesic effect of Mag was associated with blocking Na+ channels. Inflammatory pain was induced by the injection of carrageenan into the hind paw of mice. Mag was administered orally. Mechanical hyperanalgesia was evaluated by using von Frey filaments. Na+ currents and neuronal excitability in acutely isolated mouse dorsal root ganglion (DRG) neurons were recorded with the whole-cell patch clamp technique. Results showed that Mag (10 ~ 40 mg/kg) dose-dependently inhibited the paw edema and reduced mechanical pain in the inflammatory animal model. Injection of carrageenan significantly increased the amplitudes of TTX-sensitive and TTX-resistant Na+ currents. Compared with the carrageenan group, Mag inhibited the upregulation of two types of Na+ currents induced by carrageenan in a dose-dependent manner. Mag 40 mg/kg shifted the inactivation curves of two types of Na+ currents to hyperpolarization and returned to normal animal level without changing their activation curves. Mag 40 mg/kg significantly reduced the percentage of cells firing multiple spikes and inhibited the neuronal hyperexcitability induced by carrageenan. Our data suggest that the analgesic effect of Mag may be associated with a decreased neuronal excitability by blocking Na+ current.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Gânglios Espinais/efeitos dos fármacos , Lignanas/uso terapêutico , Neurônios/efeitos dos fármacos , Dor/tratamento farmacológico , Bloqueadores dos Canais de Sódio/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Carragenina/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Gânglios Espinais/fisiologia , Lignanas/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Neurônios/fisiologia , Dor/fisiopatologia , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/fisiologiaRESUMO
Objective To observe the role of ultrasound biomicroscopy(UBM)in two-year post-operative follow-up for primary open-angle glaucoma patients with modified CO2 laser-assisted sclerectomy surgery(CLASS).Methods This was a case series study.A combination of modified CLASS and preoperative laser iris management was administered to 28 eyes.Visual acuity,intraocular pressure(IOP),and slit-lamp examinations,visual field testing,and gonioscopy were carried out at baseline and until 24 months postoperatively.UBM examination was performed at 1,3,12 and 24 months postoperatively.Results Compared with the mean preoperative IOP [(30.61±10.59)mmHg],the IOP at each time point after operation was significantly lowered [(15.15±5.87),(12.56±3.24),(13.15±2.73),(13.75±2.55)and(13.75±2.46)mmHg at 1,3,6,12 and 24 months,respectively;all P<0.001].Complete success rates and qualified success rates at 12 months and 24 months were 60.71%,89.29% and 53.57%,85.71%,respectively.UBM images can present "dolphin head sign" after successful CLASS.The thickness of trabeculo-Descemet's window was(0.13±0.03)mm,which had no significant correlation with postoperative IOP at 12(r=-0.278,P=0.144)and 24 months(r=0.026,P=0.895).UBM examination revealed a severe scleral lake diminution(a change > 50%)in 1 eye(3.57%)at 12 months and 3 eyes(10.71%)at 24 months.There was no statistical significance detected between the size of the scleral lake and IOP after CLASS.Non-founctional blebs were found in 16 eyes(57.14%)at 12 months and 25 eyes(89.28%)at 24 months.Two eyes(7.14%)demonstrated severe peripheral anterior synechiae at 24 months,requiring surgical intervention.Conclusions UBM can effectively observe the morphology of the scleral lake,anterior chamber angle and filtering blebs in post-operative follow-up after modified CLASS,and give early warning of complications.It plays an important role in ensuring the success of CLASS.
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Glaucoma de Ângulo Aberto , Dióxido de Carbono , Seguimentos , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Microscopia Acústica , Esclera/diagnóstico por imagem , Resultado do TratamentoRESUMO
AIMS: Endothelial progenitor cells (EPCs) are widely accepted to be applied in ischemic diseases. However, the therapeutic potency is largely impeded because of its inviability in these ischemic conditions. Autophagy is recognized to be vital in cell activity. Therefore, we explore the role and the mechanism of autophagy in ischemic EPCs. METHODS AND RESULTS: We applied 7d-cultured bone marrow EPCs to investigate the autophagy status under the oxygen and glucose deprivation (OGD) conditions in vitro, mimicking the in-vivo harsh ischemia and anoxia microenvironment. We found increased EPC apoptosis, accompanied by an impaired autophagy activation. Intriguingly, mTOR inhibitor Rapamycin was incapable to reverse this damped autophagy and EPC damage. We further found that autophagy pathway downstream Vps34-Beclin1-Atg14 complex assembly and activity were impaired in OGD conditions, and an autophagy-inducing peptide Tat-Beclin1 largely recovered the impaired complex activity and attenuated OGD-stimulated EPC injury through restoring autophagy activation. CONCLUSIONS: The present study discovered that autophagy activation is inhibited when EPCs located in the ischemia and anoxia conditions. Restoration of Vps34 complex activity obtains sufficient autophagy, thus promoting EPC survival, which will provide a potential target and advance our understanding of autophagy manipulation in stem cell transplantation.
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Autofagia , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Isquemia/patologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Glucose/deficiência , Masculino , Camundongos Endogâmicos C57BL , Oxigênio , Sirolimo/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismoRESUMO
INTRODUCTION: Repeat ablation strategy for atrial fibrillation (AF) recurrence after multiple ablation procedures is known to be challenging. This study evaluated the insights of adjunctive ablation for epicardial arrhythmogenic substrates in those patients via a percutaneous epicardial approach. METHODS AND RESULTS: Thirty-five consecutive patients with AF/atrial tachycardia (AT) recurrence, who had two or more prior ablation procedures, were enrolled from September 2016 to December 2018. In addition to a standard endocardial approach, epicardial mapping and ablation were performed via a percutaneous subxiphoid access in the electrophysiology lab. Adjunctive epicardial ablations for left lateral ridge (LLR) were performed in 31 of 35 patients (88.6%) for efficient transmural lesions with pacing capture loss. Marshall Bundle (MB) potentials were documented on epicardial LLR in three patients and abolished by direct epicardial ablation. Bachmann's bundle (BB) was ablated as an epicardial conduction gap in four patients with a refractory anterior wall line. Two epicardial AT/AF triggers were detected followed by successful termination with epicardial ablation. No periprocedural complications occurred. About 23 of 35 patients (65.7%) remained free from AF/AT after 23.2 ± 9 months of the procedure. CONCLUSIONS: Patients with multiple failed prior AF procedures refractory to antiarrhythmic therapy might warrant a percutaneous epicardial mapping and ablation strategy, with adjunctive therapy for targeting LLR/MB, BB, and underlying epicardial triggers in addition to a standard endocardial approach.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Frequência Cardíaca , Pericárdio/cirurgia , Taquicardia Supraventricular/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiopatologia , Estudos Prospectivos , Recidiva , Reoperação , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901â mA h g-1 with capacity retention up to 94.0 % after 200â cycles at 0.2â A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of αâγ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.
RESUMO
BACKGROUND: During ablation for atrial fibrillation (AF), energy delivery toward the left atrial posterior wall may cause esophageal injury (EI). Ablation index (AI) was introduced to estimate ablation lesion size, however, the impact of AI technology on the risk of EI has not been explored. METHOD: From March 2019 to December 2019, 60 patients with paroxysmal AF undergoing first-time ablation were prospectively enrolled. The first 30 consecutive patients were ablated with the AI target value of 400 (AI-400 group), and the later 30 consecutive patients were ablated with the AI target value of 350 at the posterior wall (AI-350 group). Endoscopic ultrasonography was used to evaluate EI postablation. EI was classified as a category 1 (erythema or erosion) or a category 2 (hematoma or ulceration). RESULTS: Compared with the AI-400 group (59.9 ± 8.4 years; male, 60%), the AI-350 group (59.1 ± 9.9 years; male, 50%) had a lower incidence of EI (3.3% vs 26.7%, P = .03). There was no significant difference in the percentage of first-pass PVI between the AI-400 group and the AI-350 group (left PVI: 80% vs 73.4%, P = .54; right PVI: 80% vs 60%, P = .1). Neither ablation time nor fluoroscopy time was significantly different between the AI-400 group and the AI-350 group. CONCLUSIONS: AF ablation guide by AI target value of 350 may reduce esophageal thermal injury and has a similar efficiency on the acute success rate of first-pass PVI compared with an AI target value of 400 at the posterior wall.