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Quasi-2D (Q-2D) perovskites with typical varied n-phase structures deserve promising candidates in pursuing high-performance perovskite light-emitting diodes (PeLEDs). Whereas their weakness in precise n-phase distribution control disables the optical property of PeLEDs since the n = 1 phase is dominated by severe nonradiative recombination. Here, an effective phase distribution tailoring strategy is developed for pure blue PeLEDs by introducing taurine (TAU) into mixed halide Q-2D perovskites. The sulfonic acid group in TAU can coordinate with Pb2+ to suppress the formation of the n = 1 phase while promoting the growth of Q-2D perovskites into domains with the graded distribution of n = 2 and 3. The amino group in TAU forms hydrogen bonds with electronegative halide ions, suppressing the formation of halide vacancies and reducing the defect density in the Q-2D perovskite films. As a result, optimized blue Q-2D perovskite films boosted PLQY to 92%. Target blue PeLED was endowed with a peak EQE of 14.82% (average 12.6%) at 475 nm and a maximum luminance of 1937 cd m-2 , which is among the reported high-level pure blue PeLEDs. This work demonstrates a feasible approach to regulate the phase distribution of Q-2D perovskites for high-performance blue PeLEDs.
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Hybridized local and charge-transfer (HLCT) with the utilization of both singlet and triplet excitons through the "hot excitons" channel have great application potential in highly efficient blue organic light-emitting diodes (OLEDs). The proportion of charge-transfer (CT) and locally excited (LE) components in the relevant singlet and triplet states makes a big difference for the high-lying reverse intersystem crossing process. Herein, three novel donor (D)-acceptor (A) type HLCT materials, 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-phenyl-1H-isochromen-1-one (pPh-7P), 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-7M), and 6-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-6M), were rationally designed and synthesized with diphenylamine derivative as donor and oxygen heterocyclic coumarin moiety as acceptors. The proportions of CT and LE components were fine controlled by changing the connection site of diphenylamine derivative at C6/C7-position and the substituent at C3-position of coumarin moiety. The HLCT characteristics of pPh-7P, pPh-7M, and pPh-6M were systematically demonstrated through photophysical properties and density functional theory calculations. The solution-processed doped OLEDs based on pPh-6M exhibited deep-blue electroluminescence with the maximum emission wavelength of 446â nm, maximum luminance of 8755â cd m-2, maximum current efficiency of 5.83â cd A-1, and maximum external quantum efficiency of 6.54 %. The results reveal that pPh-6M with dominant 1LE and 3CT components has better OLED performance.
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BACKGROUND: The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. STUDY DESIGN AND METHODS: Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. RESULTS: In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). CONCLUSION: Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.
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BACKGROUND: Studies have suggested that acute myeloid leukemia (AML) patients with incomplete hematologic recovery undergoing allogeneic stem cell transplantation (allo-HSCT) had inferior overall survival (OS). STUDY DESIGN AND METHODS: This single-center, retrospective study of AML patients evaluated the relationship between red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 30 days and long-term outcomes after allo-HSCT through multivariate analyses. RESULTS: A total of 692 AML patients received peripheral blood stem cells (89.2%), marrow (5.6%), or umbilical cord (5.2%) from matched related (37.4%), unrelated (49.1%), or haploidentical (8.2%) donors in 2011-2017. Transfusion requirements during the first 30 days for RBC (89.5% transfused, median 3, range 1-18 units) or PLT (98.2% transfused, median 6, range 1-144 units) were variable. By Day 30, 56.7% (95% confidence interval [CI]: 52.8-60.3%) and 86.1% (95% CI: 83.2-88.5%) had achieved RBC and PLT transfusion independence, respectively. Median follow-up among survivors (n = 307) was 7.1 years (range: 2.7-11.8). Lack of RBC transfusion independence by Day 30 was strongly and independently associated with worse 5-year OS (39.2% vs. 59.6%, adjusted hazard ratio [HR] 1.83, 95% CI: 1.49-2.25), leukemia-free survival (35.8% vs. 55.5%, HR = 1.75, 95% CI: 1.43-2.14), and NRM (29.7% vs. 13.7%, HR = 2.05, 95% CI: 1.45-2.89) (p < .001). There was no difference in relapse rates among patients who achieved or did not achieve RBC (p = .34) or PLT (p = .64) transfusion independence. CONCLUSION: Prolonged RBC dependence predicted worse survival and NRM rates, but not increased relapse. Posttransplant surveillance of such patients should be adjusted with more attention to non-relapse complications.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Recidiva , Doença Enxerto-Hospedeiro/etiologiaRESUMO
CRISPR-Cas12a with robust trans-cleavage activity were employed to mitigate background fluorescence signal, achieving sensitive detection of miRNA-21. The activation of trans-cleavage activity of Cas12a was achieved by utilizing cDNA as a trigger. Upon the presence of target miRNA-21, cDNA hybridizes with it forming a DNA/RNA double-stranded structure. Exonuclease III (ExoIII) facilitates the degradation of cDNA, releasing the target for subsequent cycles. Due to cDNA degradation, the trans-cleavage activity of Cas12a remains unactivated and does not disrupt the synthesis template of copper nanoparticles. Addition of Cu2+ and AA leads to the formation of highly fluorescent copper nanoparticles. Conversely, in absence of miRNA-21, intact cDNA activates trans-cleavage activity of Cas12a, resulting in degradation of the synthesis template and failure in synthesizing fluorescent copper nanoparticles. This method exhibits excellent selectivity with a low limit of detection (LOD) at 5 pM. Furthermore, we successfully applied this approach to determine miRNA-21 in cell lysates and human serum samples, providing a new approach for sensitive determination of biomarkers in biochemical research and disease diagnosis.
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Sistemas CRISPR-Cas , Cobre , Limite de Detecção , Nanopartículas Metálicas , MicroRNAs , Cobre/química , Nanopartículas Metálicas/química , Humanos , MicroRNAs/sangue , MicroRNAs/análise , Sistemas CRISPR-Cas/genética , Fluorometria/métodos , Proteínas Associadas a CRISPR/genética , Proteínas Associadas a CRISPR/química , Técnicas Biossensoriais/métodos , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , EndodesoxirribonucleasesRESUMO
Nonalcoholic fatty liver disease (NAFLD) is substantiated by the reprogramming of liver metabolic pathways that disrupts the homeostasis of lipid and glucose metabolism and thus promotes the progression of the disease. The metabolic pathways associated with NAFLD are regulated at different levels from gene transcription to various post-translational modifications including ubiquitination. Here, we used a novel orthogonal ubiquitin transfer platform to identify pyruvate dehydrogenase A1 (PDHA1) and acetyl-CoA acetyltransferase 1 (ACAT1), two important enzymes that regulate glycolysis and ketogenesis, as substrates of E3 ubiquitin ligase UBE3A/E6AP. We found that overexpression of UBE3A accelerated the degradation of PDHA1 and promoted glycolytic activities in HEK293 cells. Furthermore, a high-fat diet suppressed the expression of UBE3A in the mouse liver, which was associated with increased ACAT1 protein levels, while forced expression of UBE3A in the mouse liver resulted in decreased ACAT1 protein contents. As a result, the mice with forced expression of UBE3A in the liver exhibited enhanced accumulation of triglycerides, cholesterol, and ketone bodies. These results reveal the role of UBE3A in NAFLD development by inducing the degradation of ACAT1 in the liver and promoting lipid storage. Overall, our work uncovers an important mechanism underlying the regulation of glycolysis and lipid metabolism through UBE3A-mediated ubiquitination of PDHA1 and ACAT1 to regulate their stabilities and enzymatic activities in the cell.
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Acetiltransferases , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Acetiltransferases/genética , Células HEK293 , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Oxirredutases/metabolismo , Lipídeos , Acetil-CoA C-Acetiltransferase/genéticaRESUMO
The 1 H nuclear magnetic resonance (1 H-NMR) spectrum is a useful tool for characterizing the hydrogen bonding (H-bonding) interactions in ionic liquids (ILs). As the main hydrogen bond (H-bond) donor of imidazolium-based ILs, the chemical shift (δH2 ) of the proton in the 2-position of the imidazolium ring (H2) exhibits significant and complex solvents, concentrations and anions dependence. In the present work, based on the dielectric constants (ϵ) and Kamlet-Taft (KT) parameters of solvents, we identified that the δH2 are dominated by the solvents polarity and the competitive H-bonding interactions between cations and anions or solvents. Besides, the solvents effects on δH2 are understood by the structure of ILs in solvents: 1) In diluted solutions of inoizable solvents, ILs exist as free ions and the cations will form H-bond with solvents, resulting in δH2 being independent with anions but positively correlated with ßS . 2) In diluted solutions of non-ionzable solvents, ILs exist as contact ion-pairs (CIPs) and H2 will form H-bond with anions. Since non-ionizable solvents hardly influence the H-bonding interactions between H2 and anions, the δH2 are not related to ßS but positively correlated with ßIL .
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XYG3-type doubly hybrid (xDH) approximations have gained widespread recognition for their accuracy in describing a diverse range of chemical and physical interactions. However, a recent study [Song et al., J. Phys. Chem. Lett. 12, 800-807 (2021)] has highlighted the limitation of xDH methods in calculating the dissociation of NaCl molecules. This issue has been related to the density and orbitals used for evaluating the energy in xDH methods, which are obtained from lower-rung hybrid density functional approximations (DFAs) and display substantial density errors in the dissociation limit. In this work, we systematically investigate the influence of density on several challenging datasets and find that xDH methods are less sensitive to density errors compared to semi-local and hybrid DFAs. Furthermore, we demonstrate that the self-interaction corrected SCAN density approach offers superior accuracy compared to the self-consistent SCAN density and Hartree-Fock density approaches, as evidenced by performing charge analysis on the dissociation of heterodimers, such as NaCl and LiF. Building on these insights, we propose a five-parameter xDH method using the SCAN density and orbitals corrected by the PZ-SIC scheme. This new xDH@SCAN(SIC) method provides a balanced and accurate description across a wide range of challenging systems.
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Two undescribed p-terphenyl derivatives, asperterphenylcins A-B (1-2), and two undescribed diphenyl ether derivatives, asperdiphenylcins A-B (3-4), together with three previously described p-terphenyl derivatives-4â³-deoxyterprenin (5), terphenyllin (6), and 3â³-hydroxyterphenyllin (7)-were obtained from the solid-rice culture of the marine-derived fungus Aspergillus candidus HM5-4, which was isolated from sponges from the South China Sea. Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound 1 showed a strong inhibitory effect on Neoscytalidium dimidiatum, with an inhibition circle diameter of 31.67 ± 2.36 mm at a concentration of 10.0 µg/disc. Compounds 5 and 7 displayed cytotoxic activity against human chronic myeloid leukemia cells (K562), human liver cancer cells (BEL-7402), human gastric cancer cells (SGC-7901), human non-small cell lung cancer cells (A549) and human HeLa cervical cancer cells, with IC50 values ranging from 3.32 to 60.36 µM, respectively. Compounds 2, 6 and 7 showed potent inhibitory activity against α-glucosidase, with IC50 values of 1.26 ± 0.19, 2.16 ± 0.44 and 13.22 ± 0.55 µM, respectively.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Aspergillus , FungosRESUMO
Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.
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Fibrilação Atrial , Humanos , Proteína C-Reativa/metabolismo , Interleucina-6/metabolismo , Estudos de Casos e Controles , Inflamação , Biomarcadores , Estresse Oxidativo , PerfusãoRESUMO
BACKGROUND: The outbreak of Lumpy skin disease (LSD) in cattle caused by LSD virus (LSDV) was first reported in August 2019 in China. Since then, several LSD outbreaks have been reported in seven different provinces of China. Until now, several Lumpy skin disease virus (LSDV) strains from China have been reported and sequenced including LSDV/Xinjiang/2019 (MN598005.1), China/GD01/2020 (MW355944.1), and LSDV/Hongkong/2021 (MW732649.1). In October 2020, more than 1,700 cattle imported from Chile arrived in Xilingol, Inner Mongolia, and were diagnosed with LSD. Currently, limited data on the origin of the virus is available. METHODS: Nucleotide sequences of the ORF11, ORF36, ORF74, ORF117, ORF126 genes and the complete genome of LSDV strains and isolates were downloaded from NCBI database. MEGA7.0 was used to perform phylogenetic analysis with Neighbor-Joining (NJ). DNASTAR software is used to analyze homologous comparison analysis with related genes of reference strains included in Genbank. RESULTS: Compared with other strains isolated from China, the results of full genome sequence analysis showed the LSDV/NMG/2020 strain belonged to the recombinant strains. The LSDV/NMG/2020 strain is different from the current LSDV field isolates in Africa, the Middle East, Europe, and the newly emerged LSDV Russia variants. Based on the identities of P32, RPO30, EEV, GPCR and LSDV117 genes (99.8%, 99%, 99.8%, 99% and 98.7%), the sub-cluster recombinant containing LSDV/NMG/2020 strain is phylogenetically closer to the Russia strain (Saratov/2017). CONCLUSIONS: In this study, we reported a new isolated LSDV strain named LSDV/NMG/2020. The results of genomic characterization and phylogenetic analysis demonstrated that the LSDV/NMG/2020 isolate was a vaccine-like recombinant strain.
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Doenças dos Bovinos , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Doença Nodular Cutânea/epidemiologia , FilogeniaRESUMO
BACKGROUND: Peripheral blood stem cells (PBSCs) are the predominant graft source for adult allogeneic hematopoietic stem cell transplantation (HSCT). In poorly mobilized autologous donors, plerixafor improves collection outcomes. We examine plerixafor use in allogeneic donors who mobilize poorly with granulocyte colony-stimulating factor (G-CSF) in those who are healthy and those with pre-existing medical conditions, and determine the optimal threshold to add plerixafor. STUDY DESIGN/METHODS: We retrospectively examined all allogeneic PBSC collections from January 2013 to October 2020 at our center. Donors received G-CSF 10 mcg/kg daily for 4 days before undergoing apheresis collection on day 5. Plerixafor was added based on poor CD34+ cell collection yield after the first or second collection day. RESULTS: Of the 1008 allogeneic donors, 41 (4.1%) received one dose of plerixafor in addition to G-CSF due to poor collection yield. After starting plerixafor there was a 0.75- to 7.74-fold (median 2.94) increase in CD34+ yield from the previous day. No donors with G-CSF-only mobilization who collected <2.0 × 106 CD34+ cells/kg recipient weight on day one achieved the goal of ≥4.0 × 106 CD34+ cells/kg recipient weight total over 2 days but 59.2% of donors who used rescue plerixafor did. CONCLUSION: Donors both healthy and those with pre-existing disease responded well to plerixafor with minimal side effects. If the first-day collection yield is less than ~63% of the collection goal, addition of plerixafor may be necessary to reach the collection goal and limit the number of collection days in allogeneic donors.
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Ciclamos , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Células-Tronco de Sangue Periférico , Adulto , Antígenos CD34/metabolismo , Benzilaminas , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Humanos , Estudos RetrospectivosRESUMO
Long-term durability is critically important for the commercialization of perovskite solar cells (PSCs). The ionic character of the perovskite and the hydrophilicity of commonly used additives for the hole-transporting layer (HTL), such as lithium bis(trifluoromethanesulfonyl)imide (Li-TFSI) and tert-butylpyridine (tBP), render PSCs prone to moisture attack, compromising their long-term stability. Here we introduce a trifluoromethylation strategy to overcome this drawback and to boost the PSC's solar to electric power conversion efficiency (PCE). We employ 4-(trifluoromethyl)benzylammonium iodide (TFMBAI) as an amphiphilic modifier for interfacial defect mitigation and 4-(trifluoromethyl)pyridine (TFP) as an additive to enhance the HTL's hydrophobicity. Surface treatment of the triple-cation perovskite with TFMBAI largely suppressed the nonradiative charge carrier recombination, boosting the PCE from 20.9% to 23.9% and suppressing hysteresis, while adding TFP to the HTL enhanced the PCS's resistance to moisture while maintaining its high PCE. Taking advantage of the synergistic effects resulting from the combination of both fluoromethylated modifiers, we realize TFMBAI/TFP-based highly efficient PSCs with excellent operational stability and resistance to moisture, retaining over 96% of their initial efficiency after 500 h maximum power point tracking (MPPT) under simulated 1 sun irradiation and 97% of their initial efficiency after 1100 h of exposure under ambient conditions to a relative humidity of 60-70%.
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Caprine parainï¬uenza virus type 3 (CPIV3) was first identified in goats named JS2013 in China. In 2019, a sheep herd broke a disease with respiratory disease in Hebei province, China. In order to confirm the pathogen of the disease, the nasal swabs, stool swabs and blood samples were collected from the sheep. Virus isolation was performed on MDBK cells and identification was conducted by RT-PCR. The complete genome of the isolate was sequenced and phylogenetic analyzed. In order to evaluate the pathogenicity of the virus, five seronegative sheep were experimental infected with the virus suspension. The phylogenetic analyses based on the complete genome and the M gene indicated that the isolate strain was distinguished distinct from previously reported CPIV3 lineage of JS2013. The virus-inoculated sheep displayed the syndrome with depression, cough, and fever. Virus shedding were detected by RT-PCR from nasal swabs. All infected showed virus shedding during 2 - 21dpi and viremia could be detected in serum samples. Gross pathological assessment of sheep in infected group showed gross lesion in the lungs. Histopathological observation results indicated that lungs had mild to moderate interstitial pneumonia, with thickened alveolar walls, decreased alveolar space, and increased amounts of inflammatory cells infiltration. This is the first report of pathogenicity of the novel lineage of sheep-derived CPIV3. The results would be helpful for further studies on the prevention and control strategies for CPIV3 infections in goat and sheep.
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Doenças das Cabras , Infecções por Respirovirus , Doenças dos Ovinos , Animais , China , Cabras , Vírus da Parainfluenza 3 Humana/genética , Filogenia , Infecções por Respirovirus/veterinária , Ovinos , VirulênciaRESUMO
We report an omnidirectional light absorption enhancement of a perovskite solar cell (PSC) using antireflection (AR) film with soft imprinted microstructures from master molds via holographic lithography technology, which has high throughput and repeatability. The PSC's omnidirectional power conversion efficiency (PCE) enhancement is achieved by reducing Fresnel surface reflections and enhancing the optical path length. The maximum PCE of PSCs with AR film is up to 20.27%, corresponding to an absolute increase of 0.93% compared to 19.34% of control devices. Significantly, the enhancements of PCE increase with incident angle enlargement, which attributes to more effective Fresnel surface reflection suppression. Moreover, AR films exhibit water and dust repellent properties due to hydrophobicity, which is beneficial for PSC's long-term stability and light harvesting.
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A generalized energy-based fragmentation (GEBF) approach has been combined with a universal solvation model based on solute electron density (SMD) to compute the solvation energies of general large systems (such as protein molecules) in solutions. In the GEBF-SMD method, the solvation energy of a target system could be combined by the corresponding solvation energies of various subsystems, each of which is embedded in the background point charges and surface charges on the surface of solute cavity at the positions of its atoms and neighbouring atoms outside of the subsystem. Our results show that the GEBF-SMD model could reproduce the conventional SMD solvation energies quite well for various proteins in solutions, and could significantly reduce the computational costs for the SMD calculations of large proteins. In addition, the GEBF-SMD approach is almost independent of the basis sets and the types of solvents (including protic, polar, and nonpolar ones). Also, the GEBF-SMD approach could reproduce the relative energies of various conformers of large systems in solutions. Therefore, the GEBF-SMD method is expected to be applicable for computing the solvation energies of a broad range of large systems.
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Beige adipocytes have become a promising therapeutic target to combat obesity. Our senior author Dr. B. Xue previously discovered a transient but significant induction of beige adipocytes in mice during early postnatal development, which peaked at postnatal day (P) 20 and then disappeared thereafter. However, the physiological mechanism underlying the transient induction of the developmental beige cells remains mystery. Interestingly, there exists a postnatal surge of leptin in mice at P10 before the appearance of the developmental beige adipocytes. Given the neurotropic effect of leptin during neuronal development and its role in activating the sympathetic nervous system (SNS), we tested the hypothesis that postnatal leptin surge is required for the transient induction of developmental beige adipocytes through sympathetic innervation. Unlike wild-type (WT) mice that were able to acquire the developmentally induced beige adipocytes at P20, ob/ob mice had much less uncoupling protein 1 (UCP1)-positive multilocular cells in inguinal white adipose tissue at the same age. This was consistent with reduced expression of UCP1 mRNA and protein levels in white fat of ob/ob mice. In contrast, daily injection of ob/ob mice with leptin between P8 and P16, mimicking the postnatal leptin surge, largely rescued the ability of these mice to acquire the developmentally induced beige adipocytes at P20, which was associated with enhanced sympathetic nerve innervation assessed by whole mount adipose tissue immunostaining of tyrosine hydroxylase. Our data demonstrate that the postnatal leptin surge is essential for the developmentally induced beige adipocyte formation in mice, possibly through increasing sympathetic nerve innervation.
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Adipócitos Bege/metabolismo , Tecido Adiposo/crescimento & desenvolvimento , Leptina/metabolismo , Adipócitos Bege/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/inervação , Envelhecimento , Animais , Relação Dose-Resposta a Droga , Feminino , Leptina/farmacologia , Masculino , Camundongos , Camundongos Obesos , Sistema Nervoso Simpático , Tirosina 3-Mono-Oxigenase/metabolismo , Proteína Desacopladora 1/metabolismoRESUMO
We performed a meta-analysis comparing the procedural and outcomes data and related to left atrial appendage occlusion guided by intracardiac echocardiography (ICE) and transesophageal echocardiography (TEE) in nonvalvular atrial fibrillation patients. Technical success with ICE was significantly similar to that of TEE (odds ratio [OR] 1.38, 95% CI [0.62, 3.09], I2 = 0%, P = 0.43). The peri-procedural complications showed no significant difference between the two groups (OR 0.84, 95% CI [0.57, 1.23], I2 = 0%, P = 0.37). Mortality was similar in procedures using ICE vs TEE (OR 0.89, 95% CI [0.51, 1.57], I2 = 0%, P = 0.69). Landing zones, procedural time and fluoroscopic times between ICE and TEE showed no significant differences (MD 1.96, 95% CI [-0.01, 3.94], I2 = 90%, P = 0.05; MD -1.64, 95% CI [-13.45, 10.17], I2 =95%, P =0.79; and MD 0.49, 95% CI [-2.18, 3.16], I2 = 87%, P = 0.72, respectively). Imaging with ICE or TEE is associated with similar outcomes in left atrial appendage occlusion procedures.
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Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Ecocardiografia Transesofagiana , Idoso , Idoso de 80 Anos ou mais , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Patients who respond inadequately to plerixafor salvage during autologous peripheral blood stem cell (PBSC) collection are frequently remobilized with plerixafor to collect additional stem cells. However, in patients who fail remobilization, it is unclear whether additional mobilization efforts with plerixafor are useful. STUDY DESIGN AND METHODS: We retrospectively examined the PBSC collections of 15 consecutive patients with lymphoma and multiple myeloma who underwent three mobilizations with plerixafor. RESULTS: Of the 821 patients who underwent autologous stem cell collections, 15 patients were mobilized three times with plerixafor (1.8%), which enabled 11 (73.3%) patients to reach 2.0 × 106 CD34+ cells/kg or greater. Among patients who eventually collected successfully the median yields from the three collection attempts were 0.46, 0.76, and 1.54 × 106 CD34+ cells/kg, respectively. Among those who collected less than 2.0 × 106 CD34+ cells/kg cumulatively, the median yields were 0.14, 0.33, and 0.22 × 106 CD34+ cells/kg from the three collection attempts. The combined collection yields from the first two mobilization attempts were significantly lower (p = 0.003; range, 0.09-0.73 vs. 0.63-1.84; median, 0.51 vs. 1.36) in those who failed collection. CONCLUSIONS: The majority (73.3%) of patients who underwent three mobilization attempts were eventually able to collect enough cells to permit autologous transplantation. Extremely low peripheral blood CD34+ count after the first dose of plerixafor and collection yields during the first two attempts were associated with a poor collection yield on the third attempt. The risks and benefits of a third mobilization should be weighed to facilitate judicious use of resources.
Assuntos
Benzilaminas/administração & dosagem , Ciclamos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Linfoma , Mieloma Múltiplo , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Adulto , Idoso , Feminino , Humanos , Linfoma/sangue , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante AutólogoRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients often require substantial but variable transfusion support. STUDY DESIGN AND METHODS: This single-center, retrospective study evaluated the red blood cell (RBC) and platelet (PLT) transfusion data of first-time allo-HSCT recipients transplanted in 2011 to 2017. Multivariate analyses were performed to assess the associations between patient and transplant-related factors and transfusion requirements. RESULTS: The study included 1762 patients who received peripheral blood stem cells (88.2%), marrow (7.0%), or umbilical cord (4.8%) from matched related (38.3%), unrelated (49.2%), or haploidentical (7.8%) donors. Almost all patients required RBCs (88.3%) or PLTs (97.4%) during the first 30 days, with medians of 3 (range, 1-37) RBC and 6 (range, 1-144) PLT units transfused. Fewer patients required RBC (43.8%) or PLT (27.3%) transfusions during Days 31 to 100, but the median (range) numbers of RBC and PLT units remained high at 3 (1-36) and 6 (1-116) among transfused patients. RBC and PLT transfusion independence was reached in medians of 24 (95% confidence interval [CI], 22-26) and 12 (95% CI, 11-12) days, respectively. Haploidentical donor, cord graft, and requiring RBC transfusions in the 10 days before HSCT were the most significant independent factors predictive of increased transfusion requirements. Advanced disease, diagnosis, ABO incompatibility, conditioning intensity, CD34+ cell dose, presence of severe acute graft-vs-host disease, and changes in recommended transfusion triggers were also shown to independently impact transfusion requirements. CONCLUSIONS: This study provided for the first time quantitative and comparative transfusion data on a large contemporary cohort of HSCT recipients, including haploidentical and cord graft recipients, and identified factors predictive of increased transfusions.