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New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. The 22 N-glycan sites of Spike remain highly conserved among SARS-CoV-2 variants, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single-molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.
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Receptores Mitogênicos/metabolismo , SARS-CoV-2/metabolismo , Animais , Sítios de Ligação/fisiologia , COVID-19/virologia , Linhagem Celular , Chlorocebus aethiops , Glicosilação , Células HEK293 , Humanos , Camundongos , Simulação de Dinâmica Molecular , Ligação Proteica/fisiologia , Células Vero , Internalização do VírusRESUMO
Here, we report a set of new polymerization reactions enabled by the 1,2-regioselective hydro- and silylcupration of enyne-type propargylic electrophiles. Highly regioregular head-to-tail poly(2-butyne-1,4-diyl)s (HT-PBD), bearing either methyl or silylmethyl side chains, are synthesized for the first time. A rapid entry into carbon-rich copolymers with adjustable silicon content is developed via in situ monomer bifurcation. Furthermore, a one-pot polymerization/semireduction sequence is developed to access a cis-poly(butadiene)-derived backbone by a ligand swap on copper hydride species. Interestingly, borocupration, typically exhibiting identical regioselectivity with its hydro- and silyl analogues, seems to proceed in a 3,4-selective manner. Computational studies suggest the possible role of the propargylic leaving group in this selectivity switch. This work presents a new class of regioregular sp-carbon-rich polymers and meanwhile a novel approach to organosilicon materials.
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Polymer mechanochemistry has been established as an enabling tool in accessing chemical reactivity and reaction pathways that are distinctive from their thermal counterparts. However, eliciting diversified reaction pathways by activating different constituent chemical bonds from the same mechanophore structure remains challenging. Here, we report the design of a bicyclo[2.2.0]hexene (BCH) mechanophore to leverage its structural simplicity and relatively low molecular symmetry to demonstrate this idea of multimodal activation. Upon changing the attachment points of pendant polymer chains, three different C-C bonds in bicyclo[2.2.0]hexene are specifically activated via externally applied force by sonication. Experimental characterization confirms that in different scenarios of polymer attachment, the regioisomers of BCH undergo different activation reactions, entailing retro-[2+2] cycloreversion, 1,3-allylic migration, and retro-4π ring-opening reactions, respectively. Control experiments with small-molecule analogues reveal that the observed diversified reactivity of BCH regioisomers is possible only with mechanical force. Theoretical studies further elucidate that the differences in the positions of substitution between regioisomers have a minimal impact on the potential energy surface of the parent BCH scaffold. The mechanochemical selectivity between different C-C bonds in each constitutional isomer is a result of selective and effective coupling of force to the aligned C-C bond in each case.
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Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.
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Proteínas Adaptadoras de Sinalização CARD , Humanos , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/deficiência , Feminino , Adulto Jovem , Mutação , Neutrófilos/imunologia , Células Th17/imunologia , Candidíase Mucocutânea Crônica/genética , Candidíase Mucocutânea Crônica/imunologia , Monócitos/imunologia , CitocinasRESUMO
A glucosyl-rich pectin, JMMP-3 (Mw, 2.572 × 104 g/mol, O-methyl % = 3.62%), was isolated and purified from the pericarp of the immature fruit of Juglans mandshurica Maxim. (QingLongYi). The structure of JMMP-3 was studied systematically by infrared spectroscopy, monosaccharide compositions, methylation analysis, partial acid hydrolysis, and 1/2D-NMR. The backbone of JMMP-3 possessed a smooth region (â 4GalA1 â) and a hairy region (â 4GalA1 â 2Rha1 â) with a molar ratio of 2: 5. The substitution of four characteristic side chains (R1-R4) occurs at C-4 of â 2,4)-α-Rhap-(1â, where R1 is composed of â 5)-α-Araf-(1â, R2 is composed of â 4)-ß-Galp-(1 â and ß-Galp-(1â, R3 is composed of α-Glcp-(1â, â4)-α-Glcp-(1 â and â 4,6)-α-Glcp-(1â, and R4 is composed of â 5)-α-Araf-(1â, ß-Galp-(1â, â 4)-ß-Galp-(1â, â 3,4)-ß-Galp-(1â, â 4,6)-ß-Galp-(1 â and â 2,4)-ß-Galp-(1 â . In addition, the antitumor activity of JMMP-3 on HepG2 cells was preliminarily investigated.
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Frutas , Juglans , Pectinas , Juglans/química , Pectinas/química , Pectinas/isolamento & purificação , Humanos , Frutas/química , Células Hep G2 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificaçãoRESUMO
BACKGROUND: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. METHODS: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. RESULTS: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. CONCLUSION: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization.
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Hipertensão Portal , Trombose Venosa , Humanos , Veia Porta/patologia , Esplenectomia/efeitos adversos , Cirrose Hepática/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Hipertensão Portal/cirurgia , Hipertensão Portal/complicaçõesRESUMO
BACKGROUND: Acute suppurative terminal cholangitis (ASTC) is rarer than acute obstructive cholangitis and is not well studied. To explore this subtype of acute cholangitis, we described our clinical experience with ASTC. METHODS: We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020. We analyzed their clinical characteristics, including etiology, clinical manifestations, imaging features, treatment and prognosis. RESULTS: A total of 32 ASTC patients were included in the analysis. The majority of the patients had a history of biliary operations, and clinical manifestations were occult and atypical. The positive rate of bacterial culture was 46.9%. All the patients had typical imaging features on computed tomography and magnetic resonance imaging. Treatment with effective antibiotics was provided as soon as diagnosis was established. After treatment, most patients had a good outcome. Elevated levels of total bilirubin, aspartate aminotransferase, procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis. CONCLUSIONS: Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis, and that earlier diagnosis and more personalized treatments are needed.
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Colangite , Humanos , Supuração/complicações , Prognóstico , Colangite/diagnóstico , Colangite/terapia , Hospitalização , Tomografia Computadorizada por Raios X , Doença Aguda , Estudos RetrospectivosRESUMO
The binding of ligands to receptors within a nanoscale small space is relevant in biology, biosensing, and affinity filtration. Binding in confinement can be studied with biological systems but under the limitation that essential parameters cannot be easily controlled including receptor type and position within the confinement and its dimensions. Here we study molecular recognition with a synthetic confined nanopore with controllable pore dimension and molecular DNA receptors at different depth positions within the channel. Binding of a complementary DNA strand is studied at the single-molecule level with atomic force microscopy. Following the analysis, kinetic association rates are lower for receptors positioned deeper inside the pore lumen while dissociation is faster and requires less force. The phenomena are explained by the steric constraints on molecular interactions in confinement. Our study is the first to explore recognition in DNA nanostructures with atomic force microscopy and lays out new tools to further quantify the effect of nanoconfinement on molecular interactions.
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Nanoporos , Microscopia de Força Atômica , Espaços Confinados , DNA/química , Nanotecnologia/métodosRESUMO
Soil microbiome is a key evaluation index of soil health. Previous studies have shown that organic fertilizer from traditional Chinese medicine(TCM)residues can improve the yield and quality of cultivated traditional Chinese medicinal materials. However, there are few reports on the effects of organic fertilizer from TCM residues on soil microbiome. Therefore, on the basis of evaluating the effects of organic fertilizer from TCM residues on the yield and quality of cultivated Salvia miltiorrhiza, the metagenomic sequencing technique was used to study the effects of organic fertilizer from TCM residues on rhizosphere microbiome community and function of cultivated S. miltiorrhiza. The results showed that:(1) the application of organic fertilizer from TCM residues promoted the growth of S. miltiorrhiza and the accumulation of active components, and the above-ground and underground dry weight and fresh weight of S. miltiorrhiza increased by 371.4%, 288.3%, 313.4%, and 151.9%. The increases of rosmarinic acid and salvianolic acid B were 887.0% and 183.0%.(2)The application of organic fertilizer from TCM residues significantly changed the rhizosphere bacterial and fungal community structures, and the microbial community composition was significantly different.(3)The relative abundance of soil-beneficial bacteria, such as Nitrosospira multiformis, Bacillus subtilis, Lysobacter enzymogenes, and Trichoderma was significantly increased by the application of organic fertilizer from TCM residues.(4)KEGG function prediction analysis showed that metabolism-related microorganisms were more easily enriched in the soil environment after organic fertilizer application. The abundance of functional genes related to nitrification and denitrification could also be increased after the application of organic fertilizer from TCM residues. The results of this study provide guidance for the future application of organic fertilizer from TCM residues in the cultivation of traditio-nal Chinese medicinal materials and enrich the content of green cultivation technology of traditional Chinese medicinal materials.
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Micobioma , Salvia miltiorrhiza , Solo/química , Salvia miltiorrhiza/química , Fertilizantes , Medicina Tradicional Chinesa , Bactérias/genética , Microbiologia do SoloRESUMO
Cumulenes, sp-hybridized carbon motifs featuring consecutive double bonds, have rarely been explored as π-elements for conjugated polymers. Long cumulenic conjugated polymers can serve as models for approaching carbyne, an intriguing yet elusive carbon allotrope. However, their synthesis is notoriously difficult due to intrinsic instability. To date, only few [3]cumulene-based polymers have been synthesized, mostly relying on surface chemistry. Higher cumulene-based polymers remain unknown. Here, we present a "meet in the middle" strategy to overcome this challenge and synthesize high-molecular-weight, stable, and solution-processable conjugated [5]cumulene polymers (Mw up to 67.9 kg/mol). Our approach involves a new polymerization method called step-growth condensation polymerization of propargylic electrophiles (step-growth CPPE). The structures and molecular weights of the cumulenic polymers are established by various spectroscopic methods, including a comparative analysis of a discrete oligomer series. By introducing ortho-substituents on the aryl side groups, we successfully address the stability-conjugation dilemma. Electronic communication between cumulene units is found to be contingent upon the aromaticity of the π-spacers, enabling flexible energy-level adjustment and new narrow band gap polymers. The synthetic methodology and structure-property relationship established in this work serve as the starting points for the exploration of this fascinating family of sp-carbon-rich materials.
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Controlled polymerization of cumulenic monomers represents a promising yet underdeveloped strategy toward well-defined alkyne polymers. Here we report a stereoelectronic effect-inspired approach using simple vinylidenecyclopropanes (VDCPs) as butatriene homologues in controlled radical ring-opening polymerizations. While being thermally stable, VDCPs mimic butatrienes via conjugation of the cyclopropane ring. This leads to exclusive terminal-selective propagation that affords a highly structurally regular alkyne-based backbone, featuring complete ring-opening and no backbiting regardless of polymerization conditions.
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The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.
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Monolithic nonplanar ring oscillators (NPROs) have achieved great success in industry, scientific applications and space missions due to their excellent narrow-linewidth, low-noise, high beam-quality, lightweight and compact performances. Here, we show that stable dual-frequency or multi-frequency fundamental-mode (DFFM or MFFM) laser can be stimulated directly by tunning pump divergence-angle and beam-waist injected to NPRO. The DFFM laser has a frequency deviation of one free spectral range of the resonator and thus can be utilized for pure microwave generation by common-mode-rejection. To demonstrate the purity of the microwave signal, a theoretical phase noise model is established, and the phase noise and the frequency tunability of the microwave signal are experimentally studied. Single sideband phase noise for a 5.7â GHz carrier is measured as low as -112 dBc/Hz at 10 kHz offset, and -150 dBc/Hz at 10â MHz offset in the free running condition of the laser, which outperforms its counterparts from dual-frequency Laguerre-Gaussian (LG) modes. The frequency of the microwave signal can be efficiently tunned through two channels, with frequency tunning coefficients of 15â Hz/V by piezo, and -60.5 kHz/K by temperature, respectively. We expect that such compact, tunable, low-cost and low-noise microwave sources can facilitate multiple applications including miniaturized atomic clocks, communication and radar, etc.
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BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.
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Asma , Bronquite Crônica , Enfisema , Doença Pulmonar Obstrutiva Crônica , Humanos , Escarro , Fenótipo , InflamaçãoRESUMO
Monolithic nonplanar ring oscillators (NPROs) under an applied magnetic field can operate unidirectional single-frequency lasing due to the loss differences among its four eigenpolarizations, where the minimum was empirically estimated to be 0.01%. However, this value has never been verified because the applied magnetic field is not uniformly distributed, making it hard to resolve both theoretically and experimentally. Here, we propose a method to resolve the applied magnetic field through an NPRO by combining finite-element analysis and experimental verification. By introducing the non-uniform magnetic field information to the eigenpolarization theory, the loss differences can be calculated by path integration along the optical path in the NPRO. The critical point, where the bidirectional lasing is emerging, is identified by the relative amplitude noise (RAN) of the laser and by the beating signal between the clockwise (CW) and counterclockwise (CCW) lasing. With this method, we determine that unidirectional operation is possible with loss differences as low as 0.0001% and 0.0003%, corresponding to two different NPRO designs with out-of-plane angles of 90° and 45°, respectively, which increases the precision of the loss differences for unidirectional single-frequency lasing by more than one order of magnitude. Our findings will greatly facilitate NPRO laser design with lowered magnetic field intensity requirements.
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To investigate the impact of early response and treatment interruption on the survival of patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (r/r CLL/SLL) treated with ibrutinib. This post hoc analysis used data of patients received ibrutinib treatment from an open-label, multicenter phase 3 study comparing ibrutinib with rituximab in patients with r/r CLL/SLL. The association of complete or partial response at 6 months, interruption within the first 6 months, cumulative interruption durations during the ibrutinib-treated period with progression-free survival (PFS) and overall survival (OS) were evaluated using the adjusted Cox hazard proportional model. The study included 87 patients treated with ibrutinib, of which 74 patients had at least 6 months of ibrutinib treatment and were analyzed. The response at 6 months did not affect PFS (HR = 0.58, 95%CI: 0.22-1.49) or OS (HR = 0.86, 95%CI: 0.22-3.31). The onset of interruption before or after 6 months was not associated with PFS (HR = 0.88, 95%CI: 0.34-2.30) or OS (HR = 0.75, 95%CI: 0.23-2.52). However, a cumulative interruption of more than 35 days was independently associated with worse PFS (HR = 2.4, 95%CI: 0.99-5.74) and OS (HR = 2.6, 95%CI: 0.88-7.44). Continuous interruption for more than 14 days was associated with a numerically lower 3-year PFS rate (> 14 vs. ≤ 14 days: 42% vs. 73%) and 3-year OS rate (> 14 vs. ≤ 14 days: 58% vs. 84%, both P > 0.05). Response status at 6 months or early therapy interruptions did not affect survival in patients with r/r CLL/SLL treated with ibrutinib. However, a cumulative temporary interruption of more than 35 days could potentially impact patient outcomes.
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Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Prevenção Secundária , Adenina , Rituximab , RecidivaRESUMO
Here, using viral metagenomic method, a novel whale papillomavirus (temporarily named wPV, GenBank accession number OP856597) was discovered in a whale (Delphinapterus leucas) pharyngeal metagenomic library. The complete genome size of wPV is 7179 bp, with GC content of 54.4% and a nucleotide composition of 23.4% A, 22.3% T, 28.4% G, and 25.9% C. The viral genome has a typical papillomavirus organization pattern, and five ORFs were predicted, including two late genes encoding L1 and L2, and three early genes encoding E1, E2, and E6. Pairwise sequence comparison and phylogenetic analysis based on the L1 gene sequence indicated that wPV may be a novel species within genus Dyodeltapapillomavirus. In addition, the E2 region of wPV was predicted to have a potential recombination event. The discovery of this novel papillomavirus increases our understanding of the viral ecology of marine mammals, providing insights into possible future infectious diseases.
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Beluga , Infecções por Papillomavirus , Animais , Beluga/genética , Filogenia , Proteínas Virais/genética , Papillomaviridae/genética , Metagenômica , Genoma Viral , Infecções por Papillomavirus/veterináriaRESUMO
OBJECTIVES: We aimed to evaluate the efficacy of anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody therapy by assessing the hyper-enhanced rim phenomenon of hepatocellular carcinoma (HCC) on Sonazoid-contrast-enhanced ultrasound (CEUS) Kupffer phase images. METHODS: This retrospective study included 61 patients with HCC who received anti-PD-1/PD-L1 antibody therapy from August 1, 2020, to January 31, 2022. We compared the progression-free survival (PFS) of patients with hyper-enhanced rim+ and hyper-enhanced rim-nodules and the time to nodule progression (TTnP) of hyper-enhanced rim+ and hyper-enhanced rim- nodules. RESULTS: Thirty-nine patients received postoperative therapy, and 22 patients had unresectable HCC. The mean PFS was 11.8 months (95% confidence interval [CI]: 8.7-14.9) for patients with hyper-enhanced rim+ HCC nodules and 16.5 months (95% CI: 14.9-18.1) for patients with hyper-enhanced rim- HCC nodules in the surgery group (p = 0.017). The mean PFS was 9.2 months (95% CI: 3.6-14.8) for patients with hyper-enhanced rim+ HCC nodules and 17.8 months (95% CI: 14.9-20.6) for patients with hyper-enhanced rim- HCC nodules in the non-surgery group (p = 0.015). For hyper-enhanced rim+ HCC nodules, TTnP for each nodule exceeding the specified threshold was 10.1 months, whereas that for hyper-enhanced rim- HCC nodules was 17.6 months (p = 0 .018). The disease control rate was 42.9% (3/7) for hyper-enhanced rim+ HCC nodules and 85.7% (21/24) for hyper-enhanced rim- HCC nodules (p = 0.013). CONCLUSIONS: The presence of hyper-enhanced rim on the Kupffer phase images obtained via the non-invasive Sonazoid-CEUS is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 therapy in patients with HCC. KEY POINTS: ⢠The mean progression-free survival was 11.8 months for patients with hyper-enhanced rim+ HCC nodules and 16.5 months for patients with hyper-enhanced rim- HCC nodules in the surgery group. ⢠The mean progression-free survival was 9.2 months for patients with hyper-enhanced rim+ HCC nodules and 17.8 months for patients with hyper-enhanced rim- HCC nodules in the non-surgery group. ⢠The disease control rate was 42.9% for hyper-enhanced rim+ HCC nodules and 85.7% for hyper-enhanced rim- HCC nodules (p = 0.013).
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico , Antígeno B7-H1 , Estudos Retrospectivos , Meios de ContrasteRESUMO
Zinc oxide (ZnO)-based thin-film transistors (TFTs) have attracted increasing attention towards flat-panel displays as alternatives to silicon-based TFTs due to their transparency to visible light. Magnesium oxide (MgO) has a wide bandgap (7.8 eV) and high dielectric constant (k). This leads to the development of TFTs using MgO as a gate oxide layer, which can significantly reduce the operating voltage. However, the electrical properties and dielectric constant of MgO are determined from the percentage of oxygen in MgO. In this study, a MgO gate-oxide was deposited on ZnO by magnetron sputtering at various oxygen concentrations (0%, 66%, and 100%) to fabricate TFTs. With an increase in the oxygen concentration, the oxygen vacancies of MgO were compensated, thereby improving the crystallinity and enhancing the dielectric constant from 6.53 to 12.9 for the oxygen concentrations of 0% and 100%. No pinch-off (saturation) behavior was observed in the TFTs with 0% oxygen; however, the pinch-off voltages were significantly reduced to 17 and 2 V in the TFTs with 66% and 100% oxygen, respectively; hence, the TFT-100 could be operated at a low operating voltage (2 V). With an increase in oxygen from 0% to 100%, the threshold voltage and trap-state density significantly decreased from -159 V and 1.6 × 1018cm-3to -31.4 V and 6.5 × 1016cm-3, respectively. The TFTs with 0% oxygen exhibited a higher field-effect mobility of 12 cm2V-1s-1due to the uncompensated oxygen vacancy in ZnO, which had a higher electron concentration. After introducing oxygen atoms, the field-effect mobility decreased to 0.16 cm2V-1s-1in the TFTs with 66% oxygen, which can be attributed to the compensated oxygen vacancy and lower electron concentration. In contrast, the field-effect mobility increased to 1.88 cm2V-1s-1for the TFTs with 100% oxygen due to the enhanced dielectric constant and crystallinity of MgO.
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OBJECTIVES: This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. METHODS: Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. RESULT: There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P < 0.001), and LCWIICG and EFUCG (r = 0.540, P = 0.017). Cardiac function parameters measured using ICG were statistically different between patients with gastrointestinal cancer with or without AKI (P ≤ 0.05). Multivariate analysis revealed that AKI independently affects cardiac function in patients with gastrointestinal cancer. CONCLUSIONS: UCG and ICG methods are significantly associated with cardiac function in patients with or without AKI, and patients with gastrointestinal cancer with AKI are worse than those without AKI. AKI is an independent risk factor for cardiac function in patients with gastrointestinal cancer.