On the Determination of Elastic Properties of Single-Walled Boron Nitride Nanotubes by Numerical Simulation

The elastic properties of chiral and non-chiral single-walled boron nitride nanotubes in a wide range of their chiral indices and diameters were studied. With this aim, a three-dimensional finite element model was used to assess their rigidities and, subsequently, elastic moduli and Poisson’s ratio. An extensive study was performed to understand the impact of the input parameters on the results obtained by numerical simulation. For comparison, the elastic properties of single-walled boron nitride nanotubes are shown together with those obtained for single-walled carbon nanotubes.     

Multilayer Diamond Coatings Applied to Micro-End-Milling of Cemented Carbide

Cobalt-cemented carbide micro-end mills were coated with diamond grown by chemical vapor deposition (CVD), with the purpose of micro-machining cemented carbides. The diamond coatings were designed with a multilayer architecture, alternating between sub-microcrystalline and nanocrystalline diamond layers. The structure of the coatings was studied by transmission electron microscopy. High adhesion to the chemically pre-treated WC-7Co tool substrates was observed by Rockwell C indentation, with the diamond coatings withstanding a critical load of 1250 N. The coated tools were tested for micro-end-milling of WC-15Co under air-cooling conditions, being able to cut more than 6500 m over a period of 120 min, after which a flank wear of 47.8 μm was attained. The machining performance and wear behavior of the micro-cutters was studied by scanning electron microscopy and energy-dispersive X-ray spectroscopy. Crystallographic analysis through cross-sectional selected area electron diffraction patterns, along with characterization in dark-field and HRTEM modes, provided a possible correlation between interfacial stress relaxation and wear properties of the coatings. Overall, this work demonstrates that high adhesion of diamond coatings can be achieved by proper combination of chemical attack and coating architecture. By preventing catastrophic delamination, multilayer CVD diamond coatings are central towards the enhancement of the wear properties and mechanical robustness of carbide tools used for micro-machining of ultra-hard materials.     

Correlação entre Cardiomegalia pela Radiografia de Tórax e Diâmetro do Ventrículo Esquerdo pela Ecocardiografia em Pacientes com Doença de Chagas

BackgroundCardiomegaly on chest X-ray is an independent predictor of death in individuals with chronic Chagas cardiomyopathy (CCC). However, the correlation between increased cardiothoracic ratio (CTR) on chest X-ray and left ventricular end-diastolic diameter (LVEDD) on echocardiography is not well established in this population.ObjectivesTo assess the relationship between chest X-ray and LVEDD on echocardiography in patients with Chagas disease and its applicability to the Rassi score.MethodsRetrospective study on 63 Chagas disease outpatients who underwent chest X-ray and echocardiography. Cardiomegaly on chest X-ray was defined as a CTR>0.5. LVEDD was analyzed as a continuous variable. ROC curve was used to evaluate the ability of LVEDD in detecting cardiomegaly by chest X-ray, with a cut-off point defined by the highest sum of sensitivity and specificity.ResultsMedian age 61 years [interquartile range 48-68], 56% were women. CCC was detected in 58 patients, five patients had the indeterminate form of Chagas disease. Cardiomegaly was detected in 28 patients. The area under the ROC curve for LVEDD was 0.806 (95%CI: 0.692-0.919). The optimal cut-off for LVEDD was 60 mm (sensitivity = 64%, specificity = 89%). The use of LVEDD on echocardiography as a surrogate for CTR on chest X-ray changed the Rassi score values of 14 patients, with a reduction in the presumed risk in 10 of them.ConclusionLVEDD on echocardiography is an appropriate, highly specific parameter to distinguish between the presence and absence of cardiomegaly on chest X-ray in Chagas disease. (Arq Bras Cardiol. 2021; 116(1):68-74)     

SARS-CoV-2 Disinfection of Air and Surface Contamination by TiO2 Photocatalyst-Mediated Damage to Viral Morphology,RNA, and Protein

SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO₂-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO₂ photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO₂-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO₂ has no adverse effects on human health, and therefore, TiO₂-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation.     

Serotonin Deficiency Is Associated With Delayed Gastric Emptying

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Production and Characterization of Austenitic Stainless Steel Cast Parts Reinforced with WC Particles Fabricated by Ex Situ Technique

In this work, austenitic stainless steel specimens were locally reinforced with WC particles. The reinforcements were fabricated via an ex situ technique based on powder technology. Mixtures of WC, Fe, and M0101 binder were cold-pressed to obtain powder compacts. After debinding and sintering, the porous WC–Fe inserts were fixed in a mold cavity, where they reacted with liquid metal. Microstructural analysis was conducted for characterization of the phases constituting the produced reinforcement zone and the bonding interface. The results revealed that the reinforcement is a graded material with compositional and microstructural gradients throughout its thickness. The zone nearest to the surface has a ferrous matrix with homogeneously distributed WC particles and (Fe,W,Cr)₆C and (Fe,W,Cr)₃C carbides, formed from the liquid metal reaction with the insert. This precipitation leads to austenite destabilization, which transforms into martensite during cooling. A vast dissolution of the WC particles occurred in the inner zones, resulting in more intense carbides formation. Cr-rich carbides ((Fe,Cr,W)₇C₃, and (Fe,Cr,W)₂₃C₆) formed in the interdendritic regions of austenite; this zone is characterized by coarse dendrites of austenite and a multi-phase interdendritic network composed of carbides. An interface free of discontinuities and porosities indicates good bonding of the reinforcement zone to stainless steel.     

Probing the binding specificities of human Siglecs by cell-based glycan arrays

Siglecs are a family of sialic acid–binding receptors expressed by cells of the immune system and a few other cell types capable of modulating immune cell functions upon recognition of sialoglycan ligands. While human Siglecs primarily bind to sialic acid residues on diverse types of glycoproteins and glycolipids that constitute the sialome, their fine binding specificities for elaborated complex glycan structures and the contribution of the glycoconjugate and protein context for recognition of sialoglycans at the cell surface are not fully elucidated. Here, we generated a library of isogenic human HEK293 cells with combinatorial loss/gain of individual sialyltransferase genes and the introduction of sulfotransferases for display of the human sialome and to dissect Siglec interactions in the natural context of glycoconjugates at the cell surface. We found that Siglec-4/7/15 all have distinct binding preferences for sialylated GalNAc-type O-glycans but exhibit selectivity for patterns of O-glycans as presented on distinct protein sequences. We discovered that the sulfotransferase CHST1 drives sialoglycan binding of Siglec-3/8/7/15 and that sulfation can impact the preferences for binding to O-glycan patterns. In particular, the branched Neu5Acα2–3(6-O-sulfo)Galβ1–4GlcNAc (6′-Su-SLacNAc) epitope was discovered as the binding epitope for Siglec-3 (CD33) implicated in late-onset Alzheimer’s disease. The cell-based display of the human sialome provides a versatile discovery platform that enables dissection of the genetic and biosynthetic basis for the Siglec glycan interactome and other sialic acid–binding proteins.

Immune cells are equipped with an array of glycan-binding proteins (GPBs) capable of interpreting the biological information encoded by glycans. Endogenous GBPs recognize host-derived “self” and foreign-derived “nonself” glycans and produce cues that are integrated into the signaling network of immune cells and contribute to immune homeostasis and the immune response (1). Siglecs (sialic acid–binding immunoglobulin-like lectins) serve in self-recognition and transmit immune inhibitory signals upon binding to a select repertoire of sialoglycans expressed by host cells raising the threshold for immune activation (2, 3). The human Siglec family consists of 14 functionally expressed members, and these are composed of an N-terminal V-set immunoglobulin (Ig)-like domain that mediates sialoglycan binding followed by varying numbers of C2-set Ig-like domains. Intracellularly, most Siglecs have immunoreceptor tyrosine-based inhibition motifs, and Siglec-14/15/16 carry immunoreceptor tyrosine-based activation motifs (3–7). Siglecs are broadly expressed throughout the immune system, and several Siglecs are also found outside of the immune system, such as Siglec-4 (MAG), which is expressed by oligodendrocytes and Schwann cells in the nervous system (8). Although the diverse biological functions within and outside of the immune system of Siglecs are not fully understood, Siglecs generally contribute to immune homeostasis by dampening immune activation upon recognition of sialoglycans. For example, Siglec-2 (CD22) can suppress B cell receptor activation (9), and Siglec-9 can dampen neutrophil activation (10). Cancer cells with aberrant sialoglycans and pathogens that express sialic acids can exploit Siglec signaling to modulate immune responses (11, 12). Moreover, Siglec-3 (CD33) is strongly associated with risk for Alzheimer’s disease and expressed on microglia cells (13, 14). Given the potent immune modulatory functions of Siglecs and their wide involvement in autoimmunity, infection, cancer, and neurodegeneration, Siglecs are promising therapeutic targets (7, 15). However, many of the natural ligands of Siglecs have not been fully identified, and endogenous ligands for several Siglecs including Siglec-3/CD33 remain elusive.Human cells can produce a large diversity of glycans capped with sialic acids (Sia), a family of chemically diverse sugars with N-acetylneuraminic acid (Neu5Ac) being the predominant type in humans. Sialic acids are generally found at the termini of mammalian glycans, and most types of glycoconjugates including N-glycoproteins, multiple types of O-glycoproteins, and glycolipids carry oligosaccharides capped by sialic acids (16, 17). Sialylation is one of the most complex regulated steps in glycosylation with 20 distinct Golgi-located sialyltransferase isoenzymes dedicated to catalyze transfer of sialic acids to galactose (ST3GAL1-6, ST6GAL1 and 2), N-Acetylgalactosamine (Gal-NAc) (ST6GALNAC1-6), or sialic acid (ST8SIA1-6) via α2-3, α2-6, or α2-8 linkages, respectively and with different preferences for the underlying glycan structures and types of glycoconjugate (18–20). The resulting plethora of sialic acid-containing glycans constituting the sialome of cells provides a vast catalog of ligands for Siglecs and potential for distinct instructive cues for the immune response (16). The current insight into the interactome of Siglecs is largely derived from studies with libraries of synthetic and natural glycans printed on glass arrays (21, 22). These glycan arrays have demonstrated distinct structural glycan features that drive selective binding of individual Siglecs, including the linkage type of sialic acids, the core disaccharide carrying sialic acids, and glycan modifications such as sulfation or acetylation (23–27). However, printed glycan arrays may not present glycans in the natural context of the overall glycoconjugate structure and the cell surface with spatial organization and competition dynamics limiting insight into the fine binding specificities of Siglecs and their interactions with the host cell sialome.Here, we took advantage of our recently developed cell-based glycan array strategy (28–30) and generated an expanded sialome sublibrary with the human embryonic kidney (HEK) 293 for dissection of Siglec binding properties. First, combinatorial gene knockout (KO) was used to delete distinct subsets of sialyltransferase isoenzymes or all endogenous sialylation capacity. Second, using targeted gene knock-in (KI), individual sialyltransferase isoenzymes were introduced in the absence of other isoenzymes. Finally, we introduced selected sulfotransferase isoenzymes to explore cross-talk between sialylation and sulfation. To specifically address the influence of clustered O-glycan presentation for Siglec binding, we introduced a large panel of reporter constructs designed to display human O-glycodomains derived from mucins and mucin-like O-glycoproteins with different densities and patterns of O-glycans. The cell-based sialome array reproduced previous results for binding specificities for Siglec-2 (CD22) and Siglec-9 and led to insight into the binding specificities of Siglec-4/7/15 for distinct GalNAc-type O-glycans and their presentation on O-mucin–like glycoproteins. Finally, we demonstrate that Siglec-3/7/8/15 have preferential binding to sulfated sialoglycans yet have different specificities for underlying glycoconjugate structures. We further discovered the 6′-Su-SLacNAc (Neu5Acα2-3[6-O-sulfo]Galβ1-4GlcNAc) epitope on N-glycans and glycolipids as the ligand for Siglec-3/CD33 as well as Siglec-8. In summary, the cell-based display of the human sialome enables dissection of the Siglec interactome in the natural context of a human cell and provides the biosynthetic and genetic basis for the identified ligands.     

Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos

Fundamento:Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose.Objetivos:Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV.Métodos:Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA.Resultados:Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas.Conclusões:Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.