Non-hexagonal-ring defects and structures induced by strain in graphene and in functionalized graphene

We perform {\textit ab initio} calculations for the strain-induced formation of non-hexagonal-ring defects in graphene, graphane (planar CH), and graphenol (planar COH). We find that the simplest of such topological defects, the Stone-Wales defect, acts as a seed for strain-induced dissociation and multiplication of topological defects. Through the application of inhomogeneous deformations to graphene, graphane and graphenol with initially small concentrations of pentagonal and heptagonal rings, we obtain several novel stable structures that possess, at the same time, large concentrations of non-hexagonal rings (from fourfold to elevenfold) and small formation energies

Entrevista com Marco Antonio da Silva Mello

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Dissecting EPPIN protease inhibitor domains in sperm motility and fertilizing ability: Repercussions for male contraceptive development

EPPIN (epididymal protease inhibitor) is a mammalian conserved sperm-binding protein displaying an N-terminal WFDC (whey-acidic protein four-disulfide core) and a C-terminal Kunitz protease inhibitor domains. EPPIN plays a key role in regulating sperm motility after ejaculation via interaction with the seminal plasma protein SEMG1 (semenogelin-1). EPPIN ligands targeting the SEMG1 binding site in the Kunitz domain are under development as male contraceptive drugs. Nevertheless, the relative contributions of EPPIN WFDC and Kunitz domains to sperm function remain obscure. Here, we evaluated the effects of antibodies targeting specific epitopes in EPPIN's WFDC (Q20E antibody, Gln20-Glu39 epitope) and Kunitz (S21C and F21C antibodies, Ser103-Cys123 and Phe90-C110 epitopes, respectively) domains on mouse sperm motility and fertilizing ability. Computer-assisted sperm analysis showed that sperm co-incubation with S21C antibody (but not F21C antibody) lowered progressive and hyperactivated motilities and impaired kinematic parameters describing progressive (straight-line velocity; VSL, average path velocity; VAP and straightness; STR) and vigorous sperm movements (curvilinear velocity; VCL, amplitude of lateral head movement; ALH, and linearity; LIN) compared with control. Conversely, Q20E antibody-induced milder inhibition of progressive motility and kinematic parameters (VAP, VCL and ALH). Sperm co-incubation with S21C or Q20E antibodies affected in vitro fertilization as revealed by reduced cleavage rates, albeit without changes in capacitation-induced tyrosine phosphorylation. In conclusion, we show that targeting specific epitopes in EPPIN Kunitz and WFDC domains inhibits sperm motility and capacitation-associated events, which decrease their fertilizing ability; nevertheless, similar observations in vivo remain to be demonstrated. Simultaneously targeting residues in S21C and Q20E epitopes is a promising approach for the rational design of EPPIN-based ligands with spermostatic activity.Fil: Silva, Alan A. S.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Raimundo, Tamiris R. F.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Mariani, Noemia A. P.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Kushima, Hélio. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Avellar, Maria Christina W.. Universidade Federal de Sao Paulo; BrasilFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Paula Lopes, Fabíola F.. Universidade Federal de Sao Paulo; BrasilFil: Moura, Marcelo T.. Universidade Federal de Sao Paulo; BrasilFil: Silva, Erick J. R.. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi

[(2R,3S,6S)-3-Acet­yloxy-6-(1-phenyl-1H-1,2,3-triazol-4-yl)-3,6-dihydro-2H-pyran-2-yl]methyl acetate

In the title compound, C18H19N3O5, the 3,6-dihydro-2H-pyran ring adopts a half-chair, distorted towards a half-boat, conformation with Q T = 0.5276(14) Å. The benzene ring is twisted out of the place of the triazole ring [dihedral angle = 23.54 (8)°]. In the crystal, supra­molecular layers in the ac plane are formed through C—H⋯O and C—H⋯π(triazole) inter­actions. These stack along the b axis being connected by C—H⋯N contacts

Herbicidas na nodulação e na fixação de N2 em caupi

An experiment was carried out under greenhouse conditions in order to evaluate the effects of soil applications of different herbicides on nodulation and nitrogen fixation in cowpea [Vigna unguiculata (L.) Walp]. Treatments included a control (without herbicide) and application of the herbicides at the recommended rates and at the double of these rates (triflurarin 1.8 and 3.6 L.ha-1; EPTC 5.0 and 10.0 L.ha-1; pendimethalin 2.0 and 4.0 L.ha-1; metribuzin 1.1 and 2.2 L.ha-1; linuron 2.4 and 4.8 L.ha-1; imazaquim 1.0 and 2.0 L.ha-1). All treatments were inoculated with Bradyrhizobium, strain NBF 09. Growth of cowpea was evaluated at 20, 40, 60, and 80 days after planting. The data suggested that cowpea nodulation was affected by trifluralin (1.8 L.ha-1) linuron (2.4 L.ha-1), and imazaquim (1.0 L.ha-1), but the effects occurred only at the earlier stages of cowpea growth. Total nitrogenase activity was reduced in the soil treated with herbicides. Metribuzin and linuron showed a large degree of fitotoxicity to the crop, inhibiting its vegetative growth. Notwithstanding these effects observed on nodulation and nitrogen fixation, the herbicides seem not to have affected nitrogen uptake.Objetivando avaliar os efeitos da aplicação de distintos herbicidas na nodulação e na fixação do N2 em caupi [Vigna unguiculata (L.) Walp], foi instalado um experimento em casa de vegetação, utilizando um Latossolo Vermelho-Amarelo, da Zona da Mata Norte de Pernambuco. Os tratamentos incluíram a aplicação de herbicidas em doses correspondentes às recomendadas e ao dobro destas (trifluralin 1,8 e 3,6 L.ha-1; EPTC 5,0 e 10,0 L.ha-1; pendimethalin 2,0 e 4,0 L.ha-1; metribuzin 1,1 e 2,2 L.ha-1; linuron 2,4 e 4,8 L.ha-1; e imazaquim 1,0 e 2,0 L.ha-1), além de um tratamento sem herbicida (controle). Em todos os tratamentos as sementes de caupi (variedade BR-IPA-206) foram infectadas com a estirpe de Bradyrhizobium NFB 09. O desenvolvimento do caupi foi avaliado aos 20, 40, 60 e 80 dias após o plantio. Os resultados mostraram que a nodulação foi afetada na presença dos herbicidas trifluralin (1,8 L.ha-1), linuron (2,4 L.ha-1) e imazaquim (1,0 L.ha-1), mas os efeitos ocorreram apenas nos estádios iniciais do desenvolvimento da variedade de caupi estudada. A atividade total da enzima nitrogenase foi reduzida no solo tratado com herbicidas. O metribuzin e o linuron apresentaram elevado grau de fitotoxicidade para a cultura, inibindo o seu desenvolvimento vegetativo. Apesar dos efeitos observados na nodulação e na fixação do nitrogênio, os herbicidas não afetaram diretamente a acumulação de nitrogênio pelas plantas de caupi

Lenalidomide Maintenance and Measurable Residual Disease in a Real-World Multiple Myeloma Transplanted Population Receiving Different Treatment Strategies Guided by Access to Novel Drugs in Brazil

Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has refined the prognosis of complete response (CR) cases, until now, there have been no data on the benefits of these approaches in Latin America. Here, we evaluate the benefits of M-Len and MRD using next-generation flow cytometry (NGF-MRD) at Day + 100 post-ASCT (n = 53). After ASCT, responses were evaluated based on the International Myeloma Working Group criteria and NGF-MRD. MRD was positive in 60% of patients with a median progression-free survival (PFS) of 31 months vs. not reached (NR) for MRD-negative cases (p = 0.05). The patients who received M-Len continuously had a significantly better PFS and overall survival (OS) than those without M-Len (median PFS: NR vs. 29 months, p = 0.007), with progression in 11% vs. 54% of cases after a median follow-up of 34 months, respectively. In a multivariate analysis, MRD status and M-Len therapy emerged as independent predictors of PFS (median PFS of M-Len/MRD− vs. no M-Len/MRD+ of NR vs. 35 months, respectively; p = 0.01). In summary, M-Len was associated with improved survival outcomes in our real-world MM cohort in Brazil, with MRD emerging as a useful reproducible tool to identify patients at an earlier risk of relapse. The inequity in drug access remains a hurdle in countries with financial constraints, with a negative impact on MM survival.This work was supported by from Coordenação de Aperfeiçomento de Pessoal de Nível Superior—Brazil (CAPES) Finance code 001-8888.331795/2010-01; Programa de Oncobiologia 001/2017 and 004/2017; Centro Investigación Biomédica em Red—Cáncer (CIBERONC code CB//00400) of Instituto de Salud Carlos III, Ministry of Science and Innovation (Madrid, Spain), number CB16/12/00400; The International Myeloma Foundation-Black Swan Research Initiative (Los Angeles, CA) (Grant: LSHB-CT-2006-018708). A.B.S.S. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX, number: 88887.688096/2022-00. R.M.P. was supported by a grant from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DGPU), number: 000281/2016-06 and CAPES/PROEX 641/2018, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ), number: E01/200/537/2018. E.S.B. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX, number: 88887.335769/2019-00 and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), number: E-26/200.192/2020, Brazil

Performance of cryptococcal antigen lateral flow assay in serum, cerebrospinal fluid, whole blood, and urine in HIV-infected patients with culture-proven cryptococcal meningitis admitted at a Brazilian referral center

Cryptococcal meningitis is the most common cause of opportunistic meningitis in HIV-infected patients in Brazil and causes unacceptable high mortality rates. In this study, HIV-infected patients with a first episode of culture-proven cryptococcal meningitis in cerebrospinal fluid (CSF) were prospectively included in order to evaluate sensitivity of cryptococcal antigen (CrAg) lateral flow assay (LFA) in serum, CSF, whole blood (fingerstick), and fresh urine. In addition, HIV-infected patients with other neurological confirmed diseases were included in order to evaluate the specificity of CrAg LFA in serum. Twenty patients with cryptococcal meningitis were included and in 19 of them, CrAg LFA in CSF, serum, and whole blood were positive (95% sensitivity). In 18 patients, India ink test was positive in CSF (90% sensitivity), and in 16 cases, CrAg LFA was positive in urine (80% sensitivity). Thirty-six HIV-infected patients with other neurological diseases had negative results of CrAg LFA in serum (100% specificity). In conclusion, CrAg LFA in serum, CSF, and whole blood showed high sensitivity and specificity. Whole blood CrAg LFA seems to be a good and reliable strategy to improve AIDS-related cryptococcal meningitis diagnosis in Brazil

Multifunctional Hybrid MoS2-PEGylated/Au Nanostructures with Potential Theranostic Applications in Biomedicine

In this work, flower-like molybdenum disulfide (MoS2) microspheres were produced with polyethylene glycol (PEG) to form MoS2-PEG. Likewise, gold nanoparticles (AuNPs) were added to form MoS2-PEG/Au to investigate its potential application as a theranostic nanomaterial. These nanomaterials were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), photoelectron X-ray spectroscopy (XPS), Fourier-transformed infrared spectroscopy (FTIR), cyclic voltammetry and impedance spectroscopy. The produced hierarchical MoS2-PEG/Au microstructures showed an average diameter of 400 nm containing distributed gold nanoparticles, with great cellular viability on tumoral and non-tumoral cells. This aspect makes them with multifunctional characteristics with potential application for cancer diagnosis and therapy. Through the complete morphological and physicochemical characterization, it was possible to observe that both MoS2-PEG and MoS2-PEG/Au showed good chemical stability and demonstrated noninterference in the pattern of the cell nucleus, as well. Thus, our results suggest the possible application of these hybrid nanomaterials can be immensely explored for theranostic proposals in biomedicine