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The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1-5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT-such as the XBB variant-and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Memória Imunológica , SARS-CoV-2 , Animais , Humanos , Camundongos , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito B/imunologia , Memória Imunológica/imunologia , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , MutaçãoRESUMO
Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections2,3. Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles4,5, and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants.
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Anticorpos Antivirais , Deriva e Deslocamento Antigênicos , COVID-19 , Evolução Molecular , Imunidade Humoral , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções Irruptivas/imunologia , Infecções Irruptivas/virologia , COVID-19/imunologia , COVID-19/virologia , Soroterapia para COVID-19 , SARS-CoV-2/química , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Domínios Proteicos/genética , Domínios Proteicos/imunologia , Deriva e Deslocamento Antigênicos/imunologia , MutaçãoRESUMO
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Evasão da Resposta Imune/imunologia , Testes de Neutralização , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/classificação , Anticorpos Antivirais/classificação , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Células Cultivadas , Convalescença , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Humanos , Soros Imunes/imunologia , Modelos Moleculares , Mutação , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
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Anticorpos Antivirais , Deriva e Deslocamento Antigênicos , COVID-19 , Epitopos de Linfócito B , Tolerância Imunológica , Mutação , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Deriva e Deslocamento Antigênicos/genética , Deriva e Deslocamento Antigênicos/imunologia , COVID-19/imunologia , COVID-19/transmissão , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Imunidade Humoral , Imunização Secundária , Testes de Neutralização , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
Current understanding holds that Klinefelter syndrome (KS) is not inherited, but arises randomly during meiosis. Whether there is any genetic basis for the origin of KS is unknown. Here, guided by our identification of some USP26 variations apparently associated with KS, we found that knockout of Usp26 in male mice resulted in the production of 41, XXY offspring. USP26 protein is localized at the XY body, and the disruption of Usp26 causes incomplete sex chromosome pairing by destabilizing TEX11. The unpaired sex chromosomes then result in XY aneuploid spermatozoa. Consistent with our mouse results, a clinical study shows that some USP26 variations increase the proportion of XY aneuploid spermatozoa in fertile men, and we identified two families with KS offspring wherein the father of the KS patient harbored a USP26-mutated haplotype, further supporting that paternal USP26 mutation can cause KS offspring production. Thus, some KS should originate from XY spermatozoa, and paternal USP26 mutations increase the risk of producing KS offspring.
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Cisteína Endopeptidases/genética , Síndrome de Klinefelter/genética , Mutação/genética , Adulto , Aneuploidia , Animais , Humanos , Masculino , Camundongos , Camundongos Knockout , Cromossomos Sexuais/genética , Espermatozoides/patologia , Adulto JovemRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade RBD-targeting Class 1 public NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , COVID-19/genética , Soroterapia para COVID-19 , Anticorpos NeutralizantesRESUMO
Moiré superlattices enable the generation of new quantum phenomena in two-dimensional heterostructures, in which the interactions between the atomically thin layers qualitatively change the electronic band structure of the superlattice. For example, mini-Dirac points, tunable Mott insulator states and the Hofstadter butterfly pattern can emerge in different types of graphene/boron nitride moiré superlattices, whereas correlated insulating states and superconductivity have been reported in twisted bilayer graphene moiré superlattices1-12. In addition to their pronounced effects on single-particle states, moiré superlattices have recently been predicted to host excited states such as moiré exciton bands13-15. Here we report the observation of moiré superlattice exciton states in tungsten diselenide/tungsten disulfide (WSe2/WS2) heterostructures in which the layers are closely aligned. These moiré exciton states manifest as multiple emergent peaks around the original WSe2 A exciton resonance in the absorption spectra, and they exhibit gate dependences that are distinct from that of the A exciton in WSe2 monolayers and in WSe2/WS2 heterostructures with large twist angles. These phenomena can be described by a theoretical model in which the periodic moiré potential is much stronger than the exciton kinetic energy and generates multiple flat exciton minibands. The moiré exciton bands provide an attractive platform from which to explore and control excited states of matter, such as topological excitons and a correlated exciton Hubbard model, in transition-metal dichalcogenides.
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Change history: In this Letter, the following text has been added to the Acknowledgements section: "the scanning transmission electron microscopy measurements at the Molecular Foundry were supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract number DE-AC02-05CH11231". See accompanying Amendment.
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In this paper, low-cost electrochemical processing and heat treatment were adopted to fabricate titanium alloy surfaces with switchable wettability. Meanwhile, surface structure, roughness, and oxide content were regulated by electrochemical processing voltage. The effects of surface structure, roughness, oxide content, temperature, and time of heat treatment on switchable wettability were investigated. In addition to suitable structural conditions, surface chemistry is also crucial to preparing metal surfaces with switchable wettability. The surface chemistry of electrochemical processed surfaces was changed by organic matter transfer during heat treatment. In a certain voltage range, suitable surface structure, high roughness, and surface oxide content by high voltage contribute to the organic matter transfer. In a certain range of heating temperature and time, the concentration difference of organic matter is the premise of organic matter transfer. Concurrently, the higher the temperature, the faster the speed of organic matter transfer. Different from other relevant studies, the hypothesis that the concentration difference promotes organic matter transfer is proposed and verified by interesting experiments. The difference concentration of organic matter between the environment and the samples, as well as between the two samples, was created to promote organic matter transfer. Therefore, the electrochemical processed surfaces with switchable wettability were obtained by organic matter transfer in two ways.
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The unique intermolecular van der Waals force in emerging two-dimensional inorganic molecular crystals (2DIMCs) endows them with highly tunable structures and properties upon applying external stimuli. Using high pressure to modulate the intermolecular bonding, here we reveal the highly tunable charge transport behavior in 2DIMCs for the first time, from an insulator to a semiconductor. As pressure increases, 2D α-Sb2 O3 molecular crystal undergoes three isostructural transitions, and the intermolecular bonding enhances gradually, which results in a considerably decreased band gap by 25 % and a greatly enhanced charge transport. Impressively, the in situ resistivity measurement of the α-Sb2 O3 flake shows a sharp drop by 5 orders of magnitude in 0-3.2â GPa. This work sheds new light on the manipulation of charge transport in 2DIMCs and is of great significance for promoting the fundamental understanding and potential applications of 2DIMCs in advanced modern technologies.
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Bismuth oxyselenide (Bi2 O2 Se) has emerged as a promising candidate for electronic and optoelectronic applications due to its outstanding electron mobility and ambient stability. However, high dark current and relatively slow photoresponse that originate from high charge carrier concentration as well as bolometric effect in Bi2 O2 Se inhibit further improvement of Bi2 O2 Se based photodetectors. Here, a one-step van der Waals (vdW) epitaxy synthesis of Bi2 Te2 Se/Bi2 O2 Se vertical heterojunction with type-II band alignment and high-quality interface is demonstrated. The crystal quality and uniformity of the heterojunction are supported by Raman, transmission electron microscopy and energy dispersive spectroscopy results. A photodetector based on Bi2 Te2 Se/Bi2 O2 Se heterojunction demonstrates steady photoresponse over a large wavelength range (532-1456 nm), with a high specific responsivity of 2.21 × 103 A W-1 at 532 nm and fast response speed of 50 ms. Moreover, field effect regulation allows for further improvement of the photoresponse performance of the heterojunction field effect transistor device, where the responsivity can be increased to 3.34 × 103 A W-1 with a 60 V gate voltage. Overall, the one-step vdW epitaxy process is a promising and convenient route towards constructing high quality Bi2 O2 Se based heterojunction for improving its photodetection performance.
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Ultraviolet detection is of great significance due to its wide applications in the missile tracking, flame detecting, pollution monitoring, and so on. The nonlayered semiconductor γ-Bi2 O3 is a promising candidate toward high-performance UV detection due to the wide bandgap, excellent light sensitivity, environmental stability, nontoxic and elemental abundance properties. However, controllable preparation of ultrathin 2D γ-Bi2 O3 flakes remains a challenge, owing to its nonlayered structure, metastable nature, and other competing phases. Moreover, the UV photodetectors based on 2D γ-Bi2 O3 flake have not been implemented yet. Here, ultrathin (down to 4.8 nm) 2D γ-Bi2 O3 flakes with high crystal quality are obtained via a van der Waals epitaxy method. The as-synthesized single-crystalline γ-Bi2 O3 flakes show a body-centered cubic structure and grown along (111) lattice plane as revealed by experimental observations. More importantly, photodetectors based on the as-synthesized 2D γ-Bi2 O3 flakes exhibit promising UV detection ability, including a responsivity of 64.5 A W-1 , a detectivity of 1.3 × 1013 Jones, and an ultrafast response speed (τrise ≈ 290 µs and τdecay ≈ 870 µs) at 365 nm, suggesting its great potential for various optoelectronic applications.
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Accurate prediction of post-translational modifications (PTMs) is of great significance in understanding cellular processes, by modulating protein structure and dynamics. Nowadays, with the rapid growth of protein data at different "omics" levels, machine learning models largely enriched the prediction of PTMs. However, most machine learning models only rely on protein sequence and little structural information. The lack of the systematic dynamics analysis underlying PTMs largely limits the PTM functional predictions. In this research, we present two dynamics-centric deep learning models, namely, cDL-PAU and cDL-FuncPhos, by incorporating sequence, structure, and dynamics-based features to elucidate the molecular basis and underlying functional landscape of PTMs. cDL-PAU achieved satisfactory area under the curve (AUC) scores of 0.804-0.888 for predicting phosphorylation, acetylation, and ubiquitination (PAU) sites, while cDL-FuncPhos achieved an AUC value of 0.771 for predicting functional phosphorylation (FuncPhos) sites, displaying reliable improvements. Through a feature selection, the dynamics-based coupling and commute ability show large contributions in discovering PAU sites and FuncPhos sites, suggesting the allosteric propensity for important PTMs. The application of cDL-FuncPhos in three oncoproteins not only corroborates its strong performance in FuncPhos prioritization but also gains insight into the physical basis for the functions. The source code and data set of cDL-PAU and cDL-FuncPhos are available at https://github.com/ComputeSuda/PTM_ML.
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Aprendizado Profundo , Acetilação , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas/químicaRESUMO
Strong intermolecular interactions in 2D organic molecular crystals arising from π-π stacking have been widely explored to achieve high thermal stability, high carrier mobility, and novel physical properties, which have already produced phenomenal progress. However, strong intermolecular interactions in 2D inorganic molecular crystals (2DIMCs) have rarely been investigated, severely limiting both the fundamental research in molecular physics and the potential applications of 2DIMCs for optoelectronics. Here, the effect of strong intermolecular interactions induced by unique short intermolecular Se-Se and P-Se contacts in 2D α-P4Se3 nanoflakes is reported. On the basis of theoretical calculations of the charge density distribution and an analysis of the thermal expansion and plastic-crystal transition, the physical picture of strong intermolecular interactions can be elucidated as a higher charge density between adjacent P4Se3 molecules, arising from an orderly and close packing of P4Se3 molecules. More importantly, encouraged by the strong intermolecular coupling, the in-plane mobility of α-P4Se3 nanoflakes is first calculated with a quantum nuclear tunneling model, and a competitive hole mobility of 0.4 cm2 V-1 s-1 is obtained. Our work sheds new light on the intermolecular interactions in 2D inorganic molecular crystals and is highly significant for promoting the development of molecular physics and optoelectronics.
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OBJECTIVE: To reduce the out-of-threshold (OOT) value of the turnaround time (TAT) of semen samples in the andrology laboratory and improve the clinical diagnosis and patients' satisfaction. METHODS: We retrospectively analyzed the defect rate of TAT of semen samples in the andrology laboratory in the first two quarters of 2018. In the second two quarters, we made a table of countermeasures targeting the causes of the defects using plan-do-check-act (PDCA) circulation and the fishbone diagram drawn with the brainstorm method, followed by supervision of the implementation of the measures and observation of the changes in the OOT value of TAT of semen samples. RESULTS: The OOT rate of TAT of semen samples before seminal examination was significantly lower in the third and fourth than in the first and second quarters of 2018 (0.83% and 0.78% vs 3.43% and 2.07%, P < 0.01), and so was the total OOT rate of TAT (6.36% and 0.87% vs 7.00% and 7.15%, P < 0.01). The median of TAT of semen samples before computer assisted semen analysis was decreased from 22 min in the first to 17 min in the fourth quarter, and the 90th percentile from 54 min to 40 min. The median of total TAT in biochemical analysis was reduced from 387 min in the first to 315 min in the fourth quarter, and the 90th percentile from 1415 min to 1179 min. CONCLUSIONS: The application of PDCA circulation can significantly shorten the turnaround time of semen samples and improve the efficiency of diagnosis and treatment and quality control in the andrology laboratory.
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Andrologia , Humanos , Laboratórios , Estudos Retrospectivos , SêmenRESUMO
Proton-exchange membrane fuel cells, emerging as green and sustainable energy sources, have attracted extensive attention in recent decades. Porous organic polymers, which feature in high surface area values, tunable pore sizes, excellent thermal and chemical stabilities, and the flexibility to incorporate specific functional groups, have recently displayed their striking images as potential electrolytes for fuel cells. In this work, BO-CMP-1 and BO-CMP-2 that possess rich π-structure and permanent porosity and have high thermal and chemical stability were synthesized through Suzuki-Miyaura coupling reaction. Owing to their rigid structures and abundant electrophilic substitution positions, these two novel porous polymers were covalently decorated with dense sulfonic acid groups by postsulfonation, as denoted by SBO-CMP-1 and SBO-CMP-2. The proton conductivity of SBO-CMPs is systematically studied to evaluate their performance as proton-conductive materials. It was found that their performance is highly humidity- and temperature-dependent and they show relatively high proton conductivity. For SBO-CMP-1 and SBO-CMP-2, their proton conductivities are 1.29 × 10-2 and 5.21 × 10-3 S cm-1, respectively, at 70 °C and 100% relative humidity. Low activation energy values of 0.32 eV for SBO-CMP-1 and 0.40 eV for SBO-CMP-2 suggest the Grotthuss mechanism for proton conduction.
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OBJECTIVE: To investigate the application value of pre-implantation genetic screening (PGS) in intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) for infertile patients with high sperm DNA fragmentation index (DFI). METHODS: We selected 90 infertile patients undergoing ICSI-ET in our center from April 2015 to October 2016, 60 with sperm DFI =≥15% and 30 with sperm DFI <15%. Of the 60 cases with sperm DFI =≥15%, 30 received PGS-ICSI (high DFI-PGS group) while the other 30 did not receive PGS (high DFI-ICSI group). The 30 cases with sperm DFI <15% were included in the low DFI-ICSI group. We made comparisons between the high and low DFI-ICSI groups in the rates of normal fertilization, good-quality embryos, blastocyst formation and embryo implantation as well as between the high DFI-PGS and high DFI-ICSI groups in the ages of the males and females, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in the males, sperm concentration, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), sperm DFI, and the rates of sperm nucleoprotein immaturity, normal fertilization, good-quality embryos, blastocyst formation and embryo implantation. RESULTS: Statistically significant differences were found between the high and low DFI-ICSI groups in the rate of embryo implantation (31.25 vs 52.50%, P <0.01) but not in the rates of normal fertilization (ï¼»65.38 ± 24.62ï¼½ vs ï¼»73.00 ± 17.00ï¼½%, P >0.05), good-quality embryos (ï¼»62.41 ± 25.97ï¼½ vs ï¼»73.00 ± 22.10ï¼½%, P >0.05), or blastocyst formation (ï¼»62.55 ± 25.21ï¼½ vs ï¼»64.30 ± 18.60ï¼½%, P >0.05). The rate of embryo implantation was markedly higher in the high DFI-PGS than in the high DFI-ICSI group (60.97% vs 31.25%, P <0.01), but there were no statistically significant differences between the two groups in the ages of the males and females, the levels of FSH, LH and T in the males, sperm concentration, the percentages of PMS and MNS, sperm DFI, sperm nucleoprotein immaturity, or the rates of normal fertilization (ï¼»69.76 ± 15.82ï¼½ vs ï¼»65.38 ± 24.62ï¼½%, P >0.05), good-quality embryos (ï¼»64.42 ± 30.75ï¼½ vs ï¼»62.41 ± 25.97ï¼½%, P >0.05) and blastocyst formation (ï¼»67.53 ± 19.24ï¼½ vs ï¼»62.55 ± 25.21ï¼½%, P >0.05). CONCLUSIONS: For the infertile patients with sperm DFI =≥15%, PGS-ICSI, rather than ICSI alone, can significantly increase the rate of embryo implantation.
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Fragmentação do DNA , Transferência Embrionária , Infertilidade Masculina/genética , Injeções de Esperma Intracitoplásmicas , Adulto , Implantação do Embrião , Desenvolvimento Embrionário , Feminino , Fertilização , Fertilização in vitro , Hormônio Foliculoestimulante/sangue , Testes Genéticos , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/terapia , Hormônio Luteinizante/sangue , Masculino , Nucleoproteínas/análise , Contagem de Espermatozoides , Espermatozoides/química , Testosterona/sangueRESUMO
Recent studies have shown that vapor phase synthesis of structurally isotropic two-dimensional (2D) MoS2 and WS2 produces well-defined domains with clean grain boundaries (GBs). This is anticipated to be vastly different for 2D anisotropic materials like ReS2 mainly due to large anisotropy in interfacial energy imposed by its distorted 1T crystal structure and formation of signature Re-chains along [010] b-axis direction. Here, we provide first insight on domain architecture on chemical vapor deposited (CVD) ReS2 domains using high-resolution scanning transmission electron microscopy, angle-resolved nano-Raman spectroscopy, reflectivity, and atomic force microscopy measurements. Results provide ways to achieve crystalline anisotropy in CVD ReS2, establish domain architecture of high symmetry ReS2 flakes, and determine Re-chain orientation within subdomains. Results also provide a first atomic resolution look at ReS2 GBs, and surprisingly we find that cluster and vacancy defects, formed by collusion of Re-chains at the GBs, dramatically impact the crystal structure by changing the Re-chain direction and rotating Re-chains 180° along their b-axis. Overall results not only shed first light on domain architecture and structure of anisotropic 2D systems but also allow one to attain much desired crystalline anisotropy in CVD grown ReS2 for the first time for tangible applications in photonics and optoelectronics where direction-dependent dichroic and linearly polarized material properties are required.
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OBJECTIVE: To investigate the routine semen parameters and sperm morphological indexes of the patients with partial globozoospermia (PGZ). METHODS: We included in this study 100 infertile males with PGZ and another 180 non-PGZ infertile men as controls. According to the proportion of round-headed sperm (RHS) in the semen, we classified the PGZ males into five subgroups: 25%ï¼40%, 41%ï¼55%, 56%ï¼70%, 71%ï¼85%, and 86%ï¼99% RHS. We obtained sperm concentration, total sperm motility, the percentage of progressively motile sperm, teratozoospermia index (TZI), and sperm deformity index (SDI) from the subjects and compared them among different groups. RESULTS: Statistically significant differences were found between the PGZ patients and non-PGZ controls in total sperm motility (ï¼»35.76±24.88ï¼½% vs ï¼»62.03±10.20ï¼½%, P<0.01), the percentage of progressively motile sperm (ï¼»26.11±20.39ï¼½% vs ï¼»45.62±6.87ï¼½%, P<0.01), the percentage of morphologically normal sperm (ï¼»1.45±1.45ï¼½% vs ï¼»5.98±2.21ï¼½%, P<0.01), and SDI (1.33±0.11 vs 1.27±0.57, P<0.01), but not in age (ï¼»29.82±4.90ï¼½ vs ï¼»30.33±3.59 ï¼½ yr, P>0.05), sperm concentration (ï¼»46.01±40.38ï¼½ vs ï¼»54.00±25.15ï¼½ ×106/ml, P>0.05), or TZI (1.35±0.11 vs 1.34±0.54, P>0.05). There were also significant differences among the five PGZ subgroups in total sperm motility, progressive sperm motility, normal sperm morphology, TZI, and SDI (P<0.01), but not in age or sperm concentration (P>0.05). Morphologically, the sperm head changed from heterogeneous to homogeneous with the increased proportion of round-headed sperm. CONCLUSIONS: Different proportions of round-headed sperm are closely related to routine semen parameters and sperm morphological index in PGZ patients, which can help clinicians choose the proper assisted reproductive technology and predict the rate of fertilization for infertile males.
Assuntos
Infertilidade Masculina/patologia , Cabeça do Espermatozoide/patologia , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Teratozoospermia/patologia , Estudos de Casos e Controles , Humanos , Masculino , Análise do Sêmen , Contagem de EspermatozoidesRESUMO
Both natural and synthetic brominated furanones are known to inhibit biofilm formation by bacteria, but their toxicity to mammalian cells is often not reported. Here, we designed and synthesized a new class of brominated furanones (BBFs) that contained a bicyclic structure having one bromide group with well-defined regiochemistry. This class of molecules exhibited reduction in the toxicity to mammalian cells (human neuroblastoma SK-N-SH) and did not inhibit bacteria (Pseudomonas aeruginosa and Escherichia coli) growth, but retained the inhibitory activity towards biofilm formation of bacteria. In addition, all the BBFs inhibited the production of virulence factor elastase B in P. aeruginosa. To explore the effect of BBFs on quorum sensing, we used a reporter gene assay and found that 6-BBF and 7-BBF exhibited antagonistic activities for LasR protein in the lasI quorum sensing circuit, while 5-BBF showed agonistic activity for the rhlI quorum sensing circuit. This study suggests that structural variation of brominated furanones can be designed for targeted functions to control biofilm formation.