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Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking immunotherapy for cancer. However, the intricate and costly manufacturing process remains a hurdle. Improving the transduction rate is a potential avenue to cut down costs and boost therapeutic efficiency. Peptide nanofibrils (PNFs) serve as one such class of transduction enhancers. PNFs bind to negatively charged virions, facilitating their active engagement by cellular protrusions, which enhances virion attachment to cells, leading to increased cellular entry and gene transfer rates. While first-generation PNFs had issues with aggregate formation and potential immunogenicity, our study utilized in silico screening to identify short, endogenous, and non-immunogenic peptides capable of enhancing transduction. This led to the discovery of an 8-mer peptide, RM-8, which forms PNFs that effectively boost T cell transduction rates by various retroviral vectors. A subsequent structure-activity relationship (SAR) analysis refined RM-8, resulting in the D4 derivative. D4 peptide is stable and assembles into smaller PNFs, avoiding large aggregate formation, and demonstrates superior transduction rates in primary T and NK cells. In essence, D4 PNFs present an economical and straightforward nanotechnological tool, ideal for refining ex vivo gene transfer in CAR-T cell production and potentially other advanced therapeutic applications.

The respiratory tract is a major entry site for microbial pathogens. To combat bacterial infections, the immune system has various defense mechanisms at its disposal, including antimicrobial peptides (AMPs). To search for novel AMPs from the respiratory tract, a peptide library from human broncho-alveolar-lavage (BAL) fluid was screened for antimicrobial activity by radial diffusion assays allowing the efficient detection of antibacterial activity within a small sample size. After repeated testing-cycles and subsequent purification, we identified ß-2-microglobulin (B2M) in antibacterially active fractions. B2M belongs to the MHC-1 receptor complex present at the surface of nucleated cells. It is known to inhibit the growth of Listeria monocytogenes and Escherichia coli and to facilitate phagocytosis of Staphylococcus aureus. Using commercially available B2M we confirmed a dose-dependent inhibition of Pseudomonas aeruginosa and L. monocytogenes. To characterize AMP activity within the B2M sequence, peptide fragments of the molecule were tested for antimicrobial activity. Activity could be localized to the C-terminal part of B2M. Investigating pH dependency of the antimicrobial activity of B2M demonstrated an increased activity at pH values of 5.5 and below, a hallmark of infection and inflammation. Sytox green uptake into bacterial cells following the exposure to B2M was determined and revealed a pH-dependent loss of bacterial membrane integrity. TEM analysis showed areas of disrupted bacterial membranes in L. monocytogenes incubated with B2M and high amounts of lysed bacterial cells. In conclusion, B2M as part of a ubiquitous cell surface complex may represent a potent antimicrobial agent by interfering with bacterial membrane integrity.

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.

Change in freshwater availability is arguably one of the most pressing issues associated with global change. Agriculture, which uses roughly 70% of the total global freshwater supply, figures prominently among sectors that may be adversely affected by global change. Of specific concern are small-scale agricultural systems that make up nearly 90% of all farming systems and generate 40% of agricultural output worldwide. These systems are experiencing a range of novel shocks, including increased variability in precipitation and competing demands for water and labor that challenge their capacity to maintain agricultural output. This paper employs a robustness-vulnerability trade-off framework to explore the capacity of these small-scale systems to cope with novel shocks and directed change. Motivated by the Pumpa Irrigation System in Nepal, we develop and analyze a simple model of rice-paddy irrigation and use it to demonstrate how institutional arrangements may, in becoming very well tuned to cope with specific shocks and manage particular human interactions associated with irrigated agriculture, generate vulnerabilities to novel shocks. This characterization of robustness-vulnerability trade-off relationships is then used to inform policy options to improve the capacity of small-scale irrigation systems to adapt to changes in freshwater availability.

IFITM proteins can inhibit several viruses, but effects on SARS-CoV-2 infection are not well understood. Here, the authors show that endogenous IFITMs support SARS-CoV-2 infection in different in vitro models by binding spike and enhancing virus entry.

Tradicionalmente se han utilizado algunos índices antropométricos para el diagnóstico de exceso de peso en niños y adolescentes que han mostrado algunas desventajas por lo que se han postulado otros indicadores. En ese sentido, se plantea estimar el nivel de asociación entre indicadores antropométricos y la presencia de dislipidemia en adolescentes y adultos jóvenes. Se realizó una investigación observacional, descriptiva y de corte transversal en 123 adolescentes (68,2% mujeres, edad promedio 14,5 años) y 122 adultos jóvenes (70,5% mujeres, edad promedio 21 años) de la ciudad de Caracas. Se calcularon Índices de Masa Corporal (IMC), Índice Cintura–Talla (ICT), Índice de Masa Corporal Abdominal (IMCA) e Índice de Masa Tri-Ponderal (IMT). Se obtuvo una muestra de sangre por punción venosa, en ayuno de 12 a 14 horas, a partir de la cual se cuantificó Colesterol Total, Lipoproteína de alta densidad y Triglicéridos. Se calculó la concentración de Lipoproteína de baja densidad por la fórmula de Friedewald, así como el índice LDL-C/HDL-C y el índice LogTg/HDL. Para el análisis e interpretación de los datos se utilizó estadística descriptiva univariante y multivariante. Los resultados revelaron que los índices antropométricos IMCA e IMT no mostraron mejor desempeño en predecir dislipidemia que los indicadores IMC, Circunferencia de Cintura (CC) e ICT en adolescentes y adultos jóvenes. Los indicadores antropométricos de adiposidad abdominal, CC e ICT, tendieron a presentar mayores OR, ABC, sensibilidad y especificidad independientemente del grupo de estudio. En general, la capacidad de los indicadores antropométricos evaluados en predecir la presencia de dislipidemia en adultos jóvenes fue adecuada, situación que no se presentó en los adolescentes.

Tuberculosis is a highly prevalent infectious disease with more than 1.5 million fatalities each year. Antibiotic treatment is available, but intolerable side effects and an increasing rate of drug-resistant strains of Mycobacterium tuberculosis (Mtb) may hamper successful outcomes. Antimicrobial peptides (AMPs) offer an alternative strategy for treatment of infectious diseases in which conventional antibiotic treatment fails. Human serum is a rich resource for endogenous AMPs. Therefore, we screened a library generated from hemofiltrate for activity against Mtb. Taking this unbiased approach, we identified Angiogenin as the single compound in an active fraction. The antimicrobial activity of endogenous Angiogenin against extracellular Mtb could be reproduced by synthetic Angiogenin. Using computational analysis, we identified the hypothetical active site and optimized the lytic activity by amino acid exchanges. The resulting peptide-Angie1-limited the growth of extra‐ and intracellular Mtb and the fast-growing pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Toward our long-term goal of evaluating Angie1 for therapeutic efficacy in vivo, we demonstrate that the peptide can be efficiently delivered into human macrophages via liposomes and is not toxic for zebrafish embryos. Taken together, we define Angiogenin as a novel endogenous AMP and derive the small, bioactive fragment Angie1, which is ready to be tested for therapeutic activity in animal models of tuberculosis and infections with fast-growing bacterial pathogens.

The placenta acts as physical and immunological barrier against the transmission of viruses and bacteria from mother to fetus. However, the specific mechanisms by which the placenta protects the developing fetus from viral and bacterial pathogens are poorly understood. To identify placental peptides and small proteins protecting from viral and bacterial infections, we generated a peptide library from 10 kg placenta by chromatographic means. Screening the resulting 250 fractions against Herpes-Simplex-Virus 2 (HSV-2), which is rarely transmitted through the placenta, in a cell-based system identified two adjacent fractions with significant antiviral activity. Further rounds of chromatographic purification and anti-HSV-2 testing allowed to purify the bioactive peptide. Mass spectrometry revealed the presence of a 36-mer derived from the C-terminal region of the hemoglobin β subunit. The purified and corresponding chemically synthesized peptide, termed HBB(112–147), inhibited HSV-2 infection in a dose-dependent manner, with a mean IC50 in the median μg/ml range. Full-length hemoglobin tetramer had no antiviral activity. HBB(112–147) did not impair infectivity by direct targeting of the virions but prevented HSV-2 infection at the cell entry level. The peptide was inactive against Human Immunodeficiency Virus Type 1, Rubella and Zika virus infection, suggesting a specific anti-HSV-2 mechanism. Notably, HBB(112–147) has previously been identified as broad-spectrum antibacterial agent. It is abundant in placenta, reaching concentrations between 280 and 740 μg/ml, that are well sufficient to inhibit HSV-2 and prototype Gram-positive and -negative bacteria. We here additionally show, that HBB(112–147) also acts potently against Pseudomonas aeruginosa strains (including a multi-drug resistant strain) in a dose dependent manner, while full-length hemoglobin is inactive. Interestingly, the antibacterial activity of HBB(112–147) was increased under acidic conditions, a hallmark of infection and inflammatory conditions. Indeed, we found that HBB(112–147) is released from the hemoglobin precursor by Cathepsin D and Napsin A, acidic proteases highly expressed in placental and other tissues. We propose that upon viral or bacterial infection, the abundant hemoglobin precursor is proteolytically processed to release HBB(112–147), a broadly active antimicrobial innate immune defense peptide.

Antimicrobial peptides (AMPs) are widespread in multicellular organisms. These structurally diverse molecules are produced as the first line of defense against pathogens such as bacteria, viruses, fungi, and parasites. Also known as host defense peptides in higher eukaryotic organisms, AMPs display immunomodulatory and anticancer activities. During the last 30 years, technological advances have boosted the research on antimicrobial peptides, which have also attracted great interest as an alternative to tackling the antimicrobial resistance scenario mainly provoked by some bacterial and fungal pathogens. However, the introduction of natural AMPs in clinical trials faces challenges such as proteolytic digestion, short half-lives, and cytotoxicity upon systemic and oral application. Therefore, some strategies have been implemented to improve the properties of AMPs aiming to be used as effective therapeutic agents. In the present review, we summarize the discovery path of AMPs, focusing on preclinical development, recent advances in chemical optimization and peptide delivery systems, and their introduction into the market.

Context: Naringin (NRG) is the major flavonoid (flavanone glycoside) in grapefruit juice. Its biological activity has been only partially characterized and little is known about the mechanism of the negative inotropic action of this flavonoid. Aims: To evaluate the effects of NRG on the surface electrogram (ECG) and the force of contraction (FC) of mice hearts as well as on the sodium (INa), calcium (ICaL) and Na+ – Ca2+ exchange (INaCaX) currents of enzymatically isolated mouse ventricular cardiomyocytes. Methods: ECG and FC were recorded on mouse hearts perfused in a Langendorff column. Ventricular cardiomyocytes were enzimatically dissociated and ionic currents recorded with the patch-clamp technique. Results: NRG increased RR interval and shortened corrected QT only at high concentrations (30-100 µM). However, at a fixed heart rate, it decreased FC with an IC50 of 0.4 µM. NRG reduced INa with an IC50 of 0.07 µM but with a maximal inhibition of 60 %. NRG also depressed ICaL with an IC50 of 0.013 µM and increased its fast inactivation time constant. The effects on ICaL were not voltage-dependent. INaCaX was not affected by NRG. Conclusions: Our results indicate that NRG exerts a negative inotropic effect in mice hearts that could be explained by a decrease in INa and ICaL. These actions should be taken into account when considering this molecule either as a dietetic supplement or as a template to develop therapeutic agents for human diseases.

In this contribution the stability properties and regulation of a class of convective systems described by first order hyperbolic partial differential equations with boundary recycle is studied. The system’s setting is consistent with the first and second laws of thermodynamics, allowing to use the entropy functional as a storage function and the internal entropy production as the dissipation similarly to Hamiltonian systems, usually not well defined for systems with mass flows. It is found that the difference of the entropy evaluated at the boundaries is directly proportional to the supply rate, fulfilling the dissipation inequality. Furthermore, the dynamics of the entropy balance allow to define a saturated Proportional-Integral controller with a cascade structure: The inner loop tracks an entropy reference, while the outer loop regulates a process variable. The regulation is achieved with a lumped actuator, using continuous measurements at the boundaries. The controller is applied to an adiabatic plug flow reactor with a recycle of the output stream, a configuration known to be potentially unstable with dissociation reactions. Finally, the controller is tested to track a set point facing several disturbances using the recycle rate as the control variable.

Despite the dominance of the Caribbean as the leading cruise destination in the world, research that focuses on the network of cruise ports in the region is limited. To fill this research gap, the current study carried out social network analysis (SNA) to inquire into cruise port interconnections and their influence on the operation of the entire Caribbean port network. The results are summarized as follows: First, in terms of connections among ports linked to the Caribbean region, a European port and a Southampton harbor exhibit the most significant in-degree and out-degree centrality. Nevertheless, ports within the Caribbean region are still significantly represented as regards both indexes. Second, in the matter of port influence, Caribbean ports are considerably the most important with respect to hub and authority centrality (HAC), especially those located in Florida and the eastern Caribbean. This research contributes to industry through its presentation of an extended panorama of the cruise network in the region, subjecting several ports to respective analyses that describe their principal characteristics and attractiveness in the industry.

El presente artículo se deriva de un proceso de investigación adelantado para optar por el título de doctor en educación, en este texto se presentan una serie de elementos que influyen en el proyecto de vida de estudiantes que se forman desde la básica secundaria para ser maestros en el sector rural. El objetivo de esta pesquisa gira en torno a la concepción de maestro como uno de los muchos significados que emergen del discurso de los estudiantes y que es un eje crucial en la continuidad de los mismos en los estudios de licenciatura y formación inicial de maestros. Por lo anterior, los participantes fueron 4 estudiantes por cada nivel de formación desde la básica secundaria, la media y el Programa de Formación Complementaria. Se empleó una metodología cualitativa desde un alcance exploratorio y descriptivo, a través del análisis del discurso y el grupo focal. Entre los hallazgos se resaltan las intersubjetividades que se dan en las vivencias del estudiantado y la metamorfosis que sufren como futuros maestros a partir de la práctica pedagógica investigativa; por lo anterior, se logró evidenciar una serie de coyunturas que se movilizan a nivel histórico, social y cultural, y que determinan en gran medida que los estudiantes que se forman en estas instituciones formadoras de maestros desde la básica ya no quieran serlo cuando terminan sus estudios en la escuela, dejando al descubierto la necesidad de transformar la imagen del maestro como individuo y ser social en toda su diversidad.

A Mg-based composite material has been produced by the consolidation at room temperature of a Mg-5wt.% Ni-2wt.% Nb2O5 powder mixture subjected to high-pressure torsion (HPT), one of the processing methods to induce severe plastic deformations. The microstructure, density, and microhardness of the consolidated disks were characterized after the application of up to 30 revolutions in torsion under compression stresses of 3 and 5 GPa. According to the density measurements, the composite was consolidated in full after the application of five revolutions, although disks subjected to only one revolution exhibited densities close to the maximum measured value. On the other hand, grain size and microhardness measurements showed that differences existed at locations near the center and the periphery of the HPT-processed disks. Under the stress of 5 GPa, the grain size in the central regions stabilized at about 0.35 μm after five revolutions, while at the peripherical regions it gradually decreased with an increasing number of revolutions down to about 0.15 μm after 30 revolutions. In turn, the microhardness measured along a diametral cross section steadily increased with the number of revolutions between 1 and 10 revolutions, maintaining a gradient from the center to the periphery in all cases. With the application of 20 and 30 revolutions, only the peripheral regions increased considerably in hardness. It was discovered that the magnesium particles in the initial powder mixture had formed an oxide—hydroxide surface layer, which changed the expected final density of the consolidated material by about 2 to 4.5%. This superficial contamination of the Mg powders did not prevent the material from achieving full consolidation.

The toxigenic conversion of Escherichia coli strains by Shiga toxin-converting (Stx) bacteriophages were prominent and recurring events in the stepwise evolution of enterohemorrhagic E. coli (EHEC) O157:H7 from an enteropathogenic (EPEC) O55:H7 ancestor. Atypical, attenuated isolates have been described for both non-sorbitol fermenting (NSF) O157:H7 and SF O157:NM serotypes, which are distinguished by the absence of Stx, the characteristic virulence hallmark of Stx-producing E. coli (STEC). Such atypical isolates either never acquired Stx-phages or may have secondarily lost stx during the course of infection, isolation, or routine subculture; the latter are commonly referred to as LST (Lost Shiga Toxin)-isolates. In this study we analyzed the genomes of 15 NSF O157:H7 and SF O157:NM strains from North America, Europe, and Asia that are characterized by the absence of stx, the virulence hallmark of STEC. The individual genomic basis of the Stx (−) phenotype has remained largely undetermined as the majority of STEC genomes in public genome repositories were generated using short read technology and are in draft stage, posing a major obstacle for the high-resolution whole genome sequence typing (WGST). The application of LRT (long-read technology) sequencing provided us with closed genomes, which proved critical to put the atypical non-shigatoxigenic NSF O157:H7 and SF O157:NM strains into the phylogenomic context of the stepwise evolutionary model. Availability of closed chromosomes for representative Stx (−) NSF O157:H7 and SF O157:NM strains allowed to describe the genomic basis and individual evolutionary trajectories underlying the absence of Stx at high accuracy and resolution. The ability of LRT to recover and accurately assemble plasmids revealed a strong correlation between the strains’ featured plasmid genotype and chromosomally inferred clade, which suggests the coevolution of the chromosome and accessory plasmids. The identified ancestral traits in the pSFO157 plasmid of NSF O157:H7 strain LSU-61 provided additional evidence for its intermediate status. Taken together, these observations highlight the utility of LRTs for advancing our understanding of EHEC O157:H7/NM pathogenome evolution. Insights into the genomic and phenotypic plasticity of STEC on a lineage- and genome-wide scale are foundational to improve and inform risk assessment, biosurveillance, and prevention strategies.

El desarrollo de aplicaciones web ha alcanzado gran popularidad a lo largo del mundo. Disímiles son las aplicaciones que se realizan que responden a la solución de diversos problemas sociales. En la búsqueda de visiones y soluciones globales, en los últimos años se ha popularizado el concepto de Experiencia de Usuario o Diseño de Experiencias de Usuario. Una de las disciplinas que integran este concepto es el Diseño Emocional el cual aborda que el producto puede evocar emociones de forma explícita, expresando afecto; o implícita, a través de su estética. Todo producto intenta emular estados afectivos con la intención de modelar así los estados afectivos o emocionales del usuario. En el presente trabajo se evidencia un estudio preliminar desarrollado en la investigación en curso con el propósito de demostrar la necesidad de incluir en el proceso de desarrollo de aplicaciones web del centro de Geoinformática y Señales Digitales una estrategia basada en el diseño emocional.

O objetivo do trabalho foi identificar métodos para superar a dormência e promover a germinação de sementes de Stryphnodendron adstringens e Stryphnodendron polyphyllum. Sementes de ambas as espécies foram submetidas aos seguintes tratamentos desuperação de dormência: testemunha, escarificação mecânica (lixa número 220), H2O quente (temperatura inicial de 87oC) por 5 e por 15 minutos, escarificação química com H2SO4 (95%) por 30, 45, 60, 75, 90 e 105 minutos, choque térmico 1 (0oC e 50% UR por 1h e após imersão em água por 10 min. Ti=85oC Tf=57oC), choque térmico 2 (40oC e 40%UR por 6 h e após imersão em água por 10 min. Ti=0oC Tf=3oC), choque térmico 3 (40oC e 40% UR por 6h e após imersão em água por 10 min Ti=25oC Tf=25oC). Conclui-se que sementes pertencentes ao mesmo gênero, mas de espécies diferentes, respondem de forma diversa a alguns tratamentos de superação de dormência. Para ambas as espécies, a escarificação das sementes com H2SO4 (45 minutos) ou lixa são métodos que podem ser utilizados com máxima eficiência para a superação da dormência e promoção da germinação.The aim of this research was to identify methods for breaking dormancy and promoting germination of Stryphnodendron adstringens and S. polyphyllum seeds. Seeds of both species were submitted to the following treatments for breaking dormancy: control; mechanical scarification (sandpaper number 220); hot water (initial temperature of 87°C) for 5 and 15 minutes; chemical scarification with H2SO4 (95%) for 30, 45, 60, 75, 90 and 105 minutes; thermalshock 1 (0°C and 50% RH for 1 h and thereafter 10 minutes into water Ti=85°C, Tf=57°C); thermic shock 2 (40°C and 40% RH for 6 h and thereafter 10 minutes into water, Ti=0°C, Tf=3°C); thermal shock 3 (40°C and 40% RH for 6h and thereafter 10 minutes into water, Ti=25°C, Tf=25°C). We concluded that seeds belonging to samegenus but from different species answered differently to some treatments for breaking dormancy. Chemical scarification with H2SO4 (45 minutes) and mechanical scarification with sandpaper are methods that can be employed with efficiency to break dormancy and promote germination for both species.

The GENESIS simulation platform was one of the first broad-scale modeling systems in computational biology to encourage modelers to develop and share model features and components. Supported by a large developer community, it participated in innovative simulator technologies such as benchmarking, parallelization, and declarative model specification and was the first neural simulator to define bindings for the Python scripting language. An important feature of the latest version of GENESIS is that it decomposes into self-contained software components complying with the Computational Biology Initiative federated software architecture. This architecture allows separate scripting bindings to be defined for different necessary components of the simulator, e.g., the mathematical solvers and graphical user interface. Python is a scripting language that provides rich sets of freely available open source libraries. With clean dynamic object-oriented designs, they produce highly readable code and are widely employed in specialized areas of software component integration. We employ a simplified wrapper and interface generator to examine an application programming interface and make it available to a given scripting language. This allows independent software components to be 'glued' together and connected to external libraries and applications from user-defined Python or Perl scripts. We illustrate our approach with three examples of Python scripting. (1) Generate and run a simple single-compartment model neuron connected to a stand-alone mathematical solver. (2) Interface a mathematical solver with GENESIS 3.0 to explore a neuron morphology from either an interactive command-line or graphical user interface. (3) Apply scripting bindings to connect the GENESIS 3.0 simulator to external graphical libraries and an open source three dimensional content creation suite that supports visualization of models based on electron microscopy and their conversion to computational models. Employed in this way, the stand-alone software components of the GENESIS 3.0 simulator provide a framework for progressive federated software development in computational neuroscience.

O objetivo do trabalho foi identificar métodos para superar a dormência e promover a germinação de sementes de Stryphnodendron adstringens e Stryphnodendron polyphyllum. Sementes de ambas as espécies foram submetidas aos seguintes tratamentos de superação de dormência: testemunha, escarificação mecânica (lixa número 220), H2O quente (temperatura inicial de 87ºC) por 5 e por 15 minutos, escarificação química com H2SO4 (95%) por 30, 45, 60, 75, 90 e 105 minutos, choque térmico 1 (0ºC e 50%UR por 1h e após imersão em água por 10 min Ti=85oC Tf=57oC), choque térmico 2 (40ºC e 40%UR por 6h e após imersão em água por 10 min Ti=0ºC Tf=3ºC), choque térmico 3 (40ºC e 40%UR por 6h e após imersão em água por 10 min Ti=25ºC Tf=25ºC). Conclui-se que sementes pertencentes ao mesmo gênero, mas de espécies diferentes, respondem de forma diversa a alguns tratamentos de superação de dormência. Para ambas as espécies, a escarificação das sementes com H2SO4 (45 minutos) ou lixa são métodos que podem ser utilizados com máxima eficiência para a superação da dormência e promoção da germinação.

The aqueous zinc-sulfur battery holds promise for significant capacity and energy density with low cost and safe operation based on environmentally benign materials. However, it suffers from the sluggish kinetics of the conversion reaction. Here, we highlight the efficacy of molybdenum(IV) sulfide (MoS 2 ) to reduce the overpotential of S-ZnS conversion in aqueous electrolytes and study the discharge products formed at the solid-solid and solid-liquid interfaces using experimental and theoretical approaches. Specifically, the MoS 2 -catalyzed electrochemical conversion reaction is characterized via ex situ X-ray diffraction (XRD), transmission electron microscopy (TEM) with energy dispersive spectroscopy (EDS), Raman spectroscopy, synchrotron-based Mo K -edge X-ray absorption spectroscopy (XAS), and in situ synchrotron-based X-ray computed tomography (XCT). Additionally, operando synchrotron-based S K -edge XAS and X-ray fluorescence (XRF) maps are collected to determine the spatial evolution of sulfur-based species at the electrode-electrolyte interface. Coupling the operando S K -edge XAS data with the simulated spectra and fitting the data suggested a possible ZnS 2 intermediate phase.

Anemia is a health problem of concern among schoolchildren in underprivileged rural regions, where recurrent parasitic infections are common. A cross-sectional study was conducted in 229 schoolchildren in rural highland Bolivia in the department of La Paz, an area with a high prevalence of protozoan and helminth infections, to determine the types and mechanisms of anemia. A substantial proportion of children (40.2%) were found to be anemic based on hemoglobin measurements. No associations were found between low hemoglobin levels and helminth or protozoan infections when evaluating infectious causes of anemia, nor with Giardia lamblia or Blastocystis hominis , which are associated with iron deficiency and nutrient malabsorption and were highly prevalent in this study. The significant association between anemia and hypochromia suggests iron deficiency, aligned with low hemoglobin levels. A total of 39 out of 150 children (26%) had markers consistent with iron deficiency anemia (IDA), 26 out of 127 children (20%) met the criteria for anemia of inflammation (AI). Furthermore, 12 of the 127 tested children (9.4%) met the criteria for mixed AI with IDA according to the soluble transferrin receptor (sTfR)/log ferritin levels, which increased significantly due to overall infections by Hymenolepis nana and Ascaris lumbricoides helminths. The findings highlight the need for integrated public health interventions to address iron nutrition and parasitic infections to effectively prevent anemia in this vulnerable population.

Envenomation by reptile venom, particularly from lizards, poses significant health risks and can lead to physiological and cardiovascular changes. The venom of Heloderma horridum horridum, endemic to Colima, Mexico, was tested on Wistar rats. Electrocardiographic (ECG) data were collected pre-treatment and at 5-min intervals for 1 h post-envenomation. A specially designed computational linear regression algorithm (LRA) was used for the segmentation analysis of the ECG data to improve the detection of fiducial points (P, Q, R, S, and T) in ECG waves. Additionally, heart tissue was analyzed for macroscopic and microscopic changes. The results revealed significant electrocardiographic alterations, including pacemaker migration, junctional extrasystoles, and intraventricular conduction aberrations. By applying a linear regression algorithm, the study compensated for noise and anomalies in the isoelectric line in an ECG signal, improving the detection of P and T waves and the QRS complex with an efficiency of 97.5%. Cardiac enzyme evaluation indicated no statistically significant differences between the control and experimental groups. Macroscopic and microscopic examination revealed no apparent signs of damage or inflammatory responses in heart tissues. This study enhances our understanding of the cardiovascular impact of Heloderma venom, suggesting a greater influence on changes in conduction and arrhythmias than on direct cardiac damage to the myocardium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Layered lithiated oxides are promising materials for next generation Li-ion battery cathode materials; however, instability during cycling results in poor performance over time compared to the high capacities theoretically possible with these materials. Here we report the characterizations of a Li 1.47 Mn 0.57 Al 0.13 Fe 0.095 Co 0.105 Ni 0.095 O 2.49 high-entropy layered oxide (HELO) with the Li 2 MO 3 structure where M = Mn, Al, Fe, Co, and Ni. Using electron microscopy and X-ray spectroscopy, we identify a homogeneous Li 2 MO 3 structure stabilized by the entropic contribution of oxygen vacancies. This defect-driven entropy would not be attainable in the LiMO 2 structure sometimes observed in similar materials as a secondary phase owing to the presence of fewer O sites and a 3+ oxidation state for the metal site; instead, a Li 2-γ MO 3-δ is produced. Beyond Li 2 MO 3 , this defect-driven entropy approach to stabilizing novel compositions and phases can be applied to a wide array of future cathode materials including spinel and rock salt structures.

Endogenous antimicrobial peptides (AMPs) play a key role in the host defense against pathogens. AMPs attack pathogens preferentially at the site of entry to prevent invasive infection. Mycobacterium tuberculosis (Mtb) enters its host via the airways. AMPs released into the airways are therefore likely candidates to contribute to the clearance of Mtb immediately after infection. Since lysozyme is detectable in airway secretions, we evaluated its antimicrobial activity against Mtb. We demonstrate that lysozyme inhibits the growth of extracellular Mtb, including isoniazid-resistant strains. Lysozyme also inhibited the growth of non-tuberculous mycobacteria. Even though lysozyme entered Mtb-infected human macrophages and co-localized with the pathogen we did not observe antimicrobial activity. This observation was unlikely related to the large size of lysozyme (14.74 kDa) because a smaller lysozyme-derived peptide also co-localized with Mtb without affecting the viability. To evaluate whether the activity of lysozyme against extracellular Mtb could be relevant in vivo, we incubated Mtb with fractions of human serum and screened for antimicrobial activity. After several rounds of sub-fractionation, we identified a highly active fraction-component as lysozyme by mass spectrometry. In summary, our results identify lysozyme as an antimycobacterial protein that is detectable as an active compound in human serum. Our results demonstrate that the activity of AMPs against extracellular bacilli does not predict efficacy against intracellular pathogens despite co-localization within the macrophage. Ongoing experiments are designed to unravel peptide modifications that occur in the intracellular space and interfere with the deleterious activity of lysozyme in the extracellular environment., (© 2024. The Author(s).)

In this work, optical fiber Bragg grating sensors were used to measure water velocity and examine how it was distributed in open channels. Several types of coatings were incorporated into the design of the sensors to examine their effects on the strain that the fibers experienced as a result of the water flow. Due to their low elastic coefficient, which reduced the hysteresis, the results indicated that the aluminum- and acrylate-coated fibers had the best performance. ANSYS-CFX V2020 R2 software was used to model the strain encountered by the fibers under various flow rates to assess the performance of the FBG sensors. The calculations and actual data exhibited good convergence, demonstrating the accuracy of the FBG sensors in determining water velocity. The study illustrated the usability of the proposal in both scenarios by contrasting its application in rivers and channels., (© 2024. The Author(s).)

Introduction: In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction., Material and Methods: Plasma materials enriched to hemadsorption filters (CytoSorb ® ) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry., Results: Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage., Conclusion: Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin - cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kasper, Rodriguez-Alfonso, Ständker, Wiese and Schneider.)

The diminishing portfolio of mankind's available antibiotics urges science to develop novel potent drugs. Here, we present a peptide fitting the typical blueprint of amphipathic and membrane-active antimicrobial peptides, denominated C14R. This 2 kDa peptide consists of 16 amino acid residues, with seven being either hydrophobic, aromatic, or non-polar, and nine being polar or positively charged, strictly separated on opposite sides of the predicted α-helix. The affinity of the peptide C14R to P. aeruginosa membranes and its intrinsic tendency to productively insert into membranes of such composition were analyzed by dynamic simulations. Its biological impact on the viability of two different P. aeruginosa reference strains was demonstrated by determining the minimal inhibitory concentrations (MICs), which were found to be in the range of 10-15 µg/mL. C14R's pore-forming capability was verified in a permeabilization assay based on the peptide-triggered uptake of fluorescent dyes into the bacterial cells. Finally, the peptide was used in radial diffusion assays, which are commonly used for susceptibility testing of antimicrobial peptides in clinical microbiology. In comparison to reference strains, six clinical P. aeruginosa isolates were clearly affected, thereby paving the way for further in-depth analyses of C14R as a promising new AMP drug in the future.

Semen is an important vector for sexual HIV-1 transmission. Although CXCR4-tropic (X4) HIV-1 may be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 causes systemic infection after sexual intercourse. To identify factors that may limit sexual X4-HIV-1 transmission, we generated a seminal fluid-derived compound library and screened it for antiviral agents. We identified four adjacent fractions that blocked X4-HIV-1 but not R5-HIV-1 and found that they all contained spermine and spermidine, abundant polyamines in semen. We showed that spermine, which is present in semen at concentrations up to 14 mM, binds CXCR4 and selectively inhibits cell-free and cell-associated X4-HIV-1 infection of cell lines and primary target cells at micromolar concentrations. Our findings suggest that seminal spermine restricts sexual X4-HIV-1 transmission.

Here we present for the first time a potential wound dressing material implementing aptamers as binding entities to remove pathogenic cells from newly contaminated surfaces of wound matrix-mimicking collagen gels. The model pathogen in this study was the Gram-negative opportunistic bacterium Pseudomonas aeruginosa , which represents a considerable health threat in hospital environments as a cause of severe infections of burn or post-surgery wounds. A two-layered hydrogel composite material was constructed based on an established eight-membered focused anti- P. aeruginosa polyclonal aptamer library, which was chemically crosslinked to the material surface to form a trapping zone for efficient binding of the pathogen. A drug-loaded zone of the composite released the C14R antimicrobial peptide to deliver it directly to the bound pathogenic cells. We demonstrate that this material combining aptamer-mediated affinity and peptide-dependent pathogen eradication can quantitatively remove bacterial cells from the "wound" surface, and we show that the surface-trapped bacteria are completely killed. The drug delivery function of the composite thus represents an extra safeguarding property and thus probably one of the most important additional advances of a next-generation or smart wound dressing ensuring the complete removal and/or eradication of the pathogen of a freshly infected wound.

Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor . A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa . The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae , Listeria monocytogenes and Mycobacterium tuberculosis . On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans , Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor -derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.

An internet protocol (IP) address is the foundation of the Internet, allowing connectivity between people, servers, Internet of Things, and services across the globe. Knowing what is connecting to what and where connections are initiated is crucial to accurately assess a company's or individual's security posture. IP reputation assessment can be quite complex because of the numerous services that may be hosted on that IP address. For example, an IP might be serving millions of websites from millions of different companies like web hosting companies often do, or it could be a large email system sending and receiving emails for millions of independent entities. The heterogeneous nature of an IP address typically makes it challenging to interpret the security risk. To make matters worse, adversaries understand this complexity and leverage the ambiguous nature of the IP reputation to exploit further unsuspecting Internet users or devices connected to the Internet. In addition, traditional techniques like dirty-listing cannot react quickly enough to changes in the security climate, nor can they scale large enough to detect new exploits that may be created and disappear in minutes. In this paper, we introduce the use of cross-protocol analysis and graph neural networks (GNNs) in semi-supervised learning to address the speed and scalability of assessing IP reputation. In the cross-protocol supervised approach, we combine features from the web, email, and domain name system (DNS) protocols to identify ones which are the most useful in discriminating suspicious and benign IPs. In our second experiment, we leverage the most discriminant features and incorporate them into the graph as nodes' features. We use GNNs to pass messages from node to node, propagating the signal to the neighbors while also gaining the benefit of having the originating nodes being influenced by neighboring nodes. Thanks to the relational graph structure we can use only a small portion of labeled data and train the algorithm in a semi-supervised approach. Our dataset represents real-world data that is sparse and only contain a small percentage of IPs with verified clean or suspicious labels but are connected. The experimental results demonstrate that the system can achieve 85.28 % accuracy in detecting malicious IP addresses at scale with only 5 % of labeled data., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)

Tuberculosis remains a serious global health problem causing 1.3 million deaths annually. The causative pathogen Mycobacterium tuberculosis (Mtb) has developed several mechanisms to evade the immune system and resistances to many conventional antibiotics, so that alternative treatment strategies are urgently needed. By isolation from bronchoalveolar lavage and peptide optimization, a new antimicrobial peptide named NapFab is discovered. While showing robust activity against extracellular Mtb, the activity of NapFab against intracellular bacteria is limited due to low intracellular availability. By loading NapFab onto dendritic mesoporous silica nanoparticles (DMSN) as a carrier system, cellular uptake, and consequently antimycobacterial activity against intracellular Mtb is significantly enhanced. Furthermore, using lattice light-sheet fluorescence microscopy, it can be shown that the peptide is gradually released from the DMSN inside living macrophages over time. By electron microscopy and tomography, it is demonstrated that peptide loaded DMSN are stored in vesicular structures in proximity to mycobacterial phagosomes inside the cells, but the nanoparticles are typically not in direct contact with the bacteria. Based on the combination of functional and live-cell imaging analyses, it is hypothesized that after being released from the DMSN NapFab is able to enter the bacterial phagosome and gain access to the bacilli., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

The purpose of this study was to determine if Puerto Rican bats had previous exposure to rabies virus based on viral neutralizing antibodies. Our results demonstrate that 6.5% of the bats in this study had some exposure to rabies virus. The route of exposure is unknown but may have occurred following interaction with a rabid terrestrial animal or an unidentified bat rabies virus., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review., Objectives: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020., Selection Criteria: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia., Data Collection and Analysis: No randomized controlled trials matching the selection criteria were eligible for inclusion., Main Results: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified., Authors' Conclusions: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review., Objectives: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 16 February 2017., Selection Criteria: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia., Data Collection and Analysis: No randomized controlled trials matching the selection criteria were eligible for inclusion., Main Results: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified., Authors' Conclusions: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

The volume fraction of red blood cells (RBCs) in a capillary affects the degree to which platelets are promoted to marginate to near a vessel wall and form blood clots. In this work we investigate the relationship between RBC hematocrit and platelet adhesion activity. We perform experiments flowing blood samples through a microfluidic channel coated with type 1 collagen and observe the rate at which platelets adhere to the wall. We compare these results with three-dimensional boundary integral simulations of a suspension of RBCs and platelets in a periodic channel where platelets can adhere to the wall. In both cases, we find that the rate of platelet adhesion varies greatly with the RBC hematocrit. We observe that the relative decrease in platelet activity as hematocrit falls shows a similar profile for simulation and experiment., (Copyright © 2016 Biophysical Society. All rights reserved.)