Nontoxic and Naturally Occurring Active Compounds as Potential Inhibitors of Biological Targets in Liriomyza trifolii

In recent years, novel strategies to control insects have been based on protease inhibitors (PIs). In this regard, molecular docking and molecular dynamics simulations have been extensively used to investigate insect gut proteases and the interactions of PIs for the development of resistance against insects. We, herein, report an in silico study of (disodium 5′-inosinate and petunidin 3-glucoside), (calcium 5′-guanylate and chlorogenic acid), chlorogenic acid alone, (kaempferol-3,7-di-O-glucoside with hyperoside and delphinidin 3-glucoside), and (myricetin 3′-glucoside and hyperoside) as potential inhibitors of acetylcholinesterase receptors, actin, α-tubulin, arginine kinase, and histone receptor III subtypes, respectively. The study demonstrated that the inhibitors are capable of forming stable complexes with the corresponding proteins while also showing great potential for inhibitory activity in the proposed protein-inhibitor combinations.     

Diagnosing Czech Patients with Inherited Platelet Disorders

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.     

A Cross-Sectional and Longitudinal Analysis of Pre-Diagnostic Blood Plasma Biomarkers for Early Detection of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.     

Siponimod Modulates the Reaction of Microglial Cells to Pro-Inflammatory Stimulation

Siponimod (Mayzent^®), a sphingosine 1-phosphate receptor (S1PR) modulator which prevents lymphocyte egress from lymphoid tissues, is approved for the treatment of relapsing-remitting and active secondary progressive multiple sclerosis. It can cross the blood–brain barrier (BBB) and selectively binds to S1PR1 and S1PR5 expressed by several cell populations of the central nervous system (CNS) including microglia. In multiple sclerosis, microglia are a key CNS cell population moving back and forth in a continuum of beneficial and deleterious states. On the one hand, they can contribute to neurorepair by clearing myelin debris, which is a prerequisite for remyelination and neuroprotection. On the other hand, they also participate in autoimmune inflammation and axonal degeneration by producing pro-inflammatory cytokines and molecules. In this study, we demonstrate that siponimod can modulate the microglial reaction to lipopolysaccharide-induced pro-inflammatory activation.     

Differing Escape Responses of the Marine Bacterium Marinobacter adhaerens in the Presence of Planktonic vs. Surface-Associated Protist Grazers

Protist grazing pressure plays a major role in controlling aquatic bacterial populations, affecting energy flow through the microbial loop and biogeochemical cycles. Predator-escape mechanisms might play a crucial role in energy flow through the microbial loop, but are yet understudied. For example, some bacteria can use planktonic as well as surface-associated habitats, providing a potential escape mechanism to habitat-specific grazers. We investigated the escape response of the marine bacterium Marinobacter adhaerens in the presence of either planktonic (nanoflagellate: Cafeteria roenbergensis) or surface-associated (amoeba: Vannella anglica) protist predators, following population dynamics over time. In the presence of V. anglica, M. adhaerens cell density increased in the water, but decreased on solid surfaces, indicating an escape response towards the planktonic habitat. In contrast, the planktonic predator C. roenbergensis induced bacterial escape to the surface habitat. While C. roenbergensis cell numbers dropped substantially after a sharp initial increase, V. anglica exhibited a slow, but constant growth throughout the entire experiment. In the presence of C. roenbergensis, M. adhaerens rapidly formed cell clumps in the water habitat, which likely prevented consumption of the planktonic M. adhaerens by the flagellate, resulting in a strong decline in the predator population. Our results indicate an active escape of M. adhaerens via phenotypic plasticity (i.e., behavioral and morphological changes) against predator ingestion. This study highlights the potentially important role of behavioral escape mechanisms for community composition and energy flow in pelagic environments, especially with globally rising particle loads in aquatic systems through human activities and extreme weather events.     

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...     

Adaptive river segmentation in SAR images

There is difficulty for distinguishing of river and shadow in Synthetic Aperture Radar (SAR) images. A method of river segmentation in SAR images based on wavelet energy and gradient is proposed in this paper. It mainly includes two algorithms: coarse segmentation and refined segmentation. Firstly, The river regions are coarsely segmented by the wavelet energy feature,and then refined segmented accurately by the gradient threshold which is got adaptively. The experimental results show the validity of the method, which provides a good foundation for targets detection above the river.     

Microstructural evolution of a silicon carbide-carbon coated nanostructured ferritic alloy composite during in-situ Kr ion irradiation at 300℃ 450℃

This work focuses on irradiation behaviors of a novel silicon carbide and carbon coated nanostructured ferritic alloy (SiC-C@NFA) composite for potential applications as a cladding and structural material for next generation nuclear reactors.The SiC-C@NFA samples were irradiated with 1 MeV Kr ions up to 10 dpa at 300 and 450 ℃.Microstructures and defect evolution were studied in-situ at the IVEM-Tandem facility at Argonne National Laboratory.The effects of ion irradiation on various phases such as α-ferrite matrix,(Fe,Cr)7C3,and (Ti,W)C precipitates were evaluated.The α-ferrite matrix showed a continuous increase in dislocation density along with spatial ordering of dislocation loops (or loop strings) at ＞5 dpa.The size of the dislocation loops at 450 ℃ was larger than that at 300 ℃.The nucleation and growth of new (Ti,W)C precipitates in α-ferrite grains were enhanced with the ion dose at 450 ℃.This study provides new insight into the irradiation resistance of the SiC-C@NFA system.