Comparative pollen and foliar micromorphological studies using light microscopy and scanning electron microscopy of some selected species of Lamiaceae from Alpine Zone of Deosai Plateau,Western Himalayas

The study was conducted to highlight a detailed account of morphology of pollen chosen species of Lamiaceae through scanning electron microscopy, and the anatomical characteristics of leaf epidermis of seven species using simple light microscopy. In results, Anisomeles indica and Otostegia aucheri belong to subfamily Lamioideae because it has tricolpate pollen while the rest eight species belong to subfamily Nepetoideae (hexacolpate pollen). The exine sculpturing of pollen of studied species was found to be reticulate. In the family Lamiaceae, four kinds of stomata were found anomocytic, anisocytic, diacytic, and actinocytic, respectively. The cell wall patterns of epidermal cells were irregular or polygonal with straight or undulate walls. It was noted that the variety of the epidermal trichomes seems of taxonomically important for the identification of species of Lamiaceae. Both nonglandular and glandular trichomes were analyzed. The nonglandular trichomes were characterized with long, thin, and pointed apical unicellular cells. The nonglandular trichomes were A‐shaped in Thymus linearis. In Perovskia abrotanoides, stellate glandular trichomes were observed whereas in A. indica and Mentha royleana both glandular and nonglandular trichomes were found. In A. indica, the nonglandular trichomes were sessile and peltate in M. royleana. For the first time in this study, pollen and foliar micromorphological features of selected species of this area are carried out. These taxonomic characters were found to be important in discrimination of species from each other. In future, the detailed study with comprehensive morphology coupled with other important characters is required for delimitation of taxa at various levels.     

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.     

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.     

Identification and characterization of cytosolic Hansenula polymorpha proteins belonging to the Hsp70 protein family

We have isolated two members of the Hsp70 protein family from the yeast Hansenula polymorpha using affinity chromatography. Both proteins were located in the cytoplasm. One of these, designated Hsp72, was inducible in nature (e.g. by heat shock). The second protein (designated Hsc74) was constitutively present. Peptides derived from both Hsp72 and Hsc74 showed sequence homology to the cytosolic Saccharomyces cerevisiae Hsp70s, Ssa1p and Ssa2p. The gene encoding Hsp72 (designated HSA1) was cloned, sequenced and used to construct HSA1 disruption and HSA1 overexpression strains. Comparison of the stress tolerances of these strains with those of wild-type H. polymorpha revealed that HSA1 overexpression negatively affected the tolerance of the cells to killing effects of temperature or ethanol, but enhanced the tolerance to copper and cadmium. The tolerance for other chemicals (arsenite, arsenate, H₂O₂) or to high osmolarity was unaffected by either deletion or overexpression of HSA1. The nucleotide sequence of HSA1 was submitted to the EMBL data library and given the Accession Number Z29379.     

Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping

The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.     

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.     

Computer Simulations of Deep Eutectic Solvents: Challenges,Solutions, and Perspectives

Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications, such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can predict and reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.     

40-Gb/s OTDM to 4×10 Gb/s WDM conversion in monolithic InPMach-Zehnder interferometer module

Transformation of high bit-rate optical time-domain multiplexed (OTDM) signals into a multitude of lower bit-rate wavelength-division-multiplexed (WDM) channels is demonstrated by means of a single monolithically integrated indium phosphide Mach-Zehnder interferometer with semiconductor optical amplifiers in its arms. Full demultiplexing of 10-Gb/s OTDM signals into 4×10-Gb/s WDM channels is demonstrated. Bit-error-rate penalties are below 1.5 dB for polarization independent signal conversion throughout the 1.55-μm wavelength range     

Thermosiphon solar domestic water heating systems: long-term performance prediction using artificial neural networks

The objective of this work is to use artificial neural networks (ANN) for the long-term performance prediction of thermosiphonic type solar domestic water heating (SDWH) systems. Thirty SDWH systems have been tested and modelled according to the procedures outlined in the standard ISO 9459-2 at three locations in Greece. From these, data from 27 of the systems were used for training and testing the network while data from the remaining three were used for validation. Two ANNs have been trained using the monthly data produced by the modeling program supplied with the standard ISO 9459-2. Different networks were used depending on the nature of the required output, which is different in each case. The first network was trained to estimate the solar energy output of the system for a draw-off quantity equal to the storage tank capacity (at the end of the solar energy collection period) and the second one was trained to estimate the solar energy output of the system and the average quantity of hot water per month at demand temperatures of 35 and 40°C. The collector areas of the considered systems were varying between 1.81 m² and 4.38 m². Open and closed thermosiphonic systems have been considered both with horizontal and vertical storage tanks. In this way the networks were trained to accept and handle a number of unusual cases. The input data in both networks are similar to the ones used in the program supplied with the standard. These were the size and performance characteristics of each system and various climatic data. In the second network the demand temperature was also used as input. For the first network the statistical coefficient of multiple determination (R²-value) obtained for the training data set was equal to 0.9993. For the second network the R²-value for the two output parameters was equal to 0.9848 and 0.9926, respectively. Unknown data were subsequently used to investigate the accuracy of prediction and R²-values equal to 0.9913 for the first network and 0.9733 and 0.9940 for the second were obtained. These results indicate that the proposed method can successfully be used for the prediction of the solar energy output of the system for a draw-off equal to the volume of the storage tank or for the solar energy output of the system and the average quantity of the hot water per month for the two demand water temperatures considered.     

Proton Conducting Phase‐Separated Multiblock Copolymers with Sulfonated Poly(phenylene sulfone) Blocks for Electrochemical Applications: Preparation,Morphology, Hydration Behavior,and Transport

A family of multiblock copolymers consisting of alternating fully sulfonated hydrophilic poly(phenylene sulfone) and hydrophobic poly(phenylene ether sulfone) segments are prepared and characterized. The multiblock copolymers are formed by the coupling of preformed hydrophilic and hydrophobic blocks using a specially designed coupling agent. The block lengths (degree of polymerization) of both segment types were varied in order to control the ion exchange capacity. Solution cast films show spontaneous nanophase separation leading to distinct bicontinuous morphologies with correlation lengths around 15 nm. The hydrophobic phase gives the membranes their advantageous viscoelastic properties even at high temperatures under both wet and dry conditions, while proton conductivity takes place within the hydrophilic phase. Since the properties of fully sulfonated poly (phenylene sulfone)s are locally preserved within the hydrophilic domain, the membranes show very high proton conductivity and high hydrolytic stability. The very high degree of water dispersion within the hydrophilic domains leads to very low electro‐osmotic water drag. Because of their superior transport and stability properties these multiblock copolymers have a great potential for use as a substitute for perfluorosulfonic acid membranes which are used as separator materials in electrochemical applications such as polymer electrolyte membrane (PEM) fuel cells and redox flow batteries.