The hybrid system is analyzed and optimized to produce electric energy in Non-Interconnected Zones in the Colombian Caribbean region, contributing both to the improvement in the reduction of greenhouse gas emissions and to the rational use of energy. A comparative analysis of the performance of these systems was carried using a dynamic model in real wind and solar data. The model is integrated by a Southwest Wind Power Inc. wind turbine. AIR 403, a proton exchange fuel cell (PEM), an electrolyze, a solar panel and a charge regulator based on PID controllers to manipulate oxygen and hydrogen flows in the cell. The transient responses of the cell voltage, current, and power were obtained for the demand of 200 W for changes in solar radiation and wind speed for all days of the year 2013 in the Ernesto Cortissoz airport, Puerto Bolívar, Alfonso Lopez airport and Simon Bolívar airport, by regulating the flow of hydrogen and oxygen into the fuel cell. The maximum contribution of power generation from the fuel cell was presented for the Simon Bolívar airport in November with a value of 158,358W (9.45%). A multi-objective design optimization under a Pareto front is presented for each place studied to minimize the Levelized Cost of Energy and CO₂ emission, where the objective variables are the number of panel and stack in the PV system and PEM.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

The 6TiSCH protocol (IEEE 802.15.4e) is crucial for the Industrial Internet of Things (IIoT), utilizing a time-slotted channel hopping (TSCH) mode based on node distribution. In our experiment, we explored node position clustering and adjusted the capacity of existing cells in congested areas to understand traffic patterns and optimize cell selection for TSCH resource allocation, particularly in slot frames. Efficient cell allocation prevents packet loss, manages congestion, and enhances data transmission reliability. Node clustering increases cell usage efficiency and reduces communication latency between nodes, with each cell allocation tailored to its traffic needs through the sink node from the clustering result. We evaluated the clustering method using the K-means algorithm through experiments using the 6TiSCH simulator. Additionally, we considered using the routing protocol for low power and lossy networks (RPL) as a comparison, such as OF0 and MRHOF, as the objective function to assess clustering results and their impact on throughput and packet delivery. Our method significantly improved average performance metrics: under the OF0 routing protocol, we achieved a 30.01% latency reduction, 15.95% faster joining time, 8% higher packet delivery ratio, and 13.82% throughput increase. Similarly, with the MRHOF routing protocol, we observed a 12.34% improvement in packet delivery ratio, 21.06% latency reduction, 12.68% faster joining time, and 25.97% higher throughput speed.

Diabetic Kidney Disease (DKD) is a common complication of Type 2 Diabetes Mellitus and a major risk factor for end-stage kidney disease. The immune system plays a significant role in the pathogenesis of DKD, involving infiltration of immune cells in the kidney, upregulation of in-flammatory mediators, downregulation of anti-inflammatory mediators, and disturbance in ad-hesion molecules and growth factors. Dendritic cells are professional antigen-presenting cells acting as a bridge connecting innate and adaptive immune responses. DC is also capable of modulating inflammation. Autologous dendritic cells can be made by in vitro differentiation of peripheral blood monocytes and then utilized as a cell-based therapy. Cell-based therapy for DKD is currently focused on utilizing the anti-inflammatory properties of stem cells. However, research suggests unsatisfactory results due to several limitations. This article highlights the possibility of using DC as a cell-based therapy for DKD through its role in controlling inflammation.

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.

EphB2 is a member of the Eph family tyrosine kinase receptors. EphB2 binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators of vascular and nervous development through controlling cell migration and axon guidance. EphB2 is overexpressed in tumors, including glioma, breast cancer, hepatocellular carcinoma, and malignant mesothelioma, and it functions as a tumor promoter. Therefore, the development of monoclonal antibodies (mAbs) against EphB2 is essential for tumor diagnosis and therapy for EphB2-positive tumors. In this study, we developed novel mAbs for human EphB2 using the Cell-Based Immunization and Screening (CBIS) method. One of the established anti-EphB2 mAbs, Eb2Mab-3 (mouse IgG1, kappa), reacted with EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and an endogenously EphB2-expressing cancer cell line (LS174T) by flow cytometry. Using flow cytometry, the dissociation constant (KD) values of Eb2Mab-3 for CHO/EphB2 and LS174T were determined as 1.1 × 10−9 M and 3.6 × 10−10 M, respectively. These results indicated that Eb2Mab-3 possesses a high affinity for detecting EphB2 and could apply to tumor therapy.

Targeting drugs to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier. (BBB). The cutting edge in nanotechnology generates optimism to overcome the growing challenges in biomedical sciences through effective engineering of nanogels. The primary objective of the present report was to develop and characterize biocompatible natural chitosan (CS)-based NG that can be tracked thanks to the tricarbocyanine (CNN) fluorescent probe addition of the biopolymer backbone. FTIR shed light on the chemical groups involved in the CS and CNN interactions and between CNN-CS with tripolyphosphate, the cross-linking agent. Both in vitro and in vivo experiments were carried out to determine if CS-NG can be utilized as therapeutic delivery vehicles directed towards the brain. An ionic gelation method was chosen to generate cationic CNN-CS-NG. DLS and TEM confirmed that these entities size fell into nanoscale. CNN-CS-NG was found to be non-cytotoxic as determined in the SH-SY5Y neuroblastoma cell line through biocompatibility assays. After cellular internalization, the occurrence of an endo-lysosomal escape (a crucial event for an efficient drug delivery) of CNN-CS-NG was detected. Furthermore, CNN-CS-NG administered intraperitoneally to female CF-1 mice were detected in different brain regions after 2 h of administration using fluorescence microscopy. To conclude, the obtained findings in the present report can be useful in the field of neuro-nanomedicine when designing drug vehicles with the purpose of delivering drugs to the CNS.

In this research work, we describe the preparation process, characterization, and photo-physical studies of an ionic liquid (IL) based semiconductor Zinc Oxide (ZnO) nanoparticles synthesized by an economical wet chemical precipitation method. For the first time, an IL was synthesized with the help of a chemical reaction between triethylamine (TEA) and bromoacetic acid (BAA). A polyamide dye was prepared by a reaction between two monomers, ethylenediamine (EDA) and trimesoylchloride (TMC), under room temperature conditions. The polyamide dye was capped on ZnO nanoparticles, and the final product was divided into three different samples, A, B, and C, according to level of concentrations of IL and Polyamide dye. These samples were characterized with X-Ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS) spectra, Ultraviolet-Visible (UV-Vis), and Fluorescence spectroscopies. The formation of polyamide linkages in the ionic liquid has been confirmed by a spectroscopic method using Fourier Transform Infrared (FTIR) spectroscopy. The capping of polyamide dye molecules on the surface of ZnO nanoparticles revealed two things: (i) improved UV absorption spectra and (ii) enhanced luminescence in the photoluminescence spectra. Hence, during investigations, broad absorption bands were observed at peaks 263 nm, 278 nm, and 276 nm respectively for samples A, B, and C. Further, IL was used as an electrolyte or redox mediator and polyamide as a dye material in the fabrication of ZnO Dye-Sensitized Solar Cells (DSSCs). The samples A, B, and C were used in the fabrication of photo-anode assemblies for ZnO DSSCs. The ZnO DSSCs were tested under strong simulated light at Air Mass (AM) 1.5 solar irradiations. The observed photovoltaic results shown that solar cell SCB generated a maximum power conversion efficiency (η) of 5.65%, higher than the power conversion efficiencies of solar cells SCA (3.99%) and SCC (4.46%) respectively. The Incident Photon to Current Conversion Efficiency (IPCE) spectra values of ZnO DSSCs shown a significant improvement in the incident photon to current conversion efficiency of solar cell SCB (IPCE=61%) as compared to SCC (enhanced by 6%) and SCA (enhanced by 4%). Such solar cell assemblies can be suitable for green and clean energy applications.

Galectins are a family of beta-galactoside-binding proteins that are characterised by their carbohydrate recognition domain (CRD) and include galectin-1 and galectin-3. These galectins have been implicated in numerous diseases due to their pleiotropic nature, including cancer and fibrosis, with therapeutic inhibitors being clinically developed to block the CRD. One of the early methods developed to characterise these galectins was hemagglutination of red blood cells. Although insightful this approach has been hampered by a lack of sensitivity and accurate quantification of the agglutination observed. In this study we aimed to validate a more precise and quantitative method to enable further investigation of differences between galectins in respect to agglutination induction in different blood groups as well as characterisation of small molecule inhibitors. Quantification of hemagglutination was shown to be optimal using U-bottom plates imaged and analysed with FIJI ImageJ rather than flat bottom plates read for absorbance on an optical density plate reader. Galectin-3-induced red blood cell agglutination efficacy increased significantly from blood group O to A to B. However, for both the galectin-1 monomer and concatemer a more comparable effect was observed between blood group B and O but with more potent effects than in blood group A. Inhibition assays for both galectin-3 and galectin-1 induced-hemagglutination were able to demonstrate clear concentration-responses and expected selectivity profiles for a set of small molecule glycomimetics, confirming historical profiles obtained in biochemical binding and functional cellular assays.

Although a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) serve as the cleaving protease of vWF-multimers, its role in liver ischemia-reperfusion injury (IRI), as well as partial liver transplantation (pLT), remains unknown. First, ADAMTS13 deficient mice were subjected to IRI to investigate the impact on hepatic IRI. Hepatic IRI significantly decreased serum ADAMTS13 activity, while simultaneously up-regulated intrahepatic vWF expression. Ablation of ADAMTS13 aggravated liver IRI by promoting platelet aggregation and disturbing microcirculation in the liv-er accompanied by exacerbated transaminase release and enhanced pro-inflammatory cytokine/chemokines levels. Adjunctive supplementation of recombinant ADAMTS13 (rADAMTS13) improved hepatic microcirculatory failure observed in ADAMTS13-null mice. Immunohistochemistry revealed massive platelet aggregation within hepatic micro-vasculatures in ADAMTS13-null mice, which was attenuated by rADAMTS13 treatment. Consequently, peripheral platelet counts, transaminase release, and pro-inflammatory cytokines/chemokines levels deteriorated in ADAMTS13-null mice, while ameliorated by rADAMTS13 administration. Notably, rADAMTS13 improved IRI-induced pathologies even in WT mice compared with those without. Next, we tested rADAMTS13 in the rat pLT model. Similarly, in rat pLT, ADAMTS13 supplementation attenuated the aforementioned pathologies observed in the experimental mouse model. In conclusion, ADAMTS13 plays a pivotal role in alleviating both hepatic microcirculation and inflammatory responses, thus providing a novel therapeutic approach against LT-related stress.

Purpose: The aim of the study is an approach to a nanocomposite with copper nanoparticles, constituting a bacteriostatic surface for maintaining the human lung cells' function. Methods: The polyelectrolyte layer coating with copper nanoparticles incorporated was designed. As a bacteriostatic factor, copper nanoparticles were applied as a colloidal solution of copper nanoparticles (ColloidCuNPs) and solution of copper nanoparticles (CuNPs). The influence of polyelectrolytes on selected Gram(+) and Gram(-) strains was examined. The function of the human adenocarcinoma A549 cell line of epithelial human lung cells cultured in the presence of nanocomposite layer coatings was analyzed, as well as their morphology using flow cytometry, fluorescence microscopy, and scanning electron microscopy. In addition, the material of layer coating was assessed using AFM and SEM-EDX characterization. Results: It was observed that polyelectrolytes polyethylenimine and poly-L-lysine do not induce proliferation of E.coli strain. On the other hand, it induces the proliferation of S. aureus strain. Due to CuNPs effectiveness against E.coli strain, CuNPs were selected for further research. The designed coatings at proper NPs share sustained the function of human lung cells cultured within 10 days of culture. The AFM and EDX characterization confirmed copper presence in the layer coating nanomaterial. The presence of CuNPs in polyethyleneimine-based nanocomposite deepens the bacteriostatic effect on E. coli compared with PEI alone. Meanwhile, incorporating CuNPs in PLL at share allowed A549 cell maintenance, did not exert a bacteriostatic influence on the examined strain.Conclusion: The platform based on polyelectrolytes incorporated with copper nanoparticles ensuring the growth and morphology of the human lung epithelial cells can be considered an element of the system components for medical devices for maintaining the human lung cells' function.

Nuclear speckles are compartments enriched in splicing factors present in the nucleoplasm of mammalian cells. Their morphology is linked to the transcriptional and splicing activities of the cell through a recruitment mechanism. Speckles have been studied mostly in mammalian culture cells, and few studies are devoted to speckles in tissue cells. In mammals, speckles are present in different tissues and their morphology also depends on the hormonal cycle in rats. In the present work, we explore whether a similar situation is also present in non-mammalian tissue cells dur-ing the reproductive cycle. We studied the speckled pattern in several tissues of a viviparous rep-tile, the lizard Sceloporous torquatus, during two different stages of reproduction. We used immu-nofluorescence staining against splicing factors in hepatocytes and oviduct epithelium cells and fluorescence and confocal microscopy. The distribution of splicing factors in the nucleoplasm of oviductal cells and hepatocytes coincides with the nuclear speckled pattern described in mam-mals. In addition, the morphology of speckles varies in oviduct cells at the two stages of the re-productive cycle analyzed, paralleling the phenomenon observed in the rat. The results show that the morphology of speckles in reptile cells depends upon the reproductive stage as it occurs in mammals.

Claudins are a family of 27 proteins that have an important role in the formation of tight junc-tions. They also have an important function in ions exchange, cell mobility, and in in the epitheli-al-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evi-dence shows improved outcomes when combining monoclonal antibodies against Claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently Chimeric anti-gen receptor T-cells targeting Claudin 18 are under investigation.

The COVID-19 pandemic caused by the RNA virus SARS-CoV-2, has had a significant impact not only on bodily metabolism but also at the genomic level. This study utilizes a bibliometric approach to map and identify the relationship between COVID-19 and DNA damage, genomic instability, and cell cycle deregulation. The research began with the development of in-depth research questions and conducted two rounds of literature search in the Scopus database with stringent filters to ensure relevance and accuracy. From an initial 1098 documents, 576 relevant documents were selected for further analysis. The collected data was then visualized using bibliometric methods, enabling the identification of important patterns, trends, and relationships among the research variables. Key findings indicate that DNA damage, which can induce apoptosis, is the worst impact of the infection on cells. Term frequency analysis and science mapping revealed a close relationship between "DNA damage" and "apoptosis". Furthermore, discussions on genomic instability highlight telomere regulation issues, while cell cycle deregulation during virus replication in mammalian cells indicates the importance of maintaining cell membrane integrity.This study confirms the importance of bibliometric analysis in detecting and understanding the impact of COVID-19 at the genomic level, proposing several potential research targets and enhancing our understanding of the biological response to viral infection.

Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labelling. Anti-α-tubulin and anti-γ-tubulin antibodies revealed faint γ-tubulin signals co-localized with α-tubulin in early prophase during nuclear membrane rupture, which intensified as prophase progressed. At this stage, bright regions of α-tubulin around and on the nuclear membrane surrounding the chromatin suggested the start of microtubule assembling in the microtubule organizing centers (MTOCs). In metaphase, the number and size of γ-tubulin foci increased and were detected on both sides of the chromosomes. This resulted in a distinctive multipolar square spindle with holocentric chromosomes aligned at the metaphase plate. siRNA-mediated BmAurora B knockdown significantly reduced the γ-tubulin foci during prophase, impacting microtubule nucleation and spindle structure in metaphase. Spatiotemporal BmAurora B expression analysis provided new insights into the regulation of this mitotic kinase in silkworm larval gonads during gametogenesis. Our results suggest that BmAurora B is crucial for the formation of multipolar square spindles in holocentric insects, possibly through the activation of γ-tubulin ring complexes in multiple centrosome-like MTOCs.

Severe combined immunodeficiency disorders (SCID) are a genetically heterogeneous group of inherited defects characterized by severe abnormalities of immune system development and function that lead to a wide spectrum in clinical manifestations. A subgroup of patients presents a disabling and life-threatening clinical course. In these cases, allogeneic hematopoietic stem cell transplant provides a curative approach. The occurrence of SCID-associated lymphoproliferative disorders is rare and occur mostly in adenosine deaminase-deficient severe combined immunodeficiency disorders, after allogeneic hematopoietic stem cell transplant. Epstein Barr virus infection is present in the majority of individuals with primary immunodeficiency developing lymphoma, revealing compromised anti-tumour surveillance of virally transformed cells. Herein, we report a rare case of diffuse large B cell lymphoma occurring in an Epstein Barr virus negative, non-transplanted X-linked severe combined immunodeficiency 4-months-old infant, successfully treated with immunotherapy and allogeneic stem cell transplantation. This case suggests that Epstein Barr virus -independent mechanism of neoplastic transformation must take action in severe combined immunodeficiency associated lymphoma and unveils the curative potential of donor T cells after allogeneic transplantation.

Stroke remains one of the leading causes of death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing ischaemic penumbra. Stem cell therapy offers a promising alternative. As a regenerative medicine, stem cells offer a wider range of treatment strategies, including long-term intervention for chronic patients, through the reparation and replacement of injured cells via mechanisms of differentiation and proliferation. The purpose of this review is to evaluate the therapeutic role of stem cells for ischaemic stroke. The paper discusses the pathology during acute, subacute, and chronic phases of cerebral ischaemic injury, highlights the mechanisms involved in mesenchymal, endothelial, haematopoietic, and neural stem cell-mediated cerebrovascular regeneration and evaluates the pre-clinical and clinical data concerning the safety and efficacy of stem cell-based treatments. Treatment of stroke patients with different type of stem cells appears to be safe and efficacious even at relatively higher concentrations irrespective of the route and timing of administration. Priming or preconditioning of cells prior to administration appears to help augment their therapeutic impact. However, larger patient cohorts and later phase trials are required to consolidate these findings.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca2+-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca2+-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, Kd, values of 0.3-2 μM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the ‘hinge’ region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF/S100-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.

The emergence of antimicrobial resistance remains one of the greatest public health concerns. Biofilm formation has been postulated as a mechanism of microbial pathogens to resist antimicrobial agents. Lactic Acid Bacteria (LAB) and their metabolites have been proposed to combat bacterial biofilms, due to their antimicrobial activity. In this vein, the aim of the present study was to investigate the biofilm removal potential of cell-free supernatant (CFS) of five wild-type Lacticaseibacillus rhamnosus LAB strains, isolated from Greek natural products, in comparison to the commercial available L. rhamnosus GG strain, formed by common foodborne pathogens (Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus). Biofilm removal activity of LAB was assessed on two-days mature biofilm using a microtiter plate-based procedure. Both non-neutralized and neutralized CFSs removed biofilms in a concentration-dependent manner. Biofilm removal activity of the non-neutralized CFSs was significantly higher compared to the neutralized CFSs, as expected, ranging 40 – 90% and 10 – 78%, respectively. Biofilm removal efficiency of L. rhamnosus OLXAL-3 was signifanctly higher among the wild-type L. rhamnosus strains tested (20 – 100% v/v). In conclusion, our results suggested the great potential of application of wild-type Lacticaseibacillus rhamnosus strains CFSs as effective natural agents against pathogenic bacterial biofilms.

Soil cadmium (Cd) contamination has become a serious problem in China. In this study, the goals of the field experiments were to understand how the application of nitrogen fertilizer at the full heading stage and filling stage reduced the uptake of Cd in rice by affecting the distribution of Cd in iron plaques on the root surfaces and subcellular in the root and flag leaf. The hydroponic culture experiments aimed to explore the effect of interaction or deficiency of nitrogen and cadmium on cadmium accumulation in rice at the late growth stage. The results showed that under the condition of having enough nitrogen supply during the early growth stage, applying nitrogen fertilizer during the full heading stage and filling stage resulted in a significant increase in the concentration of Fe and Cd on the root plaques at the milk stage and mature stage. Additionally, it increased the concentration and proportion of Cd in the soluble fraction of subcellular in the flag leaves at the milk stage. On the other hand, when there was a deficiency of nitrogen, the concentration of Fe in the root plaques increased significantly, while the concentration of Cd in the root plaques decreased significantly. Moreover, the proportion of Cd in the flag leaf cell walls increased significantly. Regardless of whether there was sufficient or deficient nitrogen supply during the early growth stage, applying nitrogen at the full heading stage reduced the Cd concentration in brown rice by 35.11% and 57.25%, respectively. Under hydroponic culture conditions with both Cd exposure and later-stage nitrogen supply significantly increased the Cd concentration in brown rice. However, in the absence of Cd, nitrogen supply significantly reduced the Cd concentration in brown rice. The accumulation of Cd in brown rice was significantly correlated with the accumulation of Fe and Mn at the late growth stage. Our findings indicate that when there is sufficient nitrogen nutrition during the early growth stage of rice, topdressing nitrogen fertilizer at the full heading stage combined with lime with mineral element fertilizers such as Fe and Mn is an effective approach to reduce the presence of cadmium in rice grains.

Two new compounds, named aspergilins A (1) and B (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3 associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of these compounds were unambiguously established by extensive NMR investigations, quantum-chemical electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Most notably, the absolute configuration of aspergillin A (1) was determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas that of averufanin (3) was first clarified by quantum-chemical ECD calculations. Aspergilin A is the first orsellinic acid–ribose–​pyridazinone-Noxide hybrid containing a unique β-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas aspergilin B and averufanin are the sterigmatocystin and anthraquinone derivative, respectively. From the perspective of biosynthesis, aspergilin A could be originated from the combined assembly of three building blocks, viz., orsellinic acid, β-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-Noxide involving biosynthetic pathways of polyketide, pentose, and amino acid. Aspergilin B (2) exhibited potent antiproliferative activity against four cancer cell lines. In addition, Aspergilin B (2) dose-dependently induced G2/M phase arrest in HepG2 cells.

Biological function depends on the composition as well as structure of the organism, that is the organization of interactions between its parts. In multicellular organisms, the complex communication between cells is crucial for the coordination of cellular functions (growth, differentiation, apoptosis), compartmentalization of cellular processes within the organism, and the integration of cells into functioning higher levels of structural organization. Here we focus on the interaction among cells, as the basic level of biological organization, capable of a remarkable degree of autonomy and self-maintenance. While a wealth of data on putative cell interactions has recently become available, its biological interpretation depends on expectations we have for the structure of these interaction networks. This contribution is an attempt at formulating basic questions we may ask about cell interaction data. We build on the understanding that cells fulfill two general functions: the integrity-maintaining and the organismal service function. We derive the expected patterns of cell interactions considering two intertwined aspects: the immediate functional and the evolutionary. Based on these, we propose several guidelines for analysis and interpretation of transcriptional cell-interactome data.

Background: Colorectal cancer (CRC) is one of the major causes of cancer-related death worldwide. Aerobic glycolysis precedes obtainment of oncogenic mutations and loss of tumor suppressors, promoting the progress of CRC. Although numerous biomarkers have been identified to be associated with prognosis and survival, a glycolysis-related gene signature in CRC has not been explored. Methods: mRNA expression profiling data in a group of CRC patients (n = 540) was extracted from the Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GESA) was performed to identify gene sets that were significantly different between CRC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan–Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. Results: Five glycolysis-related genes (ENO3, GPC1, P4HA1, IDUA, ANKZF1) were identified to be significantly associated with overall survival (AUC=0.754). Based on the five‑gene signature, patients with CRC were divided into high and low‑risk subgroups. CRC patients with a low-risk score had better survival benefits than those with a high one (P < 0.001). Conclusions: A five-gene signature associated with glycolysis for predicting the outcome of CRC patients was generated, serving as a valuable prognosis model with high efficiency and potential targeted therapy of CRC patients.

In the tissue regeneration field, stem cell transplantation and the control of their differentiation represent a promising therapeutic strategy. The second aspect can be achieved using electrical stimulation. This study aims to characterize the effect of a microsecond electrical stimulation on MSCs and iNSCs, in the context of the RISEUP FET-OPEN project (n. 964562) that seeks to control these cells differentiation for the spinal cord injury treatments. Here, the effect of a specific microsecond electric pulses stimulation, characterized by bipolar pulses of 100 µs + 100 µs, delivered for 30 minutes at an intensity of 250 V/cm, on i) cell proliferation, ii) cell cycle, iii) gene expression and iv) apoptosis was evaluated. Results show that the stimulation does not affect cell proliferation, cell cycle, and apoptosis, but induced some variations in gene expression, in particular in EGR1, FOS, and POU5F1. These ob-servations led us to deeply investigate the cell proliferation until 72h from the stimulation observing an increase in the iNSCs. The main outcome of this study is that the chosen stimulation protocol is safe and not toxic for MSCs and iNSCs. The observed variations in the gene expression need to be deeply investigated to assess the molecular mechanisms involved.

Background: The most frequent non-pigmented malignancy of the ocular surface is ocular surface squamous neoplasia (OSSN), which has a frequency of 0.03 to 1.9 per 100,000 people per year. It can be diagnosed histologically as anything from mild dysplasia to aggressive squamous cell carcinoma that affects both the conjunctiva and the cornea. The purpose of this study is to determine the distribution of ocular surface squamous neoplasia at a teaching hospital in South Western Uganda.Methods: In this retrospective study, we reviewed all records of patients with ocular surface squamous neoplasia from the Mbarara University of Science and Technology (MUST)/ Mbarara Regional Referral Hospital (MRRH) pathology laboratory in South Western Uganda, from January 2015- October 2021.Results: Of the 1,133 cases of ocular neoplasia seen during this time, OSSN composed of 26.7% (n=303). OSSN occurred mainly in females (59.1%). The most common OSSN was invasive squamous cell carcinoma (60.4%). The age range was 15-106 years while the mean was 39.99 years. The commonest affected age group was 30-44years (41.3%).Conclusion: The burden of OSSN is high. It primarily affects young adults and is frequently found in women. Squamous cell carcinoma makes up the majority of the disease.

The solar cell industry is a part of the green energy sector, and effectively combining the patents of various manufacturers within the supply chain to collectively create sustainable patent market value is of paramount importance. This study aimed to establish a business strategy framework for Project-based licensing through the analysis of solar cell patents and the integration of supply chain manufacturers' patents, with the goal of collectively creating market value for patents sustainably. The research methodology included literature analysis and focus group discussions. Initially, the study analyzed solar cell industry patents from the past decade using the WIPS Global Patent database to identify projects with the highest patent count. Subsequently, through the use of focus group discussions, the feasibility of a patent pool strategy within the supply chain was explored. Finally, a strategy framework was proposed for Project-based patent pool licensing, focusing on the top 15 projects with the highest count of 5,579 patents. The results indicated that adopting this strategy framework for supply chain manufacturer patents can result in higher commercial patent value.

The advancements achieved in Tissue Engineering are based on a careful and in-depth study of cell-tissue interaction. The choice of a certain biomaterial in Tissue Engineering is fundamental as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. The aim of this re-view is to analyse the chemical, physical and biological parameters on which it is possible to act in Tissue Engineering for the optimization of polymeric scaffolds. Understanding the scaffold impact on cell fate is of paramount importance for the successful advancement of Tissue Engineering.

Rikenella microfusus is an essential intestinal probiotic with great potential. The latest research shows that its imbalance in the intestinal flora is related to the occurrence of various diseases, such as intestinal diseases, immune diseases, and metabolic diseases. Rikenella may be a target or biomarker for some diseases, providing a new possibility for preventing and treating these diseas-es by monitoring and changing the abundance of Rikenella in the intestine. However, the current detection methods have disadvantages such as long detection time, complicated operation, and high cost, which seriously limit the possibility of clinical application of this new treatment method. Therefore, developing rapid and low-cost detection methods has become an urgent problem to be solved. In this study, we used Rikenella as the target bacterium, meanwhile including five other prominent gut bacteria Akkermansia muciniphila, Allobaculum stercoricanis, Blautia producta, Rose-buria intestinalis and Parabacteroides distasonis as control organisms. The aptamer library R.m-R13 was evolved with high specificity and strong affinity (Kd = 9.597 nM) in an iterative Cell-SELEX process after 13 rounds of selection. R. microfusus can efficiently be discriminated from other major gut bacteria in complex mixtures in different analysis techniques including fluorescence micros-copy or fluorometric suspension assays and even in human stool samples. These preliminary re-sults open new avenues towards the development of aptamer-based microbiome bio-sensing ap-plications for fast and reliable R. microfusus monitoring.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first line chemoimmunotherapy. In recent years there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell therapies (CAR T-cells) and monoclonal antibodies as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are under investigation to treat R/R DLBCL.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab-deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) by flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of H2Mab-300 and H2Mab-304 for CHO/mHER2 was 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD of H2Mab-300 and H2Mab-304 for NMuMG was 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.

Thermal safety of lithium-ion traction batteries is a highly concerned issue in the field of electric transportation. The large amount of gas emission during the thermal runaway process of batteries has highly safety hazards such as fire and explosion. Quantitative analysis of emission is one of the important challenges for testing and evaluating battery safety. Focus on quantifying the gas emission through large-scale thermal propagation in battery modules and packs, based on the idea of cell result multiplication, this article conducts thermal runaway emission analysis on single cell and modules, and compares the behavior of thermal runaway and gas emission of the cell and module from the aspects of temperature, pressure, gas composition and battery morphology. The feasibility of the cell result multiplication method was verified from the perspective of experimental data.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for Type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in gluteal adipose tissue biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking or lipid therapy . Methods and Results: Fasting blood and subcutaneous gluteal adipose tissue (SAT) biopsy were obtained in MetS (n=20) and controls (n=19). Cardio metabolic features, FFA levels, hsCRP and HOMA-IR were significantly increased in patients with MetS. Waist-circumference adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, endotoxin and monocyte TLR4 abundance. Also, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal AT that correlated with cellular inflammation, fibrosis and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.

This paper focuses on the impact of defects density and carrier capture cross-section area in the electron transport material (ETM), hole transport material (HTM), and absorber layers on the performance of perovskite solar cells and quantum efficiency (QE). Furthermore, the impact of defects density at the interface between ETM/absorber and absorber/HTM is also studied. SCAPS-1D software is used in the current study in determining solar cell performance. The proposed perovskite solar cell structure is a planar FTO/TiO2/ CH3NH3PbI3/ Cu2O. The results indicated that increasing the defect density in the absorber layer significantly affects cell performance, while in ETM and HTM layers, the cell parameters remain unaffected. It is also found that the defect capture cross-section has a similar behavior to the defect density in the main layers (ETM, absorber, and HTM). In addition, it is observed that by increasing the defects density in the ETM/absorber and absorber/HTM interfaces layer, the cell parameters FF, Jsc, and PCE have been slightly decreased, with no effect on Voc. Moreover, it is also noted that the quantum efficiency QE is sharply reduced. Finally, this paper introduced the correlation between the defect density and the capture cross-section, which is the first attempt to find such a relationship in perovskite solar cells to the knowledge of the authors.

The Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling in cancers. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use in patients with colorectal cancers and head and neck squamous cell carcinomas. A reliable preclinical mouse model is essential to further develop the mAb therapy against EGFR. However, a mAb against mouse EGFR (mEGFR) for flow cytometry has not been established. In this study, we developed a specific and sensitive mAb for mEGFR using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa) reacted with mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) and endogenously mEGFR-expressed cell lines, including NMuMG (a mouse mammary gland epithelial cell) and Lewis lung carcinoma cells by flow cytometry. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of EMab-300 for CHO/mEGFR and NMuMG was 4.3 × 10−8 M and 1.9 × 10−8 M, respectively. These results indicated that EMab-300 applies to the detection of mEGFR by flow cytometry, and is expected in the use of preclinical study.

Background: The lymph nodes staging system can predict the prognosis of gastric signet ring cell carcinoma (SRCC), but the optimal system for early and advanced SRCC remains unknown. Methods: This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph node staging systems, including pN staging, lymph node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC). The kaplan⁃meier method and the log⁃rank test analyze the overall survival of patients. The Cox risk regression model identifies independent risk factors associated with patient outcomes. The nomogram was made by R studio. Results: The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (P=0.002, P<0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. Conclusion: LODDS showed a clear prognostic superiority over both pN and LNR in early and advanced SRCC.

The induction of macrophage death is regarded as a potential mechanism by which components secreted by Clostridium septicum are used to evade the innate immune response and cause tissue damage. This study aimed to determine the effect of partially purified fractions of extracellular proteins secreted by C. septicum on the death of mouse peritoneal macrophages. Elicited mouse peritoneal macrophages were incubated with partially purified fractions of proteins secreted by C. septicum into culture medium. After incubation, we found that the protein fraction with a molecular weight ≥ 100 kDa caused significant cell death in macrophages, changed cell morphology, increased markers of apoptosis and autophagy, and increased the expression (protein and mRNA) of IL-1 and TNFα. Our data suggest that the proteins secreted by C. septicum (MW ≥100kDa) induce cell death in macrophages by promoting autophagy-triggered apoptosis. This may contribute to our understanding of the molecular mechanism of immune evasion by C. septicum at the infection site.

Relapsed acute lymphoblastic leukemia (ALL) represents a continuous challenge for the clinician. Despite recent advances in treatment, the risk of relapse remains significant. The clinical, biological, cytogenetic, and molecular characteristics may be different at the time of relapse. Current comprehensive genome sequencing studies suggest that most relapsed patients, especially those with late relapses, acquire new genetic abnormalities, usually within a minor clone that emerges after ALL diagnosis. We report the case of a 23-year-old young woman diagnosed with Philadelphia chromosome negative B-cell acute lymphoblastic leukemia. The patient underwent allogeneic stem cell transplantation (allo-HSCT) after complete remission. Although having favorable prognostic factors at diagnosis, the disease relapsed early after allo-HSCT. The cytogenetic and molecular exam at relapse was positive for the Philadelphia chromosome, respectively for the bcr-abl transcript. What exactly led to the relapse of this disease in a more aggressive cytogenetic and molecular form, although there were no predictive elements in the diagnosis of this relapse?

Single-cell RNA sequencing data facilitates investigation of cell heterogeneity and subpopulations as well as differentially abundant states however modern single-cell RNA sequencing datasets are growing in size and complexity requiring advances in the bioinformatic methods that analyze them. Many methods exist for each step of analysis including read alignment, normalization, quality control, batch effect correction, imputation and dimensionality reduction. With so many options to choose from at each step of the analysis, benchmarking and a synthesis of the literature on the methods available is necessary to inform biological researchers on the most optimal workflow for their data. Here, recent key methods of analysis are highlighted with a focus on methods that facilitate identification of cell subpopulations and differentially abundant cell states. With a constantly expanding toolset for each step in single-cell RNA sequencing dataset analysis, biological researchers should stay informed to utilize the most applicable methods for their own analyses.

Exploring new ways to represent and discover organic molecules is critical for developing novel therapies. With recent advances in bioinformatics, virtual screening of databases is possible. However, biochemical data must be encoded using computer algorithms to make them machine-readable, taking into account distance and similarity measures to support tasks such as similarity searching. Motivated by the ubiquity of the carbon element and the structured patterns that emerge, we propose a parametric approach to molecular encodings of carbon-based multilevel atomic neighborhoods. It implements a walk along the carbon chain of an organic molecule to compute different representations of its feature encoding in the form of a binary or numerical array that can be exported later into an image. Resulting encodings are reproducible and readily formatted for various domain tasks including machine learning tasks. This approach was evaluated using a 10-fold stratified cross validation for binary classification with eight data sets and six different encodings (384 models) in the domain knowledge of cell-penetrating peptides. The parametric approach is built on open-source software and is implemented as a Python package (cmangoes). Source code and documentation are available at https://github.com/ghattab/cmangoes.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Background: Sinonasal squamous cell carcinoma (SNSCC) is rare in the general population. No clear and consistent etiologic correlation between human papillomavirus and SNSCC has yet been delineated in literature. p16 is a tumour suppressor protein used as a surrogate marker for HPV. This study aims to evaluate the relationship between p16 overexpression in SNSCC and its role in prognosis and survival. Methods: A population-based retrospective analysis was performed using prospectively collected data from the Northern Alberta Head and Neck Tumour Board, Alberta Cancer Registry, and Alberta Cancer Research Biobank. p16 overexpression was analyzed from pathologic sample of patients meeting study criteria, and participants were dichotomized by status. Subsequently, nonparametric analysis of demographics, initial staging, and initial treatment were performed, and a Kapan-Meier curve was developed to assess differences in survival. Results: 16 patients were included in analysis. p16 overexpression was seen in 68.8% of patients. p16 positive and negative groups were comparable for age, gender, smoking status, stage, and treatment. A statistically significant five-year survival advantage was observed in patients with p16 positive SNSCC (p = 0.013). Conclusions: This is the first Canadian study to demonstrate a high prevalence of p16 positivity in SNSCC and its presence denoting a statistically significant survival advantage. Results demonstrate a previously unconfirmed role of oncogenic HPV in SNSCC.

Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still poses a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, we report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.

Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

Air traffic congestion is caused by the unbalance between increasing traffic demand and saturating capacity. Flight delay not only causes huge economical lost, but also has very negative environmental impact in the whole air transportation system. In order to identify the impact of extended TMA on airport capacity, an airspace capacity assessment method based on augmented cell transmission model was proposed. Firstly, the airspace structure was modeled with points, segments, layers, and cells. Secondly, mixed integer linear programming model was built up with maximum throughput or capacity as the objective function. Finally, genetic algorithm was used to find the optimal result, and the results were validated by comparing with the fast-time simulation results generated by total airspace and airport modeler (TAAM) software. It is found that the proposed method could achieve a relatively accurate result in a much affordable and fast way. The numerical results could be very helpful for air traffic controllers to analyze the dynamic traffic flow entering and exiting TMA, so as to make decisions via reasonable analysis and do planning in advance by referring to the airport capacity.

Carboxypeptidase A4 (CPA4) has shown the potential possibility as a biomarker in the early diagnosis for certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via TIMER2，STRING and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA+GETx database. The connection between CPA44 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared to matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that overexpression of CPA4 is linked with shorter OS, DSF, PFI, and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes, while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.

This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in diabetic retinopathy (DR) Wistar rats, induced to diabetes by intraperitoneal injection with streptozotocin. Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres to obtain the hNPCs, characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell therapy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and verified DR, intravitreal injection of hNPCs (1 x 106 cel/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were done before and after diabetes induction and after cell therapy. Eye enucleation occurred four weeks after treatment for the histopathological and immunohistochemistry analyses. In the treated group, there was the repair of the retinal structures and their arrangements. hNPCs increased the thickness of neuroretina layers, especially in the ganglion cell and photoreceptor layers. The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regeneration of the neuroretinal tissue.

This paper seeks to examine how the Mn-Co spinel interconnect coating microstructure can in-fluence the Cr contamination in an oxygen electrode of intermediate temperature Solid Oxide Cells at the operating temperature of 750 °C. A Mn-Co spinel coating is processed on Crofer 22 APU substrates by electrophoretic deposition and subsequently sintered following both the one-step and two-step sintering, in order to obtain significantly different densification levels. The electrochemical characterization is performed on anode supported cells with a LSCF cathode. The cells were aged prior to the electrochemical characterization in contact with the spinel coated Crofer 22 APU at 750 °C for 250 hours. Current-voltage and impedance spectra of the cells were measured after the exposure with the interconnect. Post-mortem analysis of the interconnect and the cell was carried out in order to assess the Cr retention capability of coatings with different microstructures.

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo Rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the Rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with Rapamycin (10 ng/ml) for 1 hour before LPS. In contrast, Rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo Rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of Rapamycin treated DCs to WT recipients 24 hrs before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/ml) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

Endoplasmic reticulum (ER) is an important organelle responsible as protein synthesis regulator in plant. High salinity can also lead to the activation of ER stress, caused by the accumulation of misfolded protein. This could lead to a stress response mechanism, unfolded protein response (UPR). Failure of UPR to reverse the effect of protein misfolding will activate Programmed Cell Death (PCD). Metacaspase genes regulate programmed cell death (PCD) in plants. The present study was focused on comprehensive gene analyses of the expression patterns of type II rice metacaspase (OsMC) genes in response to the endoplasmic reticulum (ER) and salinity stress in rice leaf and OsMC4 in callus. A strong evidence of unfolded protein response (UPR) during tolerance to both ER and salinity stress was found in the present study. Overexpression of OsMC4 in rice callus as a fusion protein with TagRFP and controlled by the CaMV35 promoter caused major changes in the expression of the stress ER-marker genes, protein disulfide isomerase (PDI) and Binding immunoglobulin Protein (BiP), and OsMC4 in overexpressing calli. These expression analyses of the OsMC family provide valuable information for further functional studies on the biological roles of OsMCs in PCD related to ER and salinity stress responses.

Experimental evolution was utilized to produce 5 magnetite nanoparticle-resistant (FeNP1-5) populations of Escherichia coli. The control populations were not exposed to magnetite nanoparticles. The 24-hour growth of these replicates was evaluated in the presence of increasing concentrations magnetite NPs as well as other ionic metals (gallium III, iron II, iron III, silver I) and antibiotics (ampicillin, chloramphenicol, rifampicin, sulfanilamide, tetracycline). Scanning electron microscope was utilized to determine cell size and shape in response to magnetite nanoparticle selection. Whole genome sequencing was carried out to determine if any genomic changes that resulted from magnetite nanoparticle resistance. After 25 days of selection magnetite resistance was evident in the FeNP treatment. The FeNP populations also showed a highly significantly (p &lt; 0.0001) greater 24-growth as measured by optical density in metals (Fe (II), Fe (III), Ga (III), Ag and Cu II); as well as antibiotics (ampicillin, chloramphenicol, rifampicin, sulfanilamide, and tetracycline). The FeNP resistant populations also showed a significantly greater cell length compared to controls (p &lt; 0.001). Genomic analysis of FeNP identified both polymorphisms and hard selective sweeps in the RNA polymerase genes rpoA, rpoB, and rpoC. Collectively, our results show that E. coli can rapidly evolve resistance to magnetite nanoparticles and that this result is correlated resistances to other metals and antibiotics. There were also changes in cell morphology resulting from adaptation to magnetite NPs. Thus, the various applications of magnetite nanoparticles could result in unanticipated changes in resistance to both metal and antibiotics.

(1) Background: Overall survival of the patients with renal cell carcinoma (RCC) depends mostly on extra-renal extension, documented by the invasion of the pelvicalyceal system, or the perinephric/renal sinus fat or the renal vein/its segmental intraparenchymal branches. Staging may be challenging because of the high inter-observer variability. We have introduced a more accurate procedure to detect the extra-renal extension and, to possibly evaluate the impact of such more laborious approach, we have compared the RCC pathological staging obtained following both standard and modified procedures; (2) Methods: We selected 54 consecutive cases of RCC diagnosed 18 months before and 54 consecutive cases diagnosed 18 months after the introduction of the new method of sampling. Clinico-pathological characteristics have been statistically analyzed; (3) Results: Most of the features analyzed were non statistically significative, except the extra-renal invasion. More precisely, the occurrence of retrograde venous invasion was higher in the cases grossly approached with the more accurate method; (4) Conclusions: Extra-renal extension to intraparenchymal renal vein branches may be underestimated, leading to an inappropriate under-staging. Using more accurate staging procedures, to disclose the occurrence of intra-renal veins tumoral thrombosis, helps to better define the pathological stage, allowing patients to benefit of better fitting treatments.

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, though immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergize with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection, and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency and to improve reproductive health for a significant number of women worldwide.

The corrected mechanism model of battery voltammetric function is helpful to guide the development and application of battery. There are two scientific issues that need to be answered: First, how many mechanisms do batteries have; Second, how to establish the mechanism model separately under the overlapping of these mechanisms. Volt-ampere characteristics of both linear state and nonlinear state exist; the monotonic decreasing of volt-ampere characteristics indicates that the battery have only three kinds of mechanisms. Without changing the basic form of the function and under the principle of the mechanism function’s working region considered, we propose a mechanism function which satisfies the monotonic decreasing characteristic of the voltammetric curve of battery, via the derivative law of each mechanism function in the voltammetric function of battery. By using the voltammetric data, the obtained cell mechanism function can accurately predict the potential (current or voltage) when the independent variable of the cell is zero, and provide the theoretical basis for the internal working mechanism of the cell, which can guide the practice.

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.

It has been demonstrated that a decrease in cellular adenosine triphosphate (c-ATP) causes cellular dysfunction. T-cells are not an exception. One of their roles is to properly detect and eliminate cancer cells. These processes occur at the expense of ATP. Therefore, it can be concluded that a decrease in c-ATP can defect T-cell function and promote cancer evolution. In this article, we provide a hypothesis to describe the correlation between the expression of PD-1 protein on T-cells and their c-ATP levels. Moreover, we present the possible predictive factors of Anti–PD(L)-1 therapy which has not yet been determined definitely.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in China towards the end of 2019, and has spread rapidly ever since. Previous studies showed that some virus could affect the reproductive system and cause long-term complications. Recent studies exploring the source of SARS-CoV-2 using genomic sequencing have revealed that SARS-CoV-2 enters the host cells via the angiotensin-converting enzyme II (ACE2), the receptor that recognizes SARS-CoV. To investigate the expression of ACE2 and to explore the potential risk of infection in the reproductive system, we performed a thorough bioinformatic analysis on data from public databases involving RNA expression, protein expression, and single-cell RNA expression studies. The analyzed data showed high levels of ACE2 mRNA and protein expression in the testis and spermatids and equal levels of ACE2 expression in the uterus and lung. Comprehensive single-cell analysis identified ACE2 expression in the lung, testis, spermatids, and uterus. In conclusion, this study revealed the potential risk associated with the SARS-CoV-2 infection in the reproductive system and predicted that long-term complications might have a significant impact on the prevention and management of COVID-19, the disease caused upon infection with SARS-CoV-2.

Sickle cell disease (SCD) is an inherited condition characterized by chronic haemolytic anaemia. SCD is associated with moderate to severe anaemia, hypercoagulable state and inconsistent platelet count and function. However, studies have yielded conflicting results with regards to the effect of anaemia on coagulation in SCD. The purpose of this study was to determine the effect of anaemia severity on selected coagulation parameters of SCD patients. Four milliters of venous blood samples were taken from the participants (SCD and non-SCD patients) and used for analysis of full blood count and coagulation parameters. Data was analyzed using SPSS version-16. From the results, it was seen that individuals with SCD had a prolonged mean PT, APTT and high platelet count compared to the controls. There was also significant difference in the mean PT (p=0.039), APTT (p=0.041) and platelet count (p=0.010) in HbSS participants with severe anaemia. Mean APTT also showed significant difference (p=0.044) with severe anaemia in HbSC participants. It can be concluded that SCD patients have prolonged PT, APTT and increased platelet count which might predispose them to bleeding episodes and thrombocytosis. Significant difference was also seen between severity of anaemia and mean PT, APTT and platelet count in HbSS individuals.

InGaN/GaN samples grown on c-plane sapphire substrate with different In concentrations by metal organic chemical vapor deposition are demonstrated. The subsequent capping GaN layer growth opens a possibility for dislocation reduction due to the lateral strain relaxation in growth geometry. We present the further growth optimization and innovative characterization of InGaN layers overgrown on different structures with varying In concentrations. The photoelectrical and optical properties of the InGaN layers with or without capping GaN layer were investigated by time-resolved picosecond transient grating and temperature dependence photoluminescence. We note a 10-fold increase in carrier lifetime in the InGaN layers when the sample structure changes from PIN to single InGaN layer.

Morphogenesis remains a riddle, wrapped in a mystery, inside an enigma. It remains a formidable problem viewed from many different perspectives of morphology, genetics, and computational modelling. We propose a biochemical reductionist approach that shows how both internal and external physical forces contribute to plant morphogenesis via mechanical stress-strain transduction from the primary cell wall tethered to the plasma membrane by a specific arabinogalactan protein (AGP). The resulting stress vector with direction defined by Hechtian adhesion sites, has a magnitude of a few picoNewtons amplified by a hypothetical Hechtian growth oscillator. This paradigm shift involves stress activated plasma membrane Ca2+channels and auxin-activated H+-ATPase. The proton pump dissociates periplasmic AGP-glycomodules that bind Ca2+. Thus, as the immediate source of cytosolic Ca2+ an AGP-Ca2+ capacitor directs vectorial exocytosis of cell wall precursors and auxin efflux (PIN) proteins. In toto these components comprise the Hechtian Oscillator and also the gravisensor. Thus interdependent auxin and Ca2+ morphogen gradients account for the predominance of AGPs. The size and location of a cell surface AGP-Ca2+ capacitor is essential to differentiation and explains AGP correlation with all stages of morphogenetic patterning from embryogenesis to root and shoot. Finally, evolutionary origins of the Hechtian Oscillator in the unicellular Chlorophycean algae reflect the ubiquitous role of chemiosmotic proton pumps that preceded DNA at the dawn of life.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), and U87 (human glioblastoma) cells. The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA (at 100 µg/mL) increased the number of apoptotic cells to 27.0% in DU145, 27.0% in MCF-7, and 15.7% in U87 cells, when compared to control cells. This enhanced apoptosis was due to increases in p53, cytochrome c, and Bax expression. OA-treated DU145 cells were arrested in G2 because of the activation of p-ERK and p21, and the decrease in cyclin B1 and cyclin E expression. Furthermore, OA-treated MCF-7 cells were arrested in G1 owing to the activation of p-JNK, p-ERK, p21, and p27, and the decrease in p-AKT, cyclin E, and CDK2. U87 cells also exhibited G1 phase arrest caused by the increase in p-ERK, p-JNK, p21, and p27, and the decrease in CDK2. Thus, OA arrests the cell cycle in different phases, and increases apoptosis in cancer cells. These results suggest that OA may alter the expression of cell cycle regulatory proteins in a cancer type-dependent manner.

Exergy analysis evaluates the efficiency of system components by quantifying the rate of entropy generation. In general, the exergy destruction rate or irreversibility rate was directly obtained through the exergy-balance equation. However, this method cannot determine the origin of the component's entropy generation rate, which is a very important factor in system design and improvement. In this study, a thorough energy, exergy thermoeconomic analysis of a proton exchange membrane fuel cell (PEMFC) was performed, providing the heat transfer rate, entropy generation rate and cost loss rate of each component. The irreversibility rate of each component is obtained by the Gouy-Stodolar theorem. Detailed and extensive exergy and thermoeconomic analyses of PEMFC system have determined that water cooling units experience the greatest heat transfer among the components in the studied PEMFC system, resulting in the greatest irreversibility and thus the greatest monetary flow loss.

The microbiome is capable of modulating the bioavailability of chemotherapy drugs mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic properties on cancer cells. In this study we addressed the question whether the cytostatic bacterial metabolites (cadaverine, indolepropionic acid, indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil, paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range and the effects on cell proliferation were assessed. There was no interference between doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib and the bacterial metabolites. Nevertheless, cadaverine increased the Hill coefficient of the inhibitory curve of 5-fluorouracil and indolepropionic acid increased the IC50 value of 5-fluorouracil that are either disadvantageous effects or effects of unknown significance. Nevertheless, indolepropionic acid decreased the IC50 value of paclitaxel that is a potentially advantageous combination.

The advent of immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), improving the prognosis of this disease and becoming a key part of the treatment, especially in the population without an oncogenic driver mutation. Two different groups of immune checkpoint inhibitors (ICIs) are used in lung cancer: Anti- Cytotoxic T-lymphocyte antigen-4 (Anti-CTLA 4) and Anti- T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti PD-L1). Here in, we review an uptodate on the use of immunotherapy for advanced NSCLC.

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Accumulating clinical and experimental evidence suggests the role of cyclo-oxygenase (COX) enzymes in the pathogenesis of cancers including HCC. Deuterium-enriched water (DEW) and deuterium-depleted water (DDW) play a role both in the treatment and prevention of cancers. Combination therapy using COX-inhibitors and DDW/DEW could be a rational strategy to enhance the cytotoxicity of either agent in HCC. The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW or DEW was determined in the Hep-G2 HCC cell line by MTT assay. The COX-2, MAPK pathway proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins, and caspase-3 activity were determined by SDS-PAGE and western blot. Co-treatment of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and apoptosis of Hep-G2 cells. These events were associated with the activation of p38 and JNK MAPKs and a decrease in pro-survival proteins Bcl-2, COX-2, and ERK1/2. Furthermore, the combination therapy activated caspase-3, and the apoptosis mediator, and disabled poly ADP-ribose polymerase (PARP), the key DNA repair enzyme, by cleaving it. The combination of DEW with NSAIDs might be effective against HCC cells by influencing principal cell signaling pathways, and this has a potential to become a candidate for chemotherapy.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to resolution of questions regarding the pathogenesis of PASC.

Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symp-tomatic benefit in Parkinson’s disease (PD) treatment and found to exert preclinical neuroprotec-tive effects. Here, we investigated the neuroprotective signaling pathways of rasagiline in the PC12 neuronal cultures exposed to an ischemic-like insult. Exposure of neurons to oxy-gen-glucose deprivation for 4 h followed by 18 h of reoxygenation caused 40% aponecrotic cell death. Rasagiline induced dose-dependent neuroprotection by decreasing cell death and produc-tion of the neurotoxic reactive oxygen species, and reducing the nuclear translocation of glycer-aldehyde-3-phosphate dehydrogenase (GAPDH). Rasagiline increased protein kinase B (Akt) phosphorylation and decreased protein expression of the ischemia-induced α-synuclein protein, in correlation to the neuroprotective effect. Treatment with rasagiline induced nuclear shuttling of transcription factor Nrf2 and increased the mRNA levels of the antioxidant enzymes heme oxy-genase-1, (NAD (P) H- quinone dehydrogenase, and catalase. These results indicate that rasagiline provides neuroprotection in the ischemic neuronal cultures with inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, and via mitochondrial protection, as by increasing mi-tochondria-specific antioxidant enzymes by a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma (ccRCC) samples were re-analyzed from the Genomic Fabric Perspective that considers the transcriptome a multi-dimensional mathematical object, constrained by a dynamic set of expression correlations among genes. Every gene in the chest wall metastasis (MET), two primary tumors (PTA, PTB) and the surrounding normal tissue (NOR) of the right kidney was characterized by three independent measures: average expression level (AVE), relative expression variation (REV) and expression correlation (COR) with each other gene. AVE was used to determine the regulation of the genomic fabrics of ccRCC, apoptosis, chemokine and VEGF signaling pathways. REV quantified the alteration of the transcripts’ abundances control, while COR determined the remodeling of the transcriptomic networks of chemokine signaling and oxidative phosphorylation genes. The gene hierarchy was established in based on Gene Commanding Height and the Gene Master Regulators (GMR) TASOR (PTA), FAM27C (PTB) and ALG13 (MET) and DAPK3 (NOR) were identified in each profiled region. We predict that TASOR overexpression would block transcription in PTA but not in PTB, while slightly stimulating it in NOR. Silencing of ALG3 would slow-down the cell-cycle in all three cancer regions with practically no effect in NOR.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

In this study the formation of thin-film barrier coatings based on a highly-conducting Bi1.60Er0.4O3 (EDB) solid electrolyte on supporting Ce0.8Sm0.2O1.9 (SDC) electrolyte substrates is implemented for the first time using electrophoretic deposition (EPD). Electrokinetic properties of EDB-based suspensions in a non-aqueous dispersion medium of isopropanol modified with small additions of polyethyleneimine (PEI, 0.26 g/L) and acetylacetone (0.15 g/L), as well as in a mixed isopropanol/acetylacetone (70/30 vol.%) medium are studied. The dependences of the thickness of EDB coatings on voltage and deposition time are obtained using deposition on a model Ni-foil electrode. Preliminary synthesis of a conductive polypyrrole (PPy) polymer film is used to create surface conductivity of non-conductive SDC substrates. The efficiency of using a modified dispersion medium based on isopropanol to obtain a continuous EDB coating 12 μm thick, sintered at a temperature of 850 °C for 5 h, is shown. The microstructure and morphology of the surface of the EDB coating are studied. Pt/SDC/EDB/Pt cell is used to characterize the coating conductivity. The EPD method is shown to be promising for the formation of barrier coatings based on doped bismuth oxide. The developed method can be used for creating cathode barrier layers in SOFC technology.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

The authors determined mass concentrations of 12 elements (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Sr, Tl, V, Zn) in blood and urine taken from 100 rural children living in unremarkable condition in the West Ural region of the Russian Federation. We applied inductively coupled plasma mass spectrometry in conformity with Methodical Guidelines 4.1. 3230-14 (FR.1.31.2014.17064) designed by us and detailed in the paper. The article contains setting parameters for Agilent 7500cx quadrupole inductively coupled plasma mass spectrometer . The authors present grounds for an optimal scheme of samples preparation which helps to eliminate "matrix" effect and explain why it is advisable to use reaction/collision functioning mode as it enables interference overlaps suppression.To prepare whole blood samples for analysis, we used acid dissolution in concentrated nitric acid followed by centrifugation. The arithmetic mean (AM) of element content in blood amounted to 0.34 µg/l (As); 0.39 µg/l (Cd); 6.41 µg/l (Cr); 866.11 µg/l (Сu); 13.73 µg/l (Mn); 5.86 µg/l (Ni); 23.65 µg/l (Pb); 87.43 µg/l (Se); 33.54 µg/l (Sr); 0.04 µg/l (Tl); 0.16 µg/l (V); 4713.48 µg/l (Zn). The validity of the results was confirmed by means of SERONORM ^TM Whole Blood L2 standard samples (Norway). Urine samples were directly analyzed after 1/10 (V/V) dilution with 1% nitric acid solution. The arithmetic mean of element content of urine corresponded to 18.99 µg/l (As); 0.12 µg/l (Cd); 1.91 µg/l (Cr); 13.28 µg/l (Сu); 0.96 µg/l (Mn); 1.84 µg/l (Ni); 0.83 µg/l (Pb); 22.55 µg/l (Se); 239.09 µg/l (Sr); 0.16 µg/l (Tl); 0.68 µg/l (V); 270.56 µg/l (Zn). The validity of the results was confirmed by analyzing the SERONORM ^TM standard urine samples (Norway). Regional differences from levels found in other countries included higher concentrations of Cr, Mn and Ni in blood and lower levels of Se and Zn levels in West Ural children. Urine concentrations of West Ural children showed higher levels of As and Sr.

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.

To obtain an accurate and reproducible experimental results in microbial fuel cell (MFC), it is important to know ‘anode maturation biofilm’ to produce a stable and maximum performance. For this purpose, four single chamber MFCs were tested in this study. The linear sweep voltammetry (LSV) polarization tests illustrated that maximum power densities of three MFCs became stable after 9 weeks. Although there were variations afterwards, such variations were negligible. Average maximum power densities from the 9th to the 17th week were 2,990 mW/m2 (MFC-4), 2,983 mW/m2 (MFC-2), 2,368 mW/m2 (MFC-3) and 837 mW/m2 (MFC-1). Polarization resistance shows that MFC-1 had much larger anode resistance (36.6-85.4 Ω) than the other MFCs (1.7-11.6 Ω). Anodic cyclic voltammetry (CV) shows that current production increased over time and MFC-1 had much smaller current production (24.4 mA) than the other MFCs (31.0-34.9 mA) at 17th week. The increased current production indicates anode biofilm became more mature over time, but overall cell performance did not increased accordingly. Possibly due to the bad inoculation, MFC-1 showed the lowest performance. However, its performance was restored to the initial performance and anode resistance was reduced by 47% at 17th week. This study shows that the optimum anode maturation time is 9 weeks and that bioanode performance is a key factor for MFC performance. This study also shows than LSV polarization and CV tests are accurate and non-destructive measurement methods for diagnosing anode performance.

γδT have functions of innate and adaptive immunity, with the potential to induce durable responses while being well-tolerated, with limited adverse effects, making it attractive as a tool for immunotherapy. γδT faces challenges as a frontline tool in clinical oncology, with limited response rates due to difficulties in reaching tumor sites with consistent cytotoxic activity and strength. Modulated Electro-hyperthermia (mEHT) is a loco-regional treatment, whereby energy-transmission from an electromagnetic field selectively targets the plasma membrane of tumor cells, inducing apoptosis and activating immune cells. We hypothesized that mEHT could enhance therapeutic effects by drawing γδT to tumor cells, while also rendering tumor cells to be more susceptible to cytotoxic effects. In this study, NOD/SCID mice harboring subcutaneous human HepG2 tumors were treated with intravenous injections of γδT after mEHT treatment. This method increased infiltration of γδT into the tumor site, significantly inhibiting tumor growth as compared to monotherapy with either modality. These data suggest that γδT could mediate a potent anti-tumor effect when combined with mEHT, and provide a strong rationale for combining these modalities in clinical application for cancer treatment.

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Today the characterization of this type of cells with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: f_x01 in low frequency range (below 500 kHz) and f_x02 in Ultra High Frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. U87-MG cell lines were cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients’ primary cell culture, were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low frequency range DEP does not allow the discrimination of the undifferentiated from the differentiated phenotypes of GBM cells. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetic of U87-MG phenotype transformation in a CSC enrichment medium and their cancer stem cells phenotype acquirement.

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

Stabilized un-doped Zinc Telluride (ZnTe) thin films were grown on glass substrates under vacuum using closed space sublimation (CSS) technique. A dilute copper nitrate solution (0.1/100 ml) was prepared for copper doping known as ion exchange process in the matrix of ZnTe thin film. The reproducible polycrystalline cubic structure of undoped and Cu doped ZnTe thin films with preferred orientation (111) was confirmed by X-rays diffraction (XRD) technique. Lattice parameter analyses verified the expansion of unit cell volume after incorporation of Cu species into ZnTe thin films samples. The micrographs of scanning electron microscopy (SEM) were used to measure the variation in crystal sizes of samples. The energy dispersive X-rays was used to validate the elemental composition of undoped and Cu-doped ZnTe thin films. The bandgap energy 2.24 eV of ZnTe thin film decreased after doping Cu to 2.20 eV may be due to the introduction of acceptors states near to valance band. Optical studies showed that refractive index was measured from 2.18 to 3.24 whereas thicknesses varied between 220 nm to 320 nm for un-doped and Cu doped ZnTe thin film respectively using Swanepoel model. The oxidation states of Zn⁺², Te⁺² and Cu⁺¹ through high resolution X-ray photoelectron spectroscopy (XPS) analyses was observed. The resistivity of thin films changed from ~10⁷ Ω-cm for undoped ZnTe to ~1 Ω-cm for Cu-doped ZnTe thin film, whereas p-type carrier concentration increased from to respectively. These results predicted that Cu-doped ZnTe thin film can be used as an ideal, efficient and stable intermediate layer between metallic and absorber back contact for the heterojunction thin film solar cell technology.

We analyzed signal transduction of three constitutively activating mutants (M410T, L469R, and D590Y) and two inactivating mutants (D417N and Y558F) of the eel luteinizing hormone receptor (eel LHR), known to occur in human LHR. The objective of this study was to assess the functional effects of these mutations in signal transduction and cell surface loss of receptor. Mutant receptors were transiently expressed in Chinese hamster ovary (CHO-K1) cells. Eel LH-stimulated accumulation of cyclic adenosine monophosphate (cAMP) was measured by homogeneous time-resolved fluorescence (HTRF) assays. The loss of receptors from the cells surface was measured using an enzyme-linked immunosorbent assay (ELISA) in human embryonic kidney (HEK) 293 cells. The cAMP response in cells expressing the wild type eel LHR was increased in a dose-dependent manner using eel LH ligand stimulation. Compared with the wild type, cells expressing the activating mutants (M410T, L469R, and D590Y), exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response without agonist stimulation, respectively. Their maximal responses to agonist stimulation were approximately 65%, 52%, and 98%, respectively, of those of the wild type. The inactivating mutants (D417N and Y558F) did not completely impair signal transduction, and their maximal responses were only 33% and25 % of those of wild type. These data clearly showed that the eel LHR-L469R and D590Y, activating mutants enhanced the rate of the loss of cell surface receptors following treatment with eel LH. Thus, the loss of cell surface receptors in cells expressing mutant eel LHRs was consistent with the eel LH agonist-induced production of cAMP. Our results suggested that the activation of the eel LHR requires appropriate loss of LHR-ligand complexes from the cell surface.

Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with „no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agent’s pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we have reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 ml of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (n=22) were considered responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (n=13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI) and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP ˃ 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (n=22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (n=20) had significantly reduced pain scale after BMCs transplant, compared to the NON-RAS group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (n=17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responder and previous treatment before BMCs transplant with RAS-acting agents alone or atorvastatin were significant.

Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 is a master regulator of oxidative stress. Here we reported that the FDA-approved, oral agent simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A reductase, significantly activates the expression of Nrf2 and antioxidant enzymes. Simvastatin also induces fetal hemoglobin expression in SCD patient erythroid progenitors and a transgenic mouse model. Simvastatin alleviates SCD symptoms by decreasing hemoglobin S sickling, oxidative stress, and inflammation stress in erythroblasts. Particularly, simvastatin increases cellular levels of cystine, the precursor for the biosynthesis of antioxidant reduced glutathione and decreases the iron content in SCD mouse spleen and liver tissues. Mechanistic studies suggest that simvastatin suppresses the expression of critical histone methyltransferase, Enhancer of zeste homolog 2 to reduce both global and gene-specific histone H3 lysine 27 trimethylation. These chromatin structural changes promote the assembly of transcription complexes to fetal γ-globin and antioxidant genes regulatory regions, in an antioxidative response element-dependent manner. In summary, our findings suggest that simvastatin activates fetal hemoglobin and antioxidant protein expression and modulates iron and cystine/reduced glutathione levels to improve the phenotype of SCD and represents a therapeutic strategy for further development.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Laryngeal squamous cell carcinoma (SCC) is a head and neck cancer (about 5% of all cancers, and up to 95% of laryngeal cancers; more frequent in males than in females, ratio of 3.9/1) with characteristics depending on its location, with glottis, supraglottis, and subglottis being the most frequent. In African Americans, it appears at younger ages and has lower survival rates than in Caucasians, Hispanics, and Asians. Primary risk factors are tobacco and alcohol consumption. Treatments vary based on the site and stage of the tumor and include radiotherapy, transoral laser microsurgery, and surgery, including partial or total laryngectomy. This study aimed to map by immunohistochemistry four members of the Chaperone System (CS), namely Hsp10, Hsp27, Hsp60, and Hsp90, in laryngeal tissue during the progression from healthy stage to full malignancy, passing through dysplasia. The four chaperones increased in the tissues and changed distribution with the progression of carcinogenesis. The findings provide a histopathological platform for launching in-depth analyses of the mechanisms underpinning the role of the four chaperones in the development of squamous cell carcinoma of the larynx. Also, the data indicate that the four chaperones have potential as biomarkers for diagnosis, prognostication, and patient follow-up.

One-Dimensional Solar Cell Capacitance Simulator (1D-SCAPS) and n-i-p planar configuration have been employed for the simulation of the caesium tin iodide (CsSnI₃)-based perovskite solar cell (PSC) with titanium (IV) oxide (TiO₂) and copper thiocyanate (CuSCN) as the electron and hole transport materials respectively. The results obtained for the initially modeled PSC compared well with similar devices in the literature but marred with high recombination rate. As such, the defect density in the CsSnI₃ absorber was varied from 10¹³ cm^-3 to 10¹⁷ cm^-3 and enriched with SnCl₂ (additive) and Br⁻(dopant) respectively. This strategy ensured a reduced concentration of Sn⁴⁺ vacancy (V_Sn) in the CsSnI₃ absorber with improved carrier lifetime and diffusion length beyond 0.05 ns and 1.1µm by a magnitude of the order of 10³ and 10² respectively for the enriched CsSnI₃ –based PSC. For the optimized PSC, we recorded V_OC=1.289 V, J_SC=32.60 mA.cm^-2, FF=83.56% and PCE=35.12%.

Given the pathological role of hyperphosphorylated Tau aggregation in Alzheimer’s disease (AD) our laboratory previously developed the novel Tau aggregation inhibitor peptide, RI-AG03. As Tau aggregates accumulate intracellularly, it is essential that Tau-targeting peptides efficiently traverse the cell membrane. In addition, these peptides need to avoid sequestration into cell organelles, particularly those involved in degradation, to ensure interaction with Tau in the cytoplasm. Here, we examine the cellular uptake and intracellular trafficking of RI-AG03 when the peptide is unconjugated or linked to nanoliposome carrier particles. The impact of adding the cell penetrating peptide (CPP) sequences, polyarginine (polyR) and transactivator of transcription (TAT), to RI-AG03 was also characterised. Our data show that the conjugation of CPP-containing RI-AG03 to liposomes dramatically increases cellular liposomes uptake. The majority of this uptake occurs via direct cell penetration. However, we find that macropinocytosis is also an important mechanism for unconjugated and RI-AG03-polyR-conjugated, but not RI-AG03-TAT-conjugated, liposome uptake. In agreement with this macropinocytosis-mediated internalisation, liposome lipids localise to lysosomes and macropinosomes following cellular uptake. However, while unconjugated RI-AG03 peptides also localise to lysosomes, liposome conjugation prevents this localisation, with the peptide detaching from the liposomes at the cell surface and evading organelle entrapment. Overall, this study demonstrates that CPP sequences and nanoliposomes carriers enhance the intracellular delivery of RI-AG03, furthering the possibility of the peptide’s use in targeting Tau pathology in AD.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.