Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

The increasing global demand for energy and the pressing challenge of environmental pollution necessitates a paradigm shift towards sustainable energy sources. Hydrogen, a viable renewable energy carrier, has the potential to substantially alleviate these concerns. This review offers a comprehensive exploration of the technologies imperative to the production and operation of fuel cell vehicles (FCVs), ranging from various fuel cell types, hydrogen storage methods, fueling station logistics, batteries in hydrogen vehicles, and the emerging influence of artificial intelligence and quantum computing. An analytical overview of global adoption patterns reveals significant geographical disparities, with the United States and South Korea at the forefront of FCV integration, primarily in the form of passenger cars, followed by buses and trucks. Asia emerges as the region with the highest proportion of FCVs. This paper also delves into the diverse challenges facing FCV implementation, shedding light on the essential role of continued investment in the evolution of sustainable transportation systems. Furthermore, it provides insights into the varying contributions of different companies in the field, demonstrating the collective effort required to advance this promising technology. The comprehensive exploration provided in this review aids in understanding the opportunities, challenges, and potential of hydrogen as an integral player in the future of sustainable transportation. The increasing need for energy carriers and the rise of environmental pollution have driven the exploration of renewable energy sources, with hydrogen being a promising option.

Our findings indicate that all five phytocannabinoids reduce HG-HL-induced -cell loss likely through reducing apoptosis and pyroptosis. The protective effects of CBD, THCV, CBC, and CBN were seen in the GSIS impairment by HG-HL. Although all five phytocannabinoids tested in this research demonstrated the capability to inhibit β-cell dedifferentiation induced by HG-HL, CBD seems to be more effective compared to the other phytocannabinoids, as indicated by the specific biomarker responses of β-cells and progenitor cells to CBD.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

Djeya1 (RKLAFRYRRIKELYNSYR), is a very effective cell penetrating peptide (CPP) which mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species variable sites: 10,13,16. CD analyses indicted that Djeya1 is highly helical and that Aib-substitution had little influence on secondary structure. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells which express high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblast are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

Bacterial transformation is the essential tool for introducing foreign DNA into bacterial cells in a host of recombinant technology applications useful for biomanufacturing and drug production. Thus far, chemically competent cells remain an important enabling technology for bacterial transformation given its facile transformation approach. However, many parameters affect transformation efficiency, and there is relatively little documentation of their cross-interacting effect in the literature. This work explores the roles played by incubation time on ice, competent cell concentration, and plasmid-to-cell ratio on transformation efficiency in Escherichia coli DH5α. Results revealed that increases in incubation time improve transformation efficiency, but 2 minutes incubation still yield appreciable efficiency. On the other hand, low concentration competent cells (10⁶ CFU/mL) yielded significant improvement in transformation efficiency compared to high concentration competent cells (10⁸ CFU/mL). In terms of plasmid-to-cell ratio, higher ratio increases transformation efficiency. Overall, bacterial transformation is incompletely understood particularly in the area of cross-interacting parameters. Experiments reported here revealed the possibility of short duration transformation where lower competent cell concentration and higher plasmid-to-cell ratio could improve transformation.

The global context of research for new sustainable energy storage technologies makes it a very active sector with significant scientific and economic challenges. Indeed, due to the irregular development of renewable energies and the shutdown of traditional power facilities, it is difficult to maintain a stable balance in terms of supply and demand: energy storage can help in particular for substantial changes in the latter. Metal air batteries have a higher energy density and are safer than other available energy storage devices. Based on the existing and proven lead-acid battery technology, this paper proposed an open cell foam manufactured by the Excess Salt Replication process for use as an anode for lead-air battery cellsies with sulphuric acid as the electrolyte. This will save lead and reduce the battery weight. A 25% antimonial lead alloy was used to produce open cell foams with a cell diameter between 2 mm and 5 mm for the antimonial lead-air battery. Preliminary results of the effective electrical conductivity of self-discharged primary battery cells, measured experimentally, showed that all antimonial lead foam-air battery cellsies performed better than that made from the same dense non porous antimonial lead alloy. This is generally due to their important specific surface area where oxidation-reduction reactions took place. A correlation between the effective electrical conductivity and the cell diameter has been established and the highest conductivity was obtained with a cell diameter of 5mm. The feasibility of such an electrical system has been demonstrated.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. This phenomenon, termed Post-Acute Sequelae of SARS-CoV-2 (PASC) or Long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of auto-antibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include degree of host response (inflammation, NETinjury), residual viral antigen (persistent antigen) and exogenous factors (microbial translocation). Determinants of PASC may be amplified by co-morbidities, age, and sex. Keywords: long COVID, PASC, long haulers, NETosis, T cell, NK cell, DC, neutrophil,

Although the first cancer immunotherapy was given in the clinic more than a century ago, this line of treatment has remained more of a distant goal than a practical therapy due to limited understanding of the tumor microenvironment and the mechanisms at play within it, which lead to failures of numerous clinical trials. However, in the last two decades, the immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies have revolutionized the treatment of cancer and provided proof-of-concept that immunotherapies are a viable option. So far, immunotherapies have majoritarily focused on utilizing T cells, however T cells are not autonomous but rather function as part of, and therefore are influenced by, a vast cast of other immune cells, including innate lymphoid cells (ILCs). Here, we summarize the role of ILCs, especially helper ILCs, in tumor development, progression and metastasis, as well as their potential to be used as immunotherapy for cancer. By reviewing the studies that used helper ILCs as adoptive cell therapy, we highlight the rationale behind considering these cells as novel adoptive cell therapy for cancer as well as identify open questions and areas for future research.

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and potentially accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine if ototoxins can effectively silence the lateral line during early development, we repeatedly expose zebrafish larvae to the ototoxin neomycin during a 36-hour period from 3-4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6- hour and 12-hour repeated treatment timelines and neomycin concentrations between 0–400 µM in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate lateral line hair cells between 3–4 dpf in larval zebrafish.

Electrochemical-mechanical interactions, in particular pressure-induced ones, have been identified to be a cause for lithium-plating in lithium-ion cells. Mechanically-induced porosity inhomogeneities in the separator layers due to electrode expansion during charging especially lead to cell internal balancing currents and can cause localized plating. To identify cell-format and cell-material dependent mechanical weak spots, a layer-resolved mechanical simulation of different cell types and cell-material combinations is presented in this work. The simulation results show distinctive layer strain patterns for different cell-types that coincide with localized lithium-plating found in post-mortem cells. Additionally, the effects of cell bracing in battery modules is investigated and a method to mitigate the increased layer strain due to bracing counterforces is proposed that also increases cell energy density for hardcase-type automotive cells.

Understanding the biology underlying the mechanisms and pathways regulating pancreatic β-cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin producing β-cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β-cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β-cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive toβ-cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1⁺/NKX6.1⁺), warrants their future commitment to monohormonal β-cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1⁺/NKX6.1^-) results in an undesirable generation of non-functional polyhormonal β-cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β-cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a mean to increase β-cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β-cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

Cellular substructure has been widely observed in the sample fabricated by laser powder bed fusion, while its growth direction and the crystallographic orientation have seldom been studied. This research tries to build a general model to construct the substructure from its two-dimensional morphology. All the three Bunge Euler angles to specify a unique growth direction are determined, and the crystallographic orientation corresponding to the growth direction is also obtained. Based on the crystallographic orientation, the substructure in the single track of austenitic stainless steel 316L is distinguished between the cell-like dendrite and the cell. It is found that, with the increase of scanning velocity, the substructure transits from cell-like dendrite to cell. When the power is 200 W, the critical growth rate of the transition in the single track can be around 0.31 ms^-1.

Fossil fuels and carbon origin resources are affecting our environment. Therefore, alternative energy sources have to be established to co-produce energy along with fossil fuels and carbon origin resources until it is the right time to replace them. Microbial Fuel Cell (MFC) is a promising technology in the field of energy production. Compared to the conventional power sources it is more efficient and not controlled by the Carnot cycle. Its high efficiencies, low noise, and less pollutant output could make it revolutionize in the power generation industry with a shift from centrally located generating stations and long-distance transmission lines to dispersed power generation at load sites. In this review, several characteristics of the MFC technology will be highlighted. First, a brief history of abiotic to biological fuel cells and subsequently, microbial fuel cells is presented. Second, the focus is then shifted to elements responsible for the making MFC working with efficiency. Setup of the MFC system for every element and their assembly is then introduced, followed by an explanation of the working machinery principle. Finally, microbial fuel cell designs and types of main configurations used are presented along with scalability of the technology for the proper application.

Cells take decisions on their responses depending on the stimuli received by the surrounding extracellular environment, that provides the essential cues at the micro and the nano-lengthscales required for adhesion, orientation, proliferation and differentiation. In this study, discontinuous microcones on silicon (Si) and continuous microgrooves on polyethylene terephthalate (PET) substrates were fabricated via ultrashort-pulsed laser irradiation at various fluences, resulting in microstructures with different roughness and geometrical characteristics. The topographical models attained were specifically developed to imitate the guidance and alignment of Schwann cells for oriented axonal regrowth, towards nerve regeneration. At the same time, positive replicas of the silicon microstructures formed were successfully reproduced, via soft lithography, on the biodegradable polymer poly(lactide-co-glycolide) (PLGA). The anisotropic continuous (PET) and discontinuous (PLGA replicas) microstructured polymeric substrates were assessed in terms of their influence on the Schwann cells responses. It is shown that the developed micropatterned substrates enable control over the cellular adhesion, proliferation and orientation and are thus useful to engineer cell alignment in vitro. This property could be potentially useful in the fields of neural tissue engineering and for dynamic microenvironment systems that simulate in vivo conditions.

In this paper, the single event burnout(SEB) and reinforcement structure of 1200V SiC MOSFET (SG-SBD-MOSFET) with split gate and schottky barrier diode(SBD) embedded were studied. The device structure was established using Sentaurus TCAD, and the transient current changes of single event effect(SEE), SEB threshold voltage, as well as the regularity of electricfield peak distribution transfer were studied when heavy ions were incident from different regions of the device. Based on SEE analysis of new structural device, two reinforcement structure designs for SEB resistance were studied, namely the expansion of P+body contact area and the design of multi-layer N-type interval buffer layer. Firstly, two reinforcement schemes for SEB were analyzed separately, and then comprehensive design and analysis were carried out. The results showed that the SEB threshold voltage of heavy ions incident from the N+source region was increased by 16% when using the P+body contact area extension alone; When the device is reinforced with multi-layer N-type interval buffer layer alone, the SEB threshold voltage increases by 29%; The comprehensive use of P+body contact area expansion and multi-layer N-type interval buffer layer reinforcement increased the SEB threshold voltage by 33%. Overall, the breakdown voltage of the reinforced device decreased from 1632.935V to 1403.135V, which can be seen as reducing the remaining redundant voltage to 19%. The device performance was not significantly affected.

We investigate a single-particle density of states in the three-dimensional system described by effective two-band Hamiltonian which describes a ground state in two distant electronic phases: the semimetalic nodal-loop phase and the insulating gapped phase. Analysis of valence bands and Fermi surfaces in both phases indicates that the density of states crucially depends on the parameter in the Hamiltonian of the system that controls a topological alternation of the Fermi surface. The signature of that alternation is expected to play an important role in all quantities closely related to the density of electronic states, such as charge transport and optical conductivity of the system for example.

Aspergillus fumigatus is a ubiquitous, critical priority human fungal pathogen. Despite its clinical importance, there is limited knowledge regarding the variations of the genome within mitochondria, the powerhouse organelle within eukaryotic cells. In this study, we leveraged publicly available raw, whole genome sequence data from 1939 isolates to investigate the variations in the mitochondrial genomes of A. fumigatus. These isolates were isolated from 22 countries on six continents, as well as from outer space and from within the International Space Station. In total, our analysis revealed 39 mitochondrial single nucleotide polymorphisms (mtSNPs) within this global sample and together, these 39 mtSNPs grouped the 1939 isolates into 79 mitochondrial multilocus genotypes (MLGs). Among the 79 MLGs, 39 were each distributed in at least two countries and 30 were each shared by at least two continents. The two most frequent MLGs were also broadly distributed: MLG11 represented 420 isolates from 11 countries and four continents and while MLG79 represented 418 isolates from 18 countries and five continents, consistent with long-distance dispersals of mitogenomes. Our population genetic analyses of the mtSNPs revealed limited differentiation among continental populations but highly variable genetic differences among national populations, largely due to localized clonal expansions of different MLGs. Phylogenetic analysis and Discriminant Analysis of Principal Components of mtSNPs suggested the presence of at least three mitogenome clusters. Linkage disequilibrium, Index of Association, and phylogenetic incompatibility analyses collectively suggested evidence for mitogenome recombination in natural populations of A. fumigatus. In addition, sequence read depth analyses revealed an average ratio of ~20 mitogenomes per nuclear genome in this global population but the ratios varied among strains within and between certain geographic populations. Together, our results suggest evidence for organelle dynamics, genetic differentiation, recombination, and both widespread and localized clonal expansion of the mitogenomes in the global A. fumigatus population.

Background: Identifying genetic mutations that lead to spermatogenic impairment is essential for offering patients informed genetic counseling and preventing the transmission of genetic defects to their offspring, often through the use of advanced reproductive technologies. Objectives: The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Methods and Materials: Genetic variants that may cause infertility are identified by combining targeted next generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Results: Our analysis revealed five distinct affected genes covering seven SNPs: based on targeted NGS panel and WES data, namely SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150) and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. Discussion and Conclusions: These findings strongly support the hypothesis that dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2 and DRC7 mutations are associated with male infertility, specifically azoospermia, further examination of this genetic function is required.

Event-related potentials (ERPs) are estimated by averaging time-locked single trial electroencephalography (EEG) signals in response to specific events or stimuli. Classifying ERPs accurately is a challenge because (a) single trials have poor signal-to-noise-ratios (SNRs) and (b) it is difficult to collect large single trial ensembles to generate high SNR ERPs for classifier training and testing. The m-subsample averaging (m-SA) strategy which generates small-sample ERPs by repeated averaging of a small number of single trials drawn without replacement, has been proposed as a solution to the two problems. An ERP formed by averaging m single trials is referred to as an m-ERP where m is referred to as the averaging parameter. In this study, we conduct thorough analyses of m-SA and focus on issues not addressed in previous studies to better understand the beneficial properties of m-SA and to further support its application for ERP classification. Specifically, we (a) analyze the improvement in SNR as a function of m using the mean-root-mean-square SNR and visual analyses of m-ERP plots with confidence intervals, (b) analyze the improvement in interclass separation as a function of m, (c) determine how the SNR and interclass separation analyses can help to select the averaging parameter m, (d) determine the number of distinct m-ERPs that can be drawn from a single-trial ensemble, and (e) determine several probabilities related to the generation of distinct m-ERPs. Furthermore, an extensive set of experiments are designed to analyze the performance of support vector machine and convolution neural network classifiers employing m-SA with various combinations of the averaging parameters used for generating the training and test sets. The results confirm that ERPs can be classified accurately using small subsample averaging. Most importantly, it is concluded that m-SA can be deployed in practice to accurately classify ERPs in brain activity research and in clinical applications without having to collect a prohibitively large number of single trials.

In this work, the use of graphite-like carbon nitride (g-C3N4) with improved texture characteristics for the synthesis of supported palladium catalysts of dehydrogenation of nitrogen-containing heterocycles was studied. This process is key to the creation of liquid organic carrier technology (LOHC) using N-heterocycles as reversibly hydrogenated/dehydrogenated substrates. For the preparation of g-C3N4-mca supports with advanced textural characteristics, well-established technology of the melamine cyanurate complex carbonization and standard techniques of adsorption precipitation together with wet impregnation were used for the synthesis of Pd-containing systems. The activity of the synthesized catalysts was studied in decahydroquinoline dehydrogenation. The high weight content of extractable hydrogen (7.2 wt %) and the high extraction rate, respectively, make it possible to consider these substances as the most promising N-heterocyclic compounds for this technology. It was shown that an increase in the specific surface area of g-C3N4 allows for achieving a slightly lower, but comparable fineness of palladium particles for the 1 wt% Pd/MCA-500 sample, compared to the standard 1 wt% Pd/C. In this case, the catalytic activity of 1 wt% Pd/MCA-500 in dehydrogenation of both substrates exceeded the analogous parameter for catalysts supported by nitrogen free supports. This regularity is presumably associated with the electron-donor effect of surface nitrogen, which favorably affects the dehydrogenation rate as well as the stability of catalytic systems.

For children born with congenital heart defects (CHD), extracorporeal life support may be necessary. This study aimed to investigate the outcomes of children on extracorporeal membrane oxygenation (ECMO), focusing on various risk factors, including the type of CHD. The study was conducted as a retrospective single-center analysis at the Children's Hospital Zurich. All patients with CHD who required ECMO (veno-arterial or veno-venous) between 2009 and 2019 were included. Among the 88 patients, 36 (41%) had a single ventricle heart defect while 52 (59%) had a biventricular heart defect. Out of the total patients, 25 (28%) survived, with 7 (8%) having a single ventricle heart defect and 18 (20%) having a biventricular heart defect. Statistical analysis with a p-value of 0.19 revealed no significant difference in survival rates between the two groups. At the one-year follow-up, all children who survived to discharge were still alive. The rate of complications on ECMO was higher in children with a single ventricle (odds ratio [OR] 1.57, 95% confidence interval [CI] 0.67 - 3.7). The occurrence of a second ECMO run was more frequent in patients with a single ventricle compared to those with a biventricular physiology (22% vs. 9.6%). Although the study did not identify a significant difference in survival rates, it did indicate that patients with a single ventricle faced a higher risk of complications during ECMO and a greater likelihood of requiring a second ECMO run.

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD. We compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score &gt;5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop RBD in PD. Additional investigations are needed.

This paper presents a novel approach of welding thick steel plates that offers time and energy savings compared with conventional techniques. The combination of gas metal arc welding (GMAW) and hot-wire technology simplifies the joint configuration and enhances the process tolerance. In this study, a square butt joint was prepared with as-cut edges and a thickness of 15 mm. The relationship between the welding current and the deposition rate of solo GMAW showed limitations and low process tolerance. Increasing the welding current led to a larger deposited volume with unnecessary weld penetration. An independent deposition volume due to hot-wire insertion was used to improve process tolerance. This approach provided an additional volume without increasing the welding current and reduced unnecessary penetration. With optimized parameters, full-penetration single-pass welding was achieved. Compared with the formation of a typical single-v butt joint at a similar welding speed of 30 cm/min, the proposed process reduced the minimum arc time and power consumption by approximately 83% and 62%, respectively. Moreover, a single pass at a travel speed of 60 cm/min was achieved with approximately 91% and 81% less arc time and power consumption, respectively. In summary, the combined process simplifies the joint configuration, enables full-penetration single-pass welding, and reduces time and energy requirements.

The preparation of sulfur-single walled carbon nanohorns active material via a simple and sustainable evaporation method for application as cathode in lithium-sulfur batteries is reported. We show that the synthesis process enables the infiltration of elemental sulfur within the carbon nanohorns thus obtaining a morphology responsible for the ameliorating of the shuttle effect. The sulfur-carbon composite is characterized in terms of structure, morphology, and composition through x-ray diffraction, transmission electron microscopy, and thermogravimetric analyses. From the electrochemical point of view, cyclic voltammetry, rate capability, and galvanostatic cycling tests are performed employing a solution of bis(trifluoromethane)sulfonimide lithium salt and lithium nitrate in a mixture of 1,2-dimethoxyethane and 1,3-dioxolane in order to evaluate the electrode design applicability within lithium-sulfur cells. In this respect, further insights are provided by the estimation of the lithium-ion diffusion coefficient through the Randles-Sevcik equation, and by electrochemical impedance spectroscopy. The obtained results reveal a remarkable cycle life lasting around 800 cycles with a stable capacity of 520 mA h g-1 for the first 400 cycles at C/4, while reaching a value around 300 mA h g-1 at the 750th cycle. These results suggest sulfur-carbon nanohorns active material as a potential candidate for the next-generation battery technology.

In this contribution, we present a high-speed multiplex grating spectrometer based on a spectral coding approach that is founded on principles of compressive sensing. The spectrometer employs a single-pixel InGaAs detector to measure the signals encoded by an amplitude spatial light modulator (digital micromirror device, DMD). This approach leads to a speed advantage and multiplex sensitivity advantage atypical for standard dispersive systems. Exploiting the 18.2 kHz pattern rate of the DMD, we demonstrate 4.2 ms acquisition times for full spectra with a bandwidth of 450 nm (5250 cm-1 – 4300 cm-1; 1.9 µm – 2.33 µm). Due to the programmability of the DMD, spectral regions of interest can be chosen freely, thus reducing acquisition times further, down to the sub-millisecond regime. The adjustable resolving power of the system accessed by means of computer simulations is discussed, quantified for different measurement modes, and verified by comparison with a state-of-the-art Fourier-transform infrared spectrometer. We show measurements of characteristic polymer absorption bands in different operation regimes of the spectrometer. The theoretical multiplex advantage of 8 was experimentally verified by comparison of the noise behavior of the spectral coding approach and a standard line-scan approach.

A single coronary artery is a very rare condition, commonly associated with other congenital anomalies. It could be generally classified as neither benign nor malignant form of congenital coronary artery anomalies since its pathophysiological and clinical implications grossly depend on different anatomical patterns defined by the site of origin and distribution of the branches. By presenting the patient with an isolated single coronary artery, who underwent successful combined aortic valve replacement and coronary artery bypass grafting surgery, we intend to distinguish casual from causal in this extremely rare clinical and surgical scenario. This is the first-ever case published, combining such underlying pathology, clinical presentation, and surgical treatment.

Single molecule de novo protein sequencing based on the 'superspecificity' of amino-acyl tRNA synthetases (aaRS) is proposed. An unfolded protein molecule is threaded through a nanopore in an electrolytic cell (e-cell) to expose the terminal residue in the e-cell's trans chamber. After the residue is cleaved with an exopeptidase, a set of tRNAs, their aaRSs, and ATP are added to trans. An aaRS charges a cognate tRNA molecule with the residue. The charged tRNA (along with the other reactants) is transferred to an extended e-cell with N (20 ≤ N ≤ 61) pores in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is exposed in trans. The charged tRNA's anticodon base-pairs with the terminal codon of an RNA. If tRNAs and residues are fluorescently tagged with two different colors, the residue can be identified from the observed position of the resulting color pair. As charging is 'superspecific' identification is unambiguous. The protein molecule in the first e-cell is advanced by one residue and the process repeated. In this approach there is no need for precise pore current or optical intensity measurements. Potential implementation issues are discussed. Other possibilities, including one in which the terminal residue is cleaved after charging, are also examined.

A review of influence of drag-reducing agents on curved pipe flows is presented in this work. In addition, this review outlined proposed mechanism, friction factor and fluid flux models for drag-reducing agents in curved pipe flows. Our finding reveals that drag reduction by additives in curved pipes is quite significant but generally lower than the corresponding drag reduction in straight pipes. It decreases with increase in curvature ratio and more pronounced in the transition and turbulent flow regimes. Drag reduction strongly depends on the polymers and surfactants’ concentrations as well as the bubble fraction of micro-bubbles. It is also reported that drag reduction in curved pipes depends on temperature and existence of dissolved salts in the fluids. Maximum drag reduction asymptote differed between straight and curved pipes and between polymer and surfactant. No definite conclusion could be drawn as regards drag reduction for two-phase flow in curved pipes due to the limited studies in this area. Many questions such as the mechanism of drag reduction in curved pipes and how drag-reducing agents interact with secondary flows still remained unanswered. Hence, some research gaps have been identified with recommendations for areas of future researches.

New flaxseed cultivars differing in seed mucilage content (MC) with low hull content (HC) represent an attractive option to simultaneously target the food and feed markets. Here, a genome-wide association study (GWAS) was conducted for MC and HC in 200 diverse flaxseed accessions genotyped with 1.7 million SNP markers. The data obtained for MC and HC indicated a broad phenotypic variation and high (~70%) and a moderate (~49%) narrow sense heritability, respectively. MC and HC did not differ statistically between fiber and oil morphotypes, but yellow-seeded accessions had 2.7% less HC than brown-seeded ones. The genome wide linkage disequilibrium (LD) decayed to r2 = 0.1 at a physical distance of ~100 Kb. Seven and four QTL were identified for MC and HC, respectively. Promising candidate genes included Linum usitatissimum orthologs of the Arabidopsis thaliana genes TRANSPARENT TESTA 8, SUBTILISIN-LIKE SERINE PROTEASE, GALACTUROSYL TRANSFERASE-LIKE 5, MUCILAGE-MODIFIED 4, AGAMOUS-LIKE MADS-BOX PROTEIN AGL62, GLYCOSYL HYDROLASE FAMILY 17 and UDP-GLUCOSE FLAVONOL 3-O-GLUCOSYLTRANSFERASE that have been shown to play a role in mucilage synthesis and release, seed coat development and anthocyanin biosynthesis in A. thaliana were identified. The favorable alleles will be useful in flaxseed breeding towards the goal of achieving the ideal flaxseed cultivars for food and feed by genomic-based breeding.

This paper proposes a single-stage asymmetrical half-bridge fly-back (AHBF) converter with resonant mode using dual-mode control. The presented converter has an integrated boost converter and asymmetrical half-bridge fly-back converter and operates in resonant mode. The boost-cell always operates in discontinuous conduction mode (DCM) to achieve high power factor. The presented converter operates simultaneously using a variable-frequency-controller (VFC) and pulse-width-modulation (PWM) controller. Unlike the conventional single-stage design, the intermediate bus voltage of this controller can be regulated depending on the main power switch duty ratio. The asymmetrical half-bridge fly-back converter utilizes a variable switching frequency controller to achieve the output voltage regulation. The asymmetrical half-bridge fly-back converter can achieve zero-voltage-switching (ZVS) operation and significantly reduce the switching losses. Detailed analysis and design of this single-stage asymmetrical half-bridge fly-back converter with resonant mode is described. A wide AC input voltage ranging from 90 to 264 Vrms and output 19 V/ 120 W prototype converter was built to verify the theoretical analysis and performance of the presented converter.

In this paper, a kind of single-walled carbon nanotube nonlinear model is developed, and the strongly nonlinear dynamic characteristics of such carbon nanotubes subjected to random magnetic field are studied. The nonlocal effect of microstructure is considered based on the theory of nonlocal elasticity. The natural frequency of the strongly nonlinear dynamic system is obtained by the energy function method, the drift coefficient and the diffusion coefficient are verified. The stationary probability density function of the system dynamic response is given and the fractal boundary of the safe basin is provided. Theoretical analysis and numerical simulation show that stochastic resonance occurs when varying the random magnetic field intensity. The boundary of safe basin has fractal characteristics and the area of safe basin decreases when the intensity of the magnetic field permeability increases.

All-polyamide composite coated fabric (APCCF) materials were developed and used as the material of construction of textile bioreactors as a replacement of traditional costly steel-/concreate-based bioreactors. Then, APCCF-bioreactor was used to cultivate filamentous fungus Neurospora intermedia to produce ethanol and fungal biomass. The results showed similar performance of the fungus cultivated in stain-less steel bioreactors. Techno-economical analysis for a 5000-m³ APCCF bioreactor for fermentation facility would lead to a reduction of the annual production cost of the facility by $128,000,000 compared to similar stainless-steel processes. The comparative analyses (including mechanical and morphological analyses, density measurements and techno-economical analysis) revealed that the APCCF is a better candidate for material of construction of the textile bioreactor. The APCCF is a 100% recyclable single polymer composite which was prepared from textile production line waste.

In this paper, a new approach to the sliding-mode control of single-phase inverters under linear and non-linear loads is introduced. The main idea behind this approach is to utilize a non-linear, flexible and multi-slope function in controller structure. This non-linear function makes the controller possible to control the inverter by a non-linear multi-slope sliding surface. In general, this sliding surface has two parts with different slopes in each part and the flexibility of the sliding surface makes the multi-slope sliding-mode controller (MSSMC) possible to reduce the total harmonic distortion, to improve the tracking accuracy, and to prevent overshoots leading to undesirable transient-states in output voltage which are occurred when the load current sharply rises. In order to improve the tracking accuracy and to reduce the steady-state error, an integral term of the multi-slope function is also added to the sliding surface. The improved performance of the proposed controller is confirmed by simulations and finally, the results of the proposed approach are compared with a conventional SMC and a SRFPI controller.

Gene electrotransfer is one of the main non-viral methods for intracellular delivery of plasmid DNA, wherein pulsed electric fields are used to transiently permeabilize the cell membrane allowing enhanced transmembrane transport. By localizing the electric field over small portions of the cell membrane using nanostructured substrates, it is possible to increase considerably the gene electrotransfer efficiency while preserving cell viability. In this study, we design an electrotransfer approach based on commercially available cell culture inserts with polyethylene-terephthalate (PET) porous substrate. We first use multiscale numerical modelling to determine the pulse parameters, substrate pore size, and other factors that are expected to result in successful gene electrotransfer. Based on numerical results we design a simple device combining an insert with substrates containing pores with 0.4 um and 1.0 um diameter, a multiwell plate, and a pair of wire electrodes. We test the device in three mammalian cell lines and obtain transfection efficiencies similar to those achieved with bulk electroporation, but with low-voltage pulses that do not require the use of expensive electroporators. Our combined theoretical and experimental analysis calls for further systematic studies that will investigate the influence of substrate pore size and porosity on gene electrotransfer efficiency and cell viability.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

This study aimed to optimize the bioelectricity production process using a vinasse solution through the application of Plackett-Burman and Box-Behnken designs. An electrochemical cell was constructed using Arduino to measure the potential difference between the anode and cathode immersed in the vinasse solution, a byproduct of wine production containing organic compounds and ions that undergo redox reactions. The Plackett-Burman design identified the most influential variables among eight previously selected, including vinasse concentration, agitation, and yeast, which positively affected millivolt production, while temperature showed a negative correlation. Based on these results, the Box-Behnken design was used for process optimization, varying parameters such as concentration, stirring, and sodium chloride. Response surface graphs demonstrated the relationship between these variables and millivolt production. The findings indicate that higher agitation levels, lower concentrations of vinasse, and the addition of sodium chloride can enhance bioelectricity generation. The study provides insights into the bioelectricity production process from vinasse, contributing to the understanding and potential for sustainable energy generation. The methodology involving Arduino-based measurement and the utilization of experimental designs offers a systematic approach to optimize bioelectricity production from vinasse.

Cellular response to mechanical stimuli is a crucial factor for maintaining cell homeostasis. The interaction between extracellular matrix and mechanical stress plays a significant role in organ-izing the cytoskeleton and aligning cells. Tools that apply mechanical forces to cells and tissues, as well as those capable of measuring the mechanical properties of biological cells, have greatly contributed to our understanding of fundamental mechanobiology. These tools have been exten-sively employed to unveil the substantial influence of mechanical cues on the development and progression of various diseases. In this report, we present an economical and high-performance uniaxial cell stretching device. This paper reports the detailed operation concept of the device, ex-perimental design, and characterization. The device was tested with MDA-MB-231 breast cancer cells. Experimental results agree well with previously documented morphological changes re-sulting from stretching forces on cancer cells. Remarkably, our new device demonstrates compa-rable cellular changes within a 30-minute compared to the previous 2-hour stretching duration. Moreover, the device design incorporates an open-source software interface, facilitating conven-ient parameter adjustments such as strain, stretching speed, frequency, and duration. Its versatil-ity enables seamless integration with various optical microscopes, thereby yielding novel insights into the realm of mechanobiology.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

Retinitis pigmentosa (RP) is a frequent cause of blindness among the working population in industrial countries, due to the inheritable death of photoreceptors. Though a gene therapy was recently approved for mutations in the RPE65 gene, there is generally no effective treatment presently. Previously, abnormally high-level cGMP and overactivation of its dependent protein kinase (PKG) have been suggested as causative for the fatal effects on photoreceptors, making it meaningful to explore the cGMP-PKG downstream signaling for more pathological insights and novel therapeutic target development purposes. Here we manipulated the cGMP-PKG system in degenerating retinas from the rd1 mouse model pharmacologically via adding a PKG inhibitory cGMP-analogue to organotypic retinal explant cultures. A combination of phosphorylated peptides enrichment and mass spectrometry was then applied to study the cGMP-PKG-dependent phosphoproteomics. We identified a host of novel potential cGMP-PKG downstream substrates and related kinases using this approach, and selected the RAF1 protein, which may act as both a substrate and a kinase, for further validation. We showed that the RAS/RAF1/MAPK/ERK pathway may be involved in retinal degeneration in a yet unclarified mechanism, thus deserving further investigation in the future.

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

Necroptosis is an inflammatory form of lytic programmed cell death that is thought to have evolved to defend against pathogens. Genetic deletion of the terminal effector protein – MLKL – shows no overt phenotype in the C57BL/6 mouse strain under conventional laboratory housing conditions. Small molecules that inhibit necroptosis by targeting the kinase activity of RIPK1, one of the main upstream conduits to MLKL activation, have shown promise in several murine models of non-infectious disease and in phase II human clinical trials. This has triggered multi-billion-dollar investments into the emerging class of necroptosis blocking drugs, and the potential utility of targeting the terminal effector is being closely scrutinised. Here we review murine models of disease, both genetic deletion and mutation, that investigate the role of MLKL. We summarize a series of examples from several broad disease categories including ischemia reperfusion injury, sterile inflammation, pathogen infection and haematological stress. Elucidating MLKL’s contribution to mouse models of disease is an important first step to identify human indications that stand to benefit most from MLKL-targeted drug therapies.

Magnetic Particle Imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs). Many labs have been developing cellular magnetic resonance imaging (MRI) tools using both SPIONs and fluorine-19 (19F)-based contrast agents for numerous important applications, including tracking of immune and stem cells used for cellular therapies. SPION-based MRI cell tracking has very high sensitivity, but low specificity. SPIONs produce negative contrast in MRI, or signal voids. SPIO is not directly detected by MRI, but indirectly through its relaxation effects on protons, therefore, it is not possible to reliably quantify the local tissue concentration of SPION particles and cell number cannot be determined. 19F based cell tracking uses perfluorocarbons (PFC) to label cells. The number of 19F atoms can be directly measured from 19F MR images and related to cell number. 19F MRI has high specificity, but low sensitivity. MPI cell tracking displays great potential for overcoming the challenges of MRI-based cell tracking allowing for both high cellular sensitivity and high specificity and quantification of SPIO labeled cell number. In this paper we describe nanoparticle and MPI system factors that influence MPI sensitivity and resolution, quantification methods and give our perspective on testing and applying MPI for cell tracking.

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.

Propagation of human cytomegalovirus (CMV) in cultured cells results in genetic adaptations that confer improved growth in vitro and significant attenuation in vivo. Mutations in RL13 arise quickly during cell culture passage, while mutations in the UL128-131A locus emerge later during fibroblast passage and disrupt expression of a glycoprotein complex that is important for entry into epithelial and endothelial cells. As in vivo CMV replicates in the context of host antibodies, we reasoned that antibodies might mitigate the accumulation of adaptive mutations during cell culture passage. To test this, CMV in infant urine was used to infect replicate fibroblast cultures. One lineage was passaged in the absence of CMV-hyperimmuneglobulin (HIG) while the other was passaged with HIG in the culture medium. The former lost epithelial tropism and aquired mutations disrupting RL13 and UL131A expression, whereas the latter retained epithelial tropism and both gene loci remained intact after 22 passages. An epitheliotropic RL13+/ UL131A+ virus was isolated by limiting-dilution in the presence of HIG and expanded to produce a working stock sufficient to conduct cell tropism experiments. Thus, culture in the presence of antibodies may facilitate in vitro experiments using viruses that are genetically more authentic than has been previously possible.

Cellular response to mechanical stimuli is an integral part of cell homeostasis. The interaction of the extracellular matrix with the mechanical stress plays an important role in cytoskeleton organisation and cell alignment. Insights from the response can be utilised to develop cell culture methods that achieve predefined cell patterns, which are critical for tissue remodelling and cell therapy. We report the working principle, design, simulation and characterisation of a novel electromagnetic cell stretching platform based on the double-sided axial stretching approach. The device is capable of introducing a cyclic and static strain pattern on a cell culture. The platform was tested with fibroblasts. The experimental results are consistent with the previously reported cytoskeleton reorganisation and cell reorientation induced by strain. The orientation of the cells is highly influenced by external mechanical cues. Cells reorganise their cytoskeleton to avoid external strain and to maintain intact extracellular matrix arrangements.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Tight junctions (TJ) are cell-cell adhesive structures that define the permeability of barrier-forming epithelia and endothelia. In contrast to this seemingly static function, TJs display a surprisingly high molecular complexity and an unexpected dynamic regulation, which allows the TJs to maintain a barrier in the presence of physiological forces and in response to perturbations. Cell-cell adhesion receptors play key roles during the dynamic regulation of TJs. They connect individual cells within cellular sheets and link sites of cell-cell contacts to the underlying actin cytoskeleton. Recent findings support roles of adhesion receptors in transmitting mechanical forces and promoting phase separation. In this review, we discuss newly discovered functions of cell adhesion receptors localized at the TJs and their role in the regulation of the barrier function.

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive creating immunocompromised conditions or hyperactive causing autoimmune tissue destruction. Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Dielectric spectroscopy (DS) is a promising cell screening method that can be used for diagnostic and drug discovery purposes. The primary challenge of using DS in physiological buffers is the electrode polarization (EP) that overwhelms the impedance signal within a large frequency range. These effects further amplify with miniaturization of the measurement electrodes. In this study, we present a microfluidic system and the associated equivalent circuit models for real-time measurements of cell membrane capacitance and cytoplasm resistance in physiological buffers with 10s increments. The current device captures several hundreds of biological cells in individual microwells through gravitational settling and measures the system’s impedance using microelectrodes covered with dendritic gold nanostructures. Using PC-3 cells (a highly metastatic prostate cancer cell line) suspended in cell growth media (CGM), we demonstrate stable measurements of cell membrane capacitance and cytoplasm resistance in the device for over 15 minutes. We also describe a consistent application of the equivalent circuit model, starting from the reference measurements used to determine the system parameters. The circuit model is tested using devices with varying dimensions, and the obtained cell parameters between different devices are nearly identical. Further analyses of the impedance data have shown that accurate cell membrane capacitance and cytoplasm resistance can be extracted using a limited number of measurements in the 5 MHz to 10 MHz range. This will potentially reduce the timescale required for real-time DS measurements below 1s. Overall the new microfluidic device can be used for dielectric characterization of biological cells in physiological buffers for various cell screening applications.

Background/methods: For mechanistic studies, in vitro human B cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T cell-dependent (TD) and T cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols makes interpretation of results challenging. The aim of the present study was to achieve the most optimal B cell differentiation conditions using isolated CD19⁺ B cells and PBMC cultures. We addressed multiple seeding densities, different durations of culturing and various combinations of TD stimuli and TI stimuli including B cell receptor (BCR) triggering. B cell expansion, proliferation and differentiation was analyzed after 6 and 9 days by measuring B cell proliferation and expansion, plasmablast and plasma cell formation and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared. Results: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B cell and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2500 and 25.000 B cells per culture well for TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B cell cultures, which allows dismissal of additional B cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed little effect on phenotypic B cell differentiation, however it interferes with Ig secretion measurements. Addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B cell differentiation and Ig secretion in B cell but not in PBMC cultures. With this approach, efficient B cell differentiation and Ig secretion was accomplished when starting from fresh or cryopreserved samples. Conclusion: Our methodology demonstrates optimized TD and TI stimulation protocols for more indepth analysis of B cell differentiation in primary human B cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B cell differentiation of patient samples from different cohorts of B cell-mediated diseases.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point-patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups, and multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; P = .04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs 37μm, respectively; P < .001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT response. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the possible pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PFA) autoantibodies.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

With ongoing colony losses driven in part by the Varroa mite and the associated exacerbation of virus load, there is an urgent need to protect honey bees (Apis mellifera) from fatal levels of virus infection and from nontarget effects of insecticides used in agricultural settings. A continuously replicating cell line derived from the honey bee would provide a valuable tool for study of molecular mechanisms of virus – host interaction, for screening of antiviral agents for potential use within the hive, and for assessment of the risk of current and candidate insecticides to the honey bee. However, the establishment of a continuously replicating, honey bee cell line has proved challenging. Here we provide an overview of attempts to establish primary and continuously replicating hymenopteran cell lines, methods (including recent results) for establishing honey bee cell lines, challenges associated with the presence of latent viruses (especially Deformed wing virus), in established cell lines and methods to establish virus-free cell lines. We also describe the potential use of honey bee cell lines in conjunction with infectious clones of honey bee viruses for examination of fundamental virology.

Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumor models. The complex tumor microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Facial recognition systems are widely used systems around the globe. Their applications in real world scenarios like law enforcement, surveillance, ID card identification, information security, access control and many more has made them very important in today’s world. These systems have shown promising results and excellent performance; however, these systems need tremendous number of facial images for training before they are implemented in the real-world scenarios. The problem arises when we face lack of training images due to which the performance of such systems decreases exponentially. The problem becomes even worse when there is only one image per subject for training our facial recognition system, the probe image might contain variation like illumination, expression and disguise which are hard to be accurately recognized. Generative models have achieved great success for handling the lack of training data by generating synthetic data that resembles the original data. We have created a new method by fine tuning the basic Conditional Generative Adversarial Network (CGAN) to generate synthetic facial images provided only single image per subject. These synthetic facial images contain six variations that are smile, anger, stare, illumination and disguise. We increased the size of the dataset and then applied a convolutional neural network for facial recognition, which improved the accuracy of our system from 0.76 to 0.99.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents and 75 with a single incision sling. The ICIQ-UI-SF, PISQ-12, FSFI, FSDS, and PGI-I were used to assess efficiency and quality of life. In the 29-month follow-up, the bulking agents showed significantly increased efficacy and safety. Compared to the ones treated with a single-incision sling, the patients treated with bulking agents showed less and mild postoperative complications. Furthermore, at our follow-up there was no discernible difference in terms of effectiveness or quality of life between patients treated with bulking agents and those treated with single-incision slings

Recently, the indications for Cochlear Implant (CI) have also been extended to subjects with Single Sided Deafness (SSD) in order to restore binaural hearing. The primary objective of this study was to investigate the advantages of CI following one year of usage in SSD subjects. Secondarily we want to assess the long-term stability of the CI. 57 participants performed a complete audiological assessment (speech audiometry in quiet and in noise and localization test). For each was also evaluated subjective hearing profile (with Speech Spatial and Qualities_SSQ questionnaire) and the impact of tinnitus (with the use of Tinnitus Handicap Inventory_THI questionnaire) After one year of CI usage, we observed a significant improvement in speech-to-noise ratio, in sound localization abilities, in the Speech (p-value 0.001) and Spatial (p-value 0.001) subscales of the SSQ questionnaire and in THI questionnaire (p-value 0.001). The improvements in speech in noise and localization abilities and the reduction of the SSQ and THI questionnaires scores were maintained over time (6th to 60th month follow-up). Only eight participants did not fully utilize the CI. CI in SSD represents an effective method for improving speech recognition in noisy environments, restoring sound localization abilities, reducing tinnitus and improve subjective listening skills.

CubeSats, known for their compact size and cost-effectiveness, have gained significant popularity. However, their limited size imposes restrictions on optical aperture and, consequently, Ground Resolution Distance in Earth Observation missions. To overcome this limitation, the concept of deployable optical payloads with segmented primary mirrors which can unfold like petals has emerged, enabling larger synthetic apertures and enhanced spatial resolution. This study explores the potential benefits of leveraging Additive Manufacturing (AM) and Topology Optimization (TO) in the realm of ultra-precision machining, specifically single point diamond machining. The goal is to reduce fixture weight while improving stiffness to minimize deformations caused by rotational and cutting forces which compromise optical performance. Through Finite Element Analysis, this research compares conventionally machined fixtures with those produced using AM and TO techniques. The results reveal that concept designs created through TO can achieve a remarkable 68% reduction in weight. This reduction makes the assembly, including the machining fixture and 12U deployable segments, manageable by a single operator without the need for specialized lifting equipment. Moreover, these innovative designs lead to substantial reductions of up to 86% and 51% in deformation induced by rotational and cutting forces, respectively.

Single crystals of quaternary adamantine type Cu•GaGeS4 were grown by chemical vapor transport technique using iodine as transport agent. Dark red transparent crystals grew in a temperature gradient of dT = 900–750 °C. Chemical characterization by X-ray fluorescence showed an off-stoichiometric composition of the Cu•GaGeS4 crystals, in particular a slight Ge-deficit. By X-ray diffraction, Cu•GaGeS4 was found to adopt the chalcopyrite-type structure with the space group I-42d. The cation distribution in this structure was analyzed by multiple energy anomalous synchrotron X-ray diffraction and it was found that Cu and vacancies occupy the 4a site, whereas Ga and Ge occupy the 4b site. The band gap energies of several off-stoichiometric Cu•GaGeS4 crystals were determined by UV-Vis spectroscopy and are in the range of 2.1 to 2.4 eV. A non-linear correlation of the band gap energy with the Ge-content of the compound follows the usual bowing behaviour of semiconductor alloys with a bowing parameter of b = 1.45(0.08).

Functional dependence of the axial zero-field splitting parameter D with respect to a properly chosen geometrical parameter (Dstr) in metal complexes is termed the Magnetostructural D-Correlation. In mononuclear hexacoordinate Ni(II) complexes with the ground electronic term 3B1g (3A2g in the regular octahedron) it proceeds along two intercepting straight lines allowing to predict the sign and magnitude of the D-parameter by knowing the X-ray structure alone; Dstr is constructed from the metal-ligand bond lengths. In hexacoordinate Co(II) complexes it is applicable only in the segment of the compressed bipyramid where the ground electronic term 4B1g is orbitally non-degenerate so that the spin Hamiltonian formalism holds true. The D vs Dstr correlation is strongly non-linear and it is represented by a set of decreasing exponentials. In tetracoordinate Co(II) complexes, on the contrary, the angular distortion from the regular tetrahedron is crucial so that the appropriate structural parameter Dstr is constructed of bond angles. All of these empirical correlations originate in the electronic structure of metal complexes that can be modelled by the generalized crystal-field theory. As the barrier to spin reversal in the single-molecule magnets is proportional to the D-value, for a rational tuning and/or prediction of the single-molecule magnetic behavior knowledge/prediction of the D-parameter is beneficial. In this review, we present the statistical processing of an extensive set of structural and magnetic data of Co(II) and Ni(II) complexes, which were published over the past 15 years. Magnetostructural D-correlations defined for this data set are reviewed in detail.

Building carbon footprint analysis is a key instrument for assessing the impact of different constructions on climate change. Several standards and methodologies are available to calculate the footprint of buildings, including standards and norms, life cycle assessment (LCA), and dedicated software tools. The use of BIM software for these calculations is both scientifically justified and very practical. This scientific publication focusses on the application of a BIM-based research methodology for the analysis of the carbon footprint of a single-family house. The research process included the following steps: (i) design of a single-family house with timber frame construction using Archicad BIM software, (ii) simulation of the building energy performance using the EcoDesigner Star plug-in, (iii) life cycle assessment (LCA) using the plug-in for Archicad, (iv) preparation of a second model with traditional masonry construction for comparison, and (v) comparative analysis of the single-family house models with timber frame and masonry construction. Analysis of the results highlights significant differences in CO2e emissions between masonry and timber buildings and the varying impact of individual elements on the total CO2e emissions of the buildings studied. These findings are relevant for future work on sustainable building design and construction, which aims to minimise negative environmental impacts. The goal of minimising the cumulative carbon footprint of buildings is critical to achieving the Sustainable Development Goals and combating climate change.

Dendrite growth and parasitic reactions with liquid electrolyte are the two key factors that restrict the practical application of the lithium metal anode. Herein, a bis(benzene sulfonyl)imide based single-ion polymer artificial layer for lithium metal anode is successfully constructed, which is prepared via blending the as-prepared copolymer of lithiated 4, 4’-dicarboxyl bis(benzene sulfonyl)imide and 4,4’-diaminodiphenyl ether on the surface of lithium foil. This single-ion polymer artificial layer enables compact structure with unique continuous aggregated Li+ clusters, thus reducing the direct contact between lithium metal and electrolyte, and ensuring Li+ transport fast and homogeneous simultaneously. Based on which, the coulombic efficiency of the Li|Cu half-cell is effectively improved, and the cycle stability of the Li|Li symmetric cell can be prolonged from 160 h to 240 h. Surficial morphology and elemental valence analysis confirm that the bis(benzene sulfonyl)imide based single-ion polymer artificial layer effectively facilitates the Li+ uniform deposition and suppresses parasitic reactions between lithium metal anode and liquid electrolyte in the LFP|Li full-cell. This strategy provides a new perspective to achieve steady lithium metal anode, which can be a promising candidate in practical application.

There have been several developments in the field of nanopore biosensor development and sequencing applications that address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making these platforms a mainstay in contemporary research labs. Equipped with the ability to provide long and short-read sequencing information with quick turn-around times and simple sample preparation, nanopore sequencers are quickly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We conclude with examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

Being hospitalized is a threatening and stressful experience for many children. From a psychological point of view, children may experience increased feelings of anxiety and fear that can negatively interfere with behavioral, cognitive, and emotional outcomes. To limit these impacts on children's well-being and mental health, interventions that could contribute to protecting the emotional domain of hospitalized children are welcomed. The present research reported a single-setting case study intervention to evaluate the impact of educational play-based activity with a CoderBot robot in a pediatric short-term recovery ward (N=61). The methodology included multiple sources of data (i.e., children, parents, nurses), observations on the field, and a sequential (quantitative-qualitative) mixed-method approach to data analysis. Results supported the idea that robot-based activities were associated with increased participant well-being (particularly positive emotions). The conclusions of this pilot study discuss the strengths, limitations, and further developments of using robots with hospitalized children.

The application of optimization techniques to improve the performance of polymer processing technologies is of great practical consequence, since it may result in significant savings of materials and energy resources, assist recycling schemes and generate products with better properties. The present review aims at identifying and discussing the most important characteristics of polymer processing optimization problems in terms of the nature of the objective function, optimization algorithm, and process modelling approach that is used to evaluate the solutions and the parameters to optimize. Taking into account the research efforts developed so far, it is shown that several optimization methodologies can be applied to polymer processing with good results, without demanding important computational requirements. Also, within the field of artificial intelligence, several approaches can be reach significant success. The first part of this review demonstrated the advantages of the optimization approach in polymer processing, discussed some concepts on multi-objective optimization and reported the application of optimization methodologies in single and twin screw extruders, extrusion dies and calibrators. This second part focus on injection molding, blow molding and thermoforming technologies.

Given the global economic and societal importance of the polymer industry, the continuous search for improvements in the various processing techniques is of practical primordial importance. This review evaluates the application of optimization methodologies to the main polymer processing operations. The most important characteristics related with the usage of optimization techniques, such as the nature of the objective function, the type of optimization algorithm, the modelling approach used to evaluate the solutions, and the parameters to optimize, are discussed. The aim is to identify the most important features of an optimization system for polymer processing problems, and define the best procedure for each particular practical situation. For this purpose, a state-of-the-art of the optimization methodologies usually employed is first presented, followed by an extensive review of the literature dealing with the major processing techniques, the discussion being completed by considering both the characteristics identified and the available optimization methodologies. This first part of the review focus on extrusion, namely extruders, extrusion dies and calibrators. It is concluded that there is a set of methodologies that can be confidently applied in polymer processing, with a very good performance and without the need of demanding computation requirements.

Single sample face recognition (SSFR) is a computer vision challenge. In this scenario, there is only one example from each individual on which to train the system, making it difficult to identify persons in unconstrained environments, particularly when dealing with changes in facial expression, posture, lighting, and occlusion. This paper suggests a different method based on a variant of the Binarized Statistical Image Features (BSIF) descriptor called Multi-Block Color-Binarized Statistical Image Features (MB-C-BSIF) to resolve the SSFR Problem. First, the MB-C-BSIF method decomposes a facial image into three channels (e.g., red, green, and blue), then it divides each channel into equal non-overlapping blocks to select the local facial characteristics that are consequently employed in the classification phase. Finally, the identity is determined by calculating the similarities among the characteristic vectors adopting a distance measurement of the k-nearest neighbors (K-NN) classifier. Extensive experiments on several subsets of the unconstrained Alex &amp; Robert (AR) and Labeled Faces in the Wild (LFW) databases show that the MB-C-BSIF achieves superior results in unconstrained situations when compared to current state-of-the-art methods, especially when dealing with changes in facial expression, lighting, and occlusion. Furthermore, the suggested method employs algorithms with lower computational cost, making it ideal for real-time applications.

Background: Developing patient-centric baseline standards that enable the detection of clinically significant outlier gene products on a genome-scale remains an unaddressed challenge required for advancing personalized medicine beyond the small pools of subjects implied by “precision medicine”. This manuscript proposes a novel approach for reference standard development to evaluate the accuracy of single-subject analyses of metabolomes, proteomes, or transcriptomes. Since distributional assumptions of statistical testing may inadequately model genome dynamics of gene products, the so-called significant results of previous studies may artefactually conflate with real signals. Model confirmation biases escalate when studies use the same analytical methods in the discovery sets and reference standards, as corroboration of results leads to an evaluation of reproducibility confounded with replicated biases rather than a measure of accuracy. We hypothesized that developing method-agnostic reference standards using effect-size and expression-level filtering of results, obtained from multiple discovery methods that are distinct from the one evaluated, would maximize the evaluation of clinical-transcriptomic signals and minimize statistical artefactual biases. We developed and released an R package “referenceNof1” to facilitate the construction of robust reference standards. Results: Since RNA-Seq data analysis methods often rely on binomial and negative binomial assumptions to non-parametric analyses, the differences create statistical noise and make the reference standards method dependent. In our experimental design, the accuracy of 30 distinct combinations of fold changes (FC) and expression levels (EL) were determined for five types of RNA analyses in two different datasets. This design was applied to two distinct datasets: breast cancer cell lines and a yeast study with isogenic biological replicates in two experimental conditions. In addition, the reference standard (RS) comprised all RNA analytical methods with the exception of the method testing accuracy. To mitigate for biased optimization of the RS parameters towards a specific analytical method, similarity between observed results of distinct analytical methods were calculated across all methods (Jaccard Concordance Index). The greatest differences were observed across diametric extremes. For example, filtering out differentially expressed genes (DEGs) using a fold change < 1.2 leads to a 50% increase in concordance between techniques when compared to results with FC > 1.2. Combining this FC cutoff with genes with mean expressions > 30 counts leads to a 65% increase in concordance in comparison to genes with expression levels < 30 counts and with FC < 1.2. Conclusions: We have demonstrated that comparing accuracies of different single-subject analysis methods for clinical optimization requires a new evaluation framework. Reliable and robust reference standards, independent of the evaluated method, can be obtained under a limited number of parameter combinations: fold change (FC) ranges thresholds, expression level cutoffs, and exclusion of the tested method from the RS development process. When applying anticonservative reference standard frameworks (e.g., using the same method for RS development and for prediction), a majority of the concordant signal between prediction and Gold Standard (GS) cannot be confirmed by other methods, which we conclude as biased results. Statistical tests to determine DEGs from a single-subject study generate many biased results that require subsequent filtering for increasing their reliability. Conventional single-subject studies pertain to one or a few measures in one patient over time [1]and need a substantial conceptual framework extension in order to address the tens of thousands of measures in genome-wide analyses of gene products. The proposed referenceNof1 framework addresses some of the inherent challenges in improving transcriptome scale single-subject analyses by providing a robust approach to constructing reference standards. Github: https://github.com/SamirRachidZaim/referenceNof1

This paper presents a concise exploration of several analytical methods for extracting the parameters of the single-diode model (SDM) of a photovoltaic (PV) module under standard test conditions (STC). The paper investigates six methods and presents the detailed mathematical analysis leading to the development of each method. To evaluate the performance of these methods, MATLAB-based software has been developed and deployed to synthesize the results of each method when used to extract the SDM parameters of various PV test modules of different PV technologies. Similar software has also been developed to extract the same parameters using well-established numerical and iterative techniques. A comparison is subsequently made between the synthesized results and those obtained using numerical and iterative methods. The comparison indicates that in spite of the fact that analytical methods may involve fair amount of approximations, their accuracy can be comparable to that of their numerical and iterative counterparts, with the added advantage of significant reduction in computational complexity, and without the initialization and convergence difficulties, which are normally associated with numerical methods.

The model proposed in this study was based on the assumption that the biomass attached to the anode served as biocatalysts for MFC exoelectrogenesis, and this catalytic effect was quantified by the exchange current density of anode. By modifying the Freter model and combining it with the Butler-Volmer equation, this model could adequately describe the processes of electricity generation, substrate utilization, and the suspended and attached biomass concentrations, at both batch and continuous operating modes. MFC performance is affected by the operating variables such as initial substrate concentration, external resistor, influent substrate concentration, and dilution rate, and these variables were revealed to have complex interactions by data simulation. The external power generation and energy efficiency were considered as indices for MFC performance. The simulated results explained that an intermediate initial substrate concentration (about 100 mg/L under this reactor configuration) needed to be chosen to achieve maximum overall energy efficiency from substrate in the batch mode. An external resistor with the value about that of the internal resistance boosted the power generation, and a resistor with several times of that of the internal resistance achieved better overall energy efficiency. At continuous mode, dilution rate significantly impacted the steady-state substrate concentration level (thus substrate removal efficiency and rate), and attached biomass could be fully developed when the influent substrate concentration was equal to or higher than 100 mg/L at any dilution rate of the tested range. Overall, this relatively simple model provided a convenient way for evaluating and optimizing the performance of MFC reactors by regulating operating parameters.

The emerging use of visualization techniques in pathology and microbiol- ogy has been accelerated by machine learning (ML) approaches towards image preprocessing, classification, and feature extraction in an increasingly complex series of datasets. Modern Convolutional Neural Network (CNN) architectures have developed into an umbrella of vast image reinforcement and recognition methods, including a combined classification-localization of single/multi-object featured images. As a subtype neural network, CNN cre- ates a rapid order of complexity by initially detecting borderlines, edges, and colours in images for dataset construction, eventually capable in mapping intricate objects and conformities. This paper investigates the disparities between Tensorflow object detection APIs, exclusively, Single Shot Detector (SSD) Mobilenet V1 and the Faster RCNN Inception V2 model, to sample computational drawbacks in accuracy-precision vs. real time visualization capabilities. The situation of rapid ML medical image analysis is theoretically framed in regions with limited access to pathology and disease prevention departments (e.g. 3rd world and impoverished countries). Dark field mi- croscopy datasets of an initial 62 XML-JPG annotated training files were processed under Malaria and Syphilis classes. Model trainings were halted as soon as loss values were regularized and converged.

Polyamides (PAs) are one of the most important engineering polymers; however, the difficulty in dissolving them hinders their applications. Formic acid (FA) is the most common solvent for PAs, but it has industrial limitations. In this contribution, we proposed a new solvent system for PAs by replacing a portion of the FA with urea and calcium chloride (FAUCa). Urea imparts the hydrogen bonding and calcium ion from the calcium chloride, as a Lewis acid was added to the system to compensate for the pH decrease due to the addition of urea. The results showed that the proposed solvent (FAUCa) could readily dissolve PAs, resulting in less decrease in the mechanical properties during the dissolution. The composite prepared using the FAUCa has almost the same properties like the one prepared using the FA solution. The solution was applied on a polyamide 66 fabric to make an all-polyamide composite coated-fabric, which then was characterized. The FAUCa solution had a higher viscosity than the one prepared using the neat FA solvent, which can be an advantage in the applications which needs higher viscosity like preparing the all-polyamide composite coated-fabric. A more viscouse solution makes a denser coating which will increase the water-/gas-tightness. In conclusion, using the FAUCa solvent has two merits: 1. replacement of 40 % of the FA with less harmful and environmentally-friendly chemicals and 2. enabling for the preparation of more viscouse solutions, which makes denser coating.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.

The fuel cell particularly the Proton Exchange Membrane Fuel Cell (PEMFC) is a new energy technology that plays a critical role in achieving market viability. The PEMFC has high power density, zero CO₂ emissions, and high conversion efficiency. However, with uniform distribution of fuel in PEMFC, we can improve the performance and reduce the cost. The PEMFC will be more efficient and effective in terms of renewable energy as a byproduct only water. Metal foam is used as an alternative for the channels in PEMFC. The model of PEMFC was established by using the ANSYS Fluent 3D Model. Then we proposed four configurations of PEMFC. The outcome demonstrates that Case IV provided outstanding performance if it is compared with the other three cases. In terms of power density, Case IV provided a high power density that is double that of Case I. The porosity of metal foam was investigated. The 0.6 porosity value is found as the optimal value. The uniform distribution of the fuel can be achieved at this value which leads to the outstanding current density.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, which subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer bi-ology and potential therapeutic strategies.

Sarcomas are a group of malignancies of mesenchymal origin with plethora of subtypes. Given the sheer heterogeneity of various subtypes and rarity of the disease, management of sarcomas has been challenging with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has rev-olutionized the treatment of various solid and hematological malignancies. In this review, we discuss basics of immunotherapy and immune microenvironment in sarcomas, various modalities of im-munotherapy such as immune checkpoint blockade, oncolytic viruses, cancer targeted antibodies, vaccine therapy and adoptive cell therapies like CAR T-cell therapy, T cell therapy, TCR therapy.

The human immunodeficiency virus 1 (HIV-1) viral protease (PR) is one of the most studied viral enzymes, and approval of drugs targeting its catalytic activity opened the door to the develop-ment of highly active antiretroviral therapy (HAART). Despite the fact that its crucial role in viri-on maturation is well characterized, an increasing body of research is starting to focus on its abil-ity to cleave host cell proteins, based on recent advances in proteomics and genomics technologies. Such findings are apparently in contrast with the dogma of HIV-1 PR activity being restricted to the interior of nascent virions, and suggest catalytic activity within the host cell environment. Given the limited amount of PR present in the virion at the time of infection, it is tempting to specu-late that such events mainly occur during viral late gene expression, mediated by newly synthe-sized Gag-Pol polyprotein precursors, rather than at a very early stage of infection, before pro-viral integration. Among cellular targets of HIV-1 PR, three major clusters can be identified: pro-teins involved in viral and cellular translation, those controlling cell survival, and restriction fac-tors responsible for innate/intrinsic antiviral responses. Indeed, by cleaving host cell translation initiation factors HIV-1 PR can impair cap-dependent translation, thus promoting IRES-mediated translation of late viral transcripts and viral production, while by targeting several apoptotic fac-tors it modulates cell survival, thus promoting immune evasion and viral dissemination. Addi-tionally, HIV-1 PR counteracts restriction factors incorporated in the virion that would otherwise interfere with nascent virus vitality. Thus, HIV-1 PR appears to modulate host cell function at dif-ferent times and locations during its life cycle, to ensure efficient viral persistency and propaga-tion. This kind of PR-mediated host cell modulation is found in a plethora of different viruses and HIV-1 is no exception, and although we are far from having a complete picture, it is clear that the PR has a multifaceted role in interfering with host machineries to better suit viral replication, and is a field that needs to be explored further.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4 and c-MYC in all samples while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n=6) and reverse-transcription quantitative polymerase chain reaction (n=5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of four primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

Cancer is a disease that encompasses multiple and different malignant conditions and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options and potential candidates that can be used as treatments or adjuvants to control this disease is urgent. Natural products, especially those obtained from plants, have played an important role as a source of specialized metabolites with recognized pharmacological properties against cancer, therefore, they are an excellent alternative to be used. The objective of this research was to evaluate the action of the monoterpene isoespintanol (ISO) against the human tumor cell lines MDA-MB-231, A549, DU145, A2780, A2780-cis and the non-tumor line MRC-5. Experiments with MTT and fluorescence with propidium iodide (PI), DAPI and green plasma revealed the cytotoxicity of ISO against these cells; furthermore, morphological and chromogenic studies revealed the action of ISO on cell morphology and the inhibitory capacity on reproductive viability to form colonies in MDA-MB-231 cells. Likewise, 3D experiments validated the damage in these cells caused by this monoterpene. These results serve as a basis for progress in studies of the mechanisms of action of these compounds and the development of derivatives or synthetic analogues with a better antitumor profile.

Some global difficulties in the modern period include energy storage conversion. Researchers have looked to renewable energy resources to discover long-term answers to this dilemma. Fuel cells are one example of prospective energy producing technology. Although these technologies appear to be very enticing, they are known to be expensive due to high expenses. Catalyst costs, as well as concerns concerning energy density. Pt based Electrocatalysts have traditionally been used to drive ORR and offer efficient power outputs. However, cost constraints have limited the use of these electrocatalysts, rendering them inefficient. Apart from the high price, Pt-based Electrodes are prone to time-dependent drift and CO deactivation, both of which occur gradually. Electrocatalysts deteriorate over time, reducing the efficiency of fuel cells. This is why alternative electrocatalysts are in high demand for future energy applications. This review covers the comparative study of Platinium and Non-Platinium based electrocatalyst in fuel cells, their shortcomings and recent advancement for efficient and optimized electrocatalyst.

The quality of cellular products used in biological research can directly impact the ability to ob-tain accurate results. Epstein-Barr virus (EBV) is a latent virus that spreads extensively world-wide, and cell lines used in experiments may carry EBV and pose an infection risk. The presence of EBV in a single cell line can contaminate other cell lines used in the same laboratory, affecting experimental results. We developed three EBV detection systems: (1) a polymerase chain reac-tion (PCR)-based detection system, (2) a recombinase polymerase amplification (RPA)-based de-tection system, and (3) a combined RPA-lateral flow assay (LFA) detection system. The mini-mum EBV detection limits were 1×103 copy numbers for the RPA-based and RPA-LFA systems and 1×104 copy numbers for the PCR-based system. Both the PCR and RPA detection systems were applied to 192 cell lines, and the results were consistent with those obtained by the EBV assay methods specified in the pharma-ceutical industry standards of the People's Republic of China. 10 EBV-positive cell lines were identified. The combined RPA-LFA system is simple to operate, allowing for rapid results visualization. This system can be implemented in laborato-ries and cell banks as part of a daily quality control strategy to ensure cell quality and experi-mental safety and may represent a potential new technique for the rapid detection of EBV in clinical samples.

This study was conducted to recover valuable metals (silicon and silver) using acid leaching and substitution reactions with copper powder from the pulverized solar cell separated from the PV ribbon. Leaching experiments were conducted according to nitric acid concentration by molar solution as 1M, 2M, and 3M using an ultrasonic cleaner at a reaction temperature of 60 °C for the leaching times of 30 to 120 minutes. Si phases were detected at all leaching reaction times, it was confirmed that the aluminium was removed effectively if the nitric acid leaching time was more than 30 minutes, and silicon with a purity above 99% could be recovered. The silver was precipitated by adding copper, which has greater reducibility than Cu, Al, Si, Pb, and Sn. When the addition of copper powder was 0.75 and 1.0 g, precipitate was produced 0.23 and 0.55 g, respectively. The optimal condition for the recovery of silver by the addition of copper powder was 1 g, where is recovery rate reached 93.3%.